An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes.

In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools to access and manipulate fine neuronal subtypes are still limited. Here, we performed systematic analysis of single cell genomic data to identify enhancer candidates for each of the cortical interneuron subtypes. We established a set of enhancer-AAV tools that are highly specific for distinct cortical interneuron populations and striatal cholinergic neurons. These enhancers, when used in the context of different effectors, can target (fluorescent proteins), observe activity (GCaMP) and manipulate (opto- or chemo-genetics) specific neuronal subtypes. We also validated our enhancer-AAV tools across species. Thus, we provide the field with a powerful set of tools to study neural circuits and functions and to develop precise and targeted therapy.

Use of Electropolishing in Orthodontic Appliances: An Option to Reduce the Risk of Metal Hypersensitivity.

Electropolishing is a common treatment in the industry; however, how it behaves in the mouth and what benefits it can bring over metal dental attachments have not yet been established. Thus, the aim of this study was to determine the levels of corrosion, the released metal ions, and the changes in structural composition in metallic orthodontic appliances following electropolishing treatment. This study included 56 orthodontic brackets and 28 archwires. The samples were subjected to a pH cycle to simulate an oral environment. Using UV-Vis spectrophotometry, the release of metallic particles was evaluated, and using scanning electron microscopy, the structural and composition changes were evaluated. Groups were compared using Student's t-tests with a value of p ≤ 0.05. The cyclical pH solutions showed variations between groups and days (1, 3, 5, 7 and 15), reaching the highest acidification in the self-ligating brackets; the absorbance between solutions did not differ significantly. As seen from the SEM results, the experimental group showed minor irregularities compared with the control groups. The experimental brackets decreased in iron and increased in chromium after electropolishing, while for the NiTi archwires, they decreased in nickel. Therefore, electropolishing treatments in metallic orthodontic attachments improve their surface structure and corrosion resistance could reduce the risk of metal hypersensitivity, mainly from nickel.

Platelet releasates mitigate the endotheliopathy of trauma.

BACKGROUND: Platelets are well known for their roles in hemostasis, but they also play a key role in thromboinflammatory pathways by regulating endothelial health, stimulating angiogenesis, and mediating host defense through both contact dependent and independent signaling. When activated, platelets degranulate releasing multiple active substances. We hypothesized that the soluble environment formed by trauma platelet releasates attenuates thromboinflammation via mitigation of trauma induced endothelial permeability and metabolomic reprogramming. METHODS: Blood was collected from injured and healthy patients to generate platelet releasates and plasma in parallel. Permeability of endothelial cells when exposed to trauma platelet releasates (TPR) and plasma (TP) was assessed via resistance measurement by Electric Cell-substrate Impedance Sensing (ECIS). Endothelial cells treated with TPR and TP were subjected to mass spectrometry-based metabolomics. RESULTS: TP increased endothelial permeability, whereas TPR decreased endothelial permeability when compared to untreated cells. When TP and TPR were mixed ex vivo, TPR mitigated TP-induced permeability, with significant increase in AUC compared to TP alone. Metabolomics of TPR and TP demonstrated disrupted redox reactions and anti-inflammatory mechanisms. CONCLUSION: TPRs provide endothelial barrier protection against TP-induced endothelial permeability. Our findings highlight a potential beneficial action of activated platelets on the endothelium in injured patients through disrupted redox reactions and increased antioxidants. Our findings support that soluble signaling from platelet degranulation may mitigate the endotheliopathy of trauma. The clinical implications of this are that activated platelets may prove a promising therapeutic target in the complex integration of thrombosis, endotheliopathy, and inflammation in trauma. LEVEL OF EVIDENCE: Prognostic/Epidemiological, Level III.

The white grunt, Haemulon plumierii (Lacepède, 1801) as paratenic and definitive host of two acanthocephalan species, with the description of a new species of Dollfusentis (Palaeacanthocephala: Leptohynchoididae) from the Yucatán Peninsula, Mexico.

Acanthocephalans are a group of obligate endoparasites that alternate between vertebrates and invertebrates to complete their life cycles. Occasionally, the same individual host acts as a definitive or paratenic host for different acanthocephalan species. In this study, acanthocephalans were sampled in marine fish in three localities of the Yucatán Peninsula; adults and cystacanths were recovered from the intestine and body cavity, respectively, of Haemulon plumierii from off the coast of Sisal, Yucatán. Ribosomal DNA sequences (small and large subunits) were used to test the phylogenetic position of the species of the genus Dollfusentis, whereas the mtDNA gene cox 1 was used for assessing species delimitation. The cox 1 analysis revealed an independent genetic lineage, which is recognized herein as a new species, Dollfusentis mayae n. sp. The new species is morphologically distinguished from the other six congeners by having a cylindrical proboscis armed with 22-25 longitudinal rows bearing 12 hooks each. The cystacanths were morphologically identified as Gorgorhynchus medius by having a cylindrical trunk covered with tiny irregular spines on the anterior region, and a cylindrical proboscis armed with 17-18 longitudinal rows of 21 hooks each; small and large subunit phylogenetic analyses yielded G. medius within the family Isthomosacanthidae, suggesting that Gorgorhynchus should be transferred to this family from Rhadinorhynchidae where it is currently allocated.

Effectiveness of a diagnostic algorithm for dengue based on an artificial neural network.

Introduction: Dengue is a disease with a wide clinical spectrum. The early identification of dengue cases is crucial but challenging for health professionals; therefore, it is necessary to have effective diagnostic instruments to initiate timely care. Objective: To evaluate the effectiveness of an algorithm based on an artificial neural network (ANN) to diagnose dengue in an endemic area. Methods: A single-center case-control study was conducted in a secondary-care hospital in Ciudad Obregón, Sonora. An algorithm was built with the official operational definitions, which was called the "direct algorithm," and for the ANN algorithm, the brain.js library was used. The data analysis was performed with the diagnostic tests of sensitivity, specificity, positive predictive value (ppv), and negative predictive value (npv), with 95% confidence intervals and Cohen's kappa index. Results: A total of 233 cases and 233 controls from 2022 were included. The ANN presented a sensitivity of 0.90 (95% CI [0.85, 0.94]), specificity of 0.82 (95% CI [0.77, 0.87]), npv of 0.91 (95% CI [0.87, 0.94]) and ppv of 0.81 (95% CI [0.76, 0.85]) and a kappa of 0.72. The direct algorithm had a sensitivity of 0.97 (95% CI [0.94, 0.99]), specificity of 0.96 (95% CI [0.92, 0.98]), npv 0.97 (95% CI [0.94, 0.98]), ppv 0.96 (95% CI [0.93, 0.98]) and kappa 0.93. Conclusions: The direct algorithm performed better than the ANN in the diagnosis of dengue.

Structure, Absolute Configuration, Antiproliferative and Phytotoxic Activities of Icetexane and Abietane Diterpenoids from Salvia carranzae and Chemotaxonomic Implications.

From the aerial parts of Salvia carranzae Zamudio and Bedolla, three new icetexane-type diterpenoids were isolated. Their structures were established through spectroscopic methods and named the following: salvicarranzanolide (1), 19-deoxo-salvicarranzanolide (2) and 19-deoxo-20-deoxy-salvicarranzanolide (3). In addition, the known icetexane-type diterpenoids, 6,7,11,14-tetrahydro-7-oxo-icetexone (4), iso-icetexone (5), 19-deoxo-iso-icetexone (6), icetexone (7), 19-deoxo-icetexone (8) and 7α-acetoxy-6,7-dihydroicetexone (9), were also isolated, along with the abietanes sessein (10) and ferruginol (11). α-Tocopherol was also identified. Compounds 5, 6 and 8 were tested for their antiproliferative activity using the sulforhodamine B assay on six cancer and one normal human cell lines. Diterpenoids 5 and 6 showed noteworthy antiproliferative activity, exhibiting an IC50 (µM) = 0.43 ± 0.01 and 1.34 ± 0.04, respectively, for U251 (glioblastoma), an IC50 (µM) = 0.45 ± 0.01 and 1.29 ± 0.06 for K5621 (myelogenous leukemia), 0.84 ± 0.07 and 1.03 ± 0.10 for HCT-15 (colon cancer), and 0.73 ± 0.06 and 0.95 ± 0.09 for SKLU-1 (lung adenocarcinoma) cell lines. On the other hand, the phytotoxicity of compounds 5-7 and 9-10 was evaluated on seed germination and root growth in some weeds such as Medicago sativa, Panicum miliaceum, Amaranthus hypochondriacus and Trifolium pratense as models. While compounds 5 and 10 exhibited a moderate inhibitory effect on the root growth of A. hypochondriacus and T. pratense at 100 ppm, the diterpenoids 6, 7 and 9 were ineffective in all the plant models. Taxonomic positions based on the chemical profiles found are also discussed.

An Alternative Method for the Selective Synthesis of Ortho-nitro Anilines Using Bismuth Nitrate Pentahydrate.

BACKGROUND: Nitroaromatic compounds are important scaffolds used for the syn-thesis of a variety of compounds, such as explosives, herbicides, dyes, perfumes and phar-maceuticals. Bismuth nitrate pentahydrate is a widely used reagent in organic synthesis; how-ever, its utility as a nitrating agent for anilines is underexplored. OBJECTIVE: The aim of this work is to propose and find the proper reaction conditions of an alternative nitrating agent constituted by a mixture of bismuth nitrate / acetic anhydride in DCM with a series of substituted anilines under mild reflux. METHODS: Several anilines having both activating and deactivating substituents in the ortho, meta and para positions were the substrate for the nitration reaction. Experimental conditions were performed in "one-pot" conditions before product purification. RESULTS: Bi(NO3)3•5H2O demonstrated to be effective and somehow regioselective when it came to the nitration of anilines in the ortho position. Although other products were also identified under these conditions, in most cases, the ortho derivative was the major or even the only product obtained with moderate to high yields in the range of 50% - 96%. CONCLUSION: Bi(NO3)3•5H2O is an efficient and safe nitrating agent since the use of concen-trated and corrosive acids like sulfuric and nitric is avoided; furthermore, bismuth nitrate is low-priced and no special care nor equipment is required.

A retinotopic code structures the interaction between perception and memory systems.

Conventional views of brain organization suggest that regions at the top of the cortical hierarchy processes internally oriented information using an abstract amodal neural code. Despite this, recent reports have described the presence of retinotopic coding at the cortical apex, including the default mode network. What is the functional role of retinotopic coding atop the cortical hierarchy? Here we report that retinotopic coding structures interactions between internally oriented (mnemonic) and externally oriented (perceptual) brain areas. Using functional magnetic resonance imaging, we observed robust inverted (negative) retinotopic coding in category-selective memory areas at the cortical apex, which is functionally linked to the classic (positive) retinotopic coding in category-selective perceptual areas in high-level visual cortex. These functionally linked retinotopic populations in mnemonic and perceptual areas exhibit spatially specific opponent responses during both bottom-up perception and top-down recall, suggesting that these areas are interlocked in a mutually inhibitory dynamic. These results show that retinotopic coding structures interactions between perceptual and mnemonic neural systems, providing a scaffold for their dynamic interaction.

The complete mitochondrial genome of 3 species of allocreadiids (Digenea, Allocreadiidae): characterization and phylogenetic position within the order Plagiorchiida.

Trematodes of the family Allocreadiidae are primarily found in the intestines of freshwater fishes around the world. The family includes 15 genera and c. 130 species. The last 2 decades have witnessed an increase in the genetic library of its species. Molecular data have been crucial for species delimitation and species description within Allocreadiidae and for understanding their evolutionary and biogeographical history and classification. Here, the mitogenomes of 3 species of allocreadiids were obtained using high throughput sequencing methods. Mitogenomes were compared with other members of the order Plagiorchiida to determine their molecular composition, gene rearrangement and phylogenetic interrelationships. The complete circular mitogenomes of Allocreadium lobatum, Creptotrematina aguirrepequenoi and Wallinia mexicana were 14 424, 13 769 and 13 924 bp long respectively, comprising 12 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 2 non-coding regions. Gene arrangements were identical to other Xiphidiatan trematodes. Phylogenetic analyses using the mitogenomes revealed Allocreadiidae as a monophyletic group closely related to other members of the suborder Xiphidiata; A. lobatum was yielded as the sister taxon of C. aguirrepequenoi + W. mexicana. Our study increases the complete mitochondrial genome library of trematodes and strengthens our understanding of the phylogenetic relationships and classification of this parasite group.

Utility of Bedside Ultrasound in Percutaneous Tracheostomy.

Background: Percutaneous tracheostomy placement is a common procedure performed in the intensive care unit. The use of an anterior neck ultrasound exam is routinely performed preprocedure, allowing for vessel visualization in determining the safety and feasibility of performing the procedure bedside. This prospective observational cohort study was conducted to determine whether vasculature in the anterior neck, seen on bedside ultrasound exam, contributes to bleeding complications during or after percutaneous tracheostomy (PCT) placement. Research Question: Do the vessels identified on preprocedure neck ultrasound affect the risk of bleeding during and after bedside PCT placement? Study Design and Methods: Preprocedural ultrasound was used to identify standard anatomical landmarks and vascular structures in the anterior neck in all patients undergoing bedside PCT placement under bronchoscopic guidance. A blinded survey of our recorded preprocedural images was provided to an expert panel who regularly perform bedside PCTs to determine the influence the images have on their decision to perform the procedure at the bedside. Results: One out of 15 patients (7%) had intra-operative minimal bleeding which was not clinically significant and resolved by gauze compression for 30 s. None of the patients had post-procedural bleeding after tracheostomy placement. Based on the blinded interpretation of neck ultrasound, there was 0.214 inter-operator variability among the expert panelists for decision-making regarding performing bedside PCT. Interpretation: Vessels visualized with anterior neck ultrasound were found to be small venous structures and did not significantly contribute to bleeding risk in patients who underwent PCT placement. The size and location of veins on neck ultrasound may commonly contribute to abandoning bedside PCT. This study suggests that veins measuring 3.9 mm or smaller identified at the site of access do not increase the risk of bleeding in PCT placement.

Molecular species delimitation of marine trematodes over wide geographical ranges: Schikhobalotrema spp. (Digenea: Haplosplanchnidae) in needlefishes (Belonidae) from the Pacific Ocean and Gulf of Mexico.

Geographical distribution plays a major role in our understanding of marine biodiversity. Some marine fish trematodes have been shown to have highly restricted geographical distributions, while some are known to occur over very wide ranges; however, very few of these wide distributions have been demonstrated genetically. Here, we analyse species of the genus Schikhobalotrema (Haplosplanchnidae) parasitizing beloniforms from the tropical west Pacific, the eastern Pacific and the Gulf of Mexico (GoM). We test the boundaries of these trematodes by integrating molecular and morphological data, host association, habitat of the hosts and geographical distribution, following a recently proposed and standardized delineation method for the recognition of marine trematode species. Based on the new collections, Schikhobalotrema huffmani is here synonymized with the type-species of the genus, Schikhobalotrema acutum; Sch. acutum is now considered to be widely distributed, from the GoM to the western Pacific. Additionally, we describe a new species, Schikhobalotrema minutum n. sp., from Strongylura notata and Strongylura marina (Belonidae) from La Carbonera coastal lagoon, northern Yucatán, GoM. We briefly discuss the role of host association and historical biogeography of the hosts as drivers of species diversification of Schikhobalotrema infecting beloniforms.

Molecular data aids pinworm diagnosis in night monkeys (Aotus spp., Primates: Aotidae) with the resurrection of a Trypanoxyuris species (Nematoda: Oxyuridae).

Neotropical primates (Platyrrhines) are commonly parasitized by pinworm nematodes of the genus Trypanoxyuris Vevers, 1923. The taxonomic identity of Trypanoxyuris sampled in night monkeys (Aotus Iliger) has been rather controversial. Two species have been described, namely T. microon (Linstow, 1907) and T. interlabiata (Sandosham, 1950). The latter was synonymized with T. microon considering that the observed morphological differences corresponded to different developmental stages of the nematode rather than to differences between both species. Here, we used an integrative taxonomy approach, based on morphological and molecular data along with host identity, in order to assess the validity of both species. Our results evidenced that these different morphotypes correspond to different and reciprocally monophyletic groups; thus, we propose the resurrection of T. interlabiata. We redescribe both pinworm species using specimens sampled in Aotus monkeys from Colombia and discuss the advantages of combining molecular and morphological data to uncover pinworm diversity, and to understand the potential forces determining the diversification process in pinworms from platyrrhine primates.

Description of new species of Trematoda from bats of Southeastern Mexico and a new classification for Brachylecithum rileyi n. comb. (Dicrocoeliidae).

To date, 23 species of trematodes have been reported in bats from Mexico. However, in some regions of Mexico, such as the Yucatan Peninsula, many species of bats do not have helminthological records. Here, we sampled bats in four localities in Southeastern Mexico from April 2017 to February 2022. Parasites were collected from the intestine of four species of bats: Pteronotus fulvus, Eumops nanus, Noctilio leporinus and Nyctinomops laticaudatus. Conventional morphological techniques and molecular tools with the 28S ribosomal gene were used to describe the helminths. We discovered that our parasites represent three new species and a new combination of trematodes. We found that the new species have morphological differences with their congeneric species, and we complement this information whit molecular data. Furthermore, we found morphological and molecular evidence that places Dicrocoelium rileyi within the genus Brachylecithum. This study points out the importance of comparing morphological and phylogenetic information.

Bioremediation of Automotive Residual Oil-Contaminated Soils by Biostimulation with Enzymes, Surfactant, and Vermicompost.

Contamination of soils by automotive residual oil represents a global environmental problem. Bioremediation is the technology most suitable to remove this contaminant from the medium. Therefore, this work aimed to evaluate the effectiveness of bioremediation of automotive residual oil-contaminated soils by biostimulation with enzymes, surfactant, and vermicompost. The bioremediation efficiency was examined using a factorial design of 24 to determine the effect of the time, pH and temperature conditions, biostimulation with enzyme-vermicompost, and biostimulation with enzyme-surfactant. Enzymes obtained from Ricinus communis L. seeds, commercial vermicompost, and Triton X-100 were used. Results showed that the highest removal efficiency (99.9%) was achieved at 49 days, with a pH of 4.5, temperature of 37 °C, and using biostimulation with enzyme-vermicompost (3% w/v-5% w/w). The addition of surfactant was not significant in increasing the removal efficiency. Therefore, the results provide adequate conditions to bioremediate automotive residual oil-contaminated soils by biostimulation using enzymes supported with vermicompost.

Scene Perception and Visuospatial Memory Converge at the Anterior Edge of Visually Responsive Cortex.

To fluidly engage with the world, our brains must simultaneously represent both the scene in front of us and our memory of the immediate surrounding environment (i.e., local visuospatial context). How does the brain's functional architecture enable sensory and mnemonic representations to closely interface while also avoiding sensory-mnemonic interference? Here, we asked this question using first-person, head-mounted virtual reality and fMRI. Using virtual reality, human participants of both sexes learned a set of immersive, real-world visuospatial environments in which we systematically manipulated the extent of visuospatial context associated with a scene image in memory across three learning conditions, spanning from a single FOV to a city street. We used individualized, within-subject fMRI to determine which brain areas support memory of the visuospatial context associated with a scene during recall (Experiment 1) and recognition (Experiment 2). Across the whole brain, activity in three patches of cortex was modulated by the amount of known visuospatial context, each located immediately anterior to one of the three scene perception areas of high-level visual cortex. Individual subject analyses revealed that these anterior patches corresponded to three functionally defined place memory areas, which selectively respond when visually recalling personally familiar places. In addition to showing activity levels that were modulated by the amount of visuospatial context, multivariate analyses showed that these anterior areas represented the identity of the specific environment being recalled. Together, these results suggest a convergence zone for scene perception and memory of the local visuospatial context at the anterior edge of high-level visual cortex.SIGNIFICANCE STATEMENT As we move through the world, the visual scene around us is integrated with our memory of the wider visuospatial context. Here, we sought to understand how the functional architecture of the brain enables coexisting representations of the current visual scene and memory of the surrounding environment. Using a combination of immersive virtual reality and fMRI, we show that memory of visuospatial context outside the current FOV is represented in a distinct set of brain areas immediately anterior and adjacent to the perceptually oriented scene-selective areas of high-level visual cortex. This functional architecture would allow efficient interaction between immediately adjacent mnemonic and perceptual areas while also minimizing interference between mnemonic and perceptual representations.

A retinotopic code structures the interaction between perception and memory systems.

Conventional views of brain organization suggest that the cortical apex processes internally-oriented information using an abstract, amodal neural code. Yet, recent reports have described the presence of retinotopic coding at the cortical apex, including the default mode network. What is the functional role of retinotopic coding atop the cortical hierarchy? Here, we report that retinotopic coding structures interactions between internally-oriented (mnemonic) and externally-oriented (perceptual) brain areas. Using fMRI, we observed robust, inverted (negative) retinotopic coding in category-selective memory areas at the cortical apex, which is functionally linked to the classic (positive) retinotopic coding in category-selective perceptual areas in high-level visual cortex. Specifically, these functionally-linked retinotopic populations in mnemonic and perceptual areas exhibit spatially-specific opponent responses during both bottom-up perception and top-down recall, suggesting that these areas are interlocked in a mutually-inhibitory dynamic. Together, these results show that retinotopic coding structures interactions between perceptual and mnemonic neural systems, thereby scaffolding their dynamic interaction.

Monorchiids (Digenea, Trematoda) of fishes in the Yucatán Peninsula, Mexico, with the description of three new species based on morphological and molecular data.

Adult specimens of monorchiids (Digenea) were collected from the intestines of the white grunt, Haemulon plumierii Lacepède (Haemulidae), and the white mullet, Mugil curema Valenciennes (Mugilidae) from five localities off the Yucatán Peninsula and one locality in the Gulf of Mexico. Some specimens were photographed and sequenced for two molecular markers, the large subunit (LSU) of nuclear rDNA and the cytochrome c oxidase subunit 1 (cox1) of mitochondrial DNA. Other specimens were processed for morphological analyses. Newly generated sequences were aligned with other sequences available in GenBank. Bayesian inference and maximum likelihood analyses were implemented using the data sets of LSU and cox1 independently. Reciprocal monophyly evidenced through phylogenetic analyses, sequence divergence values for both molecular markers, and detailed morphological analyses, including scanning electron microscopy photomicrographs, revealed three new genetic lineages, i.e., species, as parasites of M. curema. The three new species are Sinistroporomonorchis mexicanus n. sp., Sinistroporomonorchis yucatanensis n. sp., and Sinistroporomonorchis minutus n. sp. Two additional species of monorchiids were sampled, characterised molecularly, and re-described, namely Sinistroporomonorchis glebulentus (Overstreet, 1971) from the white mullet, and Alloinfundiburictus haemuli (Overstreet, 1969), from the white grunt.

Title: Monorchiidae (Digenea, Trematoda) de poissons de la péninsule du Yucatán, Mexique, avec description de trois nouvelles espèces sur la base de données morphologiques et moléculaires. Abstract: Des spécimens adultes de Monorchiidae (Digenea) ont été collectés dans les intestins de la gorette blanche, Haemulon plumierii Lacepède (Haemulidae), et du mulet blanc, Mugil curema Valenciennes (Mugilidae) de cinq localités au large de la péninsule du Yucatán et d'une localité dans le Golfe du Mexique. Certains spécimens ont été photographiés et séquencés pour deux marqueurs moléculaires, la grande sous-unité (LSU) de l'ADNr nucléaire et la sous-unité 1 de la cytochrome c oxydase (cox1) de l'ADN mitochondrial. D'autres spécimens ont été traités pour des analyses morphologiques. Les séquences nouvellement générées ont été alignées avec d'autres séquences disponibles dans GenBank. L'inférence bayésienne et les analyses de vraisemblance maximale ont été mises en œuvre en utilisant les ensembles de données de LSU et cox1 indépendamment. La monophylie réciproque mise en évidence par des analyses phylogénétiques, des valeurs de divergence de séquence pour les deux marqueurs moléculaires et des analyses morphologiques détaillées, y compris des photomicrographies au microscope électronique à balayage, a révélé trois nouvelles lignées génétiques, c'est-à-dire des espèces, qui sont parasites de M. curema. Les trois nouvelles espèces sont Sinistroporomonorchis mexicanus n. sp., Sinistroporomonorchis yucatanensis n. sp. et Sinistroporomonorchis minutus n. sp. (Monorchiidae). Deux espèces supplémentaires de Monorchiidae ont été échantillonnées, caractérisées moléculairement et redécrites, à savoir Sinistroporomonorchis glebulentus (Overstreet, 1971) du mulet blanc et Alloinfundiburictus haemuli (Overstreet, 1969) de la gorette blanche.

Association of SARS-CoV-2 nucleocapsid viral antigen and the receptor for advanced glycation end products with development of severe disease in patients presenting to the emergency department with COVID-19.

Introduction: There remains a need to better identify patients at highest risk for developing severe Coronavirus Disease 2019 (COVID-19) as additional waves of the pandemic continue to impact hospital systems. We sought to characterize the association of receptor for advanced glycation end products (RAGE), SARS-CoV-2 nucleocapsid viral antigen, and a panel of thromboinflammatory biomarkers with development of severe disease in patients presenting to the emergency department with symptomatic COVID-19. Methods: Blood samples were collected on arrival from 77 patients with symptomatic COVID-19, and plasma levels of thromboinflammatory biomarkers were measured. Results: Differences in biomarkers between those who did and did not develop severe disease or death 7 days after presentation were analyzed. After adjustment for multiple comparisons, RAGE, SARS-CoV-2 nucleocapsid viral antigen, interleukin (IL)-6, IL-10 and tumor necrosis factor receptor (TNFR)-1 were significantly elevated in the group who developed severe disease (all p<0.05). In a multivariable regression model, RAGE and SARS-CoV-2 nucleocapsid viral antigen remained significant risk factors for development of severe disease (both p<0.05), and each had sensitivity and specificity >80% on cut-point analysis. Discussion: Elevated RAGE and SARS-CoV-2 nucleocapsid viral antigen on emergency department presentation are strongly associated with development of severe disease at 7 days. These findings are of clinical relevance for patient prognostication and triage as hospital systems continue to be overwhelmed. Further studies are warranted to determine the feasibility and utility of point-of care measurements of these biomarkers in the emergency department setting to improve patient prognostication and triage.

Effects of the circulating environment of COVID-19 on platelet and neutrophil behavior.

Introduction: Thromboinflammatory complications are well described sequalae of Coronavirus Disease 2019 (COVID-19), and there is evidence of both hyperreactive platelet and inflammatory neutrophil biology that contributes to the thromoinflammatory milieu. It has been demonstrated in other thromboinflammatory diseases that the circulating environment may affect cellular behavior, but what role this environment exerts on platelets and neutrophils in COVID-19 remains unknown. We tested the hypotheses that 1) plasma from COVID-19 patients can induce a prothrombotic platelet functional phenotype, and 2) contents released from platelets (platelet releasate) from COVID-19 patients can induce a proinflammatory neutrophil phenotype. Methods: We treated platelets with COVID-19 patient and disease control plasma, and measured their aggregation response to collagen and adhesion in a microfluidic parallel plate flow chamber coated with collagen and thromboplastin. We exposed healthy neutrophils to platelet releasate from COVID-19 patients and disease controls and measured neutrophil extracellular trap formation and performed RNA sequencing. Results: We found that COVID-19 patient plasma promoted auto-aggregation, thereby reducing response to further stimulation ex-vivo. Neither disease condition increased the number of platelets adhered to a collagen and thromboplastin coated parallel plate flow chamber, but both markedly reduced platelet size. COVID-19 patient platelet releasate increased myeloperoxidasedeoxyribonucleic acid complexes and induced changes to neutrophil gene expression. Discussion: Together these results suggest aspects of the soluble environment circulating platelets, and that the contents released from those neutrophil behavior independent of direct cellular contact.