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This work deals with the assessment of balance of pressor hemodynamic responses on the stage of induction of anesthesia and tracheal intubation in elderly patients, their prevention and treatment. The study included 47 patients with ischemic heart disease, who underwent coronary artery bypass grafting. The average age of the patients was 69.3 ± 4.5 years, the average weight — 82.5 ± 7.4 kg. Depending on the method of the prevention and treatment of pressor reactions occurred in patients at the stage of tracheal intubation, all patients were divided into three groups. The first group (n = 12) consisted of patients, in whom we have used 2% lidocaine solution (100 mg) for the irrigation of vocal cords before introduction of the endotracheal tube. The second group (n = 18) consisted of patients, who were administered urapidil in a dose of 15–20 mg at the stage of laryngoscopy. In the third group of examinees (n = 17), a deepening of anesthesia was performed by additional fentanyl and propofol administration. In all patients at the stage of laryngoscopy, blood pressure (BP) increased by 23.6 ± 3.2 % from baseline. Immediately after intubation, in the first and third groups a further increase of systolic BP occurred, while in group 2, in which urapidil prophylactic administration was used, BP was lower by an average of 27.4 ± 2.6 % compared with BP values recorded in the first and third groups. Thus, patients with arterial hypertension at the stage of laryngoscopy and tracheal intubation are subject to pronounced hemodynamic pressor responses, for the prevention and treatment of which the introduction of urapidil is the most effective method.

Purpose. To compare the capabilities of CT perfusion and MR elastography in predicting the risk of developing pancreatic fistula in patients with periampular tumors at the planning stage of pancreatoduodenectomy.Materials and methods. CT perfusion and MR elastography were performed in 30 patients with no pancreatic diseases and 53 patients with periampular tumors, who were subsequently operated on in the volume of pancreatoduodenectomy.Results. In patients with periampular tumors in 18 (44%) cases, the perfusion and stiffness indices in the pancreatic parenchyma did not differ from the control group, 35 (85,3%) showed a decrease in the main perfusion parameters, while a moderate increase in stiffness was noted in 23 (65,7%), expressed in 12 (34,3%). Against the background of preventive measures, only 3 (5,6%) patients, in all cases with a «soft» pancreas in the postoperative period, developed a pancreatic fistula.Conclusion. CT perfusion and MR elastography are highly informative methods of quantitative and qualitative assessment of the pancreatic parenchyma, detection of fibrotic changes, and are effective in predicting the risk of developing pancreatic fistula.

Cardiovascular diseases (CVD) are the main cause of death worldwide, and according to experts, they will continue to dominate the structure of global mortality.The effectiveness of the multimodal low-opioid anesthesia technique in performing coronary artery bypass graft operations with artificial blood circulation.Ninety-six patients aged 61.8 ±10.4 years underwent coronary artery bypass grafting under artificial blood circulation. Group I: propofol, sevoflurane, fentanyl, pipecuronium bromide (standard doses). Group II: dexketoprofen trometamol (50 mg), intravenous lidocaine (1% - 1 mg/kg bolus) and continuous lidocaine infusion (1.5-2 mg/kg/h), propofol, ketamine (0.5 mg/kg), magnesia sulfate, minimal doses of fentanyl.Average duration of anesthesia - 257.4 ±19.1 min; assisted blood circulation - 55 ±10 min. Mean dose of fentanyl in group I - 4.66 ±1.58 µg/kg/h, in group II - 1.29 ±0.32 µg/kg/h.Standard lab values and stress hormonal changes were within the normal range (mean cortisol: 479.3 ±26.4 nmol/l, lactate 1.61 ±0.2 mmol/l, glucose 6.42 ±0.9 mmol/l). Changes in heart rate within group I had a significant amplitude of dynamics, while in group II, these values were relatively at the same level throughout the entire anesthetic provision. Mean arterial pressure changes in group I were characterized by a significant reduction at the stage of induction, support and sternum reduction, whereas in group II it was relatively at the same level during the entire anesthetic management and significantly differed from baseline only at the stage of induction.Multimodal low-opioid anesthesia during coronary artery bypass surgery with artificial blood circulation allows one to ensure adequate analgesia and avoid the intraoperative usage of routine doses of fentanyl, as indicated by the absence of hemodynamic and endocrine-metabolic changes.Choroby sercowo-naczyniowe (CVD) stanowią główną przyczynę zgonów na świecie i według ekspertów nadal będą przeważać w strukturze globalnej śmiertelności.Ocena skuteczności złożonego znieczulenia niskoopioidowego podczas operacji pomostowania tętnic wieńcowych w warunkach krążenia pozaustrojowego.U 96 pacjentów w wieku 61,8 ±10,4 roku przeprowadzono pomostowanie tętnic wieńcowych z wykorzystaniem krążenia pozaustrojowego. Grupa I: propofol, sewofluran, fentanyl, bromek pipekuronium (dawki standardowe). Grupa II: trometamol deksketoprofenu (50 mg), lidokaina dożylnie (1% – bolus 1 mg/kg) i lidokaina w ciągłym wlewie (1,5–2 mg/kg/h), propofol, ketamina (0,5 mg/kg), siarczan magnezu, fentanyl w minimalnych dawkach.Średni czas trwania znieczulenia – 257,4 ±19,1 min; wspomaganie krążenia – 55 ±10 min. Średnia dawka fentanylu w grupie I – 4,66 ±1,58 µg/kg/h, w grupie II – 1,29 ±0,32 µg/kg/h. Standardowe parametry laboratoryjne i zmiany w stężeniu hormonów stresu mieściły się w zakresie normy (średnie stężenie kortyzolu: 479,3 ±26,4 nmol/l, mleczan 1,61 ±0,2 mmol/l, glukoza 6,42 ±0,9 mmol/l). Zmiany częstości akcji serca w grupie I charakteryzowały się znaczną amplitudą, natomiast w grupie II wartości utrzymywały się na relatywnie tym samym poziomie przez cały okres znieczulenia. Średnie zmiany ciśnienia tętniczego w grupie I były znamiennie mniejsze podczas indukcji, podtrzymania i zamknięcia mostka, natomiast w grupie II utrzymywały się na tym samym poziomie przez całe znieczulenie i różniły się znamiennie od wartości wyjściowych wyłącznie na etapie indukcji.Złożone znieczulenie niskoopioidowe podczas pomostowania tętnic wieńcowych z wykorzystaniem krążenia pozaustrojowego umożliwia właściwą analgezję i pozwala uniknąć śródoperacyjnego podawania rutynowych dawek fentanylu, czego potwierdzeniem jest brak zmian hemodynamicznych i endokrynologiczno-metabolicznych.

Objective. To reveal the impact degree of independent one from another preoperative factors on the only one dependent factor - duration of stationary stay in the patients, suffering an acute coronary syndrome, after the еmergency еndovascular revascularization of myocardium (EERM). Маterials and methods. There were gathered and statistically elaborated the data from the disease histories charts of 40 patients, ageing up to 60 yrs (1-st Group) and 40 patients, ageing 60 yrs old and more (2-nd Group). Correlation-regression analysis was applied as a method for statistical processing. Results. In the 1-st Group patients several factors have had impact on a hospital stay duration (in order of the significance reduction): preoperative indices of hemoglobin and hematocrit, the levels of troponin І and general cholesterol, the coronary arteries occlusion degree, a body mass index, the left ventricle output fraction and volume of the postoperative blood loss. In patients of 2-nd Group the only one factor, essentially impacting the hospital stay duration, was the patients’ age. Conclusion. For the patients ageing up to 60 yrs old almost all independent factors, included into the investigation, have served as predictors for a hospital stay duration, while in the patients, ageing 60 yrs old and more, a constant correlation was characteristic for the age factor only.

CXCR1 and CXCR2 signaling play a critical role in neutrophil migration, angiogenesis, and tumorigenesis and are therefore an attractive signaling axis to target in a variety of indications. In human, a total of seven chemokines signal through these receptors and comprise the ELR+CXC chemokine family, so named because of the conserved ELRCXC N-terminal motif. To fully antagonize CXCR1 and CXCR2 signaling, an effective therapeutic should block either both receptors or all seven ligands, yet neither approach has been fully realized clinically. In this work, we describe the generation and characterization of LY3041658, a humanized monoclonal antibody that binds and neutralizes all seven human and cynomolgus monkey ELR+CXC chemokines and three of five mouse and rat ELR+CXC chemokines with high affinity. LY3041658 is able to block ELR+CXC chemokine-induced Ca2+ mobilization, CXCR2 internalization, and chemotaxis in vitro as well as neutrophil mobilization in vivo without affecting other neutrophil functions. In addition to the in vitro and in vivo activity, we characterized the epitope and structural basis for binding in detail through alanine scanning, crystallography, and mutagenesis. Together, these data provide a robust preclinical characterization of LY3041658 for which the efficacy and safety is being evaluated in human clinical trials for neutrophilic skin diseases.

Glioblastoma (GBM) is one of the most malignant tumors with poor prognosis and outcomes. Although smaller particle size can lead to higher blood-brain barrier (BBB)-permeability of the nanomaterials, most of the reported BBB-crossable nanomaterials for targeted GBM therapy are larger than 24 nm. To realize theranostics of GBM, co-loading of therapeutic and diagnostic agents on the same nanomaterials further results in larger particle size. In this study, we developed a kind of novel BBB-transportable nanomaterials smaller than 14 nm for high-efficiency theranostics of GBM (i.e., high contrast magnetic resonance imaging (MRI) and radiosensitization of GBM). Typically, poly(acrylic acid) (PAA) stabilized extremely small gadolinium oxide nanoparticles with modification of reductive bovine serum albumin (ES-GON-rBSA) was synthezed in water phase, resulting in excellent water-dispersibility. RGD dimer (RGD2, Glu-{Cyclo[Arg-Gly-Asp-(D-Phe)-Lys]}(2)) and lactoferrin (LF) were then conjugated to the ES-GON-rBSA to obtain composite nanoparticle ES-GON-rBSA-LF-RGD2 with extraordinary relaxivities (r(1) = 60.8 mM(−1) s(−1), r(2)/r(1) = 1.1). The maximum signal enhancement (SNR) for T(1)-weighted MRI of tumors reached up to 423 ± 42 % at 12 h post-injection of ES-GON-rBSA-LF-RGD2, which is much higher than commercial Gd-chelates (< 80%). ES-GON-rBSA-LF-RGD2 exhibited high biocompatibility and can transport across the in vitro BBB model and the in vivo BBB of mice due to its small particle size (d(h) = 13.4 nm) and LF receptor mediated transcytosis. Orthotopic GBM studies reinforce that ES-GON-rBSA3-LF-RGD2 can accumulate in the orthotopic GBM and enhance the radiation therapy of GBM as an effective radiosensitizing agent.

The enhancer-of-zeste homolog 2 (EZH2) gene product is an 87 kDa polycomb group (PcG) protein containing a C-terminal methyltransferase SET domain. EZH2, along with binding partners, i.e., EED and SUZ12, upon which it is dependent for activity forms the core of the polycomb repressive complex 2 (PRC2). PRC2 regulates gene silencing by catalyzing the methylation of histone H3 at lysine 27. Both overexpression and mutation of EZH2 are associated with the incidence and aggressiveness of various cancers. The novel crystal structure of the SET domain was determined in order to understand disease-associated EZH2 mutations and derive an explanation for its inactivity independent of complex formation. The 2.00 Å crystal structure reveals that, in its uncomplexed form, the EZH2 C-terminus folds back into the active site blocking engagement with substrate. Furthermore, the S-adenosyl-L-methionine (SAM) binding pocket observed in the crystal structure of homologous SET domains is notably absent. This suggests that a conformational change in the EZH2 SET domain, dependent upon complex formation, must take place for cofactor and substrate binding activities to be recapitulated. In addition, the data provide a structural context for clinically significant mutations found in the EZH2 SET domain.

The 23S rRNA nucleotides 2604-12 and 2448-58 fall within the central loop of domain V, which forms a major part of the peptidyl transferase center of the ribosome. We report the synthesis of radioactive, photolabile 2'-O-methyloligoRNAs, PHONTs 1 and 2, complementary to these nucleotides and their exploitation in identifying 50S ribosomal subunit components neighboring their target sites. Photolysis of the 50S complex with PHONT 1, complementary to nts 2604-12, leads to target site-specific photoincorporation into protein L2 and 23S rRNA nucleotides A886, Alpha1918, A1919, G1922-C1924, U2563, U2586, and C2601. Photolysis of the 50S complex with PHONT 2, complementary to nts 2448-58, leads to target site-specific probe photoincorporation into proteins L2, L3, one or more of proteins L17, L18, L21, and of proteins L9, L15, L16, and 23S rRNA nucleotides C2456 and psi2457. Chemical footprinting studies show that 2'-O-methyloligoRNA binding causes little distortion of the peptidyl transferase center but do provide suggestive evidence for the location of flexible regions within 23S rRNA. The significance of these results for the structure of the peptidyl transferase center is considered.

The association between alcoholism and the Taq1 "A" and "B" polymorphic alleles at the DRD2 gene and 48-bp tandem repeat in exon 3 of dopamine D4 receptor (DRD4) gene in 42 unrelated Slavic-surnamed patients and 76 normal controls was examined. The frequency of the A1 allele was higher in alcoholic patients and in alcoholic patients with a family history of alcoholism than in controls (χ²= 3.45, p < 0.001 and χ²)= 3.97, p < 0.001, respectively). Moreover, the frequency of the A1 allele was higher in alcoholics with a family history of alcoholism than in alcoholics without a family history (χ²= 3.33, p < 0.001).The results of association analysis for both the Taq1 "B" and DRD4 alleles were negative for alcoholics in general, subgroups of alcoholics and normal controls. However, the 7-repeat allele (DRD4*7R) of DRD4 gene occurred at significantly higher frequency in alcoholics with a family history of alcoholism compared with those without a family history (χ²= 3.42, p < 0.01).The results indicate that the A1 allele of the DRD2 gene is associated with susceptibility to alcoholism in general.The A1 allele, as well as the DRD4*7R allele, is significantly prevalent among alcoholics with a family history, in comparison with alcoholics without a family history, reflecting different roles of genetic factors in development of alcoholism.

Growth advantage in stationary phase (GASP) is the term used to describe the ability of mutants with an increased fitness from 10-day-old enterobacteria culture to out-compete 1-day-old cells of the same initial strain during a prolonged stationary phase, although the aged cells are introduced as a minority. We studied this bacterial trait in mixed cultures of two enterobacterial species, Escherichia coli and Salmonella enterica, wild type in addition to derived mutants from both strains that contain chromosomal-encoded resistance to either nalidixic acid or streptomycin. The strong GASP phenotype was obtained in mixed cultures with the aged mutant strains, but not when the isogenic antibiotic-sensitive strains were used. This phenomenon was associated with chromosomal rearrangements in 10-day-old bacterial antibiotic-resistant mutated cells.

High anxiety and poor emotion regulation have been found to function as independent causes of stress to the autonomic nervous system. The aim of this study was to further explore how these factors may interact to control heart rate variability. Fifty college students took part in a three-part cardiac recording session followed by questionnaires on trait worry and emotion regulation. An interaction for trait worry and emotion reappraisal was found on two markers of heart rate variability. Low trait worriers with high emotion reappraisal had higher vagal tone than the other three groups. This finding was across all three phases with no specific reactivity or recovery difference. Emotion suppression was not found to significantly impact vagal tone. The negative impacts of trait worry and emotion regulation on heart rate variability were found in this sample of healthy college-aged individuals. Specifically, high trait worry could have a deleterious effect on parasympathetic control of the heart. Emotion regulation skills meanwhile can function as a buffer to stress and a reliance on sympathetic control.

ALTHOUGH much has been written and A discussed about payment for health, the extent of undisciplined data is great. This is understandable, because much of the information is obtained for specific purposes which do not make comparability straightforward. In this study, no attempt will be made to suggest a system of analysis that will lead to principles that might alter this problem. The aim of this effort is to analyze the trends in gross fiscal data gathered principally through the reporting system maintained by the Public Health Service. It is our purpose to draw some conclusions of the import of such trends and thereby suggest attitudes toward fiscal policy that might be considered if proper program support is to continue at adequate levels.