Development and application of a colloidal-gold immunochromatographic strip for detecting Getah virus antibodies.

Getah virus (GETV) is a re-emerging mosquito-borne alphavirus that is highly pathogenic, mainly to pigs and horses. There are no vaccines or treatments available for GETV in swine in China. Therefore, the development of a simple, rapid, specific, and sensitive serological assay for GETV antibodies is essential for the prevention and control of GETV. Current antibody monitoring methods are time-consuming, expensive, and dependent on specialized instrumentation, and these features are not conducive to rapid detection in clinical samples. To address these problem, we developed immunochromatographic test strips (ICTS) using eukaryotically expressed soluble recombinant p62-E1 protein of GETV as a labelled antigen, which has good detection sensitivity and no cross-reactivity with other common porcine virus-positive sera. The ICTS is highly compatible with IFA and ELISA and can be stored for 1 month at 37 °C and for at least 3 months at room temperature. Hence, p62-E1-based ICTS is a rapid, accurate, and convenient method for rapid on-site detection of GETV antibodies. KEY POINTS: • We established a rapid antibody detection method that can monitor GETV infection • We developed colloidal gold test strips with high sensitivity and specificity • The development of colloidal gold test strips will aid in the field serologic detection of GETV.

Structure and Conformational Mobility of OLED-Relevant 1,3,5-Triazine Derivatives.

A series of OLED-relevant compounds, consisting of 1,3,5-triazine core linked to various aromatic arms by amino group, has been synthesized and characterized. The studied compounds exist in solution as a mixture of two conformers, a symmetric propeller and asymmetric conformer, in which one of the aromatic arms is rotated around the C-N bond. At temperatures below -40 °C, the VT NMR spectra in DMF-d7 are in a slow exchange regime, and the signals of two conformers can be elucidated. At temperatures above 100 °C, the VT NMR spectra in DMSO-d6 are in a fast exchange regime, and the averaged spectra can be measured. The ratio of symmetric and asymmetric conformers in DMF-d7 varies from 14:86 to 50:50 depending on the substituents. The rotational barriers of symmetric and asymmetric conformers in DMF-d7 were measured for all compounds and are in the interval from 11.7 to 14.7 kcal/mol. The ground-state energy landscapes of the studied compounds, obtained by DFT calculations, show good agreement with the experimental rotational barriers. The DFT calculations reveal that the observed chemical exchange occurs by the rotation around the C(1,3,5-triazine)-N bond. Although some of the compounds are potentially tautomeric, the measured absorption and emission spectra do not indicate proton transfer neither in the ground nor in the excited state.

Azo-hydrazone molecular switches: Synthesis and NMR conformational investigation.

A series of five intramolecularly hydrogen-bonded arylhydrazone (aryl = phenol, p-nitrophenol, anisole, quinoline) derived molecular switches have been synthesized and characterized by NMR and HRMS techniques. It was found that the compounds exist as different isomers in solution. An investigation of both conformational and/or configurational changes of the azo-hydrazone compounds was carried out by 1D 1 H- and 13 C- spectra, 2D NOESY, COSY, HSQC, and HMBC techniques. It was found that these stimuli-responsive molecular switches exist mainly in the E form by intramolecularly hydrogen bonded between NH and the pyridine nitrogen at equilibrium. Deprotonation of the neutral E form yields the E' deprotonated isomer. Prediction of 13 C-NMR chemical shifts was achieved by DFT quantum mechanical calculations. Anions have traditionally been difficult to calculate correctly, so calculations of the anion using different functionals, basis sets, and solvent effects are also included. Deuterium isotope effects on the 13 C-NMR chemical shifts were employed in the assignments and furthermore utilized as indicators of intramolecular hydrogen bonding. Studies in various organic solvents including CDCl3 , CD3 CN, and DMSO-d6 were also performed aiming to monitor dynamic changes over several days. The effect of the hydrogen bonded solvents leads to Z forms.

Chiral Aminoalcohols and Squaric Acid Amides as Ligands for Asymmetric Borane Reduction of Ketones: Insight to In Situ Formed Catalytic System by DOSY and Multinuclear NMR Experiments.

A series of squaric acid amides (synthesized in 66-99% isolated yields) and a set of chiral aminoalcohols were comparatively studied as ligands in a model reaction of reduction of α-chloroacetophenone with BH3•SMe2. In all cases, the aminoalcohols demonstrated better efficiency (up to 94% ee), while only poor asymmetric induction was achieved with the corresponding squaramides. A mechanistic insight on the in situ formation and stability at room temperature of intermediates generated from ligands and borane as possible precursors of the oxazaborolidine-based catalytic system has been obtained by 1H DOSY and multinuclear 1D and 2D (1H, 10/11B, 13C, 15N) NMR spectroscopy of equimolar mixtures of borane and selected ligands. These results contribute to better understanding the complexity of the processes occurring in the reaction mixture prior to the possible oxazaborolidine formation, which play a crucial role on the degree of enantioselectivity achieved in the borane reduction of α-chloroacetophenone.

[Rheumatic pain and chronic pain in children, adolescents and young adults]. / Rheumaschmerz und chronischer Schmerz bei Kindern, Jugendlichen und jungen Erwachsenen.

BACKGROUND: Rheumatic diseases, such as juvenile idiopathic arthritis (JIA), are typically associated with acute pain mainly caused by inflammation. Chronic pain is described as pain lasting at least 3 months. In JIA patients chronic pain may occur despite successful treatment. Chronic pain and pain disorders frequently occur during the course of the disease despite successful control of inflammation. OBJECTIVE: Possible interrelations between JIA and pain disorders are presented. METHOD: Besides a review of the available literature, a retrospective cohort study was conducted, including 906 patients with a chronic pain disorder with somatic and psychological factors (CPD) and/or a complex regional pain syndrome type I (CRPS I). The frequency of pre-existing rheumatic illnesses was analyzed. RESULTS: The JIA is a risk factor for the development of a CPD. Especially polyarticular, extended oligoarticular, enthesitis-associated JIA and psoriatic arthropathy were found to be significantly associated with an increased risk for developing CPD. In contrast, an increased risk for development of CRPS I was not observed. CONCLUSION: Our study demonstrates JIA to be a risk factor for the development of chronic pain not only as a result from malpositioning or arthrosis but also as a chronic pain disorder (CPD). Further studies are necessary to clarify the relevance of disease activity and duration and also of psychological factors for the pathogenesis.

Anti-enteroviral activity of new MDL-860 analogues: Synthesis, in vitro/in vivo studies and QSAR analysis.

A series of 60 nitrobenzonitrile analogues of the anti-viral agent MDL-860 were synthesized (50 of which are new) and evaluated for their activity against three types of enteroviruses (coxsackievirus B1, coxsackievirus B3 and poliovirus 1). Among them, six diaryl ethers (20e, 27e, 28e, 29e, 33e and 35e) demonstrated high in vitro activity (SI > 50) towards at least one of the tested viruses and very low cytotoxicity against human cells. Compound 27e possesses the broadest spectrum of activity towards all tested viruses in the same way as MDL-860 does. The most active derivatives (27e, 29e and 35e) against coxsackievirus B1 were tested in vivo in newborn mice experimentally infected with 20 MLD50 of coxsackievirus B1. Compound 29e showed promising in vivo activity (protection index 26% and 4 days lengthening of mean survival time). QSAR analysis of the substituent effects on the in vitro cytotoxicity (CC50) and anti-viral activity of the nitrobenzonitrile derivatives was carried out and adequate QSAR models for the anti-viral activity of the compounds against poliovirus 1 and coxsackievirus B1 were constructed.

Decreased electrogustometric taste sensitivity in patients with acquired olfactory dysfunction.

BACKGROUND: Cross-modal chemosensory dysfunction between olfaction and gustation is not well known. METHODOLOGY: 180 participants were classified into three groups (60 with olfactory dysfunction, 60 with gustatory dysfunction and 60 healthy controls without chemosensory dysfunction). Olfactory functions were obtained with Sniffin Sticks; gustatory function was measured by suprathreshold gustatory stimuli (taste sprays) and a quasi-threshold measure of taste function (taste strips) for five taste qualities (sweet, salty, sour, bitter and umami). Electric taste threshold was measured using electrogustometry (EGM). In addition, group differences in dietary behaviors were investigated with a specifically designed questionnaire. RESULTS: Patients with olfactory dysfunction had increased electric taste thresholds and decreased scores for the umami taste strip test as compared to healthy controls. Overall there was no major difference between patients with chemosensory dysfunction and healthy controls regarding dietary behaviors, although some patients certainly exhibited dietary problems. Importantly, patients with taste loss, but not patients with smell loss, exhibited a higher degree of depression than controls. CONCLUSION: Patients with olfactory dysfunction showed decreased taste sensitivity which suggested an interaction between the chemical senses taste, trigeminal function, and olfaction. This provides the basis for including both smell and taste psychophysical assessment in clinical practices. In addition, patients with taste loss appeared to suffer most from chemosensory dysfunction.

[Back to school physical education despite rheumatism : Development and testing of a sport scientific-based physical education certification]. / Zurück in den Schulsport trotz Rheuma : Entwicklung und Überprüfung einer sportwissenschaftlich basierten Schulsportbescheinigung.

BACKGROUND: Taking part in physical education is an important element of social participation for children with chronic diseases. Nevertheless, children suffering from rheumatism mostly receive recommendations to stop sport activities either completely or partially, without underlying scientific guidelines. OBJECTIVE: The aim was the development of an IT-tool based on scientific data in order to create individualized recommendations for sport activities plus verification of its practical feasibility. MATERIAL AND METHODS: An interdisciplinary group of experts developed and approved a prototype of the rheumatism and sports compass (Rheuma und Sport Kompass, RSK) based on the literature and own experience. They considered individual health factors and biomechanics of sports functions. The prototype was tested, revised and reconsidered in an interim evaluation. The resulting RSKv1 was evaluated in a clinical observation phase with 61 patients. The results were subsequently incorporated into the final version of RSK during an interdisciplinary decision-making process. This was verified in a feasibility study with a follow-up survey of rheumatic patients with a RSK partial participation certification for physical education including: clinical assessment during 8 lessons of physical education and after 8 lessons of physical education. Teachers rated the RSK online after 8 lessons. The evaluation was descriptive and differences in mean values were tested. RESULTS AND DISCUSSION: In this study 50 patients and 31 teachers were evaluated. The affliction of pain decreased in terms of frequency, amount and duration after physical education with RSK. No worsening in health was reported after participation in sports. The teachers rated the RSK as understandable, practicable and they felt confident to allow the patients to participate in classes. The RSK was rated significantly better than a standard certification text. With the RSK, patients can be advised to safely take part in physical education.

Architecture of collapse: regime shift and recovery in an hierarchically structured marine ecosystem.

By the late 20th century, a series of events or 'natural experiments', for example the depletion of apex predators, extreme eutrophication and blooms of invasive species, had suggested that the Black Sea could be considered as a large ecosystem 'laboratory'. The events resulted in regime shifts cascading through all trophic levels, disturbing ecosystem functioning and damaging the water environment. Causal pathways by which the external (hydroclimate, overfishing) and internal (food web interactions) drivers provoke regime shifts are investigated. Statistical data analyses supported by an interpretative framework based on hierarchical ecosystem theory revealed mechanisms of hierarchical incorporation of environmental factors into the ecosystem. Evidence links Atlantic teleconnections to Black Sea hydroclimate, which together with fishing shapes variability in fish stocks. The hydroclimatic signal is conveyed through the food web via changes in productivity at all levels, to planktivorous fish. Fluctuating fish abundance is believed to induce a lagged change in competitor jelly plankton that cascades down to phytoplankton and influences water quality. Deprived of the stabilising role of apex predators, the Black Sea's hierarchical ecosystem organisation is susceptible to both environmental and anthropogenic stresses, and increased fishing makes fish stock collapses highly probable. When declining stocks are confronted with burgeoning fishing effort associated with the inability of fishery managers and decision-makers to adapt rapidly to changes in fish abundance, there is overfishing and stock collapse. Management procedures are ineffective at handling complex phenomena such as ecosystem regime shifts because of the shortage of suitable explanatory models. The proposed concepts and models reported here relate the hydroclimate, overfishing and invasive species to shifts in ecosystem functioning and water quality, unravelling issues such as the causality of ecosystem interactions and mechanisms and offering potential for finding ways to reverse regime shifts. We advocate a management approach aiming at restoring ecosystem hierarchy that might mitigate the costly consequences of regime shifts.

Synthesis and anti-enterovirus activity of new analogues of MDL-860.

A series of twelve novel compounds, analogues of antiviral agent MDL-860 were synthesized and their antiviral activity was evaluated in vitro against enteroviruses poliovirus 1 (PV1), Coxsackieviruses B1 (CVB1) and Coxsackieviruses B3 (CVB3). Compounds 14, 24 and 25 manifested strong antiviral effects against CVB1 and PV1 (SI values of 405 and 118 for CVB1 and PV1 respectively). In contrast to the wide anti-enteroviral activity of MDL-860, these three compounds were inactive against CVB3. Compounds 14, 24 and 25 along with MDL-860 were tested in vivo in mice infected with CVB1. Marked protective effects of compounds 14 and 24 were established, PI values of 50% and 33.3%, respectively. In addition, almost all of the tested compounds manifested very low toxicity.

Intracavity difference-frequency mixing of optical parametric oscillator signal and idler pulses in BaGa4Se7.

An overall quantum conversion efficiency of 7.8% is achieved by intracavity mixing the signal and idler of a 1.064 µm pumped Rb:PPKTP optical parametric oscillator in BaGa4Se7. In this way, a pulse energy of ∼0.71 mJ is generated at ∼7 µm for a repetition rate of 100 Hz. Tuning of the mid-IR radiation is demonstrated by heating of the Rb:PPKTP crystal.

Rb:PPKTP optical parametric oscillator with intracavity difference-frequency generation in AgGaSe2.

A 1.064 µm pumped Rb:PPKTP optical parametric oscillator (OPO) generates mid-IR radiation by intracavity mixing the resonant signal and idler waves in AgGaSe2. The ∼6 ns pulses at ∼7 µm have an energy of 670 µJ at 100 Hz, equivalent to an average power of 67 mW. The overall quantum conversion efficiency from 1.064 µm amounts to 8%, and the power conversion efficiency is 1.2%.

Widely tunable in the mid-IR BaGa4Se7 optical parametric oscillator pumped at 1064 nm.

A BaGa4Se7 nanosecond optical parametric oscillator (OPO) shows extremely wide idler tunability in the mid-IR (2.7-17 µm) under 1.064 µm pumping. The ∼10 ns pulses at ∼7.2 µm have an energy of 3.7 mJ at 10 Hz. The pump-to-idler conversion efficiency for this wavelength reaches 5.9% with a slope of 6.5% corresponding to a quantum conversion efficiency or pump depletion of 40%.

Intracavity-pumped, cascaded AgGaSe2 optical parametric oscillator tunable from 5.8 to 18 µm.

A AgGaSe2 nonlinear crystal placed in a coupled cavity is intracavity pumped by the ~1.85-µm signal pulses of a 1.064-µm pumped Rb:PPKTP doubly-resonant optical parametric oscillator (OPO) operating at a repetition rate of 100 Hz. Using two samples cut for type-I and II phase-matching, the overall idler tunability of the singly-resonant AgGeSe2 OPO covers an unprecedented spectral range from 5.8 to ~18 µm in the mid-IR.

Antimycobacterial activity generated by the amide coupling of (-)-fenchone derived aminoalcohol with cinnamic acids and analogues.

Aminoethyl substituted 2-endo-fenchol prepared from (-)-fenchone was used as scaffold for the synthesis of series of 31 amide structures by N-acylation applying cinnamic acids and analogues. The evaluation of their in vitro activity against Mycobacterium tuberculosis H37Rv showed for some of them promising activity-up to 0.2 µg/ml, combined with relatively low cytotoxicity of the selected active compounds.

Detection of Leishmania infantum Antibodies in Stray Dogs from Nonendemic Areas in Bulgaria.

Background: Leishmaniasis is a zoonotic protozoan infection which is endemic in parts of Europe. Dogs are commonly affected by Leishmania infantum and are regarded as the main reservoir for humans' infection. Sporadic human cases are reported annually, mainly from the endemic south part of Bulgaria. However, no recent data on canine leishmaniasis geographical distribution in Bulgaria have been published. The aim of this study was to investigate the current seroprevalence rate of L. infantum in stray dogs from areas where this infection was not previously reported. Results: The estimated overall seroprevalence rate was 8.3% (95% confidence interval [CI]: 2.6-14.0) with no significant difference between the two examined districts [χ2 (1, N = 90) = 0.32, p = 0.69]. In Sofia, the seropositivity was 7.2% (95% CI: 0.9-13.5) and in Sofia (stolitsa) 11.0% (95% CI: 0-23.0). No association between sex and serological status [χ2 (1, N = 90) = 1.83, p = 0.27] and age and seropositivity [χ2 (2, N = 90) = 1.98, p = 0.52] was detected. High levels of antibodies (fourfold increase from the assay's cut-off) were observed in half of the positive dogs.

Low-Complexity Tracking Control of Unknown Strict-Feedback Systems With Quantitative Performance Guarantees.

This article is concerned with the prescribed performance tracking control problem for the strict-feedback systems with unknown nonlinearities and unmatched disturbances. The challenge lies in the realization of a complete performance specification for trajectory tracking in the sense of quantitatively regulating the peak value, overshoot, settling time, and accuracy while ensuring that the initial condition holds naturally. To this end, an error transformation, equipped with a shifting function, is introduced and incorporated with a new-type barrier function. Then, a class of performance functions is exploited to quantify the settling times and steady-state bounds of the intermediate errors. Moreover, to improve the flexibility of formulating performance specifications for the tracking error, a pair of asymmetric performance boundaries are further designed. With their combination, a novel robust prescribed performance control (PPC) approach is proposed in this article. It not only achieves the quantitative performance guarantees but also preserves the unique simplicity of PPC, evading the needs for function approximation, parameter identification, disturbance estimation, derivative calculation, or command filtering. The above theoretical findings are confirmed via three simulation studies.

Adaptive fuzzy prescribed time tracking control for nonlinear systems with input saturation.

This article investigates the adaptive fuzzy prescribed time tracking control problem for a class of strict-feedback systems simultaneously considering the user-defined asymmetric tracking performance, input saturation, and external disturbances. From the perspective of ensuring the reliability for control implementation, a saturation-based fixed-time funnel boundary is constructed by embedding the modification signals related to input saturation errors into a funnel function, which is capable of automatically enlarging or recovering itself when input saturation occurs or disappears, thereby reducing the risk of system singularity. Subsequently, by constructing a fixed-time tracking performance function, any known bounded tracking error is recast into a new variable with a zero initial value. With such a treatment, funnel boundaries are no longer redeveloped for different initial tracking errors, and meanwhile the behavior of the tracking error is pre-specified as needed over a finite time interval. Also, auxiliary systems are devised to generate the aforesaid modification signals, while compensating for the adverse impact resulting from input saturation. Remarkably, by feat of the backstepping design based on the fuzzy approximation, it is proven that the tracking error converges to a user-defined region within a prescribed time (known as the practically prescribed time tracking), which is achieved without the fractional power feedback of system states. Finally, two simulation examples are presented to confirm the feasibility and effectiveness of the developed approach.

Micellar Form of a Ferrocene-Containing Camphor Sulfonamide with Improved Aqueous Solubility and Tumor Curing Potential.

The discovery of new anticancer drugs with а higher, more specific activity and diminished side effects than the conventional chemotherapeutic agents is a tremendous challenge to contemporary medical research and development. To achieve a pronounced efficacy, the design of antitumor agents can combine various biologically active subunits in one molecule, which can affect different regulatory pathways in cancer cells. We recently demonstrated that a newly synthesized organometallic compound, a ferrocene-containing camphor sulfonamide (DK164), possesses promising antiproliferative activity against breast and lung cancer cells. However, it still encounters the problem of solubility in biological fluids. In this work, we describe a novel micellar form of DK164 with significantly improved solubility in aqueous medium. DK164 was embedded in biodegradable micelles based on a poly(ethylene oxide)-b-poly(α-cinnamyl-ε-caprolactone-co-ε-caprolactone)-b-poly(ethylene oxide) triblock copolymer (PEO113-b-P(CyCL3-co-CL46)-b-PEO113), and the physicochemical parameters (size, size distribution, zeta potential, encapsulation efficiency) and biological activity of the obtained system were studied. We used cytotoxicity assays and flow cytometry to determine the type of cell death, as well as immunocytochemistry to assess the influence of the encapsulated drug on the dynamics of cellular key proteins (p53 and NFkB) and the process of autophagy. According to our results, the micellar form of the organometallic ferrocene derivate (DK164-NP) exhibited several advantages compared to the free substance, such as higher metabolic stability, better cellular uptake, improved bioavailability, and long-term activity, maintaining nearly the same biological activity and anticancer properties of the drug.

Bacterial resistance to antisense peptide phosphorodiamidate morpholino oligomers.

Peptide phosphorodiamidate morpholino oligomers (PPMOs) are synthetic DNA mimics that bind cRNA and inhibit bacterial gene expression. The PPMO (RFF)(3)RXB-AcpP (where R is arginine, F, phenylalanine, X is 6-aminohexanoic acid, B is ß-alanine, and AcpP is acyl carrier protein) is complementary to 11 bases of the essential gene acpP (which encodes acyl carrier protein). The MIC of (RFF)(3)RXB-AcpP was 2.5 µM (14 µg/ml) in Escherichia coli W3110. The rate of spontaneous resistance of E. coli to (RFF)(3)RXB-AcpP was 4 × 10(-7) mutations/cell division. A spontaneous (RFF)(3)RXB-AcpP-resistant mutant (PR200.1) was isolated. The MIC of (RFF)(3)RXB-AcpP was 40 µM (224 µg/ml) for PR200.1. The MICs of standard antibiotics for PR200.1 and W3110 were identical. The sequence of acpP was identical in PR200.1 and W3110. PR200.1 was also resistant to other PPMOs conjugated to (RFF)(3)RXB or peptides with a similar composition or pattern of cationic and nonpolar residues. Genomic sequencing of PR200.1 identified a mutation in sbmA, which encodes an active transport protein. In separate experiments, a (RFF)(3)RXB-AcpP-resistant isolate (RR3) was selected from a transposome library, and the insertion was mapped to sbmA. Genetic complementation of PR200.1 or RR3 with sbmA restored susceptibility to (RFF)(3)RXB-AcpP. Deletion of sbmA caused resistance to (RFF)(3)RXB-AcpP. We conclude that resistance to (RFF)(3)RXB-AcpP was linked to the peptide and not the phosphorodiamidate morpholino oligomer, dependent on the composition or repeating pattern of amino acids, and caused by mutations in sbmA. The data further suggest that (RFF)(3)R-XB PPMOs may be transported across the plasma membrane by SbmA.