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The fastest growing modes in anisotropic rotating magnetoconvection (RMC) processes are presented. After reminding the state of the art, we present our new approach that applies to isotropic as well as anisotropic diffusivities' conditions. We describe three cases: T (only temperature perturbation is time dependent), Q (temperature and velocity field perturbations are time dependent, but magnetic field perturbation is time independent) and G (temperature, magnetic and velocity field perturbations are time dependent). Isotropies as well as anisotropies are further distinguished by values of molecular and turbulent diffusivities. We show that T case does not describe properly convection in the Earth's outer core conditions, because it implies too huge Ekman numbers for the transition between the RMC modes of weak and strong magnetic field types. In G case, the convection is usually much more facilitated than in the T case: instabilities may arise with much smaller values of Ekman number and, in general, all types of convections occur with values of the physical parameters of the Earth consistent with the most reliable estimations. We demonstrate (and indicate) that Q and G cases can be well suited for the magnetic field of the Earth (and for other planetary magnetic fields), but only G case may correspond to turbulent stay of the Earth's core. We prove that, analogously like in the marginal modes, the value of anisotropic parameter α (the ratio between horizontal and vertical diffusivities) crucially influences the convection. The cases of $ \alpha α < 1 ( $ \alpha >1 $ α > 1) strongly decrease (increase) the Ekman numbers at which the RMC modes of weak and strong magnetic field types change between each other. Finally, we show and stress that not all types of anisotropies in the fastest growing modes can be equally strong. More specifically, we show that a fixed Rayleigh number puts a constraint on the maximum value of α, but do not put any lower positive limit on the minimum value of α. This special constraint is given by the necessary positiveness of the growth rate of the fastest growing modes. Our RMC approach allows to easily deal with very huge wave numbers and Rayleigh numbers as well as with very small Ekman numbers, what is usually not possible in the standard geodynamo simulations. [ABSTRACT FROM AUTHOR]

This article, titled "OC19.08: Effectiveness of the antihypertensive therapy based on maternal hemodynamic findings in women with HDP: a multicentre prospective study," discusses a study that aimed to compare the effectiveness of appropriate and inappropriate antihypertensive therapy in women with hypertensive disorders of pregnancy (HDP). The study included 152 women and assessed their hemodynamic profile before prescribing antihypertensive therapy. The results showed that women who received appropriate therapy had a lower occurrence of severe hypertension and were more likely to achieve target blood pressure values within 48-72 hours compared to those who received inappropriate therapy. The study suggests that considering the maternal hemodynamic profile when prescribing antihypertensive therapy can lead to better outcomes for women with HDP. [Extracted from the article]

In targeted cancer therapy, antibody-drug-conjugates using mertansine (DM1)-based cytotoxic compounds rely on covalent bonds for drug conjugation. Consequently, the cytotoxic DM1 derivative released upon their proteolytic digestion is up to 1000-fold less potent than DM1 and lacks a bystander effect. To overcome these limitations, we developed a DM1 derivative (keto-DM1) suitable for bioconjugation through an acid-reversible hydrazone bond. Its acid-reversible hydrazone conjugate with biotin (B-Hz-DM1) was generated and tested for efficacy using the cetuximab-targeted Avidin-Nucleic-Acid-NanoASsembly (ANANAS) nanoparticle (NP) platform. NP-tethered B-Hz-DM1 is stable at neutral pH and releases its active moiety only in endosome/lysosome mimicking acidic pH. In vitro, the NP/Cetux/B-Hz-DM1 assembly showed high potency on MDA-MB231 breast cancer cells. In vivo both B-Hz-DM1 and NP/Cetux/B-Hz-DM1 reduced tumor growth. A significantly major effect was exerted by the nanoformulation, associated with an increased in situ tumor cell death. Keto-DM1 is a promising acid-reversible mertansine derivative for targeted delivery in cancer therapy., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Reptiles in the wild or as pets may act as spreaders of bacteria, viruses, fungi and parasites. However, studies on the mycobiota of these animals are scanty. This study investigates the occurrence of yeasts from the cloacal swabs of snakes of different origins and the antifungal profile of the isolated strains. A total of 180 cloacal samples of snakes were collected from Morocco (Group I: n = 68) and Italy (Group II: n = 112). Yeast species were biochemically and molecularly identified. A total of 72 yeast strains belonging to 13 genera, 8 from snakes in Group I and five from snakes in Group II were identified. The most frequently isolated species were Trichosporon asahii (22.2%) and Candida tropicalis (15.3%) from snakes in Group I and Debaryomyces spp. (16.7%) and Metahyphopichia silvanorum (11.1%) from snakes in Group II. Multiple azole and amphotericin B (AmB) resistance phenomena were detected among isolated yeasts. Azole multi drug resistance phenomena were detected among yeasts from Group I and Rhodotorula mucilaginosa from Group II, whereas AmB resistance phenomena among those from Group II. Data suggest that snakes may harbor pathogenetic yeasts, being potential reservoirs and spreaders of these organisms in the environment. Since the yeast species community from different groups of animals as well as their antifungal profile reflects the epidemiology of human yeast infections in the same geographical areas, the results indicate that snakes may be considered as sentinels for human/animal pathogenic microorganisms and bio-indicators of environmental quality., (© 2024. The Author(s).)

Background: Whether ticagrelor may reduce periprocedural myocardial necrosis after elective percutaneous coronary intervention (PCI) in patients with and without chronic clopidogrel therapy is unclear., Objectives: This study sought to compare ticagrelor vs clopidogrel in patients with and without chronic clopidogrel therapy before undergoing elective PCI., Methods: In this prespecified analysis of the ALPHEUS (Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting) trial, patients were defined as clopidogrel(+) and clopidogrel(-) according to the presence and absence of clopidogrel treatment for ≥7 days before PCI, respectively. The primary endpoint was the composite of PCI-related myocardial infarction and major injury as defined by the third and fourth universal definition 48 hours after PCI., Results: A total of 1,882 patients were included, 805 (42.7%) of whom were clopidogrel(+). These patients were older, had more comorbidities, and had more frequent features of complex PCI. The primary endpoint was less frequently present in clopidogrel(-) compared to clopidogrel(+) patients (32.8% vs 40.0%; OR: 0.73; 95% CI: 0.60-0.88), but no significant differences were reported for the risk of death, myocardial infarction, stroke, or transient ischemic attack at 48 hours or 30 days. Ticagrelor did not reduce periprocedural myocardial necrosis or the risk of adverse outcomes, and there was no significant interaction regarding the presence of chronic clopidogrel treatment., Conclusions: Clopidogrel-naive patients presented less periprocedural complications compared to clopidogrel(+) patients, a difference related to a lower risk profile and less complex PCI. The absence of clopidogrel at baseline did not affect the absence of a difference between ticagrelor and clopidogrel in terms of PCI-related complications supporting the use of clopidogrel as the standard of care in elective PCI in patients with or without chronic clopidogrel treatment., Competing Interests: Funding Support and Author Disclosures This trial was led by the Allies in Cardiovascular Trials Initiatives and Organized Networks (ACTION) Study Group, an Academic Research Organization based at Pitié-Salpêtrière Hospital in Paris, France. It was sponsored by Assistance Publique-Hôpitaux de Paris and was funded by an unrestricted grant from AstraZeneca. AstraZeneca was not involved in the data collection, analysis, or in the writing of the manuscript. The Steering Committee oversaw the conduct of the trial in collaboration with representatives of the study sponsor. The trial was monitored by an independent Data and Safety Monitoring Board. Data were collected and analyzed according to the predefined statistical analysis plan by academic statisticians of the ACTION group. Drs Silvain and Montalescot had full access to the data and final responsibility for the decision to submit for publication. There was no medical writing support. Dr Manzo-Silberman has received consulting fees from Bayer, Organon, and Exeltis; has received lecture fees from Bayer, BMS, Exeltis Organon, and Terumo; and has served on the adjudication board for a study for Biotronik. Dr Beygui has received consulting and lecture fees from AstraZeneca, Bristol Myers Squibb, Medtronic, Biosensors, Boston Scientific; and has received institutional research grants from Medtronic, Biosensors, Acist, and Boston Scientific. Dr Cayla has received speaker or congress fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Microport CRM, Pfizer, and Sanofi; and has received research grants/consultant fees/lectures fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Microport CRM, Pfizer, and Sanofi. Dr Rangé has received speaker and/or consulting fees from Abbott, Biotronik, and Microport. Dr Motovska has received consulting, speaker, investigator and advisory board fees from AstraZeneca, Boehringer Ingelheim, and Idorsia. Dr Zeitouni has received research grants from Federation Française de Cardiologie and Institut Servier; and has received honoraria from BMS/Pfizer, Bayer, AstraZeneca, and Novo Nordisk. Dr Vicaut has received consulting or speaker fees from Abbott, Bristol Myers Squibb, Celgene, Edwards Lifesciences, Pfizer, Sanofi, and Novartis. Dr Montalescot has received consulting or speaker fees from Abbott, Amgen, AstraZeneca, Axis, Bayer, BMS, Boehringer-Ingelheim, Boston Scientific, Cell Prothera, CSL Behring, Idorsia, Leo-Pharma, Lilly, Medtronic, Novartis, Pfizer, Quantum Genomics, Sanofi, and Terumo. Dr Silvain has received consulting and lecture or travel support from AstraZeneca, Bayer HealthCare SAS, Biotronik, Sanofi Aventis France, Abbott Medical France, SAS, and Zoll; and is a stockholder of 4P-Pharma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and study aims Artificial Intelligence (AI) systems could make the optical diagnosis (OD) of diminutive colorectal polyps (DCPs) more reliable and objective. This study was aimed at prospectively evaluating feasibility and diagnostic performance of AI-standalone and AI-assisted OD of DCPs in a real-life setting by using a white light-based system (GI Genius, Medtronic Co, Minneapolis, Minnesota, United States). Patients and methods Consecutive colonoscopy outpatients with at least one DCP were evaluated by 11 endoscopists (5 experts and 6 non-experts in OD). DCPs were classified in real time by AI (AI-standalone OD) and by the endoscopist with the assistance of AI (AI-assisted OD), with histopathology as the reference standard. Results Of the 480 DCPs, AI provided the outcome "adenoma" or "non-adenoma" in 81.4% (95% confidence interval [CI]: 77.5-84.6). Sensitivity, specificity, positive and negative predictive value, and accuracy of AI-standalone OD were 97.0% (95% CI 94.0-98.6), 38.1% (95% CI 28.9-48.1), 80.1% (95% CI 75.2-84.2), 83.3% (95% CI 69.2-92.0), and 80.5% (95% CI 68.7-82.8%), respectively. Compared with AI-standalone, the specificity of AI-assisted OD was significantly higher (58.9%, 95% CI 49.7-67.5) and a trend toward an increase was observed for other diagnostic performance measures. Overall accuracy and negative predictive value of AI-assisted OD for experts and non-experts were 85.8% (95% CI 80.0-90.4) vs. 80.1% (95% CI 73.6-85.6) and 89.1% (95% CI 75.6-95.9) vs. 80.0% (95% CI 63.9-90.4), respectively. Conclusions Standalone AI is able to provide an OD of adenoma/non-adenoma in more than 80% of DCPs, with a high sensitivity but low specificity. The human-machine interaction improved diagnostic performance, especially when experts were involved., Competing Interests: Conflict of Interest Paggi S and Amato A: speaker honoraria from Fujifilm Co. Rondonotti E: speaker honoraria from Fujifilm Co., Medtronic Co. consultancy. Radaelli F: Speaker honoraria from Fujifilm Co; research grant from Fujifilm Co; endoscopy equipment loan from Medtronic Co. Hassan C: Medtronic Co, Fujifilm Co and Odin Co. consultancy. All the other authors declare no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Despite major advances in the pharmacologic treatment of hypertension in the nonpregnant population, treatments for hypertension in pregnancy have remained largely unchanged over the years. There is recent evidence that a more adequate control of maternal blood pressure is achieved when the first given antihypertensive drug is able to correct the underlying hemodynamic disorder of the mother besides normalizing the blood pressure values., Objective: This study aimed to compare the blood pressure control in women receiving an appropriate or inappropriate antihypertensive therapy following the baseline hemodynamic findings., Study Design: This was a prospective multicenter study that included a population of women with de novo diagnosis of hypertensive disorders of pregnancy. A noninvasive assessment of the following maternal parameters was performed on hospital admission via Ultrasound Cardiac Output Monitor before any antihypertensive therapy was given: cardiac output, heart rate, systemic vascular resistance, and stroke volume. The clinician who prescribed the antihypertensive therapy was blinded to the hemodynamic evaluation and used as first-line treatment a vasodilator (nifedipine or alpha methyldopa) or a beta-blocker (labetalol) based on his preferences or on the local protocols. The first-line pharmacologic treatment was retrospectively considered hemodynamically appropriate in either of the following circumstances: (1) women with a hypodynamic profile (defined as low cardiac output [≤5 L/min] and/or high systemic vascular resistance [≥1300 dynes/second/cm 2 ]) who were administered oral nifedipine or alpha methyldopa and (2) women with a hyperdynamic profile (defined as normal or high cardiac output [>5 L/min] and/or low systemic vascular resistances [<1300 dynes/second/cm 2 ]) who were administered oral labetalol. The primary outcome of the study was to compare the occurrence of severe hypertension between women treated with a hemodynamically appropriate therapy and women treated with an inappropriate therapy., Results: A total of 152 women with hypertensive disorders of pregnancy were included in the final analysis. Most women displayed a hypodynamic profile (114 [75.0%]) and received a hemodynamically appropriate treatment (116 [76.3%]). The occurrence of severe hypertension before delivery was significantly lower in the group receiving an appropriate therapy than in the group receiving an inappropriately treated (6.0% vs 19.4%, respectively; P=.02). Moreover, the number of women who achieved target values of blood pressure within 48 to 72 hours from the treatment start was higher in the group who received an appropriate treatment than in the group who received an inappropriate treatment (70.7% vs 50.0%, respectively; P=.02)., Conclusion: In pregnant individuals with de novo hypertensive disorders of pregnancy, a lower occurrence of severe hypertension was observed when the first-line antihypertensive agent was tailored to the correct maternal hemodynamic profile., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The effects of pharmacological therapy on cardiogenic shock (CS) survivors have not been extensively studied. Thus, this study investigated the association between guideline-directed heart failure (HF) medical therapy (GDMT) and one-year survival rate in patients who are post-CS., Methods and Results: FRENSHOCK (French Observatory on the Management of Cardiogenic Shock in 2016) registry was a prospective multicenter observational survey, conducted in metropolitan French intensive care units and intensive cardiac care units. Of 772 patients, 535 patients were enrolled in the present analysis following the exclusion of 217 in-hospital deaths and 20 patients with missing medical records. Patients with triple GDMT (beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists) at discharge (n=112) were likely to have lower left ventricular ejection fraction on admission and at discharge compared with those without triple GDMT (n=423) (22% versus 28%, P <0.001 and 29% versus 37%, P <0.001, respectively). In the overall cohort, the one-year mortality rate was 23%. Triple GDMT prescription was significantly associated with a lower one-year all-cause mortality compared with non-triple GDMT (adjusted hazard ratio 0.44 [95% CI, 0.19-0.80]; P =0.007). Similarly, 2:1 propensity score matching and inverse probability treatment weighting based on the propensity score demonstrated a lower incidence of one-year mortality in the triple GDMT group. As the number of HF drugs increased, a stepwise decrease in mortality was observed (log rank; P <0.001)., Conclusions: In survivors of CS, the one-year mortality rate was significantly lower in those with triple GDMT. Therefore, this study suggests that intensive HF therapy should be considered in patients following CS.

Background and Aims: Endoscopic activity is associated with an increased risk of surgery in patients with ulcerative colitis [UC]. Transmural activity, as defined by Milan Ultrasound Criteria [MUC] > 6.2, reliably detects endoscopic activity in patients with UC. The present study aimed to assess in UC patients whether transmural severity is a better predictor of colectomy as compared to endoscopy., Methods: Consecutive adult UC patients were recruited in two IBD Referral Centres and underwent colonoscopy and intestinal ultrasound in a blinded fashion. The need for colectomy was assessed at follow-up. Univariable and multivariable logistic and Cox regression analyses were performed. Receiver operating characteristic [ROC] analysis was used to compare MUC baseline values and Mayo Endoscopic Scores [MES] in predicting colectomy risk., Results: Overall, 141 patients were enrolled, and 13 underwent colectomy in the follow-up period. Both MES (hazard ratio [HR]: 3.15, 95% confidence interval [CI]: 1.18-8.37, p = 0.02) and MUC [HR: 1.48, 95% CI: 1.19-1.76, p < 0.001] were associated with colectomy risk, but only MUC was independently associated with this event on multivariable analysis [HR: 1.46, 95% CI: 1.06-2.02, p = 0.02]. MUC was the only independent variable associated with colectomy risk in patients with clinically active disease (odds ratio [OR]: 1.53 [1.03-2.27], p = 0.03). MUC demonstrated higher accuracy than MES (area under ROC curve [AUROC] 0.83, 95% CI: 0.75-0.92 vs 0.71, 95% CI: 0.62-0.80) and better performance for predicting colectomy [p = 0.02]. The optimal MUC score cut-off value for predicting colectomy, as assessed by the Youden index, was 7.7., Conclusions: A superior predictive value was found for transmural vs endoscopic severity for colectomy risk in UC patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

While in much of the Western world snakes are feared, in the small, rural, mountainous town of Cocullo, in the middle of central Italy, snakes are annually collected and celebrated in a sacro-profane ritual. Every 1st of May, Serpari (snake catchers) capture and showcase dozens of non-venomous snakes to celebrate the ritual of San Domenico. In order to detect potential zoonotic pathogens within this unique epidemiological context, parasites and microorganisms of snakes harvested for the "festa dei serpari" ritual were investigated. Snakes (n = 112) were examined and ectoparasites collected, as well as blood and feces sampled. Ectoparasites were identified morpho-molecularly, and coprological examination conducted through direct smear and flotation. Molecular screenings were performed to identify parasites and microorganisms in collected samples (i.e., Mesostigmata mites, Anaplasma/Ehrlichia spp., Rickettsia spp., Borrelia burgdorferi sensu lato, Coxiella burnetii, Babesia/Theileria spp., Cryptosporidium spp., Giardia spp., Leishmania spp. and helminths). Overall, 28.5% (32/112) of snakes were molecularly positive for at least one parasite and/or microorganism. Endosymbiont Wolbachia bacteria were identified from Macronyssidae mites and zoonotic vector-borne pathogens (e.g., Rickettsia, Leishmania), as well as orally transmitted pathogens (i.e., Cryptosporidium, Giardia, Proteus vulgaris, Pseudomonas), were detected from blood and feces. Thus, given the central role of the snakes in the tradition of Cocullo, surveys of their parasitic fauna and associated zoonotic pathogens may aid to generate conservation policies to benefit the human-snake interactions, whilst preserving the cultural patrimony of this event., Competing Interests: The authors report there are no competing interests to declare., (Copyright: © 2024 Mendoza-Roldan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)