Combination therapy with bosentan and sildenafil for refractory digital ulcers and Raynaud’s phenomenon in a 30-year-old woman with systemic sclerosis: Case report and literature review

BACKGROUND: Systemic sclerosis is a rare autoimmune disease characterized by skin and organ fibrosis, and vasculopathy. Raynaud’s phenomenon is almost universally present in systemic sclerosis and can be the most debilitating symptom. Raynaud’s phenomenon may lead to the development of digital ulcers, potentially complicated by infection, tissue necrosis, and auto-amputation. Recommended treatments have variable efficacy. METHODS: We report the case of a 30-year-old woman with diffuse systemic sclerosis suffering from severe Raynaud’s phenomenon and digital ulcers with digital tissue necrosis who was treated with combination therapy of an endothelin receptor antagonist and phosphodiesterase 5 inhibitor. In addition, we reviewed the literature on the topic. RESULTS: Previous therapy with calcium-channel blockers, intravenous iloprost, and bosentan had all failed to control symptoms. We added sildenafil in combination with bosentan and observed a rapid and sustained treatment effect. Raynaud’s phenomenon severity, number of attacks, and attack duration decreased within 2 weeks of initiating treatment. Furthermore, this resulted in the healing of established digital ulcers. CONCLUSION: Our case report suggests that combination therapy may be a feasible treatment for the most severely affected and refractory patients. In our literature review, we found one retrospective study and three additional cases with similarly encouraging results

Screening of microbial communities associated with endive lettuce during postharvest processing on industrial scale

In this study, the composition of the microbial community on endive lettuce (Cichorium endivia) was evaluated during different postharvest processing steps. Microbial community structure was characterized by culture-dependent and culture-independent methods. Endive lettuce was sampled exemplarily at four different stages of processing (raw material, cut endive lettuce, washed endive lettuce, and spin-dried (ready to pack) endive lettuce) and analysed by plate count analysis using non-selective and selective agar plates with subsequent identification of bacteria colonies by matrix-assisted laser desorption/ionization time-of light mass spectrometry (MALDI-TOF MS). Additionally, terminal-restriction fragment length polymorphism (TRFLP) analysis and 16S rRNA gene nucleotide sequence analysis were conducted. The results revealed structural differences in the lettuce microbiomes during the different processing steps. The most predominant bacteria on endive lettuce were detected by almost all methods. Bacterial species belonging to the families Pseudomonadaceae, Enterobacteriaceae, Xanthomonadaceae, and Moraxellaceae were detected in most of the examined samples including some unexpected potentially human pathogenic bacteria, especially those with the potential to build resistance to antibiotics (e.g., Stenotrophomonas maltophilia (0.9 % in cut sample, 0.4 % in spin-dried sample), Acinetobacter sp. (0.6 % in raw material, 0.9 % in cut sample, 0.9 % in washed sample, 0.4 % in spin-dried sample), Morganella morganii (0.2 % in cut sample, 3 % in washed sample)) revealing the potential health risk for consumers. However, more seldom occurring bacterial species were detected in varying range by the different methods. In conclusion, the applied methods allow the determination of the microbiome's structure and its dynamic changes during postharvest processing in detail. Such a combined approach enables the implementation of tailored control strategies including hygienic design, innovative decontamination techniques, and appropriate storage conditions for improved product safety

Molecular Mechanism of the pH-Dependent Calcium Affinity in Langerin

The C-type lectin receptor langerin plays a vital role in the mammalian defense against invading pathogens. Its function hinges on the affinity to its co-factor Ca2+ which in turn is regulated by the pH. We studied the structural consequences of pro-tonating the allosteric pH-sensor histidine H294 by molecular dynamics simulations (total simulation time: about 120 μs) and Markov models. We discovered a mechanism in which the signal that the pH has dropped is transferred to the Ca2+-binding site without transferring the initial proton. Instead, protonation of H294 unlocks a conformation in which a protonated lysine side-chain forms a hydrogen bond with a Ca2+-coordinating aspartic acid. This destabilizes Ca2+ in the binding pocket, which we probed by steered molecular dynamics. After Ca2+-release, the proton is likely transferred to the aspartic acid and stabilized by a dyad with a nearby glutamic acid, triggering a conformational transition and thus preventing Ca2+-rebinding

Spectroscopic studies of fluorescent perylene dyes

The lowest electronic transition of the fluorescent perylene dye bis-(3,5-di-tertbutylphenyl)-perylene-3, 4:9,10-biscarboximide has been investigated

Зміна роздільної здатності зображень на основі власних векторів матриць-операторів індукованих з піксельних наборів

The method of problem solving increase resolution image sets provided that the dimension of the set. The method is to build a matrix operator and find its eigenvectors. Using sets of eigenvectors and matrix color images developed a practical set of algorithm changes the resolution

A Polynomial Number of Random Points does not Determine the Volume of a Convex Body

We show that there is no algorithm which, provided a polynomial number of random points uniformly distributed over a convex body in R^n, can approximate the volume of the body up to a constant factor with high probability

Level density of a Fermi gas: average growth and fluctuations

We compute the level density of a two--component Fermi gas as a function of the number of particles, angular momentum and excitation energy. The result includes smooth low--energy corrections to the leading Bethe term (connected to a generalization of the partition problem and Hardy--Ramanujan formula) plus oscillatory corrections that describe shell effects. When applied to nuclear level densities, the theory provides a unified formulation valid from low--lying states up to levels entering the continuum. The comparison with experimental data from neutron resonances gives excellent results.Comment: 4 pages, 1 figur

Структурно-грамматическое оформление лингвистических терминов в крымскотатарском языке

В статье предпринята попытка исследования структурных и частеречных особенностей лингвистических терминов крымскотатарского языка. Подробно анализируется соотношение однословных и многокомпонентных терминологических единиц. Рассматриваются типология структурных моделей двухсловных терминов-словосочетаний.У статті здійснена спроба дослідження структурних особливостей лінгвістичних термінів кримськотатарської мови та їх належність до частин мови. Докладно аналізується співвідношення однослівних і багатокомпонентних терінологічних одиниць. Розглядається типологія структурних моделей двослівних термінів-словосполучень.The author of the article makes an effort to research into structural and parts-of-speech peculiarities of Crimean Tatar linguistic terminology. The correlation of one-word and multi-componential terminological units is analyzed in detail. The article also deals with the structural types of the two-word term combinations

Riemann solvers and undercompressive shocks of convex FPU chains

We consider FPU-type atomic chains with general convex potentials. The naive continuum limit in the hyperbolic space-time scaling is the p-system of mass and momentum conservation. We systematically compare Riemann solutions to the p-system with numerical solutions to discrete Riemann problems in FPU chains, and argue that the latter can be described by modified p-system Riemann solvers. We allow the flux to have a turning point, and observe a third type of elementary wave (conservative shocks) in the atomistic simulations. These waves are heteroclinic travelling waves and correspond to non-classical, undercompressive shocks of the p-system. We analyse such shocks for fluxes with one or more turning points. Depending on the convexity properties of the flux we propose FPU-Riemann solvers. Our numerical simulations confirm that Lax-shocks are replaced by so called dispersive shocks. For convex-concave flux we provide numerical evidence that convex FPU chains follow the p-system in generating conservative shocks that are supersonic. For concave-convex flux, however, the conservative shocks of the p-system are subsonic and do not appear in FPU-Riemann solutions