A review of hyperfibrinolysis in cats and dogs

The fibrinolytic system is activated concurrently with coagulation; it regulates haemostasis and prevents thrombosis by restricting clot formation to the area of vascular injury and dismantling the clot as healing occurs. Dysregulation of the fibrinolytic system, which results in hyperfibrinolysis, may manifest as clinically important haemorrhage. Hyperfibrinolysis occurs in cats and dogs secondary to a variety of congenital and acquired disorders. Acquired disorders associated with hyperfibrinolysis, such as trauma, cavitary effusions, liver disease and Angiostrongylus vasorum infection, are commonly encountered in primary care practice. In addition, delayed haemorrhage reported in greyhounds following trauma and routine surgical procedures has been attributed to a hyperfibrinolytic disorder, although this has yet to be characterised. The diagnosis of hyperfibrinolysis is challenging and, until recently, has relied on techniques that are not readily available outside referral hospitals. With the recent development of point‐of‐care viscoelastic techniques, assessment of fibrinolysis is now possible in referral practice. This will provide the opportunity to target haemorrhage due to hyperfibrinolysis with antifibrinolytic drugs and thereby reduce associated morbidity and mortality. The fibrinolytic system and the conditions associated with increased fibrinolytic activity in cats and dogs are the focus of this review article. In addition, laboratory and point‐of‐care techniques for assessing hyperfibrinolysis and antifibrinolytic treatment for patients with haemorrhage are reviewed

Gene Set Enrichment Analysis Identifies LIF as a Negative Regulator of Human Th2 Cell Differentiation

In this study we show that IL-4 is crucial during reinforcement window of human Th2 differentiation for optimal Th2 development. We have also shown here that during this stage, IL-4 helps in cellular decision-making process of differentiation versus proliferation. We have combined computational and experimental methods to analyze Th2 transcription network to name novel players of the process of Th2 differentiation. Here we report that LIF through STAT3 negatively regulates Th2 differentiation. This approach can be generalized to analyze “omics” data to identify key regulatory modules

The immunosuppressive cytokine interleukin-4 increases the clonogenic potential of prostate stem-like cells by activation of STAT6 signalling

Interleukin-4 plays a critical role in the regulation of immune responses and has been detected at high levels in the tumour microenvironment of cancer patients, where concentrations correlate with the grade of malignancy. In prostate cancer, interleukin-4 has been associated with activation of the androgen receptor, increased proliferation and activation of survival pathways such as Akt and NF-κB. However, its role in therapy resistance has not yet been determined. Here we investigate the influence of interleukin-4 on primary epithelial cells from prostate cancer patients. Our data demonstrate an increase in the clonogenic potential of these cells when cultured in the presence of interleukin-4. In addition, a Phospho-Kinase Array revealed that in contrast to previously published work, signal transducer and activator of transcription6 (STAT6) is the only signalling molecule activated after interleukin-4 treatment. Using the STAT6-specific inhibitor AS1517499 we could confirm the role of STAT6 in increasing colony-forming frequency. However, clonogenic recovery assays revealed that interleukin-4 does not rescue the effects of either irradiation or docetaxel treatment. We therefore propose that although the interleukin-4/STAT6 axis does not appear to be involved in therapy resistance, it does play a crucial role in the colony-forming abilities of the basal cell population in prostate cancer. IL-4 may therefore contribute to disease relapse by providing a niche that is favourable for the clonogenic growth of prostate cancer stem cells

Evaluation of a health promotion program in children: Study protocol and design of the cluster-randomized Baden-Württemberg primary school study [DRKS-ID: DRKS00000494]

<p>Abstract</p> <p>Background</p> <p>Increasing prevalences of overweight and obesity in children are known problems in industrialized countries. Early prevention is important as overweight and obesity persist over time and are related with health problems later in adulthood. "Komm mit in das gesunde Boot - Grundschule" is a school-based program to promote a healthier lifestyle. Main goals of the intervention are to increase physical activity, decrease the consumption of sugar-sweetened beverages, and to decrease time spent sedentary by promoting active choices for healthy lifestyle. The program to date is distributed by 34 project delivery consultants in the state of Baden-Württemberg and is currently implemented in 427 primary schools. The efficacy of this large scale intervention is examined via the Baden-Württemberg Study.</p> <p>Methods/Design</p> <p>The Baden-Württemberg Study is a prospective, stratified, cluster-randomized, and longitudinal study with two groups (intervention group and control group). Measurements were taken at the beginning of the academic years 2010/2011 and 2011/2012. Efficacy of the intervention is being assessed using three main outcomes: changes in waist circumference, skinfold thickness and 6 minutes run. Stratified cluster-randomization (according to class grade level) was performed for primary schools; pupils, teachers/principals, and parents were investigated. An approximately balanced number of classes in intervention group and control group could be reached by stratified randomization and was maintained at follow-up.</p> <p>Discussion</p> <p>At present, "Komm mit in das Gesunde Boot - Grundschule" is the largest school-based health promotion program in Germany. Comparative objective main outcomes are used for the evaluation of efficacy. Simulations showed sufficient power with the existing sample size. Therefore, the results will show whether the promotion of a healthier lifestyle in primary school children is possible using a relatively low effort within a school-based program involving children, teachers and parents. The research team anticipates that not only efficacy will be proven in this study but also expects many other positive effects of the program.</p> <p>Trial registration</p> <p>German Clinical Trials Register (DRKS), DRKS-ID: DRKS00000494</p

Molecular pathways leading to loss of skeletal muscle mass in cancer cachexia can findings from animal models be translated to humans?

Background: Cachexia is a multi-factorial, systemic syndrome that especially affects patients with cancer of the gastrointestinal tract, and leads to reduced treatment response, survival and quality of life. The most important clinical feature of cachexia is the excessive wasting of skeletal muscle mass. Currently, an effective treatment is still lacking and the search for therapeutic targets continues. Even though a substantial number of animal studies have contributed to a better understanding of the underlying mechanisms of the loss of skeletal muscle mass, subsequent clinical trials of potential new drugs have not yet yielded any effective treatment for cancer cachexia. Therefore, we questioned to which degree findings from animal studies can be translated to humans in clinical practice and research. Discussion: A substantial amount of animal studies on the molecular mechanisms of muscle wasting in cancer cachexia has been conducted in recent years. This extensive review of the literature showed that most of their observations could not be consistently reproduced in studies on human skeletal muscle samples. However, studies on human material are scarce and limited in patient numbers and homogeneity. Therefore, their results have to be interpreted critically. Summary: More research is needed on human tissue samples to clarify the signaling pathways that lead to skeletal muscle loss, and to confirm pre-selected drug targets from animal models in clinical trials. In addition, improved diagnostic tools and standardized clinical criteria for cancer cachexia are needed to conduct standardized, randomized controlled trials of potential drug candidates in the future

Progressive technology resource and energy conservation at manufacturing of products from recycled materials

Актуальность работы обусловлена тем, что использование отходов резиновой промышленности в основном производстве является оптимальным вариантом при решении многочисленных мероприятий по экономии сырья и охране окружающей среды. Цель исследования: изучить возможность создания полимерных композитов на основе отходов резиновой промышленности

Modyfikacja kompozycji poliolefinowych opartych na termoplastach

Influence of the nature and the behavior of nanofillers and microfillers on rheological and physico-mechanical properties of compositions on the basis of a polyolefin thermoplastic elastomer (ethylene-octene block copolymer) is studied. It is shown that modifying of a thermoplastic elastomer with nano- and microparticles of various chemical nature influences the structure and physico-mechanical properties of compositions: increases tensile strength, tear resistance, fatigue endurance at repetitive stretching, Shore A hardness.Badano wpływ charakteru chemicznego i zachowania się nano- i mikronapełniaczy na właściwości reologiczne, fizyczne i mechaniczne kompozycji na podstawie poliolefinowego elastomeru termoplastycznego (kopolimeru blokowego etylenowo-oktenowego). Wykazano, że modyfikowanie elastomeru termoplastycznego nano- i mikrocząstkami różnej natury chemicznej wpływa na strukturę oraz właściwości fizycznych i mechanicznych kompozycji: zwiększa wytrzymałość na rozciąganie i na rozdzieranie, wytrzymałość zmęczeniową przy wielokrotnym rozciąganiu, twardość Shore’a A

ГИДРОЛОГИЧЕСКИЙ РЕЖИМ И РОСТ СОСНОВЫХ НАСАЖДЕНИЙ В УСЛОВИЯХ ОСУШИТЕЛЬНЫХ МЕЛИОРАТИВНЫХ СИСТЕМ

A retrospective analysis of the formation and development of drainage reclamation in Volyn Polissya was carried out. The growth of pine plantations within the controlled drainage system and under the control was simulated. The data of samples and materials of the database of plantations growing on drained and control plots were used for modelling of height dynamics and changes in stocks with age. Dynamics of heights and stocks are described by the models of the polynomials of the second degree and the exponent equations. It was established that by the middle of the 3rd age class, the height of plantations on drained areas exceeds the height of plantations under the control of 2.1 m. Starting from the 3rd age class, pine stands on drained areas sharply increase the growth and at the age of quantitative ripeness, the difference in heights reached 3.0 m. Pine plantations in land reclamation areas pass into the upper class of productivity. The difference between the average heights in the 5th age class is 2.7 m. The effect of drainage is traced after 30 years, when the root system penetrates deeper horizons. The growth of roots on the control sites close to the surface of the water table is inhibited. At the same time, the soil saturated with oxygen stimulates the growth processes of the wood plants between the drainage channels, which lead to an increase in the productivity of the plantings. Comparative analyses of changes in planting stock shows that in the fourth age class the stock of pine stands on drained areas exceeds 15 %, and at the age of quantitative maturation this difference reaches 21 %, which makes 89 m3∙ha-1 and is a significant argument for the use of drainage reclamation in the wetlands of Volyn Polissya. The analysis of the hydrological regime of the drainage system "Strashevo" for the 14-year period showed that the water table during 2010–2017 sharply decreased reaching a stable value of 124–140 cm, whereas by 2009 it had fluctuated within the limits of 61–83 cm. The prolonged and significant decrease in water table leads to the declining of plantations, therefore, to ensure optimal hydrological regime of forest areas it is necessary to sluice channels or reconstruction of the drainage system in the system of bilateral action.Здійснено ретроспективний аналіз становлення і розвитку осушувальної меліорації у Волинському Поліссі. Змодельовано ріст соснових насаджень у межах регульованої осушувальної системи і на контролі. Встановлено, що до середини ІІІ класу віку висоти насаджень на осушених ділянках перевищують висоти насаджень на контролі на величину 2,1 м. Починаючи з ІІІ класу віку, сосна на осушених ділянках стрімко збільшує приріст й у віці кількісної стиглості різниця у висотах сягає 3,0 м. Соснові насадження на меліоративних ділянках переходять у вищий клас бонітету. Різниця між середніми висотами у VІІ класі віку становить 2,7 м. Порівняльний аналіз змін запасів соснових насаджень показує, що в IV класі віку запаси сосни на осушених ділянках перевищують 15 % від контролю, а у віці кількісної стиглості ця різниця сягає 21 %, що становить 89 м3∙га-1 і є вагомим аргументом застосування осушувальної меліорації на надмірно зволожених землях Волинського Полісся. Аналізуючи гідрологічний режим осушувальної системи "Страшево" за 14-річний період, з'ясовано, що рівень ґрунтових вод упродовж 2010–2017 рр. стрімко знижується, сягаючи стабільної величини 124–140 см, тоді як до 2009 р. він змінювався в межах 61–83 см. Тривале і значне пониження рівня ґрунтових вод призводить до всихання насаджень, тому для забезпечення оптимального гідрологічного режиму лісових ділянок потрібно застосовувати шлюзування каналів або реконструкцію осушувальної системи у систему двосторонньої дії.Осуществлен ретроспективный анализ становления и развития осушительной мелиорации в Волынском Полесье. Смоделирован рост сосновых насаждений в пределах регулируемой осушительной системы и на контроле. Установлено, что к середине III класса возраста высоты насаждений на осушенных участках превышают высоты насаждений на контроле на величину 2,1 м. Начиная с III класса возраста, сосна на осушенных участках резко увеличивает прирост и в возрасте количественной спелости разница в высотах достигает 3,0 м. Сосновые насаждения на мелиоративных участках переходят в более высокий класс бонитета. Разница между средними высотами в VII классе возраста составляет 2,7 м. Сравнительный анализ изменений запасов сосновых насаждений показывает, что в IV классе возраста запасы сосны на осушенных участках превышают 15 % от контроля, а в возрасте количественной спелости эта разница достигает 21 %, что составляет 89 м3∙га-1 и является весомым аргументом применения осушительной мелиорации на избыточно увлажненных землях Волынского Полесья. Анализируя гидрологический режим осушительной системы "Страшево" за 14-летний период, установлено, что уровень грунтовых вод в течение 2010–2017 гг. резко снижался, достигая стабильной величины 124–140 см, тогда как в2009 г. он колебался в пределах 61–83 см. Продолжительное и значительное понижение уровня грунтовых вод приводит к усыханию насаждений. Поэтому для обеспечения оптимального гидрологического режима лесных участков необходимо применять шлюзование каналов или реконструкцию осушительной системы в систему двустороннего действия

Catalytic hot-setting of urethane oligomers

The polyamide compounds as a curing agent (MOC A) are used for curing to produce synthetic elastomers with programmable properties based on oligomers. It is depermined that MBCA amount in the com position ranges from 11.8 to 19.1 parts by weight per 100 parts by weight polymer depending on the type of urethane rubber. The lifetime of urethane rubber and MOCA during casting at room temperature is about 6–12 minutes. It is shown that a small amount of a carboxylic acid accelerates the curing reaction and reduces the lifetime of the polyurethane rubber in the molding process at room temperature. It is proposed to use adipic acid as the hardening catalyst, while the lifetime of urethane rubber and MOCA is about 6–12 minutes in a molding process at room temperature, and physical and mechanical properties are substantially unchanged. It allows us to obtain molded articles with given set of properties by free casting

Influence of dispersants on aging and frost elastomeric compositions based on butadiene acrylonitrile rubbers

The possibility of use of dispergators of various nature for production of rubber technical products with expanded temperature conditions of operation is studied. It is investigated influences of dispergators of Dispergator FL and INT 159 on properties of rubber mixes for receiving products with high resistance to thermal aging or frost resistance. Research of influence of modifiers was conducted for rubber mixes on the basis of butadienenitrile rubbers synthetic (BNRS)-18 and BNRS-28. I’s established that at addition of a dispergator of Dispergator FL the indicator of relative deformatstion of compression (RDC) and respectively heat stability of rubbers increases. Introduction to structure of elastomeric composition of a dispergator of INT 159 practically doesn’t influence frost resistance, and Dispergator FL worsens her (the coefficient of frost resistance decreases by 15.4–17.8%). Possibly it is connected with the fact that at the lowered temperatures in the presence of Dispergator FL there is a bigger delay of relaxation processes and decrease in energy of the thermal movement of links of macromolecules of rubbers. It becomes insufficient for overcoming of intermolecular interaction in the modified system and commission of conformational transitions of macromolecules under the influence of external loading. Mechanical energy is to a large extent mentioned not on change of a form of macromolecules, and on their mechanodestruction. However, it increases heat stability since it that is higher, than molecular mobility is lower. INT 159 dispergator components, settling down on borders of supramolecular formations of elastomers, increase mobility of links of macromolecules of rubbers, weaken chemical bonds in them, reduce thermal stability, but at the same time INT 159 dispergator practically doesn’t reduce frost resistance therefore it is expedient to apply it when receiving frost-resistant elastomeric composition. Thus, when receiving thermostable elastomeric compositions it is necessary to use Dispergator FL, and frost-resistant – INT 159 dispergator