Aggressive Angiomyxoma of the Pelvis: 35-Year Experience.

BACKGROUND: Aggressive angiomyxoma is a very rare mesenchymal tumor most commonly found in the pelvic and perineal regions. Although many are estrogen and progesterone hormone receptor positive, the pathogenesis is unknown. Due to its rarity, there is a paucity of literature relating to this pathology. This article presents a case series on the management of aggressive angiomyxoma of the pelvis. OBJECTIVE: To present a 35-year experience managing aggressive angiomyxoma of the pelvis. DESIGN: This was a retrospective single-system analysis. SETTINGS: This study was conducted at a quaternary referral academic health care system. PATIENTS: All patients treated for aggressive angiomyxoma of the pelvis. INTERVENTIONS: All patients underwent surgical or medical management of their disease. MAIN OUTCOME MEASURES: The primary outcomes were disease recurrence and mortality. Secondary outcomes included risk factors for recurrence. RESULTS: A total of 32 patients (94% women) were identified with a median follow-up of 65 months. Thirty patients (94%) underwent operative resection and 2 patients were treated solely with medical management. Fifteen achieved an R0 resection (negative microscopic margins) at the index operation, of which 4 (27%) experienced tumor recurrence. There were no mortalities. No risk factors for disease recurrence were identified. LIMITATIONS: Limitations to our study include its nonrandomized retrospective nature, single health care system experience, and small patient sample size. CONCLUSIONS: Aggressive angiomyxoma is a rare, slow-growing tumor with locally invasive features and a high potential for recurrence even after resection with negative margins. Imaging modalities such as CT or MRI should be obtained to aid in diagnosis and surgical planning. Workup should be paired with preoperative biopsy and testing for hormone receptor status, which can increase diagnostic accuracy and guide medical treatment. Close posttreatment surveillance is imperative to detect recurrence. See Video Abstract . ANGIOMIXOMA AGRESIVO DE PELVIS EXPERIENCIA DE AOS: ANTECEDENTES:El angiomixoma agresivo es un tumor mesenquimal muy raro que se encuentra más comúnmente en las regiones pélvica y perineal. Aunque muchos son positivos para los receptores hormonales como el estrógeno y la progesterona, la patogénesis es aún desconocida. Debido a su rareza, existe escasa literatura relacionada con esta patología. Este artículo presenta una serie de casos sobre el tratamiento del angiomixoma agresivo de pelvis.OBJETIVO:Presentar una experiencia de 35 años en el manejo del angiomixoma agresivo de pelvis.DISEÑO:Este fue un análisis retrospectivo de sistema único.AJUSTES:Este estudio se llevó a cabo en un sistema de salud académico de referencia de nivel cuaternario.PACIENTES:Todos los pacientes tratados por angiomixoma agresivo de pelvis.INTERVENCIONES:Todos los pacientes se sometieron a tratamiento quirúrgico y/o médico de su enfermedad.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados primarios fueron la recurrencia de la enfermedad y la mortalidad. Los resultados secundarios incluyeron factores de riesgo de recurrencia.RESULTADOS:Se identificaron un total de 32 pacientes (94% mujeres) con una mediana de seguimiento de 65 meses. Treinta (94%) fueron sometidos a resección quirúrgica y dos fueron tratados únicamente con tratamiento médico. Quince lograron una resección R0 (márgenes microscópicos negativos) en la operación inicial, de los cuales cuatro (27%) experimentaron recurrencia tumoral. No hubo mortalidades. No se identificaron factores de riesgo para la recurrencia de la enfermedad.LIMITACIONES:Las limitaciones de nuestro estudio incluyen su naturaleza retrospectiva no aleatoria, la experiencia de un solo sistema de atención médica y el tamaño pequeño de la muestra de pacientes.CONCLUSIONES:El angiomixoma agresivo es un tumor raro, de crecimiento lento, con características localmente invasivas y un alto potencial de recurrencia incluso después de una resección con márgenes negativos. Se deben obtener modalidades de imágenes como CT y/o MRI para la ayuda diagnóstica y la planificación quirúrgica. El estudio debe combinarse con una biopsia preoperatoria y pruebas del estado de los receptores hormonales, que pueden aumentar la precisión del diagnóstico y guiar el tratamiento médico. Es imperativa una estrecha vigilancia posterior al tratamiento para detectar recurrencia. (Traducción-Dr Osvaldo Gauto ).

Selective Formation of Pd-DNA Hybrids Using Tailored Palladium-Mediated Base Pairs: Towards Heteroleptic Pd-DNA Systems.

The formation of highly organized metal-DNA structures has significant implications in bioinorganic chemistry, molecular biology and material science due to their unique properties and potential applications. In this study, we report on the conversion of single-stranded polydeoxycytidine (dC15 ) into a Pd-DNA supramolecular structure using the [Pd(Aqa)] complex (Aqa=8-amino-4-hydroxyquinoline-2-carboxylic acid) through a self-assembly process. The resulting Pd-DNA assembly closely resembles a natural double helix, with continuous [Pd(Aqa)(C)] (C=cytosine) units serving as palladium-mediated base pairs, forming interbase hydrogen bonds and intrastrand stacking interactions. Notably, the design of the [Pd(Aqa)] complex favours the interaction with cytosine, distinguishing it from our previously reported [Pd(Cheld)] complex (Cheld=chelidamic acid). This finding opens possibilities for creating heteroleptic Pd-DNA hybrids where different complexes specifically bind to nucleobases. We confirmed the Pd-DNA supramolecular structural assembly and selective binding of the complexes using NMR spectroscopy, circular dichroism, mass spectrometry, isothermal titration calorimetry, and DFT calculations.

Comprehensive phylogenomic time tree of bryophytes reveals deep relationships and uncovers gene incongruences in the last 500 million years of diversification.

PREMISE: Bryophytes form a major component of terrestrial plant biomass, structuring ecological communities in all biomes. Our understanding of the evolutionary history of hornworts, liverworts, and mosses has been significantly reshaped by inferences from molecular data, which have highlighted extensive homoplasy in various traits and repeated bursts of diversification. However, the timing of key events in the phylogeny, patterns, and processes of diversification across bryophytes remain unclear. METHODS: Using the GoFlag probe set, we sequenced 405 exons representing 228 nuclear genes for 531 species from 52 of the 54 orders of bryophytes. We inferred the species phylogeny from gene tree analyses using concatenated and coalescence approaches, assessed gene conflict, and estimated the timing of divergences based on 29 fossil calibrations. RESULTS: The phylogeny resolves many relationships across the bryophytes, enabling us to resurrect five liverwort orders and recognize three more and propose 10 new orders of mosses. Most orders originated in the Jurassic and diversified in the Cretaceous or later. The phylogenomic data also highlight topological conflict in parts of the tree, suggesting complex processes of diversification that cannot be adequately captured in a single gene-tree topology. CONCLUSIONS: We sampled hundreds of loci across a broad phylogenetic spectrum spanning at least 450 Ma of evolution; these data resolved many of the critical nodes of the diversification of bryophytes. The data also highlight the need to explore the mechanisms underlying the phylogenetic ambiguity at specific nodes. The phylogenomic data provide an expandable framework toward reconstructing a comprehensive phylogeny of this important group of plants.

Coconut Flour (Cocos nucifera L.) as a Partial Replacement in Wheat Flour (Triticum aestivum)-Based Tortillas and Its Effect on Dough Rheology and Tortilla Quality.

Wheat-flour (WF) tortillas are among the popular flatbreads used in northern Mexico to prepare 'burritos', which are widely accepted in the USA and other countries but have low nutritional quality. Therefore, to increase the protein and fiber contents, we replaced 10 or 20% of the WF with coconut (Cocos nucifera, variety Alto Saladita) flour (CF) and evaluated the effects on the dough rheology and quality of the composite tortillas. There were differences in the optimum mixing times among the doughs. The protein, fat, and ash contents of the tortillas increased (p < 0.05) with increasing CF content. The carbohydrate content was unchanged (p > 0.05), but the 20% CF tortillas contained more fiber than the control tortilla. Tortilla firmness increased (p < 0.05) and extensibility decreased (p < 0.05) with increasing CF content. The 80:20 blended tortillas showed the highest firmness (7.9 N), whereas the control and 90:10 blended tortillas did not differ (p > 0.05) in firmness. There were no differences (p > 0.05) in extensibility between the composite tortillas. The physicochemical properties of the tortillas indicated that the 20% CF-containing tortilla was a more nutritious option to the wheat flour tortilla due to its higher dietary fiber and protein contents, in addition to the slight reduction seen in extensibility compared to the WF tortilla.

On-Surface Synthesis and Characterization of a High-Spin Aza-[5]-Triangulene.

Triangulenes are a class of open-shell triangular graphene flakes with total spin increasing with their size. In the last years, on-surface-synthesis strategies have permitted fabricating and engineering triangulenes of various sizes and structures with atomic precision. However, direct proof of the increasing total spin with their size remains elusive. In this work, we report the combined in-solution and on-surface synthesis of a large nitrogen-doped triangulene (aza-[5]-triangulene) on a Au(111) surface, and the detection of its high-spin ground state. Bond-resolved scanning tunneling microscopy images uncovered radical states distributed along the zigzag edges, which were detected as weak zero-bias resonances in scanning tunneling spectra. These spectral features reveal the partial Kondo screening of a high-spin state. Through a combination of several simulation tools, we find that the observed distribution of radical states is explained by a quintet ground state (S=2), instead of the quartet state (S=3/2) expected for the neutral species. This confirms that electron transfer to the metal substrate raises the spin of the ground state. We further provide a qualitative description of the change of (anti)aromaticity introduced by N-substitution, and its role in the charge stabilization on a surface, resulting in an S=2 aza-triangulene on Au(111).

In vitro characterization of iridoid and phenylethanoid glycosides from Cistanche phelypaea for nutraceutical and pharmacological applications.

"Desert hyacinths" are a remarkable group of parasitic plants belonging to genus Cistanche, including more than 20 accepted species typically occurring in deserts or coastal dunes parasitizing roots of shrubs. Several Cistanche species have long been a source of traditional herbal medicine or food, being C. deserticola and C. tubulosa the most used in China. This manuscript reports the isolation and identification of some phenylethanoid and iridoid glycosides, obtained from the hydroalcoholic extract of C. phelypaea collected in Spain. The present study aims to characterize the antioxidant activity of C. phelypaea metabolites in the light of their application in nutraceutical and cosmeceutical industries and the effect of acetoside, the most abundant metabolite in C. phelypaea extract, on human keratinocyte and pluripotent stem cell proliferation and differentiation. Our study demonstrated that acetoside, besides its strong antioxidant potential, can preserve the proliferative potential of human basal keratinocytes and the stemness of mesenchymal progenitors necessary for tissue morphogenesis and renewal. Therefore, acetoside can be of practical relevance for the clinical application of human stem cell cultures in tissue engineering and regenerative medicine.

A New, Conservative Treatment for Perianal Fistula that May Halve the Need for Surgical Intervention: Case Series.

PURPOSE: In the last two decades, many sphincter preservation techniques have been proposed for the treatment of anal fistula. Since 2011, our surgical team has treated fistulas by sealing them with platelet-rich fibrin (PRF). This is performed actually as an outpatient process, without anaesthesia. METHODS: Patients were treated with PRF sealant, during the period June 2012-March 2017. The fibrin preparation is applied in the fistulous tract, with no need for any type of anaesthesia, and so the patient can go home immediately afterwards, without further observation. RESULTS: After an average follow-up of 26.49 months, the perianal fistula had healed completely in 52.86% of the patients (n = 37), who each received an average of 1.92 sealant operations. In another 10 cases, the sealing was initially successful, but a relapse occurred during the follow-up period. CONCLUSION: The outpatient treatment of perianal fistula with PRF is totally harmless, is very low cost and achieves very acceptable results. In our opinion, therefore, this could be considered an appropriate initial treatment for perianal fistula, with surgical treatment being reserved if this approach is unsuccessful, thereby avoiding many complications and producing significant economic savings for the health system.

Conformational Stabilization of Gp41-Mimetic Miniproteins Opens Up New Ways of Inhibiting HIV-1 Fusion.

Inhibition of the HIV-1 fusion process constitutes a promising strategy to neutralize the virus at an early stage before it enters the cell. In this process, the envelope glycoprotein (Env) plays a central role by promoting membrane fusion. We previously identified a vulnerability at the flexible C-terminal end of the gp41 C-terminal heptad repeat (CHR) region to inhibition by a single-chain miniprotein (named covNHR-N) that mimics the first half of the gp41 N-terminal heptad repeat (NHR). The miniprotein exhibited low stability, moderate binding to its complementary CHR region, both as an isolated peptide and in native trimeric Envs, and low inhibitory activity against a panel of pseudoviruses. The addition of a disulfide bond stabilizing the miniprotein increased its inhibitory activity, without altering the binding affinity. Here, to further study the effect of conformational stability on binding and inhibitory potency, we additionally stabilized these miniproteins by engineering a second disulfide bond stapling their N-terminal end, The new disulfide-bond strongly stabilizes the protein, increases binding affinity for the CHR target and strongly improves inhibitory activity against several HIV-1 strains. Moreover, high inhibitory activity could be achieved without targeting the preserved hydrophobic pocket motif of gp41. These results may have implications in the discovery of new strategies to inhibit HIV targeting the gp41 CHR region.

Exploring Highly Conserved Regions of SARS-CoV-2 Spike S2 Subunit as Targets for Fusion Inhibition Using Chimeric Proteins.

Since the beginning of the COVID-19 pandemic, considerable efforts have been made to develop protective vaccines against SARS-CoV-2 infection. However, immunity tends to decline within a few months, and new virus variants are emerging with increased transmissibility and capacity to evade natural or vaccine-acquired immunity. Therefore, new robust strategies are needed to combat SARS-CoV-2 infection. The viral spike composed of S1 and S2 subunits mediates viral attachment and membrane fusion to infect the host cell. In this process, interaction between the highly conserved heptad repeat 1 and 2 regions (HR1 and HR2) of S2 is crucial and for this reason; these regions are promising targets to fight SARS-CoV-2. Here, we describe the design and characterization of chimeric proteins that structurally imitate the S2 HR1 region in a trimeric coiled-coil conformation. We biophysically characterized the proteins and determined their capacity to bind the HR2 region, as well as their inhibitory activity of SARS-CoV-2 infection in vitro. HR1 mimetic proteins showed conformational heterogeneity and a propensity to form oligomers. Moreover, their structure is composed of subdomains with varied stability. Interestingly, the full HR1 proteins showed high affinity for HR2-derived peptides and SARS-CoV-2 inhibitory activity, whereas smaller proteins mimicking HR1 subdomains had a decreased affinity for their complementary HR2 region and did not inhibit the virus. The results provide insight into effective strategies to create mimetic proteins with broad inhibitory activity and therapeutic potential against SARS-CoV-2.

[Regular arrangement of collecting venules (RAC) as a predictor of the absence of Helicobacter pylori infection with conventional endoscopes in a Latin American population, diagnostic performance by subgroups]. / Disposición regular de vénulas colectoras (RAC) como predictor de ausencia de infección por Helicobacter pylori con endoscopios convencionales en población latina, rendimiento diagnóstico por subgrupos.

INTRODUCTION: The regular arrangement of collecting venules has high value to predict the absence of gastric infection by Helicobacter Pylori, the studies that have validated this finding were carried out with magnification images and digital chromoendoscopy, it is common to perform endoscopies with conventional white light equipment without magnification. OBJECTIVE: This study aims to validate this finding as a predictor of the absence of H. Pylori infection using endoscopy equipment with conventional white light without magnification. MATERIAL AND METHODS: An observational study was carried out identifying the presence of RAC with a conventional endoscope, the determination of Helicobacter pylori was established by histopathology. Sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPV) were calculated in relation to the presence of RAC and the H. pylori infection status. RESULTS: 241 patients were included, finding a sensitivity of 5%, with a specificity of 89%. The prevalence of H. Pylori decreased with age. CONCLUSION: This study reports a low sensitivity with a high specificity of the regular distribution of collecting venules to establish the state of infection by H. Pylori. The diagnostic performance was lower than that reported in studies carried out with chromium endoscopy with magnification.

Convolutional neural networks for segmentation of FIB-SEM nanotomography data from porous polymer films for controlled drug release.

Phase-separated polymer films are commonly used as coatings around pharmaceutical oral dosage forms (tablets or pellets) to facilitate controlled drug release. A typical choice is to use ethyl cellulose and hydroxypropyl cellulose (EC/HPC) polymer blends. When an EC/HPC film is in contact with water, the leaching out of the water-soluble HPC phase produces an EC film with a porous network through which the drug is transported. The drug release can be tailored by controlling the structure of this porous network. Imaging and characterization of such EC porous films facilitates understanding of how to control and tailor film formation and ultimately drug release. Combined focused ion beam and scanning electron microscope (FIB-SEM) tomography is a well-established technique for high-resolution imaging, and suitable for this application. However, for segmenting image data, in this case to correctly identify the porous network, FIB-SEM is a challenging technique to work with. In this work, we implement convolutional neural networks for segmentation of FIB-SEM image data. The data are acquired from three EC porous films where the HPC phases have been leached out. The three data sets have varying porosities in a range of interest for controlled drug release applications. We demonstrate very good agreement with manual segmentations. In particular, we demonstrate an improvement in comparison to previous work on the same data sets that utilized a random forest classifier trained on Gaussian scale-space features. Finally, we facilitate further development of FIB-SEM segmentation methods by making the data and software used open access.

Drug release from pharmaceutical tablets or pellets is often controlled by applying a phase-separated polymer film coating. Ethyl cellulose and hydroxypropyl cellulose (EC/HPC) polymer blends are commonly used. The HPC phase leaches out when in contact with water and the result is a porous EC matrix coating, with mass transport properties that can be controlled by tailoring the structure of the porous network. High-resolution 3D imaging is necessary to characterize such materials, and the resolution of e.g. X-ray computed tomography is simply insufficient. Combined focused ion beam and scanning electron microscope (FIB-SEM) tomography on the other hand is a suitable technique, but segmentation of FIB-SEM data, in this case to separate the solid matrix and the porous network, is challenging. In this work, we develop a method for segmentation of FIB-SEM image data acquired from three different EC porous films where the HPC phases have been leached out. The segmentation is based on convolutional neural networks (CNNs). CNNs is a well-established machine learning paradigm and has demonstrated state-of-the-art performance in many image analysis and segmentation tasks. CNNs are inspired from biological processes in the visual cortex and act similarly, at least conceptually. In contrast to most conventional machine learning algorithms, CNNs learn by themselves which features to extract from the images. The features are extracted at different spatial scales and may constitute e.g. edge and contrast detectors. These features are subsequently used for classification. In this work, CNNs are used for image segmentation. The goal is to identify which regions in the images that contain either pore (empty space) or solid (material), hence a binary classification task. For the CNN to learn how to perform such a task, a ground truth is needed. This is achieved by letting an expert manually segment parts of the data. This is a very time-consuming endeavor, hence only a small random subset of the full dataset is manually segmented. The CNN is trained for the task using the manually segmented data, after which automatic segmentation of the full dataset is performed. We obtain very good agreement with manual segmentations in terms of accuracy and porosity, and a clear improvement in comparison to an earlier developed random forest classifier trained on Gaussian scale-space features on the same data. The development of accurate segmentation methods is a crucial step toward better understanding and tailoring of coatings for controlled drug release.

A natural deep eutectic solvent as a novel dispersive solvent in dispersive liquid-liquid microextraction based on solidification of floating organic droplet for the determination of pesticide residues.

Current trends in analytical chemistry encourage the use of innocuous solvents to develop modern methods aligned with green chemistry. In this sense, natural deep eutectic solvents (NADESs) have emerged as a novel generation of green solvents which can be employed in sample treatments as an alternative to the toxic organic solvents commonly used so far. In this work, a new extraction method employs dispersive liquid-liquid microextraction based on a solid floating organic droplet (DLLME-SFO), by using a mixture composed of a less dense than water extraction solvent, 1-dodecanol, and a novel dispersive solvent, NADES. The methodology was proposed to extract and preconcentrate some pesticide residues (fipronil, fipronil-sulfide, fipronil-sulfone, and boscalid) from environmental water and white wine samples before analysis by liquid-chromatography coupled to ultraviolet detection (HPLC-UV). Limits of quantification (LOQs) lower than 4.5 µg L-1, recoveries above 80%, and precision, expressed as RSD, below 15% were achieved in both samples showing that the proposed method is a powerful, efficient, and green alternative for the determination of these compounds and, therefore, demonstrating a new application for NADES in sample preparation. In addition, the DLLME-SFOD-HPLC-UV method was evaluated and compared with other reported approaches using the Analytical GREEnness metric approach, which highlighted the greenness of the proposed method.

3D-Printed Surgical Steel Curettes for the Treatment of Perianal Fistula.

Need. The diversity of approaches proposed for the treatment of complex perianal fistulas reflects the fact that no method has yet been shown to be fully satisfactory. We believe the successful treatment of this condition is directly proportional to the amount of fibrous tissue that can be removed. Technical solution. We use a kit of small curettes, of different thicknesses and sizes, incorporating spicules that enable the physician to remove fibrous tissue from the fistula tract. The small size and varying thicknesses of the curettes enable them to mould to the curves of the fistula tract and to remove tissue by deroofing from the shallowest to the deepest layers, thus excising the entire fibrous tract. Our hospital has recently incorporated into clinical practice a new model of 3D-printed surgical steel curette, flanked by 2 lateral rings through which the suture is threaded. The central part of the curette contains radially graduated discs, the tips of which perform the debriding action, removing the fibrous tissue from the tract. Proof of concept. By using these curettes in conjunction with our standard technique (plugging the tract with platelet-rich fibrin), we have improved the success rate from 67% to 88%. Next steps. We have contacted several companies with a view to marketing this product. Conclusion. The results obtained are significantly better than those offered by the techniques in current use for the treatment of complex fistulas, without prejudice to outcomes such as anal continence and morbidity and mortality.

Rapid Conversion of Amyloid-Beta 1-40 Oligomers to Mature Fibrils through a Self-Catalytic Bimolecular Process.

The formation of fibrillar aggregates of the amyloid beta peptide (Aß) in the brain is one of the hallmarks of Alzheimer's disease (AD). A clear understanding of the different aggregation steps leading to fibrils formation is a keystone in therapeutics discovery. In a recent study, we showed that Aß40 and Aß42 form dynamic micellar aggregates above certain critical concentrations, which mediate a fast formation of more stable oligomers, which in the case of Aß40 are able to evolve towards amyloid fibrils. Here, using different biophysical techniques we investigated the role of different fractions of the Aß aggregation mixture in the nucleation and fibrillation steps. We show that both processes occur through bimolecular interplay between low molecular weight species (monomer and/or dimer) and larger oligomers. Moreover, we report here a novel self-catalytic mechanism of fibrillation of Aß40, in which early oligomers generate and deliver low molecular weight amyloid nuclei, which then catalyze the rapid conversion of the oligomers to mature amyloid fibrils. This fibrillation catalytic activity is not present in freshly disaggregated low-molecular weight Aß40 and is, therefore, a property acquired during the aggregation process. In contrast to Aß40, we did not observe the same self-catalytic fibrillation in Aß42 spheroidal oligomers, which could neither be induced to fibrillate by the Aß40 nuclei. Our results reveal clearly that amyloid fibrillation is a multi-component process, in which dynamic collisions between different interacting species favor the kinetics of amyloid nucleation and growth.

Determination of the Main Ergot Alkaloids and Their Epimers in Oat-Based Functional Foods by Ultra-High Performance Liquid Chromatography Tandem Mass Spectrometry.

An ultra-high performance liquid chromatography coupled to tandem mass spectrometry method is proposed for the determination of the major ergot alkaloids (ergometrine, ergosine, ergotamine, ergocornine, ergokryptine, ergocristine) and their epimers (ergometrinine, ergosinine, ergotaminine, ergocorninine, ergokryptinine, and ergocristinine) in oat-based foods and food supplements. A modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) procedure was applied as sample treatment, reducing the consumption of organic solvent and increasing sensitivity. This method involved an extraction with acetonitrile and ammonium carbonate (85:15, v/v) and a clean-up step based on dispersive solid-phase extraction, employing a mixture of C18/Z-Sep+ as sorbents. Procedural calibration curves were established and limits of quantification were below 3.2 µg/kg for the studied compounds. Repeatability and intermediate precision (expressed as RSD%) were lower than 6.3% and 15%, respectively, with recoveries ranging between 89.7% and 109%. The method was applied to oat-based products (bran, flakes, flour, grass, hydroalcoholic extracts, juices, and tablets), finding a positive sample of oat bran contaminated with ergometrine, ergosine, ergometrinine, and ergosinine (total content of 10.7 µg/kg).

Why a Virtual Assistant for Moral Enhancement When We Could have a Socrates?

Can Artificial Intelligence (AI) be more effective than human instruction for the moral enhancement of people? The author argues that it only would be if the use of this technology were aimed at increasing the individual's capacity to reflectively decide for themselves, rather than at directly influencing behaviour. To support this, it is shown how a disregard for personal autonomy, in particular, invalidates the main proposals for applying new technologies, both biomedical and AI-based, to moral enhancement. As an alternative to these proposals, this article proposes a virtual assistant that, through dialogue, neutrality and virtual reality technologies, can teach users to make better moral decisions on their own. The author concludes that, as long as certain precautions are taken in its design, such an assistant could do this better than a human instructor adopting the same educational methodology.

Doctor, please make me freer: Capabilities enhancement as a goal of medicine.

Biomedical innovations are making possible the enhancement of human capabilities. There are two philosophical stances on the role that medicine should play in this respect. On the one hand, naturalism rejects every medical intervention that goes beyond preventing and treating disease. On the other hand, welfarism advocates enhancements that foster subjective well-being. We will show that both positions have considerable shortcomings. Consequently, we will introduce a third characterization in which therapies and enhancements can be reconciled with the legitimate objectives of medicine inasmuch as they improve the capabilities that enable the freedom to pursue personal well-being.

On-Surface Synthesis and Collective Spin Excitations of a Triangulene-Based Nanostar.

Triangulene nanographenes are open-shell molecules with predicted high spin state due to the frustration of their conjugated network. Their long-sought synthesis became recently possible over a metal surface. Here, we present a macrocycle formed by six [3]triangulenes, which was obtained by combining the solution synthesis of a dimethylphenyl-anthracene cyclic hexamer and the on-surface cyclodehydrogenation of this precursor over a gold substrate. The resulting triangulene nanostar exhibits a collective spin state generated by the interaction of its 12 unpaired π-electrons along the conjugated lattice, corresponding to the antiferromagnetic ordering of six S=1 sites (one per triangulene unit). Inelastic electron tunneling spectroscopy resolved three spin excitations connecting the singlet ground state with triplet states. The nanostar behaves close to predictions from the Heisenberg model of an S=1 spin ring, representing a unique system to test collective spin modes in cyclic systems.

A first approach using micellar electrokinetic capillary chromatography for the determination of fipronil and fipronil-sulfone in eggs.

Fipronil is an insecticide that is not approved in the European Union in food. In 2017, fipronil was involved in a European health alert due to its presence in fresh hen eggs because of an illicit use in poultry farms, so reliable methods are needed to determine fipronil and its main metabolites in these matrixes. In this work, we report the first approach to the study of fipronil and two metabolites, fipronil-sulfone and fipronil-sulfide by CE. MEKC mode was employed using a solution of 50 mM ammonium perfluorooctanoate pH 9.0 with 10% (v/v) methanol as background electrolyte. The proposed method was combined with a simple sample treatment based on salting-out assisted LLE (SALLE) using acetonitrile as extraction solvent and ammonium sulfate as salt. The SALLE-MEKC-UV method allowed the simultaneous quantification of fipronil and fipronil-sulfone. Validation parameters yielded satisfactory results, with precision, expressed as relative SD, below 14% and recoveries higher than 83%. Limits of detection were 90 µg/kg for fipronil and 150 µg/kg for fipronil-sulfone, so in terms of sensitivity further studies of sample treatments allowing extra preconcentration or the use of more sensitive detection, such as MS, would be needed.

Thermodynamic dissection of the interface between HIV-1 gp41 heptad repeats reveals cooperative interactions and allosteric effects.

HIV-1 glycoprotein 41 (gp41) mediates fusion between virus and target cells by folding into a fusion active state, in which the C-terminal heptad repeat (CHR) regions associate externally to the N-terminal heptad repeat (NHR) trimer and form a very stable six-helix bundle coiled-coil structure. Therefore, interfering with the NHR-CHR interaction of gp41 is a promising therapeutic approach against HIV-1. However, a full understanding of the molecular and mechanistic details of this interaction is still incomplete. Here, we use single-chain, chimeric proteins (named covNHR) that reproduce accurately the CHR-NHR interactions to analyze the binding thermodynamics of several peptides with different length from the CHR region. The results indicate that cooperative binding involving two or more pockets of the NHR groove is necessary to obtain relevant affinities and that the binding energy is broadly distributed along the interface, underlining a crucial role of a middle pocket to achieve tight binding. In contrast, targeting only the deep hydrophobic pocket is insufficient to achieve significant affinity. Moreover, calorimetry experiments in combination with limited proteolysis performed using a mutant with occluded binding in the N-terminal pocket reveal the existence of an allosteric communication between the different regions. This study is the first detailed thermodynamic dissection of the NHR-CHR interaction in gp41 and contributes therefore to a better understanding of HIV fusion. These results are relevant for the development of potential fusion inhibitors.