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There are several pathogenetic models of localized scleroderma. At the same time, studies examining the role of endothelin-1, vascular endothelial growth factor (VEGF-A) and cell adhesion molecule-1 (VCAM) are limited. Objectives - to learn the nature of disorders of vascular, proliferative, adhesive functions of the endothelium on the content of endothelin-1, VEGF-A and VCAM-1 in localized scleroderma. The study included 78 patients with localized scleroderma and 35 healthy individuals (mean age - 44.2±17.6 years, 73 women (64.6%), 40 men (35.4%). All patients underwent clinical, laboratory, enzyme-linked immunosorbent assay examination (endothelin-1, VEGF-A, VCAM-1). In the local form of scleroderma, there are the number of disorders of vascular, proliferative and adhesive functions of the endothelium, with an increase in endothelin-1 (p<0.05), VEGF-A (p<0.05) and VCAM-1 (p<0.05) content. In idiopathic atrophodermia, the level of endothelin-1 was probably higher (p<0.05). The vasospastic type of pathogenesis of localized scleroderma was established in patients under 20 years of age (p<0.05) and in patients older than 70 years (p<0.05). U-shaped age dependence of pathogenesis was noted: high content of VEGF-A in patients under 20 years of age (p<0.05) and after 35 years (p<0.05). Higher levels of VCAM-1 were found in women compared to men (p<0.05). The analysis of the age dependence of the content revealed a U-shaped dependence of VCAM-1 - the highest content in patients under 20 years (p<0.05) and in patients 55-70 years (p<0.05). The level of biomarkers of endothelial dysfunction in patients with localized scleroderma - endothelin-1, VEGF and VCAM is associated with different phenotypes of the disease course - vasospastic, proliferative or adhesive.

Objectives: Antibiotic overuse is a significant problem in nursing homes (NHs). Strategies to improve antibiotic prescribing practices in NHs are a critical need. In this study, we analyzed antibiotic prescribing workflows to identify strategies for improving antibiotic prescribing in NHs., Design: Qualitative descriptive study using prospective field-based assessment of workflows., Setting: Six NHs in Wisconsin (n = 3) and Pennsylvania (n = 3)., Participants: A total of 44 interviews with 68 NH professionals, including leadership, nurses, and prescribers., Measurements: During a 1-day field visit in each NH, we conducted semistructured interviews with NH professionals, collected artifacts (policies, procedures, and documentation and communication tools), and observed clinical meetings. Study participants were interviewed (30-60 minutes) about antibiotic prescribing workflows in their facility. Information collected during site visits was used to create a representative workflow map of NH antibiotic prescribing. The workflow map guided thematic analysis to identify barriers corresponding to workflow steps across multiple NHs., Results: The representative antibiotic preprescribing workflow map included 17 steps, beginning with resident change in condition and ending with the decision to prescribe an antibiotic. Thematic analysis identified common step-specific barriers to antibiotic stewardship centering on three themes: (A) information barriers, comprising (A1) inconsistent nurse assessment report and (A2) misalignment between the work and tools of information sharing within the facility, (B) communication barriers, comprising (B1) mismatched perception of prescriber information needs and (B2) difficulty reaching prescribers for direct interaction, and (C) professional barriers, comprising (C1) low prescriber confidence in nurse assessment report and (C2) nurse reluctance to express their professional opinions., Conclusion: Strategies addressing workflow barriers are important targets for antibiotic stewardship. Such strategies include structured information tools, nurse and prescriber education, and organizational improvement. Future research can build on combinations of existing and new strategies to measure their effects in improving antibiotic prescribing. J Am Geriatr Soc 68:2222-2231, 2020., (© 2020 The American Geriatrics Society.)

Aim: To determine content of mononuclear ells (MNC) in peripheral blood of patients with coronary heart disease (CHD) and factors responsible for their functional state and cytokine production., Materials and Methods: Concentration of proteinkinases JNK1/2, ERK1/2, MAPK38, AKT1, JAK2, FAK, AMPK, p70S6K, STAT3, STAT5B and STAT6 was determined in MNC lysate by immune-enzyme assay. Interleukin 1β, 2, 4 and y-interferon levels were measured in blood sera., Results: In patients with angina of effort and unstable angina, the JNK level was 59,8% and 53,1% higher than the normal one respectively (р=0,013) and (р=0,012). The level of the nuclear transcription factor was 26,9% (р=0,015) and 27,9% (р=0,017), JAK2 31,5% (р=0,022) and 48,6% (р=0,018), STAT3 49,6% (р=0,025) and 55,3% (р=0,02), STAT5B 21,5% (р=0,018) and 30,2% (р=0,011) lower. These changes were associated with a 13,1% (р=0,047) and 51,4% (р=0,019) rise in the STAT6 level, 30,1% (р=0,025) and 79,4% (р=0,003) FAK level, 7,6% (р=0,09) and 15,2% (р=0,039) АКТ1 level, 65,3 (р=0,02) and 76,2% (р=0,017) p70S6K level., Conclusion: Results of the study suggest persistent pro-inflammatory activation of whole blood cells in CHD patients due to enhanced levels of IL-1 and IL-2, components of the MAPK/SAPK signal pathway in MNC and decreased STAT3 level determining cell sensitivity to IL-10. The elevated intracellular level of ERK and JNK us responsible for high responsiveness of MNC to pro-inflammatory cytokines.

The study was carried out to investigate intro-cellular concentration of factors of antiviral defense of cells of whole blood of re-convalescents of community-acquired pneumonia and healthy individuals under effect of low intensity SHF-radiation of whole blood in vitro with frequency of 1000 MGz. The technique of enzyme-linked immunosorbent assay was applied for analyzing lysates of mononuclears of whole blood exposed to impact of low intensity SHF-radiation with frequency of1000 MGz on concentration of mitochondrial antiviral signal protein MAVS, RIG-I-like receptor type III - helicase LGP2, RIG-I-like receptor - helicaseMDA5, trans-membrane protein 173 (Tmem 173), interferon-regulated factors (IRF) 3,7 and 8, sub-units p50 and p65 of nuclear factor of transcription NF-kB, phosphorylated on serine in position form 32 of inhibitor of nuclear factor of transcription (IkB-a) and also its total concentration. Besides, spontaneous production of interferon - a/β by cells of whole blood was evaluated in cellular supernatant. The capacity of single 20 minutes of SHF-radiation effect to increase intracellular level of important regulative proteins, primarily MDA5, during the phase of convalescence of community-acquired pneumonia was established. Besides, radiation stimulates increasing of intracellular level of MAVS and Tmem173. The capacity of radiation was established to increase phosphorylation of inhibitor of nuclear factor NF-kB and level of components p50 and p65 of NF-kB. The capacity of SHF-radiation effecting production of interferon-β by cells of hole blood is demonstrated. In healthy individuals, radiation contributes into decreasing of intercellular content of MAVS in more degree as compared with levels of MDA5 and Tmem173. At that, radiation of culture of cells of whole blood stimulates increasing of production of interferons.

In experiments on rabbits we evaluated the intensity of cardiomyocyte autophagia by the level beclin-1 protein and morphology of the left ventricular myocardium on days 1, 3, and 5 after the onset of focal ischemia caused by ligation of the descending branch of the left coronary artery. The morphological alterations in the left ventricular myocardium were accompanied by intensification of cardiomyocyte autophagia, which attained maximum on postligation day 1.

Background and Objective: Antiretroviral drugs have well-documented evidence-based favorable benefit-risk ratios. Although various studies have investigated and characterized the safety profile of antiretroviral medicines, there are a limited number of studies evaluating the safety of first-line antiretroviral therapy (ART) in patients with a specific co-morbidity. A cohort event monitoring (CEM) study of the safety and effectiveness of antiretroviral medicines in a target population that has a significant level of co-morbidities (chronic infectious diseases, peripheral blood cytopenias) was implemented. The aim was to evaluate the safety profile of the highly active ART (HAART) in the target population and subpopulations with risk factors, to optimize the monitoring and decision-making procedure for subgroups of patients with specific types of co-morbidity, and to implement a more vigilant approach to therapy management in risk groups of patients., Methods: Prospective observational CEM was implemented among HAART-naïve HIV-positive patients at four clinical sites from December 2012. Eligible patients were those starting first-line HAART. Close medical supervision of all enrolled patients, with regular clinical and laboratory monitoring, was provided by healthcare professionals within 1 year after commencement of therapy. Standardized forms were used for data collection on initial and subsequent visits. All objective or subjective deviations in condition (events) were assessed for a causal relationship with ART, and for severity, seriousness, reversibility, preventability, and pre-existing risk factors in the case of adverse drug reactions (ADRs)., Results: A total of 518 HAART-naïve HIV-positive patients were enrolled in the CEM study. Of these patients, 65% (337) experienced one or several ADRs related to one or more components of HAART. Most of the ADRs reported were non-serious, expected, common (very common), transient (correctable), or reversible. The most common were hematotoxic, hepatotoxic, and neurotoxic adverse reactions. In several cases, some types of toxicities, associated with zidovudine, efavirenz, and nevirapine, had a high level of severity, necessitating hospitalization and drug regimen or single-agent substitution. Severe cases of hematological, hepatobiliary, and psychiatric toxicities were associated with pre-existing risk factors., Conclusion: CEM is an effective tool for safety and effectiveness monitoring and could be successfully implemented for intensive study of important safety issues and for overcoming knowledge gaps regarding safety. In order to achieve a favorable benefit-risk ratio for HAART in the specific sections of the population with pre-existing risk factors for development of ART toxicities, more vigilant consideration and careful assessment before therapy is commenced and further regular monitoring of key laboratory parameters is required.

Long-duration gamma-ray bursts (GRBs) release copious amounts of energy across the entire electromagnetic spectrum, and so provide a window into the process of black hole formation from the collapse of massive stars. Previous early optical observations of even the most exceptional GRBs (990123 and 030329) lacked both the temporal resolution to probe the optical flash in detail and the accuracy needed to trace the transition from the prompt emission within the outflow to external shocks caused by interaction with the progenitor environment. Here we report observations of the extraordinarily bright prompt optical and gamma-ray emission of GRB 080319B that provide diagnostics within seconds of its formation, followed by broadband observations of the afterglow decay that continued for weeks. We show that the prompt emission stems from a single physical region, implying an extremely relativistic outflow that propagates within the narrow inner core of a two-component jet.

Experience of treatment of 2524 patients with diabetes mellitus (DM) for the 1990-2001 yrs period was summarized. Of all the patients 48-52% are presenting the citizens of Darnitskiy and Kharkivskiy regions of city of Kyiv. For the 1990-1994 yrs period general lethality had constituted 7.5-9.1%, postoperative mortality--9.2-13.5%, while after 1996--4.3-1.9 and 5.4-1.1% accordingly. Improvement of results of treatment was promoted by conversion in 1996 to conduction of operative interventions using spinal or epidural anesthesia. From 2000 we are planning performance of two-, three- or multistage treatment of patients because there exists possibility to preserve the foot, using several stages to excise nonviable tissues and to perform plastic operations. Right from the moment when conversion to multistaged operations happened, new demands occurred for quality of local measures of struggle against infection and for application of technology for preservation of viability in the skin-free foot tissues. Analysis of the case records of 62 patients with DM, to whom in other medical institutions operation for purulent-necrotic affection of the foot was performed, witnesses the necessity of spreading of the experience of the specialized division work among surgeons and endocrinologists.

In an inpatient setting, 67 and 70 patients with psoriasis living in contaminated and uncontaminated with radionuclides territories respectively were studied in the time-related course of some qualitative indices of immunity. Significant deviations from the norm were recordable, especially in those patients residing in the contaminated with radionuclides tcrritiry. Combined treatment involving the use of dibazol and hepatoradioprotective diet in the experiment group of psoriatic patients proved to be significantly more effective than in patients of the control group who were treated by the generally accepted method.

Influence of intraperitoneal administration of polygalacturonic acid derivatives at a dose of 100 mg/kg on the glutathione system and lipid peroxidation in the rat lung after treatment with NO2 was studied. A considerable decrease of lipid peroxidation intensity by these derivatives was caused not only by ability of these compounds to the chelate formation and absorption of free radicals, but also by the substantial activation of the glutathione system.

A course of the disease was studied in 190 patients with hepatic cirrhosis and portal hypertension without bleeding as well as in 107 patients with bleeding from esophageal and gastric varices. The Wald's consecutive analysis with derivation of a summary diagnostic coefficient on the basis of 13 clinical signs was used. Effectiveness of the method was assessed by means of retrospective analysis of 150 case records and long-term results of treatment of 30 patients. The method permits to predict the development of gastroesophageal bleeding in 95.4% of cases.