Eicosanoid signalling blockade protects middle-aged mice from severe COVID-19.

Coronavirus disease 2019 (COVID-19) is especially severe in aged populations1. Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective, but vaccine efficacy is partly compromised by the emergence of SARS-CoV-2 variants with enhanced transmissibility2. The emergence of these variants emphasizes the need for further development of anti-SARS-CoV-2 therapies, especially for aged populations. Here we describe the isolation of highly virulent mouse-adapted viruses and use them to test a new therapeutic drug in infected aged animals. Many of the alterations observed in SARS-CoV-2 during mouse adaptation (positions 417, 484, 493, 498 and 501 of the spike protein) also arise in humans in variants of concern2. Their appearance during mouse adaptation indicates that immune pressure is not required for selection. For murine SARS, for which severity is also age dependent, elevated levels of an eicosanoid (prostaglandin D2 (PGD2)) and a phospholipase (phospholipase A2 group 2D (PLA2G2D)) contributed to poor outcomes in aged mice3,4. mRNA expression of PLA2G2D and prostaglandin D2 receptor (PTGDR), and production of PGD2 also increase with ageing and after SARS-CoV-2 infection in dendritic cells derived from human peripheral blood mononuclear cells. Using our mouse-adapted SARS-CoV-2, we show that middle-aged mice lacking expression of PTGDR or PLA2G2D are protected from severe disease. Furthermore, treatment with a PTGDR antagonist, asapiprant, protected aged mice from lethal infection. PTGDR antagonism is one of the first interventions in SARS-CoV-2-infected animals that specifically protects aged animals, suggesting that the PLA2G2D-PGD2/PTGDR pathway is a useful target for therapeutic interventions.

COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice.

The ongoing coronavirus disease 2019 (COVID-19) pandemic is associated with substantial morbidity and mortality. Although much has been learned in the first few months of the pandemic, many features of COVID-19 pathogenesis remain to be determined. For example, anosmia is a common presentation, and many patients with anosmia show no or only minor respiratory symptoms1. Studies in animals infected experimentally with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID-19, provide opportunities to study aspects of the disease that are not easily investigated in human patients. Although the severity of COVID-19 ranges from asymptomatic to lethal2, most experimental infections provide insights into mild disease3. Here, using K18-hACE2 transgenic mice that were originally developed for SARS studies4, we show that infection with SARS-CoV-2 causes severe disease in the lung and, in some mice, the brain. Evidence of thrombosis and vasculitis was detected in mice with severe pneumonia. Furthermore, we show that infusion of convalescent plasma from a recovered patient with COVID-19 protected against lethal disease. Mice developed anosmia at early time points after infection. Notably, although pre-treatment with convalescent plasma prevented most signs of clinical disease, it did not prevent anosmia. Thus, K18-hACE2 mice provide a useful model for studying the pathological basis of both mild and lethal COVID-19 and for assessing therapeutic interventions.

A global phylogenomic analysis of the shiitake genus Lentinula.

Lentinula is a broadly distributed group of fungi that contains the cultivated shiitake mushroom, L. edodes. We sequenced 24 genomes representing eight described species and several unnamed lineages of Lentinula from 15 countries on four continents. Lentinula comprises four major clades that arose in the Oligocene, three in the Americas and one in Asia-Australasia. To expand sampling of shiitake mushrooms, we assembled 60 genomes of L. edodes from China that were previously published as raw Illumina reads and added them to our dataset. Lentinula edodes sensu lato (s. lat.) contains three lineages that may warrant recognition as species, one including a single isolate from Nepal that is the sister group to the rest of L. edodes s. lat., a second with 20 cultivars and 12 wild isolates from China, Japan, Korea, and the Russian Far East, and a third with 28 wild isolates from China, Thailand, and Vietnam. Two additional lineages in China have arisen by hybridization among the second and third groups. Genes encoding cysteine sulfoxide lyase (lecsl) and γ-glutamyl transpeptidase (leggt), which are implicated in biosynthesis of the organosulfur flavor compound lenthionine, have diversified in Lentinula. Paralogs of both genes that are unique to Lentinula (lecsl 3 and leggt 5b) are coordinately up-regulated in fruiting bodies of L. edodes. The pangenome of L. edodes s. lat. contains 20,308 groups of orthologous genes, but only 6,438 orthogroups (32%) are shared among all strains, whereas 3,444 orthogroups (17%) are found only in wild populations, which should be targeted for conservation.

Adaptation of SARS-CoV-2 to ACE2H353K mice reveals new spike residues that drive mouse infection.

The Coronavirus Disease 2019 (COVID-19) pandemic continues to cause extraordinary loss of life and economic damage. Animal models of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection are needed to better understand disease pathogenesis and evaluate preventive measures and therapies. While mice are widely used to model human disease, mouse angiotensin converting enzyme 2 (ACE2) does not bind the ancestral SARS-CoV-2 spike protein to mediate viral entry. To overcome this limitation, we "humanized" mouse Ace2 using CRISPR gene editing to introduce a single amino acid substitution, H353K, predicted to facilitate S protein binding. While H353K knockin Ace2 (mACE2H353K) mice supported SARS-CoV-2 infection and replication, they exhibited minimal disease manifestations. Following 30 serial passages of ancestral SARS-CoV-2 in mACE2H353K mice, we generated and cloned a more virulent virus. A single isolate (SARS2MA-H353K) was prepared for detailed studies. In 7-11-month-old mACE2H353K mice, a 104 PFU inocula resulted in diffuse alveolar disease manifested as edema, hyaline membrane formation, and interstitial cellular infiltration/thickening. Unexpectedly, the mouse-adapted virus also infected standard BALB/c and C57BL/6 mice and caused severe disease. The mouse-adapted virus acquired five new missense mutations including two in spike (K417E, Q493K), one each in nsp4, nsp9, and M and a single nucleotide change in the 5' untranslated region. The Q493K spike mutation arose early in serial passage and is predicted to provide affinity-enhancing molecular interactions with mACE2 and further increase the stability and affinity to the receptor. This new model and mouse-adapted virus will be useful to evaluate COVID-19 disease and prophylactic and therapeutic interventions.IMPORTANCEWe developed a new mouse model with a humanized angiotensin converting enzyme 2 (ACE2) locus that preserves native regulatory elements. A single point mutation in mouse ACE2 (H353K) was sufficient to confer in vivo infection with ancestral severe acute respiratory syndrome-coronavirus-2 virus. Through in vivo serial passage, a virulent mouse-adapted strain was obtained. In aged mACE2H353K mice, the mouse-adapted strain caused diffuse alveolar disease. The mouse-adapted virus also infected standard BALB/c and C57BL/6 mice, causing severe disease. The mouse-adapted virus acquired five new missense mutations including two in spike (K417E, Q493K), one each in nsp4, nsp9, and M and a single nucleotide change in the 5' untranslated region. The Q493K spike mutation arose early in serial passage and is predicted to provide affinity-enhancing molecular interactions with mACE2 and further increase the stability and affinity to the receptor. This new model and mouse-adapted virus will be useful to evaluate COVID-19 disease and prophylactic and therapeutic interventions.

Hydrogenolysis of Glycerol over NiCeZr Catalyst Modified with Mg, Cu, and Sn at the Surface Level.

Biomass valorization is an essential strategy for converting organic resources into valuable energy and chemicals, contributing to the circular economy, and reducing carbon footprints. Glycerol, a byproduct of biodiesel production, can be used as a feedstock for a variety of high-value products and can contribute to reducing the carbon footprint. This study examines the impact of surface-level modifications of Mg, Cu, and Sn on Ni-Ce-Zr catalysts for the hydrogenolysis of glycerol, with in situ generated hydrogen. The aim of this approach is to enhance the efficiency and sustainability of the biomass valorization process. However, the surface modification resulted in a decrease in the global conversion of glycerol due to the reduced availability of metal sites. The study found that valuable products, such as H2 and CH4 in the gas phase, and 1,2-PG in the liquid phase, were obtained. The majority of the liquid fraction was observed, particularly for Cu- and Sn-doped catalysts, which was attributed to their increased acidity. The primary selectivity was towards the cleavage of the C-O bond. Post-reaction characterizations revealed that the primary causes of deactivation was leaching, which was reduced by the inclusion of Cu and Sn. These findings demonstrate the potential of Cu- and Sn-modified Ni-Ce-Zr catalysts to provide a sustainable pathway for converting glycerol into value-added chemicals.

Interdisciplinary Delphi study by PROSEC North America: Recommendations on single indirect restorations made from ceramic and nonmetallic biomaterials for posterior teeth.

OBJECTIVE: This article puts forward consensus recommendations from PROSEC North America regarding single indirect restorations made from ceramic and nonmetallic biomaterials in posterior teeth. OVERVIEW: The consensus process involved a multidisciplinary panel and three consensus workshops. A systematic literature review was conducted across five databases to gather evidence. The recommendations, informed by findings from systematic reviews and formulated based on a two-phase e-Delphi survey, emphasize a comprehensive treatment strategy that includes noninvasive measures alongside restorative interventions for managing dental caries and tooth wear. The recommendations advocate for selecting between direct and indirect restorations on a case-by-case basis, favoring inlays and onlays over crowns to align with minimally invasive dentistry principles. The recommendations highlight the critical role of selecting restorative biomaterials based on clinical performance, esthetic properties, and adherence to manufacturer guidelines. They emphasize the importance of precision in restorative procedures, including tooth preparation, impression taking, contamination control, and luting. Regular follow-up and maintenance tailored to individual patient needs are crucial for the longevity of ceramic and nonmetallic restorations. CONCLUSIONS: These PROSEC recommendations provide a framework for dental practitioners to deliver high-quality restorative care, advocating for personalized treatment planning and minimally invasive approaches to optimize oral health outcomes. CLINICAL SIGNIFICANCE: The PROSEC North America recommendations highlight the importance of minimally invasive techniques in posterior tooth restorations using ceramic and non-metallic biomaterials. These principles prioritize tooth structure conservation and personalized treatment planning, essential for enhancing clinical outcomes and long-term oral health.

Severe SARS-CoV-2 Pneumonia and Pneumomediastinum/Pneumothorax: A Prospective Observational Study in an Intermediate Respiratory Care Unit.

INTRODUCTION: The occurrence of pneumomediastinum (PM) and/or pneumothorax (PTX) in patients with severe pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated. METHODS: This was a prospective observational study conducted in patients admitted to the intermediate respiratory care unit (IRCU) of a COVID-19 monographic hospital in Madrid (Spain) between December 14, 2020 and September 28, 2021. All patients had a diagnosis of severe SARS-CoV-2 pneumonia and required noninvasive respiratory support (NIRS): high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and bilevel positive airway pressure (BiPAP). The incidences of PM and/or PTX, overall and by NIRS, and their impact on the probabilities of invasive mechanical ventilation (IMV) and death were studied. RESULTS: A total of 1306 patients were included. 4.3% (56/1306) developed PM/PTX, 3.8% (50/1306) PM, 1.6% (21/1306) PTX, and 1.1% (15/1306) PM + PTX. 16.1% (9/56) of patients with PM/PTX had HFNC alone, while 83.9% (47/56) had HFNC + CPAP/BiPAP. In comparison, 41.7% (521/1250) of patients without PM and PTX had HFNC alone (odds ratio [OR] 0.27; 95% confidence interval [95% CI] 0.13-0.55; p < .001), while 58.3% (729/1250) had HFNC + CPAP/BiPAP (OR 3.73; 95% CI 1.81-7.68; p < .001). The probability of needing IMV among patients with PM/PTX was 67.9% (36/53) (OR 7.46; 95% CI 4.12-13.50; p < .001), while it was 22.1% (262/1185) among patients without PM and PTX. Mortality among patients with PM/PTX was 33.9% (19/56) (OR 4.39; 95% CI 2.45-7.85; p < .001), while it was 10.5% (131/1250) among patients without PM and PTX. CONCLUSIONS: In patients admitted to the IRCU for severe SARS-CoV-2 pneumonia requiring NIRS, incidences of PM/PTX, PM, PTX, and PM + PTX were observed to be 4.3%, 3.8%, 1.6%, and 1.1%, respectively. Most patients with PM/PTX had HFNC + CPAP/BiPAP as the NIRS device, much more frequently than patients without PM and PTX. The probabilities of IMV and death among patients with PM/PTX were 64.3% and 33.9%, respectively, higher than those observed in patients without PM and PTX, which were 21.0% and 10.5%, respectively.

Compartments of the crural fascia: clinically relevant ultrasound, anatomical and histological findings.

PURPOSE: Compartment syndrome is a surgical emergency that can occur in any part of the body and can cause cell necrosis when maintained over time. The resulting defects can affect the nerves, muscle cells, bone tissue, and other connective tissues inside the compartment, and fasciotomy has to be performed. The anatomical and histological characteristics of the leg make acute, chronic, and exertional compartment syndrome more likely in this limb. For these reasons, knowledge of the ultrasound, anatomical, and histological features of the crural fascia can help in the treatment of leg compartment syndrome. METHODS: Twenty-one cryopreserved lower limbs from adult cadavers and from one 29-week-old fetus were obtained from the dissection room. They were examined by ultrasound and a subsequent anatomical dissection and microscopy to study the crural fascia and its relationship with the different muscles. Anthropometric measurements were taken of the distances from the head of the fibula and lateral malleolus to the origin of the tibialis anterior muscle in the crural fascia, the exit of the superficial fibular nerve, and the fascia covering the deep posterior muscles of the leg. RESULTS: The crural fascia has very important clinical relationships, which can be identified by ultrasound, as the origin of the tibialis anterior muscle at 16.25 cm from the head of the fibula and the exit of the superficial fibular nerve that crosses this fascia at 21.25 cm from the head of the fibula. Furthermore, the presence of a septum that fixes the deep posterior muscles of the leg and the vessels and nerve can be seen by ultrasound and can explain the possible development of a posterior compartmental syndrome of the leg. Awareness of these features will help to keep these structures safe during the surgical treatment of compartment syndrome. CONCLUSION: The ultrasound study allows identification of anatomical structures in the leg and, thus, avoids damage to them during surgery for compartmental syndromes.

Differences in nanoscale organization of regulatory active and inactive human chromatin.

Methodological advances in conformation capture techniques have fundamentally changed our understanding of chromatin architecture. However, the nanoscale organization of chromatin and its cell-to-cell variance are less studied. Analyzing genome-wide data from 733 human cell and tissue samples, we identified 2 prototypical regions that exhibit high or absent hypersensitivity to deoxyribonuclease I, respectively. These regulatory active or inactive regions were examined in the lymphoblast cell line K562 by using high-throughput super-resolution microscopy. In both regions, we systematically measured the physical distance of 2 fluorescence in situ hybridization spots spaced by only 5 kb of DNA. Unexpectedly, the resulting distance distributions range from very compact to almost elongated configurations of more than 200-nm length for both the active and inactive regions. Monte Carlo simulations of a coarse-grained model of these chromatin regions based on published data of nucleosome occupancy in K562 cells were performed to understand the underlying mechanisms. There was no parameter set for the simulation model that can explain the microscopically measured distance distributions. Obviously, the chromatin state given by the strength of internucleosomal interaction, nucleosome occupancy, or amount of histone H1 differs from cell to cell, which results in the observed broad distance distributions. This large variability was not expected, especially in inactive regions. The results for the mechanisms for different distance distributions on this scale are important for understanding the contacts that mediate gene regulation. Microscopic measurements show that the inactive region investigated here is expected to be embedded in a more compact chromatin environment. The simulation results of this region require an increase in the strength of internucleosomal interactions. It may be speculated that the higher density of chromatin is caused by the increased internucleosomal interaction strength.

Protein content of the Oenococcus oeni extracellular vesicles-enriched fraction.

Malolactic fermentation is essential for the quality of red wines and some other wine styles. Spontaneous malolactic fermentation is often driven by Oenococcus oeni, and commercial starters for this purpose are also often of this species. The increasing number of microbial species and inoculation strategies in winemaking has prompted a growing interest in microbial interactions during wine fermentation. Among other interaction mechanisms, extracellular vesicles have been hypothesized to play a role in this context. Extracellular vesicles have already been described and analysed for several wine yeast species. In this work, the production of extracellular vesicles by O. oeni is reported for the first time. The protein content of these extracellular vesicles is also characterised. It shows differences and similarities with the recently described protein content of Lactiplantibacillus plantarum, a bacterial species also capable of performing malolactic fermentation of wine (and used sometimes as an alternative starter). This work further contributes to the development of the field of extracellular vesicles in food biotechnology.

The posterior/medial dry needling approach of the tibialis posterior muscle is an accurate and safe procedure: a cadaveric study.

BACKGROUND: Evidence suggests that tibialis posterior muscle plays an important role in equinovarus foot deformity in patients who had suffered a stroke and it is one of the most frequently injected lower-extremity muscles for the management of spasticity. Our aim was to assess if a needle accurately and safely penetrates the tibialis posterior muscle during the application of dry needling.  METHODS : We conducted a cadaveric descriptive study. Needling insertion of the tibialis posterior was conducted in 11 cryopreserved cadavers with a 70 mm needle. The needle was inserted using two common approaches, at midpoint (posterior/medial approach) and at upper third (anterior approach) of the leg towards the tibialis posterior. The needle was advanced into the tibialis posterior based upon clinician judgement. Cross-sectional anatomical dissections were photographed and analyzed by photometry. Safety was assessed by calculating the distances from the tip and the path of the needle to proximate neurovascular structures. RESULTS: Accurate needle penetration of the tibialis posterior muscle was observed in all cadavers with both approaches. In general, distances from the needle to the neurovascular bundles were larger with the posterior/medial approach than with the anterior approach, reaching statistically significance for needle tip to nerve (mean difference: 0.6 cm, 95%CI 0.35 to 0.85 cm) and vascular bundle (mean difference: 0.55 cm, 95%CI 0.3 to 0.8 cm) distances (P < 0.001) and needle path to vascular bundle distance (difference: 0.25 cm, 95%CI 0.1 to 0.4 cm, P = 0.045). Age and gender did not influence the main results. CONCLUSIONS: This cadaveric study suggests that needling of the tibialis posterior muscle can be accurately and safely conducted. Safety seems to be larger with the posterior/medial approach when compared with the anterior approach.

Effects on Neuromuscular Function After Ischemic Compression in Latent Trigger Points in the Gastrocnemius Muscles: A Randomized Within-Participant Clinical Trial.

OBJECTIVE: The purpose of this study was to evaluate changes in neuromuscular function, pain perception, and basic physical properties in latent myofascial trigger points (TrPs) after a single treatment session of ischemic compression in the gastrocnemius muscle. METHODS: A randomized within-participant clinical trial with a blinded assessor was conducted. Twenty-nine asymptomatic volunteers with latent gastrocnemius-muscle TrPs were bilaterally explored. Each extremity was randomly assigned to the control group (no treatment) or the experimental group (90 seconds of ischemic compression over each TrP). Neuromuscular function of the gastrocnemius muscle was assessed using a MyotonPro. Muscle flexibility was analyzed using the lunge test and the passive ankle range of motion. The strength was determined with a handheld dynamometer (MicroFET2). Pain perception was analyzed with a 0-to-10 numerical pain rating scale and determination of pressure pain thresholds over each latent TrP. RESULTS: The results revealed a reduction of 15.8% in pain perception and an increment of pressure tolerance of 9.9% without pain in the treatment group. Changes in muscle flexibility (active and passive) and most parameters for neuromuscular response (rigidity, elasticity, and relaxation) were also observed, but they were not significantly different between groups. The clinical effect sizes were moderate for pain perception (d = 0.69), pressure pain threshold (d = 0.78), muscle tone (d = 0.51), and elasticity (d = 0.54) in favor of the treated extremity. Small clinical effect sizes were observed for muscle physical outcomes. CONCLUSION: The present study shows that the use of a single session of ischemic compression for latent gastrocnemius-muscle TrPs improved some sensory outcomes. The effects on ankle range of motion and neuromuscular responses were inconclusive.

Linker Molecules Convert Commercial Fluorophores into Tailored Functional Probes during Biolabelling.

Many life-science techniques and assays rely on selective labeling of biological target structures with commercial fluorophores that have specific yet invariant properties. Consequently, a fluorophore (or dye) is only useful for a limited range of applications, e.g., as a label for cellular compartments, super-resolution imaging, DNA sequencing or for a specific biomedical assay. Modifications of fluorophores with the goal to alter their bioconjugation chemistry, photophysical or functional properties typically require complex synthesis schemes. We here introduce a general strategy that allows to customize these properties during biolabelling with the goal to introduce the fluorophore in the last step of biolabelling. For this, we present the design and synthesis of 'linker' compounds, that bridge biotarget, fluorophore and a functional moiety via well-established labeling protocols. Linker molecules were synthesized via the Ugi four-component reaction (Ugi-4CR) which facilitates a modular design of linkers with diverse functional properties and bioconjugation- and fluorophore attachment moieties. To demonstrate the possibilities of different linkers experimentally, we characterized the ability of commercial fluorophores from the classes of cyanines, rhodamines, carbopyronines and silicon-rhodamines to become functional labels on different biological targets in vitro and in vivo via thiol-maleimide chemistry. With our strategy, we showed that the same commercial dye can become a photostable self-healing dye or a sensor for bivalent ions subject to the linker used. Finally, we quantified the photophysical performance of different self-healing linker-fluorophore conjugates and demonstrated their applications in super-resolution imaging and single-molecule spectroscopy.

Using Incentives and Nudging to Improve Non-Targeted HIV Testing in Ecuador: A Randomized Trial.

Under-detection of HIV/AIDS still burdens many low- and middle-income countries (LMICs). Our randomized trial investigated the effects of financial incentives and a behavioral nudge to induce HIV testing and learning HIV status in Ecuador. In the control group, 12.2% of participants agreed to testing, and 5.3% learned results. A financial incentive paid at testing increased the fraction of participants tested by 50.1 percentage points (95% CI 38.8 to 61.4) and the fraction who learned their status by 8.9 percentage points (95% CI 5.3 to 12.5); the nudge had no effect. The HIV-positive rate was 1.2% in the control group, and incentives prompted a 4.7 percentage point (95% CI 0.5 to 8.9) higher proportion of HIV-positive detection. Incentives also induced earlier testing, suggesting reduced procrastination. This suggests that information with appropriately timed small financial incentives can improve HIV testing and detection of new cases in the general population in LMIC settings.

"Cancer is in style": lifestyle change and the perceived impact of globalization on Andean indigenous communities in Ecuador.

Introduction: There is a paucity of information on cancer among Indigenous populations in Latin America.Methods: Guided by tenets of community engaged research and syndemic theory, we conducted eight focus groups (n = 59) with Kichwa men and women in the province of Imbabura, Ecuador. Data were analyzed using applied thematic analysis techniques.Results: Cancer emerged as an important health problem and was reported as a growing concern. Kichwa participants in this study attributed the rise in cancer to (1) exposure to chemicals and pesticides, (2) urbanization and development, and (3) the rise of innutritious, westernized diets.Conclusion: Our findings suggest that the Kichwa are attuned to the global phenomena in which traditional diet has been replaced by western, processed foods and fast food, which result in higher levels of chronic diseases such as cancer. More research is needed to understand the cancer burden among Indigenous peoples in Latin America.

Early Diagnosis of Multiple Sclerosis Using Swept-Source Optical Coherence Tomography and Convolutional Neural Networks Trained with Data Augmentation.

BACKGROUND: The aim of this paper is to implement a system to facilitate the diagnosis of multiple sclerosis (MS) in its initial stages. It does so using a convolutional neural network (CNN) to classify images captured with swept-source optical coherence tomography (SS-OCT). METHODS: SS-OCT images from 48 control subjects and 48 recently diagnosed MS patients have been used. These images show the thicknesses (45 × 60 points) of the following structures: complete retina, retinal nerve fiber layer, two ganglion cell layers (GCL+, GCL++) and choroid. The Cohen distance is used to identify the structures and the regions within them with greatest discriminant capacity. The original database of OCT images is augmented by a deep convolutional generative adversarial network to expand the CNN's training set. RESULTS: The retinal structures with greatest discriminant capacity are the GCL++ (44.99% of image points), complete retina (26.71%) and GCL+ (22.93%). Thresholding these images and using them as inputs to a CNN comprising two convolution modules and one classification module obtains sensitivity = specificity = 1.0. CONCLUSIONS: Feature pre-selection and the use of a convolutional neural network may be a promising, nonharmful, low-cost, easy-to-perform and effective means of assisting the early diagnosis of MS based on SS-OCT thickness data.

Compartments of the antebrachial fascia of the forearm: clinically relevant ultrasound, anatomical and histological findings.

PURPOSE: Acute compartment syndrome is defined as a limb-threatening condition caused by bleeding or oedema in a closed muscle compartment surrounded by fascia or bone. It is most commonly encountered in the forearm, which has three compartments: posterior, anterior and lateral. These are surrounded and closed in by the antebrachial fascia, formed by dense connective tissue that facilities their study on ultrasound and is key to fasciotomy treatment. The purpose of this study was to broaden existing ultrasound, anatomical and histological knowledge of the fascia of the forearm to facilitate their identification on ultrasound, with possible clinical and therapeutic applications. METHODS: The study was performed in 50 cryopreserved upper limbs from adult cadavers from the dissection room of the Faculty of Medicine and Health Sciences. They were examined on ultrasound and subsequent anatomical dissection and microscopy to study the fascia and its relationship with different muscles of the forearm compartments. RESULTS: Distinct anatomical relationships were observed on ultrasound and dissection between the fascia and the extensor carpi ulnaris, extensor digiti minimi, and anconeus muscle in the posterior compartment, and the flexor carpi radialis and flexor carpi ulnaris in the anterior compartment. They were isolated by the antebrachial fascia and had distinct relationships with the neurovascular structures. CONCLUSION: These results demonstrate that high-definition ultrasound enables us to locate the antebrachial fascia and particular muscles with a distinct relationship with neurovascular structures. This helps better identify these structures, facilitating diagnosis of any pathology in the area, with potential therapeutic and clinical applications.

In-hospital outcomes after bariatric surgery in patients with heart failure.

Based on the largest publicly available all-payer inpatient database in the United States, this study sought to evaluate real-world outcomes after bariatric surgery among patients with heart failure.

An estimate of the number of white sharks Carcharodon carcharias interacting with ecotourism in Guadalupe Island.

The aim of the present study is to provide an estimate of the number of white sharks Carcharodon carcharias that seasonally interact with ecotourism boats in Guadalupe Island using Schnabel's mark-recapture method and 6316 records of white sharks during 2012-2014. The results of the estimation highlight an abundance of 78 white sharks 95% C.I. (62.1, 105.6) interacting with ecotourism. The regulations regarding the number of tourists, boats and the monitoring of white sharks should be assessed to improve management decisions regarding the conservation and sustainable use of this threatened species.

Synthesis of novel (-)-epicatechin derivatives as potential endothelial GPER agonists: Evaluation of biological effects.

To potentially identify proteins that interact (i.e. bind) and may contribute to mediate (-)-epicatechin (Epi) responses in endothelial cells we implemented the following strategy: 1) synthesis of novel Epi derivatives amenable to affinity column use, 2) in silico molecular docking studies of the novel derivatives on G protein-coupled estrogen receptor (GPER), 3) biological assessment of the derivatives on NO production, 4) implementation of an immobilized Epi derivative affinity column and, 5) affinity column based isolation of Epi interacting proteins from endothelial cell protein extracts. For these purposes, the Epi phenol and C3 hydroxyl groups were chemically modified with propargyl or mesyl groups. Docking studies of the novel Epi derivatives on GPER conformers at 14 ns and 70 ns demostrated favorable thermodynamic interactions reaching the binding site. Cultures of bovine coronary artery endothelial cells (BCAEC) treated with Epi derivatives stimulated NO production via Ser1179 phosphorylation of eNOS, effects that were attenuated by the use of the GPER blocker, G15. Epi derivative affinity columns yielded multiple proteins from BCAEC. Proteins were electrophoretically separated and inmmunoblotting analysis revealed GPER as an Epi derivative binding protein. Altogether, these results validate the proposed strategy to potentially isolate and identify novel Epi receptors that may account for its biological activity.