Transtendinous course of the infrapatellar branch of saphenous nerve. A contribution to the aetiology of entrapment neuropathy and modification of the existing classification

Background: The course of the infrapatellar branch of saphenous nerve (IPBSN) in relation to the Sartorius muscle has been classified into presartorial, transsartorial and retrosartorial types. Mechanical compression of the IPBSN within the Sartorius tendon has been surgically recognised as a cause of entrapment neuropathy. Purpose of the present study was to differentiate the IPBSNs penetrating the Sartorius tendon from those penetrating the Sartorius muscle, from an anatomical and clinical point of views and thus modifying the existing classification. Materials and methods: The IPBSN was bilaterally dissected in 27 cadavers. The cases of the IPBSNs penetrating the Sartorius tendon were recorded separately from those penetrating the Sartorius muscle belly. Results: In 11 out of 54 limbs (20.4%) the IPBSN ran through the Sartorius muscle belly. In 3 out of 54 (5.6%) limbs, the IPBSN penetrated the Sartorius tendon. Conclusions: The penetrating type of IPBSN includes two distinct subtypes: the muscle-penetrating type and the tendon-penetrating type. These subtypes are also distinct from a clinical point of view, since only the tendon-penetrating type has been associated with the IPBSN entrapment neuropathy. According to these findings we suggest a modification of the current classification. Further clinical studies are necessary to fully demonstrate whether the tendon-penetrating type should be considered as a predisposing factor for the IPBSN entrapment neuropathy. Distinguishing the two subtypes might be helpful for that purpose

Model-Driven Chatbot Development

Esta versión del artículo ha sido aceptada para su publicación, después de la revisión por pares (cuando corresponda) y está sujeta a los términos de uso de AM de Springer Nature, pero no es la Versión de Registro y no refleja mejoras posteriores a la aceptación, ni ninguna corrección. La versión del registro está disponible en línea en: https://doi.org/10.1007/978-3-030-62522-1_15Chatbots are software services accessed via conversation in natural language. They are increasingly used to help in all kinds of procedures like booking flights, querying visa information or assigning tasks to developers. They can be embedded in webs and social networks, and be used from mobile devices without installing dedicated apps. While many frameworks and platforms have emerged for their development, identifying the most appropriate one for building a particular chatbot requires a high investment of time. Moreover, some of them are closed – resulting in customer lock-in – or require deep technical knowledge. To tackle these issues, we propose a model-driven engineering approach to chatbot development. It comprises a neutral meta-model and a domainspecific language (DSL) for chatbot description; code generators and parsers for several chatbot platforms; and a platform recommender. Our approach supports forward and reverse engineering, and model-based analysis. We demonstrate its feasibility presenting a prototype tool and an evaluation based on migrating third party Dialogflow bots to RasaWork funded by the Spanish Ministry of Science (RTI2018095255-B-I00) and the R&D programme of Madrid (P2018/TCS-4314

Defining the microbial effluxome in the content of the host-microbiome interaction

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A Novel Flow Cytometric HTS Assay Reveals Functional Modulators of ATP Binding Cassette Transporter ABCB6

ABCB6 is a member of the adenosine triphosphate (ATP)-binding cassette family of transporter proteins that is increasingly recognized as a relevant physiological and therapeutic target. Evaluation of modulators of ABCB6 activity would pave the way toward a more complete understanding of the significance of this transport process in tumor cell growth, proliferation and therapy-related drug resistance. In addition, this effort would improve our understanding of the function of ABCB6 in normal physiology with respect to heme biosynthesis, and cellular adaptation to metabolic demand and stress responses. To search for modulators of ABCB6, we developed a novel cell-based approach that, in combination with flow cytometric high-throughput screening (HTS), can be used to identify functional modulators of ABCB6. Accumulation of protoporphyrin, a fluorescent molecule, in wild-type ABCB6 expressing K562 cells, forms the basis of the HTS assay. Screening the Prestwick Chemical Library employing the HTS assay identified four compounds, benzethonium chloride, verteporfin, tomatine hydrochloride and piperlongumine, that reduced ABCB6 mediated cellular porphyrin levels. Validation of the identified compounds employing the hemin-agarose affinity chromatography and mitochondrial transport assays demonstrated that three out of the four compounds were capable of inhibiting ABCB6 mediated hemin transport into isolated mitochondria. However, only verteporfin and tomatine hydrochloride inhibited ABCB6’s ability to compete with hemin as an ABCB6 substrate. This assay is therefore sensitive, robust, and suitable for automation in a high-throughput environment as demonstrated by our identification of selective functional modulators of ABCB6. Application of this assay to other libraries of synthetic compounds and natural products is expected to identify novel modulators of ABCB6 activity

Antimicrobial and Efflux Pump Inhibitory Activity of Caffeoylquinic Acids from Artemisia absinthium against Gram-Positive Pathogenic Bacteria

Background: Traditional antibiotics are increasingly suffering from the emergence of multidrug resistance amongst pathogenic bacteria leading to a range of novel approaches to control microbial infections being investigated as potential alternative treatments. One plausible antimicrobial alternative could be the combination of conventional antimicrobial agents/antibiotics with small molecules which block multidrug efflux systems known as efflux pump inhibitors. Bioassay-driven purification and structural determination of compounds from plant sources have yielded a number of pump inhibitors which acted against gram positive bacteria. Methodology/Principal Findings: In this study we report the identification and characterization of 4′,5′-O-dicaffeoylquinic acid (4′,5′-ODCQA) from Artemisia absinthium as a pump inhibitor with a potential of targeting efflux systems in a wide panel of Gram-positive human pathogenic bacteria. Separation and identification of phenolic compounds (chlorogenic acid, 3′,5′-ODCQA, 4′,5′-ODCQA) was based on hyphenated chromatographic techniques such as liquid chromatography with post column solid-phase extraction coupled with nuclear magnetic resonance spectroscopy and mass spectroscopy. Microbial susceptibility testing and potentiation of well know pump substrates revealed at least two active compounds; chlorogenic acid with weak antimicrobial activity and 4′,5′-ODCQA with pump inhibitory activity whereas 3′,5′-ODCQA was ineffective. These intitial findings were further validated with checkerboard, berberine accumulation efflux assays using efflux-related phenotypes and clinical isolates as well as molecular modeling methodology. Conclusions/Significance: These techniques facilitated the direct analysis of the active components from plant extracts, as well as dramatically reduced the time needed to analyze the compounds, without the need for prior isolation. The calculated energetics of the docking poses supported the biological information for the inhibitory capabilities of 4′,5′-ODCQA and furthermore contributed evidence that CQAs show a preferential binding to Major Facilitator Super family efflux systems, a key multidrug resistance determinant in gram-positive bacteria.National Institutes of Health (U.S.) (grant R01GM59903)National Institutes of Health (U.S.) (grant R01AI050875)Netherlands Organization for Scientific Research (VICI grant 700.56.442)Massachusetts Technology Transfer Center (MTTC)National Institutes of Health (U.S.) (grant 5U54MH084690-02

Videodensitometric analysis of advanced carotid plaque: correlation with MMP-9 and TIMP-1 expression

<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP (TIMP) promote derangement of the extracellular matrix, which is ultimately reflected in plaque images seen on ultrasound. Videodensitometry can identify structural disturbances in plaques.</p> <p>Objectives</p> <p>To establish the correlations between values determined using videodensitometry in B-mode ultrasound images of advanced carotid plaques and the total expression of MMP-9 and TIMP-1 in these removed plaques.</p> <p>Methods</p> <p>Thirty patients underwent ultrasonic tissue characterization of carotid plaques before surgery, using mean gray level (MGL), energy, entropy and homogeneity. Each patient was assigned preoperatively to one of 2 groups: group I, symptomatic patients (n = 16; 12 males; mean age 66.7 ± 6.8 years), and group II, asymptomatic patients (n = 14; 8 males; mean age 67.6 ± 6.81 years). Tissue specimens were analyzed for MMP-9 and TIMP-1 expression. Nine carotid arteries were used as normal tissue controls.</p> <p>Results</p> <p>MMP-9 expression levels were elevated in group II and in normal tissues compared to group I (p < 0.001). TIMP-1 levels were higher in group II than in group I, and significantly higher in normal tissues than in group I (p = 0.039). The MGL was higher in group II compared to group I (p = 0.038). Energy had greater values in group II compared to group I (<it>p </it>= 0.02). There were no differences between patient groups in homogeneity and entropy. Energy positively correlated with MMP-9 and TIMP-1 expression (p = 0.012 and p = 0.031 respectively). Homogeneity positively correlated with MMP-9 and TIMP-1 expression (p = 0.034 and p = 0.047 respectively). There were no correlations between protein expression and MGL or entropy.</p> <p>Conclusions</p> <p>Videodensitometric computer analysis of ultrasound scanning images can be used to identify stable carotid plaques, which have higher total expression levels of MMP-9 and TIMP-1 than unstable plaques.</p

XR-RF Imaging Enabled by Software-Defined Metasurfaces and Machine Learning: Foundational Vision, Technologies and Challenges

We present a new approach to Extended Reality (XR), denoted as iCOPYWAVES, which seeks to offer naturally low-latency operation and cost-effectiveness, overcoming the critical scalability issues faced by existing solutions. iCOPYWAVES is enabled by emerging PWEs, a recently proposed technology in wireless communications. Empowered by intelligent (meta)surfaces, PWEs transform the wave propagation phenomenon into a software-defined process. We leverage PWEs to i) create, and then ii) selectively copy the scattered RF wavefront of an object from one location in space to another, where a machine learning module, accelerated by FPGAs, translates it to visual input for an XR headset using PWEdriven, RF imaging principles (XR-RF). This makes for an XR system whose operation is bounded in the physical layer and, hence, has the prospects for minimal end-to-end latency. Over large distances, RF-to-fiber/fiber-to-RF is employed to provide intermediate connectivity. The paper provides a tutorial on the iCOPYWAVES system architecture and workflow. A proof-of-concept implementation via simulations is provided, demonstrating the reconstruction of challenging objects in iCOPYWAVES produced computer graphics

Severity of asymptomatic carotid stenosis and risk of ipsilateral hemispheric ischaemic events: Results from the ACSRS study

Objectives. This study determines the risk of ipsilateral ischaemic neurological events in relation to the degree of asymptomatic carotid stenosis and other risk factors. Methods. Patients (n = 1115) with asymptomatic internal carotid artery (ICA) stenosis greater than 50% in relation to the bulb diameter were followed up for a period of 6-84 (mean 37.1) months. Stenosis was graded using duplex, and clinical and biochemical risk factors were recorded. Results. The relationship between ICA stenosis and event rate is linear when stenosis is expressed by the ECST method, but S-shaped if expressed by the NASCET method. In addition to the ECST grade of stenosis (RR 1.6; 95% CI 1.21-2.15), history of contralateral TIAs (RR 3.0; 95% CI 1.90-4.73) and creatinine in excess of 85 μmol/L (RR 2.1; 95% CI 1.23-3.65) were independent risk predictors. The combination of these three risk factors can identify a high-risk group (7.3% annual event rate and 4.3% annual stroke rate) and a low risk group (2.3% annual event rate and 0.7% annual stroke rate). Conclusions. Linearity between ECST percent stenosis and risk makes this method for grading stenosis more amenable to risk prediction without any transformation not only in clinical practice but also when multivariable analysis is to be used. Identification of additional risk factors provides a new approach to risk stratification and should help refine the indications for carotid endarterectomy. © 2005 Elsevier Ltd. All rights reserved

Effect of Virulence Factors on the Photodynamic Inactivation of Cryptococcus neoformans

Opportunistic fungal pathogens may cause an array of superficial infections or serious invasive infections, especially in immunocompromised patients. Cryptococcus neoformans is a pathogen causing cryptococcosis in HIV/AIDS patients, but treatment is limited due to the relative lack of potent antifungal agents. Photodynamic inactivation (PDI) uses the combination of non-toxic dyes called photosensitizers and harmless visible light, which produces singlet oxygen and other reactive oxygen species that produce cell inactivation and death. We report the use of five structurally unrelated photosensitizers (methylene blue, Rose Bengal, selenium derivative of a Nile blue dye, a cationic fullerene and a conjugate between poly-L-lysine and chlorin(e6)) combined with appropriate wavelengths of light to inactivate C. neoformans. Mutants lacking capsule and laccase, and culture conditions that favoured melanin production were used to probe the mechanisms of PDI and the effect of virulence factors. The presence of cell wall, laccase and melanin tended to protect against PDI, but the choice of the appropriate photosensitizers and dosimetry was able to overcome this resistance.Fundação de Amparo à Pesquisa do Estado de São Paulo (2010/13313–9

Development of Non-Natural Flavanones as Antimicrobial Agents

With growing concerns over multidrug resistance microorganisms, particularly strains of bacteria and fungi, evolving to become resistant to the antimicrobial agents used against them, the identification of new molecular targets becomes paramount for novel treatment options. Recently, the use of new treatments containing multiple active ingredients has been shown to increase the effectiveness of existing molecules for some infections, often with these added compounds enabling the transport of a toxic molecule into the infecting species. Flavonoids are among the most abundant plant secondary metabolites and have been shown to have natural abilities as microbial deterrents and anti-infection agents in plants. Combining these ideas we first sought to investigate the potency of natural flavonoids in the presence of efflux pump inhibitors to limit Escherichia coli growth. Then we used the natural flavonoid scaffold to synthesize non-natural flavanone molecules and further evaluate their antimicrobial efficacy on Escherichia coli, Bacillus subtilis and the fungal pathogens Cryptococcus neoformans and Aspergillus fumigatus. Of those screened, we identified the synthetic molecule 4-chloro-flavanone as the most potent antimicrobial compound with a MIC value of 70 µg/mL in E. coli when combined with the inhibitor Phe-Arg-ß-naphthylamide, and MICs of 30 µg/mL in S. cerevesiae and 30 µg/mL in C. neoformans when used alone. Through this study we have demonstrated that combinatorial synthesis of non-natural flavonones can identify novel antimicrobial agents with activity against bacteria and fungi but with minimal toxicity to human cells