Dengue Virus Entry as Target for Antiviral Therapy

Dengue virus (DENV) infections are expanding worldwide and, because of the lack of a vaccine, the search for antiviral products is imperative. Four serotypes of DENV are described and they all cause a similar disease outcome. It would be interesting to develop an antiviral product that can interact with all four serotypes, prevent host cell infection and subsequent immune activation. DENV entry is thus an interesting target for antiviral therapy. DENV enters the host cell through receptor-mediated endocytosis. Several cellular receptors have been proposed, and DC-SIGN, present on dendritic cells, is considered as the most important DENV receptor until now. Because DENV entry is a target for antiviral therapy, various classes of compounds have been investigated to inhibit this process. In this paper, an overview is given of all the putative DENV receptors, and the most promising DENV entry inhibitors are discussed

2-(4-Meth­oxy­benz­yl)-4,6-diphenyl-2,5-diaza­bicyclo­[2.2.2]oct-5-en-3-one

In the crystal structure of the title compound, C26H24N2O2, weak inter­molecular C—H⋯π inter­actions involving the benzene of the p-methoxy benzyl group and one of the phenyl rings result in the formation of chains consisting of alternating enanti­omers. Weak C—H ⋯O inter­actions with the methoxy O atom lead to the formation of layers, which are inter­linked by further C—H⋯O inter­actions into a three-dimensional assembly

Suitability of treated wastewater with respect to pH, electrical conductivity, selected cations and sodium adsorption ratio for irrigation in a semi-arid region

Increasing incidents of drought spells in most Sub-Saharan African countries call for exploration of innovative alternative sources of water for irrigation. A study was conducted to investigate the cation concentrations for different disposal points of treated wastewater and for borehole water. A 4 × 5 factorial experiment included a borehole as a reference sampling site plus three other sampling sites along the wastewater disposal system over 5 months. Monthly collected water samples were analysed for pH, EC, Ca, Mg, Na and K, with sodium adsorption ratio (SAR) computed and compared with those of water from the borehole, the FAO-desired ranges and the South African (SA) quality standards for irrigation water. Except at two sampling sites during one month, pH values were within the FAO-desired range. Relative to the FAO desired ranges and SA water quality standards, most variables in treated wastewater were much lower, suggesting that the test treated wastewater was suitable for irrigation.Keywords: cation content, temporal effects, treated wastewater disposal, water scarcit

trans-Chlorido[6-chloro-4-(4-methoxy­benz­yl)-3-oxo-3,4-dihydro­pyrazin-2-yl]­bis­(triphenyl­phosphine)palladium(II)

The title compound, [Pd(C12H10ClN2O2)Cl(C18H15P)2], is the inter­mediate of the reduction of a 3,5-dichloro­pyrazinone [Loosen, Tutonda, Khorasani, Compernolle & Hoornaert (1991 ▶). Tetra­hedron, 47, 9259–9268]. This species is formed by oxidative addition of coordinatively unsaturated Pd0 to the reactive 3-position of the heterocycle. The coordination around the Pd atom is square planar, with two trans PPh3 ligands. π–π inter­actions are observed between the centroid of the pyrazinone ring and planes of two adjacent phenyl rings, one from each PPh3 group (3.25 and 3.078 Å), stabilizing the inter­mediate structure. This could explain the reduced reactivity towards substitution of the Cl atom by the formate anion, resulting in poor yield of the reduced compound. 3-Substituted pyrazinones are important precursors in the synthesis of 5-amino­piperidinone-2-carboxyl­ate (APC) systems

A two-step strategy for designing optimal-based active control of human-induced vibrations

Civil structures such as floor systems with open-plan layouts or lightweight footbridges can be susceptible to excessive levels of vibrations caused by human activities. Active vibration control (AVC) via inertial-mass actuators has been shown to be a viable technique to mitigate vibrations, allowing structures to satisfy vibration serviceability limits. The application of AVC to complex structures requires the use of several Actuator/Sensor, being necessary the implementation of multiple-input multiple-output (MIMO) strategy. The present work proposes a two-step strategy for designing MIMO optimal-based AVC suitable for structures with a large number of vibration modes and with a large number of test points.Fundacion Caja MadridEngineering and Physical Sciences Research Council (EPSRC

Increased Use and Large Variation in Strong Opioids and Metamizole (Dipyrone) for Minor and Major Musculoskeletal Injuries Between 2008 and 2018: An Analysis of a Representative Sample of Swiss Workers.

PURPOSE Musculoskeletal (MSK) injuries are a major contributing factor for chronic pain. To date, little is known how pain medication use in MSK injuries has changed over time. We assessed pain medication prescription for MSK injuries in a representative sample of Swiss workers between 2008 and 2018. METHODS Retrospective analysis of the Swiss Accident Insurance Fund (Suva) data. We calculated annual pain medication use, treatment days, and costs associated with pain medication use in minor and major MSK injuries. RESULTS In total, 1,921,382 cases with MSK injuries with ≥ 1 pain medication were analyzed. Whereas MSK injuries with ≥ 1 pain medication increased by 9.4%, we observed a larger increase in metamizole (+ 254%), strong opioids (+ 88.4%), coxibs (+ 85.8%), and paracetamol (+ 28.1%). Strong opioids were increasingly used in minor (+ 91.4%) and major (+ 88.3%) injuries. The increase in metamizole (+ 390.6%) and coxibs (+ 115.5%) was larger in minor injuries compared to major injuries (+ 238.7% and + 80.6%, respectively). Medical expenses decreased in all medications except for strong opioids where a substantial increase was observed (+ 192.4% in minor; + 34% in major injuries). CONCLUSIONS We observed a disproportionate increase in metamizole, strong opioids, coxibs, and paracetamol prescriptions even in minor MSK injuries between 2008 and 2018. Whereas treatment costs decreased for all pain medications, there was a substantial increase in strong opioids. A more liberal prescription practice of opioids conflict with current evidence-based practice recommendations and need to be addressed by physicians and policy makers

Stabilization of Black Cotton Soil using Lime, Coir Fiber & Rice Husk

Because of their low bearing capacity, the expansive black cotton soils' high swelling and shrinking characteristics have posed numerous challenges to construction projects. When subjected to varying levels of moisture, black cotton soil expands and contracts rapidly. As a result, stabilising the soil is necessary to address these issues. Rice Husk Ash (RHA), Cori Fiber, and Lime are being tested in this study to see if they can act as a stabilising material in the expansive black cotton soil. The impact of RHA, CF, and LIME on the expansive soil's index and engineering properties was studied in the lab. Coir fibre concentration is 1.5 percent, lime is 5 percent by weight of dry soil, and RHA is mixed in at a ratio of 20 percent. The virgin soil sample is first tested for specific gravity and grain size distribution. With and without these admixtures soil's index properties like its plastic limit, liquid limit and shrinkage limit and its strength properties like its California Bearing Ratio, Unconfined Compressive Strength tests are discovered. According to the test results, a combination of 5 percent lime and 1.5 percent coir fibre yielded the strongest soil and best index properties

Inaugurating a Dutch Napoleon? Conservative criticism of the 1815 constitution of the United Kingdom of The Netherlands

International audienc

Sputum microbiome profiling in COPD:beyond singular pathogen detection

Culture-independent microbial sequencing techniques have revealed that the respiratory tract harbours a complex microbiome not detectable by conventional culturing methods. The contribution of the microbiome to chronic obstructive pulmonary disease (COPD) pathobiology and the potential for microbiome-based clinical biomarkers in COPD are still in the early phases of investigation. Sputum is an easily obtainable sample and has provided a wealth of information on COPD pathobiology, and thus has been a preferred sample type for microbiome studies. Although the sputum microbiome likely reflects the respiratory microbiome only in part, there is increasing evidence that microbial community structure and diversity are associated with disease severity and clinical outcomes, both in stable COPD and during the exacerbations. Current evidence has been limited to mainly cross-sectional studies using 16S rRNA gene sequencing, attempting to answer the question 'who is there?' Longitudinal studies using standardised protocols are needed to answer outstanding questions including differences between sputum sampling techniques. Further, with advancing technologies, microbiome studies are shifting beyond the examination of the 16S rRNA gene, to include whole metagenome and metatranscriptome sequencing, as well as metabolome characterisation. Despite being technically more challenging, whole-genome profiling and metabolomics can address the questions 'what can they do?' and 'what are they doing?' This review provides an overview of the basic principles of high-throughput microbiome sequencing techniques, current literature on sputum microbiome profiling in COPD, and a discussion of the associated limitations and future perspectives