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Abstract Dynamic xanthophyll cycle (XC) related non-photochemical quenching (NPQd, also called qE) is present in most phototrophs. It allows dissipating excess light energy under adverse growing conditions. Generally, NPQd rapidly reverses for photosynthesis to resume when light intensity decreases back toward optimal intensity. Under certain environmental conditions and/or in some species, NPQ can be strongly sustained (NPQs showing hours-to-days relaxation kinetics). Tisochrysis lutea is a South Pacific haptophyte phytoplankton with a strong potential for aquaculture and biotechnology applications. It was previously reported to show a surprisingly low NPQd capacity while synthesizing large amounts of diatoxanthin (Dt), a pigment involved in the XC. In order to better understand this paradox, we investigated the characteristics of NPQ in T. lutea under various growth conditions of light and nutrient availability (different photoperiods, low and high light, nutrient starvations). We found a strong NPQs, unmeasurable with usual fluorometry protocols. Along with confirming the involvement of Dt in both NPQd and NPQs (by using the dithiothreitol inhibitor), we highlighted a strong relationship between Dt and the maximum quantum yield of photochemistry (Fv/Fm) across growing conditions and during relaxation experiments in darkness. It suggests that changes in Fv/Fm, usually attributed to the ‘photoinhibitory’ quenching (qI), are simultaneously largely impacted by photoprotective NPQ. The overlap of xanthophyll pigments-related photoprotective NPQ with several other mechanisms involved in the cell response (Photosystem II photoinactivation, changes in pigments composition, and detoxification by antioxidants) to energy unbalance is further discussed. Our findings question both how widespread NPQs is in the global ocean, particularly in nutrient starved environments (oligotrophic waters) and situations (post-bloom), and the use of adapted active fluorescence protocols (i.e. with extended NPQ relaxation period prior to measurement).

The Green Edge initiative was developed to investigate the processes controlling the primary productivity and fate of organic matter produced during the Arctic phytoplankton spring bloom (PSB) and to determine its role in the ecosystem. Two field campaigns were conducted in 2015 and 2016 at an ice camp located on landfast sea ice southeast of Qikiqtarjuaq Island in Baffin Bay (67.4797∘ N, 63.7895∘ W). During both expeditions, a large suite of physical, chemical and biological variables was measured beneath a consolidated sea-ice cover from the surface to the bottom (at 360 m depth) to better understand the factors driving the PSB. Key variables, such as conservative temperature, absolute salinity, radiance, irradiance, nutrient concentrations, chlorophyll a concentration, bacteria, phytoplankton and zooplankton abundance and taxonomy, and carbon stocks and fluxes were routinely measured at the ice camp. Meteorological and snow-relevant variables were also monitored. Here, we present the results of a joint effort to tidy and standardize the collected datasets, which will facilitate their reuse in other Arctic studies. The dataset is available at https://doi.org/10.17882/59892 (Massicotte et al., 2019a).

The accumulation of dissolved mercury (Hg) by phytoplankton is the largest concentration step along aquatic food chains. However, the cell uptake mechanisms remain unclear. In this study, the marine haptophyte Tisochrysis lutea , a model phytoplankton species, was examined for its interactions with picomolar levels of dissolved inorganic divalent Hg (iHg) and monomethyl Hg (MMHg). For both these Hg species, the study observed their successive sorption and internalization over time, yielding Hg partition coefficients as well as sorption, uptake, and release rates. These results were integrated into a time-dependent, three-compartment model for marine cellular Hg accumulation that included exposure medium, phycosphere, and internalized mercury. Assuming equilibria and pseudo-first-order kinetics between compartments, this study obtained transfer rates of Hg between compartments. The results provide insight into the phycosphere as an intermediate compartment for Hg species accumulation and quantify its role in the internalization of Hg. Ultimately, the new model and its parametrization were successfully applied to literature data showing Hg cellular accumulation in different groups of marine phytoplankton, lending confidence in its robustness and potential contributions to help model the uptake of Hg in the aquatic food web., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Diatoms, the main eukaryotic phytoplankton of the polar marine regions, are essential for the maintenance of food chains specific to Arctic and Antarctic ecosystems, and are experiencing major disturbances under current climate change. As such, it is fundamental to understand the physiological mechanisms and associated molecular basis of their endurance during the long polar night. Here, using the polar diatom Fragilariopsis cylindrus, we report an integrative analysis combining transcriptomic, microscopic and biochemical approaches to shed light on the strategies used to survive the polar night. We reveal that in prolonged darkness, diatom cells enter a state of quiescence with reduced metabolic and transcriptional activity, during which no cell division occurs. We propose that minimal energy is provided by respiration and degradation of protein, carbohydrate and lipid stores and that homeostasis is maintained by autophagy in prolonged darkness. We also report internal structural changes that manifest the morphological acclimation of cells to darkness, including the appearance of a large vacuole. Our results further show that immediately following a return to light, diatom cells are able to use photoprotective mechanisms and rapidly resume photosynthesis, demonstrating the remarkable robustness of polar diatoms to prolonged darkness at low temperature., (© 2023 The Authors. New Phytologist © 2023 New Phytologist Foundation.)

Many harmful algae are mixoplanktonic, i.e. they combine phototrophy and phagotrophy, and this ability may explain their ecological success, especially when environmental conditions are not optimal for autotrophic growth. In this study, laboratory experiments were conducted with the mixotrophic and ichthyotoxic haptophyte Prymnesium parvum (strain CCAP 946/6) to test the effects of phosphorus (P) sufficiency and deficiency on its growth rate, phagotrophic and lytic activities. P-deficient P. parvum cultures were grown without or with addition of P in the form of inorganic phosphorus (nutrients) and/or living algal prey (i.e. the cryptophyte Teleaulax amphioxeia). The ingestion rate of P. parvum and prey mortality rate were calculated using flow cytometry measurements based on pigment-derived-fluorescence to distinguish between prey, predators and digesting predators. The first aim of the study was to develop a method taking into account the rate of digestion, allowing the calculation of ingestion rates over a two-week period. Growth rates of P. parvum were higher in the treatments with live prey, irrespective of the concentration of inorganic P, and maximum growth rates were found when both inorganic and organic P in form of prey were added (0.79 ± 0.07 d -1 ). In addition, the mortality rate of T. amphioxeia induced by lytic compounds was 0.2 ± 0.02 d -1 in the P-deficient treatment, while no mortality was observed under P-sufficiency in the present experiments. This study also revealed the mortality due to cell lysis exceeded that of prey ingestion. Therefore, additional experiments were conducted with lysed prey cells. When grown with debris from prey cells, the mean growth rate of P. parvum was similar to monocultures without additions of prey debris (0.30 ± 0.1 vs. 0.38 ± 0.03 d -1 ), suggesting that P. parvum is able to grow on prey debris, but not as fast as with live prey. These results provide the first quantitative evidence over two weeks of experiment that ingestion of organic P in the form of living prey and/or debris of prey plays an important role in P. parvum growth and may explain its ecological success in a nutrient-limited environments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

At the end of July 2021, a bloom of Lingulodinium polyedra developed along the French Atlantic coast and lasted six weeks. The REPHY monitoring network and the citizen participation project PHENOMER contributed to its observation. A maximum concentration of 3,600,000 cells/L was reached on the 6th of September, a level never recorded on French coastlines. Satellite observation confirmed that the bloom reached its highest abundance and spatial extension early September, covering about 3200 km 2 on the 4th of September. Cultures were established, and morphology and ITS-LSU sequencing identified the species as L. polyedra. The thecae displayed the characteristic tabulation and sometimes a ventral pore. The pigment composition of the bloom was similar to that of cultured L. polyedra, confirming that phytoplankton biomass was dominated by this species. The bloom was preceded by Leptocylindrus sp., developed over Lepidodinium chlorophorum, and was succeeded by elevated Noctiluca scintillans concentrations. Afterwards, relatively high abundance of Alexandrium tamarense were observed in the embayment where the bloom started. Unusually high precipitation during mid-July increased river discharges from the Loire and Vilaine rivers, which likely fueled phytoplankton growth by providing nutrients. Water masses with high numbers of dinoflagellates were characterized by high sea surface temperature and thermohaline stratification. The wind was low during the bloom development, before drifting it offshore. Cysts were observed in the plankton towards the end of the bloom, with concentrations up to 30,000 cysts/L and relative abundances up to 99%. The bloom deposited a seed bank, with cyst concentrations up to 100,000 cysts/g dried sediment, particularly in fine-grained sediments. The bloom caused hypoxia events, and concentrations of yessotoxins up to 747 μg/kg were recorded in mussels, below the safety threshold of 3,750 μg/kg. Oysters, clams and cockles also were contaminated with yessotoxins, but at lower concentrations. The established cultures did not produce yessotoxins at detectable levels, although yessotoxins were detected in the sediment. The unusual environmental summertime conditions that triggered the bloom, as well as the establishment of considerable seed banks, provide important findings to understand future harmful algal blooms along the French coastline., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Two phenylspirodrimanes, never isolated before, stachybotrin J ( 1 ) and new stachybocin G ( epi -stachybocin A) ( 2 ), along with the already reported stachybotrin I ( 3 ), stachybotrin H ( 4 ), stachybotrylactam ( 5 ), stachybotrylactam acetate ( 6 ), 2 α -acetoxystachybotrylactam acetate ( 7 ), stachybotramide ( 8 ), chartarlactam B ( 9 ), and F1839-J ( 10 ) were isolated from the sponge-associated fungus Stachybotrys chartarum MUT 3308. Their structures were established based on extensive spectrometric (HRMS) and spectroscopic (1D and 2D NMR) analyses. Absolute configurations of the stereogenic centers of stachybotrin J ( 1 ), stachybocin G ( 2 ), and stachybotrin I ( 3 ), were determined by comparison of their experimental circular dichroism (CD) spectra with their time-dependent density functional theory (TD-DFT) circular dichroism (ECD) spectra. The putative structures of seventeen additional phenylspirodrimanes were proposed by analysis of their respective MS/MS spectra through a Feature-Based Molecular Networking approach. All the isolated compounds were evaluated for their cytotoxicity against five aggressive cancer cell lines (MP41, 786, 786R, CAL33, and CAL33RR), notably including two resistant human cancer cell lines (786R, CAL33RR), and compounds 5 , 6, and 7 exhibited cytotoxicity with IC 50 values in the range of 0.3-2.2 µM.

Nanoparticles (NPs) are present in many daily life products with particular physical-chemical properties (size, density, porosity, geometry …) giving very interesting technological properties. Their use is continuously growing and NPs represent a new challenge in terms of risk assessment, consumers being multi-exposed. Toxic effects have already been identified such as oxidative stress, genotoxicity, inflammatory effects, and immune reactions, some of which are leading to carcinogenesis. Cancer is a complex phenomenon implying multiple modes of action and key events, and prevention strategies in cancer include a proper assessment of the properties of NPs. Therefore, introduction of new agents like NPs into the market creates fresh regulatory challenges for an adequate safety evaluation and requires new tools. The Cell Transformation Assay (CTA) is an in vitro test able of highlighting key events of characteristic phases in the cancer process, initiation and promotion. This review presents the development of this test and its use with NPs. The article underlines also the critical issues to address for assessing NPs carcinogenic properties and approaches for improving its relevance., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Polar microalgae face two major challenges: 1- growing at temperatures (-1.7 to 5°C) that limit enzyme kinetics; and 2- surviving and exploiting a wide range of irradiance. The objective of this study is to understand the adaptation of an Arctic diatom to its environment by studying its ability to acclimate to changes in light and temperature. We acclimated the polar diatom Chaetoceros neogracilis to various light levels at two different temperatures and studied its growth and photosynthetic properties using semi-continuous cultures. Rubisco content was high, to compensate for low catalytic rates, but did not change detectably with growth temperature. Contrary to what is observed in temperate species, in C. neogracilis, carbon fixation rate (20 min 14C incorporation) equaled net growth rate (μ) suggesting very low or very rapid (<20 min) re-oxidation of the newly fixed carbon. The comparison of saturation irradiances for electron transport, oxygen net production and carbon fixation revealed alternative electron pathways that could provide energy and reducing power to the cell without consuming organic carbon which is a very limiting product at low temperatures. High protein contents, low re-oxidation of newly fixed carbon and the use of electron pathways alternative to carbon fixation may be important characteristics allowing efficient growth under those extreme environmental conditions., Competing Interests: The authors have declared that no competing interests exist.

At high latitudes, the polar night poses a great challenge to photosynthetic organisms that must survive up to six months without light. Numerous studies have already shed light on the physiological changes involved in the acclimation of microalgae to prolonged darkness and subsequent re-illumination. However, these studies have never considered inter-individual variability because they have mainly been conducted with bulk measurements. On the other hand, such long periods are likely to impact within-population selection processes. In this study, we hypothesized that distinct subpopulations with specific traits may emerge during acclimation of a population of diatoms to darkness. We addressed this hypothesis using flow cytometry (FCM), which allow to individually characterize large numbers of cells. The ecologically dominant polar pennate diatom Fragilariopsis cylindrus was subjected to three dark acclimation (DA) experiments of one, three, and five months duration, during which all cultures showed signs of recovery once light became available again. Our results suggest that darkness survival of F. cylindrus relies on reduction of metabolic activity and consumption of carbon reserves. In addition, FCM allowed us to record three different causes of death, each shared by significant numbers of individuals. The first rendered cells were unable to survive the stress caused by the return to light, probably due to a lack of sufficient photoprotective defenses. The other two were observed in two subpopulations of cells whose physiological state deviated from the original population. The data suggest that starvation and failure to maintain dormancy were the cause of cell mortality in these two subpopulations., (© 2022 Phycological Society of America.)

Background: Conduction abnormalities following transcatheter aortic valve replacement (TAVR) often may require permanent pacemaker implantation (PPM)., Objective: The purpose of this study was to evaluate outcomes associated with PPM after a TAVR procedure in a large, nationwide-level population., Methods: Based on the administrative hospital discharge database, the incidence of all-cause death, cardiovascular death, and hospitalization for heart failure (HF) were retrospectively collected, based on the presence or absence of PPM, in the first 30 days following all TAVRs in France from 2010 to 2019., Results: Among 520,662 patients hospitalized for aortic stenosis, 49,201 were treated with TAVR. A total of 29,422 patients had follow-up ≥6 months (median 1.7 years), 22% already had PPM at baseline, and 22% underwent PPM within the first 30 days post-TAVR. Adjusted hazard ratios for the combined risk of all-cause death and hospitalization for HF, during the whole follow-up, were higher in both patients with a previous PPM and in those implanted within 30 days (hazard ratio [95% confidence interval] 1.12 [1.07-1.17] and 1.11 [1.06-1.16], respectively)., Conclusion: PPM at baseline and within 30 days post-TAVR are independently associated with higher mortality and HF hospitalization during follow-up., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Gender-differences in survival following transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) have been suggested. The objective of this study was to analyze outcomes following TAVR according to gender and to compare outcomes between TAVR and SAVR in women, at a nationwide level. Based on the French administrative hospital-discharge database, the study collected information for all consecutive patients treated with TAVR and SAVR between 2010 and 2019. Outcomes were analyzed according to gender and propensity score matching was used for the analysis of outcomes. In total 71,794 patients were identified in the database. After matching on baseline characteristics, we analyzed 12,336 women and 12,336 men treated with TAVR. In a second matched analysis, we compared 9,297 women treated with TAVR and 9,297 women treated with SAVR. Long term follow-up showed lower risk of all-cause death (12.7% vs 14.8%, hazard ratio (HR) 0.85, 95% CI 0.81 to 0.90) in women than men. Although the difference in cardiovascular death remained non-significant (5.8% vs 6.0%, HR 0.96, 95% CI 0.88 to 1.05), non-cardiovascular death was less frequent in women than in men following TAVR (6.9% vs 8.8% HR 0.78, 95%CI 0.72 to 0.84).When TAVR was compared with SAVR in women, long-term follow-up with TAVR showed higher rates of all-cause death (11.2% vs 6.5%, HR 1.91, 95%CI 1.78 to 2.05), cardiovascular death (5.0% vs 3.2%, HR 1.44, 95%CI 1.30 to 1.59), and non-cardiovascular death (6.2% vs 3.3%, HR 2.48, 95% CI 2.25 to 2.72). In conclusion, we observed that women undergoing TAVR have lower long-term all-cause mortality as compared with TAVR in men, driven by non-cardiovascular mortality. SAVR was associated with lower rates of long-term cardiovascular adverse events in women as compared with TAVR., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Important health resources are dedicated worldwide to the management of COVID-19. This new disease, due to its large diffusion, may significantly hamper the prognosis of other pathologies, such as ST-segment elevation myocardial infarction (STEMI) because of (a) a possible direct negative impact and (b) shortage of first response medical resources and increased delays to reperfusion. We report the case of a 68-year-old man admitted for anterior STEMI and asymptomatic COVID-19. Due to extended transportation delays to a cathlab, he received intravenous fibrinolytic therapy, which failed. Reperfusion was achieved with rescue coronary angioplasty, but the patient experienced two episodes of acute stent thrombosis at 2- and 36-hr following admission and despite optimal medical therapy. He finally died because of cardiogenic shock. This raises concerns about a possible increase in platelet aggregability associated with COVID-19 leading to an increased risk of stent thrombosis, particularly in the context of STEMI. This pleads for the promotion of primary coronary angioplasty as the first-choice revascularization technique in this population and the use of new generation P2Y12 inhibitors. In addition, the use of GPIIb/IIIa inhibitors may be considered in every STEMI patient with COVID-19 to prevent the risk of acute stent thrombosis., (© 2020 Wiley Periodicals, Inc.)

Background: Valve-in-valve transcatheter aortic valve implantation (TAVI) has emerged as a treatment for aortic bioprosthesis failure in case of prohibitive risk for redo surgery. However, clinical evaluation of valve-in-valve TAVI remains limited by the number of patients analysed., Aim: To evaluate outcomes of valve-in-valve TAVI compared with native aortic valve TAVI at a nationwide level in France., Methods: Based on the French administrative hospital discharge database, the study collected information for all consecutive patients treated with TAVI for aortic stenosis or with isolated valve-in-valve TAVI for aortic bioprosthesis failure between 2010 and 2019. Propensity score matching was used for the analysis of outcomes., Results: A total of 44,218 patients were found in the database. After matching on baseline characteristics, 2749 patients were analysed in each arm. At 30 days, no significant differences were observed regarding the occurrence of major clinical events (composite of cardiovascular mortality, all-cause stroke, myocardial infarction, major or life-threatening bleeding and conversion to open heart surgery) (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.68-1.01; P=0.32). During follow-up (mean 516 days), the combined endpoint of cardiovascular death, all-cause stroke or rehospitalization for heart failure was not different between the valve-in-valve TAVI and native TAVI groups (RR 1.03, 95% CI 0.94-1.13; P=1.00)., Conclusion: We observed that valve-in-valve TAVI was associated with good short- and long-term outcomes. No significant differences were observed compared with native valve TAVI regarding clinical follow-up., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

A simple and easy way is proposed for the fabrication of a highly attenuating composite material for underwater acoustics. The approach involves the introduction of porous polymer beads into a polyurethane matrix. The porous beads are prepared through an emulsion-templating approach, and two different processes are used. The first one uses microfluidics to synthesize beads of controlled diameter and porosity. The control over the bead size allows the selection of the frequency range where the material exhibits the highest acoustic attenuation. The second one uses a double emulsion approach and allows for the production of much larger quantities of beads. Both approaches yield materials exhibiting much higher acoustic absorption than the one obtained using the most commonly used micro-balloon inclusion. We present both the synthesis procedures and the structural and acoustic characterizations of the beads and the final acoustic materials., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives: Transcatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement (AVR) in aortic stenosis (AS). Infective endocarditis (IE) in patients with prosthetic heart valves is associated with significant morbidity and mortality. Data on the incidence, risk factors, and outcomes of IE after TAVI are conflicting. We evaluated these issues in patients with percutaneous TAVI vs. isolated surgical AVR (SAVR) at a nationwide level., Methods: Based on the administrative hospital discharge database, the study collected information for all patients with aortic stenosis treated with AVR in France between 2010 and 2018., Results: A total of 47 553 patients undergoing TAVI and 60 253 patients undergoing isolated SAVR were identified. During a mean follow-up of 2.0 years (median (25th to 75th percentile) 1.2 (0.1-3.4) years), the incidence rates of IE were 1.89 (95% confidence interval (CI) 1.78-2.00) and 1.40 (95% CI 1.34-1.46) events per 100 person-years in unmatched TAVI and SAVR patients, respectively. In 32 582 propensity-matched patients (16 291 with TAVI and 16 291 with SAVR), risk of IE was not different in patients treated with TAVI vs. SAVR (incidence rates of IE 1.86 (95% CI 1.70-2.04) %/year vs 1.71 (95% CI 1.58-1.85) %/year respectively, relative risk (RR) 1.09, 95% CI 0.96-1.23). In these matched patients, total mortality was higher in TAVI patients with IE (43.0% 95% CI 37.3-49.3) than in SAVR patients with IE (32.8% 95% CI 28.6-37.3; RR 1.32, 95% CI 1.08-1.60)., Discussion: In a nationwide cohort of patients with AS, treatment with TAVI was associated with a risk of IE similar to that following SAVR. Mortality was higher for patients with IE following TAVI than for those with IE following SAVR., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Risk-benefit assessment for transcatheter aortic valve implantation (TAVI) is still a matter of debate. We aimed to identify patients with a bad outcome within 1 year after TAVI, and to develop a Futile TAVI Simple score (FTS). Based on the administrative hospital-discharge database, all consecutive patients treated with percutaneous TAVI in France between 2010 and 2018 were included. A prediction model was derived and validated for 1-year all-cause death after TAVI (considered as futility) by using split-sample validation: 20,443 patients were included in the analysis (mean age 83 ± 7 years). 7,039 deaths were recorded (yearly incidence rate 15.5%), among which 3,702 (53%) occurred in first year after TAVI procedure. In the derivation cohort (n = 10,221), the final logistic regression model included male sex, history of hospital stay with heart failure, history of pulmonary oedema, atrial fibrillation, previous stroke, vascular disease, renal disease, liver disease, pulmonary disease, anaemia, history of cancer, metastasis, depression and denutrition. The area under the curve (AUC) for the FTS was 0.674 (95%CI 0.660 to 0.687) in the derivation cohort and 0.651 (95%CI 0.637 to 0.665) in the validation cohort (n = 10,222). The Hosmer-Lemeshow test had a p-value of 0.87 suggesting an accurate calibration. The FTS score outperformed EuroSCORE II, Charlson comorbidity index and frailty index for identifying futility. Based on FTS score, 7% of these patients were categorized at high risk with a 1-year mortality at 43%. In conclusion, the FTS score, established from a large nationwide cohort of patients treated with TAVI, may provide a relevant tool for optimizing healthcare decision., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) and redo surgical aortic valve replacement (SAVR) represent the 2 treatments for aortic bioprosthesis failure. Clinical comparison of both therapies remains limited by the number of patients analyzed., Objectives: The purpose of this study was to analyze the outcomes of VIV TAVR versus redo SAVR at a nationwide level in France., Methods: Based on the French administrative hospital-discharge database, the study collected information for patients treated for aortic bioprosthesis failure with isolated VIV TAVR or redo SAVR between 2010 and 2019. Propensity score matching was used for the analysis of outcomes., Results: A total of 4,327 patients were found in the database. After matching on baseline characteristics, 717 patients were analyzed in each arm. At 30 days, VIV TAVR was associated with lower rates of the composite of all-cause mortality, all-cause stroke, myocardial infarction, and major or life-threatening bleeding (odds ratio: 0.62; 95% confidence interval: 0.44 to 0.88; p = 0.03). During follow-up (median 516 days), the combined endpoint of cardiovascular death, all-cause stroke, myocardial infarction, or rehospitalization for heart failure was not different between the 2 groups (odds ratio: 1.18; 95% confidence interval: 0.99 to 1.41; p = 0.26). Rehospitalization for heart failure and pacemaker implantation were more frequently reported in the VIV TAVR group. A time-dependent interaction between all-cause and cardiovascular mortality following VIV TAVR was reported (p-interaction <0.05)., Conclusions: VIV TAVR was observed to be associated with better short-term outcomes than redo SAVR. Major cardiovascular outcomes were not different between the 2 treatments during long-term follow-up., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background The incidence of conduction abnormalities requiring permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) with early and later generation prostheses remains debated. Methods and Results Based on the administrative hospital-discharge database, we collected information for all patients treated with TAVR between 2010 and 2019 in France. We compared the incidence of PPI after TAVR according to the type and generation of valve implanted. A total of 49 201 patients with aortic stenosis treated with TAVR using the balloon-expandable (BE) Edwards SAPIEN valve (early Sapien XT and latest Sapien 3) or the self-expanding (SE) Medtronic CoreValve (early CoreValve and latest Evolut R) were found in the database. Mean (SD) follow-up was 1.2 (1.5 years) (median [interquartile range] 0.6 [0.1-2.0] years). PPI after the procedure was reported in 13 289 patients, among whom 11 010 (22.4%) had implantation during the first 30 days. In multivariable analysis, using early BE TAVR as reference, adjusted odds ratio (95% CI) for PPI during the first 30 days was 0.88 (0.81-0.95) for latest BE TAVR, 1.40 (1.27-1.55) for early SE TAVR, and 1.17 (1.07-1.27) for latest SE TAVR. Compared with early BE TAVR, the adjusted hazard ratio for PPI during the whole follow-up was 1.01 (0.95-1.08) for latest BE TAVR, 1.30 (1.21-1.40) for early SE TAVR, and 1.25 (1.18-1.34) for latest SE TAVR. Conclusions In patients with aortic stenosis treated with TAVR, our systematic analysis at a nationwide level found higher rates of PPI than previously reported. BE technology was independently associated with lower incidence rates of PPI both at the acute and chronic phases than SE technology. Recent generations of TAVR were not independently associated with different rates of PPI than early generations during the overall follow-up.

Aims: The aim of this study was to describe the midterm outcomes in nonagenarians undergoing transcatheter aortic valve implantation (TAVI)., Methods and Results: Based on the French administrative hospital discharge database, the study collected information for all consecutive patients with aortic stenosis (AS), and specifically those treated with TAVI between 2010 and 2018. Cox regression was used for the analysis of predictors of events. We compared patients according to their age. Within the studied period, 71,095 patients older than 90 years with AS were identified. After matching on baseline characteristics, TAVI was associated with lower rates of a combined outcome of all-cause death, rehospitalisation for heart failure and stroke (relative risk [RR] 0.58, p<0.001) in comparison with matched nonagenarians with AS treated medically. During follow-up (median 161 days, interquartile range 13-625), the combined outcome occurred more frequently in nonagenarians (RR 1.22, p<0.01) who had a TAVI than in younger patients undergoing this procedure. All-cause death was reported in 17.6% versus 14.5% of nonagenarians, rehospitalisation for heart failure in 21.3% versus 18.2%, and stroke in 3.7% versus 2.9% (p<0.01 for all parameters). We identified the Charlson comorbidity index, heart failure, atrial fibrillation, stroke, vascular disease, cognitive impairment and denutrition as independent predictors of adverse outcomes in nonagenarians undergoing TAVI., Conclusions: Among nonagenarians with AS, patients treated with TAVI had a lower risk of cardiovascular events than matched patients treated medically. The patients undergoing a TAVI at this age were often highly selected; the procedure was associated with acceptable long-term outcomes.

Xanthophyll cycle-related nonphotochemical quenching (NPQ), which is present in most photoautotrophs, allows dissipation of excess light energy. Xanthophyll cycle-related NPQ depends principally on xanthophyll cycle pigments composition and their effective involvement in NPQ. Xanthophyll cycle-related NPQ is tightly controlled by environmental conditions in a species-/strain-specific manner. These features are especially relevant in microalgae living in a complex and highly variable environment. The goal of this study was to perform a comparative assessment of NPQ ecophysiologies across microalgal taxa in order to underline the specific involvement of NPQ in growth adaptations and strategies. We used both published results and data acquired in our laboratory to understand the relationships between growth conditions (irradiance, temperature, and nutrient availability), xanthophyll cycle composition, and xanthophyll cycle pigments quenching efficiency in microalgae from various taxa. We found that in diadinoxanthin-containing species, the xanthophyll cycle pigment pool is controlled by energy pressure in all species. At any given energy pressure, however, the diatoxanthin content is higher in diatoms than in other diadinoxanthin-containing species. XC pigments quenching efficiency is species-specific and decreases with acclimation to higher irradiances. We found a clear link between the natural light environment of species/ecotypes and quenching efficiency amplitude. The presence of diatoxanthin or zeaxanthin at steady state in all species examined at moderate and high irradiances suggests that cells maintain a light-harvesting capacity in excess to cope with potential decrease in light intensity., (© 2019 Phycological Society of America.)

Background: Two competing transcatheter aortic valve replacement (TAVR) technologies are currently available. Head-to-head comparisons of the relative performances of these 2 devices have been published. However, long-term clinical outcome evaluation remains limited by the number of patients analyzed, in particular, for recent-generation devices., Methods: Based on the French administrative hospital-discharge database, the study collected information for all consecutive patients treated with a TAVR device commercialized in France between 2014 and 2018. Propensity score matching was used for the analysis of outcomes during follow-up. The objective of this study was to analyze the outcomes of TAVR according to Sapien 3 balloon-expandable (BE) versus Evolut R self-expanding TAVR technology at a nationwide level in France., Results: A total of 31 113 patients treated with either Sapien 3 BE or Evolut R self-expanding TAVR were found in the database. After matching on baseline characteristics, 20 918 patients were analyzed (10 459 in each group with BE or self-expanding valves). During follow-up (mean [SD], 358 [384]; median [interquartile range], 232 [10-599] days), BE TAVR was associated with a lower yearly incidence of all-cause death (relative risk, 0.88; corrected P =0.005), cardiovascular death (relative risk, 0.82; corrected P =0.002), and rehospitalization for heart failure (relative risk, 0.84; corrected P <0.0001). BE TAVR was also associated with lower rates of pacemaker implantation after the procedure (relative risk, 0.72; corrected P <0.0001)., Conclusions: On the basis of the largest cohort available, we observed that Sapien 3 BE valves were associated with lower rates of all-cause death, cardiovascular death, rehospitalization for heart failure, and pacemaker implantation after a TAVR procedure.

Marine fungi are part of the huge and understudied biodiversity hosted in the sea. To broaden the knowledge on fungi inhabiting the Mediterranean Sea and their role in sponge holobiont, three sponges namely Aplysina cavernicola, Crambe crambe and Phorbas tenacior were collected in Villefranche sur Mer, (France) at about 25 m depth. The fungal communities associated with the sponges were isolated using different techniques to increase the numbers of fungi isolated. All fungi were identified to species level giving rise to 19, 13 and 3 species for P. tenacior, A. cavernicola and C. crambe, respectively. Of note, 35.7% and 50.0% of the species detected were either reported for the first time in the marine environment or in association with sponges. The mini-satellite analysis confirmed the uniqueness of the mycobiota of each sponge, leading to think that the sponge, with its metabolome, may shape the microbial community., (© FEMS 2020.)

Introduction: We sought to develop an efficient method to upgrade pacing-induced cardiomyopathy (PICM) patients from a leadless pacemaker (LPM) to cardiac resynchronization therapy., Methods and Results: Three consecutive patients with chronic atrial fibrillation, implanted with an LPM, with permanent right ventricular pacing, and who developed left ventricular systolic dysfunction due to PICM, were included. A conventional biventricular pacemaker with two different coronary sinus leads, one used for left lateral ventricular pacing, one for early right ventricular sensing, was implanted. It was then synchronized with the LPM working as the right ventricular pacing lead to provide biventricular pacing. The upgrading technique was feasible in all cases, without any perioperative complication. All patients had an improved clinical status during follow-up., Conclusion: This new upgrading technique allows efficient cardiac resynchronization therapy in LPM patients while preventing tricuspid valve crossing and providing an increased battery longevity., (© 2019 Wiley Periodicals, Inc.)

Nanodroplets have great, promising medical applications such as contrast imaging, embolotherapy, or targeted drug delivery. Their functions can be mechanically activated by means of focused ultrasound inducing a phase change of the inner liquid known as the acoustic droplet vaporization (ADV) process. In this context, a four-phases (vapor + liquid + shell + surrounding environment) model of ADV is proposed. Attention is especially devoted to the mechanical properties of the encapsulating shell, incorporating the well-known strain-softening behavior of Mooney-Rivlin material adapted to very large deformations of soft, nearly incompressible materials. Various responses to ultrasound excitation are illustrated, depending on linear and nonlinear mechanical shell properties and acoustical excitation parameters. Different classes of ADV outcomes are exhibited, and a relevant threshold ensuring complete vaporization of the inner liquid layer is defined. The dependence of this threshold with acoustical, geometrical, and mechanical parameters is also provided.

Objective: Compact Dry TC, a rapid method kit for determining aerobic colony counts, has been developed by Nissui Pharmaceutical Co. for food application. These plates are pre-sterilized and contain culture medium, a cold-soluble gelling agent and a colour redox indicator for rapid enumeration. In this study, the alternative method is compared with the standard method ISO 21149:2006 - Cosmetic - Microbiology - Enumeration and detection of aerobic mesophilic bacteria, for cosmetic emulsions application., Methods: An oil-in-water (o/w) cosmetic emulsion was contaminated with a pool of bacterial strains (Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538 and Pseudomonas aeruginosa ATCC 9027). One millilitre of samples was spread on agar as described in ISO 21149. The colonies were enumerated after 3 days of incubation. At the same time, 1.2 mL samples were spread on Compact Dry TC kits. The kit was incubated at 35°C ± 1°C for 48 h, and the colonies were enumerated. Accuracy determination was carried out using six replicates at four levels of concentrations (10, 50, 100 and 250 CFU mL -1 ). The repeatability study was carried out using 12 replicates at four levels of concentrations (10, 50, 100 and 250 CFU mL -1 ). Variations relative to the analyst and to the batch of emulsion have been investigated., Results: The linear correlation coefficients of Compact Dry TC Kit enumeration with standard method ISO 21149:2006 was 0.9999. In comparison study, no apparent differences were noted between the Compact Dry TC kit and the reference method ISO 21149, for the detection level of aerobic microorganisms. Relative accuracy, repeatability and intermediate precision studies were acceptable. In the repeatability study, the Shapiro-Wilk test has confirmed the normally distribution of the twelve assays. No significant variations in Compact Dry TC count results were observed with different analysts and different batches of emulsion., Conclusion: The results showed that the two compared methods 'Compact Dry TC' vs. 'conventional pour plate' performed equally well. Demonstration was achieved that the Compact Dry TC method may constitute a useful alternative tool for rapid enumeration of aerobic mesophilic bacteria in cosmetic emulsions., (© 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.)

Sessile marine sponges provide an abundance of unique and diversified scaffolds. In particular, marine guanidine alkaloids display a very wide range of biological applications. A large number of cyclic guanidine alkaloids, including crambines, crambescins, crambescidins, batzelladines or netamins have been isolated from Poecilosclerida marine sponges. In this review, we will explore the chemodiversity of tri- and pentacyclic guanidine alkaloids. NMR and MS data tools will also be provided, and an overview of the wide range of bioactivities of crambescidins and batzelladines derivatives will be given.

The goal of this study was to investigate the time response of two major carbon (C) reserves, respectively neutral lipids (NL) and total carbohydrate (TC), in the Haptophyte Isochrysis sp. growing in nitrogen (N)-sufficient or N-starved conditions and under light:dark (L:D) cycles. Experiments were carried out in a cyclostat culture system that allowed the following of the dynamics of the main cell compounds at both hourly and daily time scales. Under N-sufficient conditions, the L:D cycles cause the population to be synchronized, with most of the cells dividing at the beginning of the dark period. The C-specific growth rate was maximal around midday and negative during the dark period due to respiration processes. NL and TC both accumulated during the day and consumed during the night. We showed that NL and TC are highly dynamic compounds, as more than three quarters of NL and TC accumulated during the light period were consumed during the dark period. In contrast to NL, phospholipid and glycolipid to C ratios remained quite stable during the light/dark cycles. The major effect of N starvation on the NL and TC dynamics was to uncouple their diel variations from the L:D cycle, in two different ways depending on their respective role during short-term acclimation. Whereas the TC per cell ratio increased rapidly to reach a stable value in response to N starvation, NL per cell continued to oscillate, but with a pattern out of phase with the L:D cycle., (© 2012 Phycological Society of America.)

Partitioning of the carbon (C) fixed during photosynthesis between neutral lipids (NL) and carbohydrates was investigated in Isochrysis sp. (Haptophyceae) in relation to its nitrogen (N) status. Using batch and nitrate-limited continuous cultures, we studied the response of these energy reserve pools to both conditions of N starvation and limitation. During N starvation, NL and carbohydrate quotas increased but their specific growth rates (specific rates of variation, μCAR and μNL ) decreased. When cells were successively deprived and then resupplied with NO3 , both carbohydrates and neutral lipids were inversely related to the N quota (N:C). These negative relationships were not identical during N impoverishment and replenishment, indicating a hysteresis phenomenon between N and C reserve mobilizations. Cells acclimated to increasing degrees of N limitation in steady-state chemostat cultures showed decreasing NL quota and increasing carbohydrate quota. N starvation led to a visible but only transient increase of NL productivity. In continuous cultures, the highest NL productivity was obtained for the highest experimented dilution rate (D = 1.0 d(-1) ; i.e., for non N-limited growth conditions), whereas the highest carbohydrate productivity was obtained at D = 0.67 d(-1) . We used these results to discuss the nitrogen conditions that optimize NL productivities in the context of biofuel production., (© 2012 Phycological Society of America.)

This article proposes a dynamical model of microalgal lipid production under nitrogen limitation. In this model, intracellular carbon is divided between a functional pool and two storage pools (sugars and neutral lipids). The various intracellular carbon flows between these pools lead to a complex dynamic with a strong discrepancy between synthesis and mobilization of neutral lipids. The model has been validated with experiments of Isochrysis aff. galbana (clone T-iso) culture under various nitrogen limitation conditions and under nitrogen starvation. The hysteresis behavior of the neutral lipid quota observed experimentally is accurately predicted., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Dexmedetomidine (Dex), an alpha(2) agonist, has well-known anesthetic and analgesic-sparing effects. We designed this prospective, randomized, double-blind, and placebo-controlled dose-ranging study to evaluate the effect of Dex on both early and late recovery after laparoscopic bariatric surgery., Methods: Eighty consenting ASA II-III morbidly obese patients were randomly assigned to 1 of 4 treatment groups: (1) control group received a saline infusion during surgery, (2) Dex 0.2 group received an infusion of 0.2 microg x kg(-1) x h(-1) IV, (3) Dex 0.4 group received an infusion of 0.4 microg x kg(-1) x h(-1) IV, and (4) Dex 0.8 group received an infusion of 0.8 microg x kg(-1) x h(-1) IV. Mean arterial blood pressure values were maintained within +/-25% of the preinduction baseline values by varying the inspired desflurane concentration. Perioperative hemodynamic variables, postoperative pain scores, and the need for "rescue" analgesics and antiemetics were recorded at specific intervals. Follow-up evaluations were performed on postoperative days (PODs) 1, 2, and 7 to assess severity of pain, analgesic requirements, patient satisfaction with pain management, quality of recovery, as well as resumption of dietary intake and recovery of bowel function., Results: Dex infusion, 0.2, 0.4, and 0.8 microg x kg(-1) x h(-1), reduced the average end-tidal desflurane concentration by 19, 20, and 22%, respectively. However, it failed to facilitate a significantly faster emergence from anesthesia. Although the intraoperative hemodynamic values were similar in the four groups, arterial blood pressure values were significantly reduced in the Dex 0.2, 0.4, and 0.8 groups compared with the control group on admission to the postanesthesia care unit (PACU) (P < 0.05). The length of the PACU stay was significantly reduced in the Dex groups (81 +/- 31 to 87 +/- 24 vs 104 +/- 33 min in the control group, P < 0.05). The amount of rescue fentanyl administered in the PACU was significantly less in the Dex 0.2, 0.4, and 0.8 groups versus control group (113 +/- 85, 108 +/- 67, and 120 +/- 78 vs 187 +/- 99 microg, respectively, P < 0.05). The percentage of patients requiring antiemetic therapy was also reduced in the Dex groups (30, 30, and 10% vs 70% in the control group). However, the patient-controlled analgesia morphine requirements on PODs 1 and 2 were not different among the four groups. Pain scores in the PACU, and on PODs 1, 2, and 7, in the three Dex groups were not different from the control group. Finally, quality of recovery scores and times to recovery of bowel function and hospital discharge did not differ among the four groups., Conclusions: Adjunctive use of an intraoperative Dex infusion (0.2-0.8 microg x kg(-1) x h(-1)) decreased fentanyl use, antiemetic therapy, and the length of stay in the PACU. However, it failed to facilitate late recovery (e.g., bowel function) or improve the patients' overall quality of recovery. When used during bariatric surgery, a Dex infusion rate of 0.2 microg x kg(-1) x h(-1) is recommended to minimize the risk of adverse cardiovascular side effects.

We cloned a polyketide synthase gene (pks12) from Fusarium graminearum, a devastating fungal pathogen of cereals. Transformation-mediated gene disruption led to an easily detectable albino phenotype of the disruptants. We used the disruption of the pks12 gene as a visible marker for transformation-mediated homologous recombination and optimized the transformation procedure to achieve a high rate of homologous recombination. In combination with the published genomic sequence data and the generation of expressed sequence tags (ESTs) for F. graminearum, this is a useful tool to investigate this important plant pathogen on a molecular level. Optimized transformation of F. graminearum resulted in at least 93% homologous recombination events when the homologous genomic DNA fragment in the vector had a size of approximately 800bp and was linearized in the middle. Using a genomic sequence of approximately 500bp in the transformation vector, 70% of the transformants still exhibited homologous recombination. On the contrary, no more than 10% homologous recombination events were observed when less than 400bp DNA fragments were used. We co-transformed F. graminearum with two different vectors. One vector harboured a DNA insert homologous to the pks12 gene, while the other vector consisted of the same vector backbone carrying the selection marker specific for F. graminearum. About 70% of the transformants had a disrupted pks12 gene, and all of these showed an integration of the second vector into the pks disruption vector. Therefore, the time-consuming construction of a single transformation vector can be avoided; furthermore, it is now easily feasible to express a gene construct at a defined and mutated genomic site.

Fusion proteins of rat cytochrome P4501A1 with maize ferredoxin I (Fd) and pea ferredoxin NADP(+) reductase (FNR), the last electron transfer proteins of the photosynthetic channel in plant chloroplasts, were obtained by gene fusion in the yeast expression vector pAAH5N. The encoded fusion proteins P4501A1-Fd, P4501A1-FNR, P4501A1-Fd-FNR and P4501A1-FNR-Fd were produced in microsomes of the yeast Saccharomyces cerevisiae AH22. Enzymatic assays were carried out in vitro with the isolated microsomes. P4501A1-Fd-FNR and P4501A1-FNR-Fd were found to catalyze P450-monooxygenase activities towards 7-ethoxycoumarin and the herbicide chlortoluron. P4501A1-Fd-FNR was the most efficient enzyme as measured in vitro in ferricyanide and cytochrome c reductions, as well as P450-monooxygenase assays. Apparent K(m) and k(cat) of P4501A1-Fd-FNR were 70 microM and 7800 min(-1) for NADPH, 13.2 microM and 51.1 min(-1) for 7-ethoxycoumarin, and 21.3 microM and 23. 8 min(-1) for the herbicide chlortoluron, respectively. Fd in P4501A1-Fd-FNR fusion enzyme was found to be a limiting factor compared to P4501A1 fused to the yeast NADPH-cytochrome P450 reductase, an artificial enzyme described previously. The efficiency of electron transfer in the P4501A1 fusion proteins and a possible in vivo molecular coupling of Fd and FNR with microsomal cytochrome P4501A1 produced in plant chloroplasts are discussed.

The mammalian electron transfer chain of mitochondrial cytochrome P450 forms involved in steroidogenesis includes very specific proteins, namely adrenodoxin reductase and adrenodoxin. Adrenodoxin reductase transfers electrons from NADPH to adrenodoxin, which subsequently donates them to the cytochrome P450 forms. The Saccharomyces cerevisiae ARH1 gene product (Arh1p) presents homology to mammalian adrenodoxin reductase. We demonstrate the capacity of recombinant Arh1p, made in Escherichia coli, to substitute for its mammalian homologue in ferricyanide, cytochrome c reduction, and, more importantly, in vitro 11beta-hydroxylase assays. Electrons could be transferred from NADPH and NADH as measured in the cytochrome c reduction assay. Apparent Km values were determined to be 0.5, 0.6, and 0.1 microM for NADPH, NADH, and bovine adrenodoxin, respectively. These values differ slightly from those of mammalian adrenodoxin reductase, except for NADH, which is a very poor electron donor to the mammalian protein. Subcellular fractionation studies have localized Arh1p to the inner membrane of yeast mitochondria. The biological function of Arh1p remains unknown, and to date, no mitochondrial cytochrome P450 has been identified. ARH1 is, however, essential for yeast viability because an ARH1 gene disruption is lethal not only in aerobic growth conditions but also, surprisingly enough, during fermentation.

Adrenodoxin oxidoreductase (ADR) and adrenodoxin (ADX) are the two proteins involved in electron transport to mammalian mitochondrial P-450s capable of steroid modifications. The cloning and sequencing of a S. cervisiae ADR homologue (YADR) is presented here. The YADR protein sequence shares 36 and 37% of identical amino acids with human and bovine ADR respectively. The physiological role of this ADR homologue in yeast is unknown. We intend to study the interaction of this YADR with bovine ADX in vitro and in vivo.

In mammals, the final 11 beta-hydroxylation step of the hydrocortisone biosynthesis pathway is performed by a mitochondrial enzyme, namely cytochrome P-450(11 beta), together with the electron carriers adrenodoxin and NADPH adrenodoxin oxidoreductase. Successful production of a functional steroid 11 beta-hydroxylase activity was obtained in recombinant yeast in vivo. This conversion was achieved by coexpression of a mitochondrially targeted adrenodoxin and a modified bovine P-450(11 beta) whose natural presequence was replaced by a yeast presequence, together with an unexpected yeast endogenous NADPH-adrenodoxin-reductase-like activity. Adrenodoxin and P-450(11 beta) behave as a mitochondrial matrix and membrane protein, respectively. Saccharomyces cerevisiae apparently produces a mitochondrial protein which is capable of transferring electrons to bovine adrenodoxin, which in turn transfers the electrons to P-450(11 beta). The endogenous adrenodoxin oxidoreductase gains electrons specifically from NADPH. The notion that a yeast microsomal NADPH P-450 oxidoreductase can transfer electrons to mammalian microsomal P-450s can be extended to mitochondria, where an NADPH adrenodoxin oxidoreductase protein transfers electrons to adrenodoxin and renders a mitochondrial mammalian P-450 functional in vivo. The physiological function of this yeast NADPH adrenodoxin oxidoreductase activity is not known.