Endothelioprotective property of the combination of the thioctic acid and rosuvastatin shown in the endothelial dysfunction models

During the experiment, the modeling of endothelial dysfunction of male rats was performed by intraperitoneal administration of L-NAME at a dose of 25 mg/kg for 7 days, and the same of female rats was performed by bilateral ovarioectomy and further intraperitoneal administration of L-NAME at a dose of 25 mg/kg for 7. The deficiency of nitric oxide as a result of the NO-synthase blockade was accompanied by the impairment of the endotheliumdependent and independent vasodilatation estimated in the pharmacological tests, which was expressed in the increasing coefficient of endothelial dysfunctio

Optimality of Relationship of Cost and Quality of Hotel Services in Small Towns: Analysis of the Situation in Russia and Germany

Socio-economic development of small towns in Russia is a serious problem that can be addressed through growth of the hospitality industry. Launching new hotels would make it possible to increase the number of tourists, as well as to strengthen external economical relationships. However, client satisfaction with the quality of hotel services itself and its relation to the cost of accommodation are important. The aim of the present work is to study the relationship of cost and quality of hotel services in small towns using the case of the Central Federal District of Russia and Hessen in Germany. The working hypothesis implies that the cost of services should increase together with their quality in the optimal case. The methodology of this work includes collection of data on the cost of accommodation and customer evaluations of services in hotels of small towns of the above-mentioned territories, as well as qualitative (graphical) and quantitative (with correlation coefficient) analysis of their relationship. An analysis of prices for accommodation in standard rooms (cost) and client satisfaction scores (perceived quality) at the hotels of small towns of the Central Federal District reveals total absence of their correlation. This appears both at the level of individual collective accommodation facilities and the level of the entire municipal hospitality industry. By contrast, a similar analysis for Hessen in Germany shows a noticeable cost growth along with the improvement of the quality of services, which should be considered the optimal relationship. This proves an assumption that after reaching a certain level of quality, its further growth triggers a progressive increase in the cost of hotel services. The value of the correlation coefficient for cost and quality of services of the hotel industry of the small towns of the Central Federal District (calculated by town) is –0,12, and +0,72 in the case of Hessen. Evidently, pricing at hotels is very chaotic in small towns of Russia. This is determined by the irregularity and non-saturation of the local hotel markets and inherently wrong pricing targets (or the absence of such targets). Market mechanisms can contribute to normalization of the situation, but only in the far future. The practical significance of this work is linked to the detection of a significant problem on organizational and municipal levels and discussion of its possible solutions. Relationship of cost and quality of hotel services in small towns of Germany can be adopted as a target. The authors believe that administrative authorities and professional associations of hoteliers should define the key targets of pricing and encourage entrepreneurs to adhere to them.Социально-экономическое развитие малых городов России представляет собой серьезную проблему, решению которой может способствовать становление в них индустрии гостеприимства. Создание новых отелей позволит увеличить количество туристов и наладить внешние экономические связи. Однако при этом важное значение имеет удовлетворенность клиентов как самим качеством гостиничных услуг, так и соответствием такового стоимости размещения. Целью настоящей работы является изучение соотношения стоимости и качества гостиничных услуг в малых городах на примере Центрального федерального округа России и земли Гессен в Германии. Рабочая гипотеза заключается в том, что стоимость услуг растет одновременно с их качеством, и такое соотношение является оптимальным. Методика работы заключалась в сборе данных о стоимости размещения и клиентских оценках услуг в гостиницах малых городов вышеуказанных территорий, качественном (графическом) и количественном (с помощью коэффициента корреляции) анализе их соотношения. Анализ цен на проживание в стандартных номерах (стоимость) и клиентских оценок (воспринимаемое качество) гостиниц малых городов Центрального федерального округа выявил их полное несоответствие. Оно проявляется как на уровне отдельных коллективных средств размещения, так и для городского гостиничного хозяйства в целом. Напротив, аналогичный анализ для земли Гессен в Германии показывает хорошо выраженный рост стоимости вместе с увеличением качества услуг, что следует считать оптимальным соотношением. При этом подтверждается идея о том, что после достижения определенного уровня качества дальнейший его рост способствует прогрессивному повышению стоимости гостиничных услуг. Значение коэффициента корреляции для стоимости и качества услуг гостиничного хозяйства малых городов Центрального федерального округа (при расчете по городам) составляет –0,12, а в земле Гессен – +0,72. Представляется, что в России ценовая политика в гостиницах малых городов осуществляется в высшей степени хаотично. Этому способствуют неупорядоченность и ненасыщенность локальных рынков гостиничных услуг, изначально неверно выбираемые ориентиры при формировании ценовой политики на уровне организаций (или вообще отсутствие таковых). Действие рыночных механизмов если и может способствовать нормализации ситуации, то только в отдаленном будущем. Практическая значимость работы определяется тем, что в ней выявлена существенная проблема, требующая внимания на организационном и муниципальном уровнях, а также обсуждаются возможные варианты ее решения. Соотношение стоимости и качества гостиничных услуг в малых городах Германии при этом может считаться ориентиром. Представляется, что административные органы и профессиональные сообщества (ассоциации) отельеров должны определять ключевые ориентиры ценовой политики и стимулировать предпринимателей следовать им

Software platform virtualization in chemistry research and university teaching

<p>Abstract</p> <p>Background</p> <p>Modern chemistry laboratories operate with a wide range of software applications under different operating systems, such as Windows, LINUX or Mac OS X. Instead of installing software on different computers it is possible to install those applications on a single computer using Virtual Machine software. Software platform virtualization allows a single guest operating system to execute multiple other operating systems on the same computer. We apply and discuss the use of virtual machines in chemistry research and teaching laboratories.</p> <p>Results</p> <p>Virtual machines are commonly used for cheminformatics software development and testing. Benchmarking multiple chemistry software packages we have confirmed that the computational speed penalty for using virtual machines is low and around 5% to 10%. Software virtualization in a teaching environment allows faster deployment and easy use of commercial and open source software in hands-on computer teaching labs.</p> <p>Conclusion</p> <p>Software virtualization in chemistry, mass spectrometry and cheminformatics is needed for software testing and development of software for different operating systems. In order to obtain maximum performance the virtualization software should be multi-core enabled and allow the use of multiprocessor configurations in the virtual machine environment. Server consolidation, by running multiple tasks and operating systems on a single physical machine, can lead to lower maintenance and hardware costs especially in small research labs. The use of virtual machines can prevent software virus infections and security breaches when used as a sandbox system for internet access and software testing. Complex software setups can be created with virtual machines and are easily deployed later to multiple computers for hands-on teaching classes. We discuss the popularity of bioinformatics compared to cheminformatics as well as the missing cheminformatics education at universities worldwide.</p

Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Endothelioprotective property of the combination of the thioctic acid and rosuvastatin shown in the endothelial dysfunction models

During the experiment, the modeling of endothelial dysfunction of male rats was performed by intraperitoneal administration of L-NAME at a dose of 25 mg/kg for 7 days, and the same of female rats was performed by bilateral ovarioectomy and further intraperitoneal administration of L-NAME at a dose of 25 mg/kg for 7. The deficiency of nitric oxide as a result of the NO-synthase blockade was accompanied by the impairment of the endotheliumdependent and independent vasodilatation estimated in the pharmacological tests, which was expressed in the increasing coefficient of endothelial dysfunctio

Premises for Eff icient Climatic Risk Management in the Russian Agriculture: an Investment-Innovation

Of all industries, agriculture is the most vulnerable to climate change. The change is expected to be strong on the territory of Russia in the long-term perspective. This adds significant risks to agricultural production. Operational management of such risks includes adaptation actions (new culture growing, melioration, etc.). However, its efficiency should be secured in advance via the creation of relevant premises, which is the subject of strategic management of climatic risks. Currently, this type of management is urgent. Investment premises are determined by the accumulation of big amounts of investment in agriculture during several years, and innovation premises are determined by the accumulation of funds for scientific research and development in the sphere of agriculture. These premises can be analyzed via calculation of some indicators on the basis of official statistic data. In this work, we analyze the accumulated (2013–2017) investments in fixed assets and the accumulated (2016–2017) domestic expenditures on scientific research and development in the agricultural industry of federal districts. These are equated to the units of agricultural production, labor, and land. The results show that the best premises for efficient management of climatic risks in agriculture have appeared in the North-Western and Central federal districts, while the worst premises have appeared in the North-Caucasian District. The latter is not a serious problem because significant climate changes are not expected in the south of European Russia. A situation should be deemed alarming in the Siberian and less so in the Far East federal districts. In the former, the investment and innovation premises are not favorable, and in the latter, these are moderate, and significant climate changes are forecast for the both territories. Creation of favorable premises for timely solution of problems of agriculture under the conditions of climate change is a task for strategic management of climatic risks. To solve it, a suitable tool would be the development and implementation of a federal program (subprogram) that should prescribe target indicators (also in regard to investments and innovations), the achievement of which will make the agricultural industries of all regions of the country prepared for subsequent adaptation to new climate conditions.Из всех отраслей экономики сельское хозяйство наиболее подвержено влиянию изменений климата. Последние ожидаются весьма сильными на территории России в долгосрочной перспективе, что создает существенные риски для АПК. Оперативное управление такими рисками предполагает адаптационные мероприятия (выращивание новых культур, мелиорация и т.п.). Однако его эффективность должна быть обеспечена заблаговременно путем формирования должных предпосылок, что составляет предмет стратегического управления климатическими рисками. В настоящее время актуален именно этот тип управления. Инвестиционные предпосылки определяются накоплением большого объема инвестиций в АПК в течение нескольких лет, а инновационные – накоплением затрат на научные исследования и разработки в области сельского хозяйства. Данные предпосылки можно проанализировать путем расчета индикаторов на основе официальной статистической информации. В данной работе анализируются накопленные (за 2013–2017 гг.) инвестиции в основные фонды и накопленные (за 2016–2017 гг.) внутренние затраты на научные исследования и разработки в АПК федеральных округов. Они рассматриваются в удельном исчислении (на единицу продукции, работников, земельных угодий). Результаты показывают, что наилучшие предпосылки для эффективного управления климатическими рисками в сельском хозяйстве сложились в Северо-Западном и Центральном федеральных округах, а наихудшие – в Северо-Кавказском округе. Последнее не является существенной проблемой, так как на юге Европейской России значительных изменений климата не ожидается. Сложной стоит признать ситуацию в Сибирском и отчасти Дальневосточном федеральных округах. В первом инвестиционные и инновационные предпосылки неблагоприятны, а во втором – умеренны, однако на обеих территориях прогнозируются значительные изменения климата. Формирование благоприятных предпосылок для оперативного решения проблем АПК в условиях изменений климата по всей территории страны – задача стратегического управления климатическими рисками. Подходящим инструментом для ее решения является разработка и имплементация федеральной программы (или подпрограммы), которая призвана обозначить целевые показатели (в том числе в аспекте инвестиционной и инновационной деятельности), достижение которых обеспечит АПК всех регионов страны готовность к последующей адаптации к новым климатическим условиям