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Celem artykułu jest przybliżenie procesu napływu galicyjskich uchodźców wojennych do Żywca w okresie od sierpnia 1914 do maja 1915 roku. W tekście przedstawiono dane liczbowe oraz informacje pozwalające scharakteryzować pod względem wyznaniowym i zawodowym przybyłych do Żywca uchodźców. Zwrócono również uwagę na zaangażowanie mieszkańców miasta w pomoc przybyłej ludności. Brak danych w literaturze historycznej uniemożliwia pełne porównanie zjawiska napływu uchodźców w innych miastach skrajnie zachodniej części Galicji. Zebrane w artykule informacje mogą posłużyć za materiał porównawczy w badaniach tego zagadnienia w kontekście innych miejscowości.

The aim of the work is to perform numerical and experimental analyses of the wind flow around two structures with a circular cross-section placed side by side. These structures can have a smooth and a rough surface. In that case, the values of interference coefficient presented in Eurocode differ from those obtained from the author's numerical analyses, concerning very large Reynolds numbers Re. The aerodynamic drag force of the cylinder systems is determined on the basis of numerical Finite Volume Method analyses using the Computational Fluid Dynamics (CFD) module. Velocity and pressure fields are also presented. In order to verify the results, experimental tests were carried out in a wind tunnel. The results obtained at all stages (numerical models with a large number of Re; experimental studies of models with a lower Re number; numerical models with a lower Re number) were compared with each other. Each of the flow ranges (turbulent, transitional, laminar) is characterized by a different behavior and therefore, the aim of the work is also the correct creation of numerical models. Thus it is necessary to adjust the parameters of the numerical model. These analyses are used for testing the possibility of estimating wind load acting on a fragment of a structure of more complex, curved shape (e.g., water slide) using simplified models (e.g., helices, toruses, and cylinders). Eurocode EN 1991-1-4 does not cover complex structures based on circular cylinders.

Low-grade inflammatory processes and related oxidative stress may have a key role in the pathogenesis of hypertension and hypertension-mediated organ damage. Innate immune cells, such as neutrophils, dendritic cells, monocytes/macrophages, as well as unconventional T lymphocytes like γδ T cells contribute to hypertension and may trigger vascular inflammation. Adaptive immunity has been demonstrated to participate in elevation of blood pressure and in vascular and kidney injury. In particular, effector T lymphocytes (Th1, Th2, and Th17) may play a relevant role in promoting hypertension and microvascular remodeling, whereas T-regulatory lymphocytes may have a protective role. Effector cytokines produced by these immune cells lead to increased oxidative stress, endothelial dysfunction and contribute to target organ damage in hypertension. A possible role of immune cell subpopulations in the development and regression of microvascular remodeling has also been proposed in humans with hypertension. The present review summarizes the key immune mechanisms that may participate in the pathophysiology of hypertension-mediated inflammation and vascular remodeling; advances in this field may provide the basis for novel therapeutics for hypertension.

Aims The functional capacity of the immune cells is strongly dependent on their metabolic state and inflammatory responses are characterized by a greater use of glucose in immune cells. This study is aimed to establish the role of glucose metabolism and its players [glucose transporter 1 (GLUT-1) and pyruvate kinase isozyme M2 (PKM2)] in the dysregulation of adaptive immunity and inflammation observed in patients with non-ST-segment elevation myocardial infarction (NSTEMI). Methods and results We enrolled 248 patients allocated to three groups: NSTEMI patients, chronic coronary syndromes (CCS) patients, healthy subjects (HSs). NSTEMI patients showed higher expression of GLUT-1 and an enhanced glucose uptake in T cells when compared with CCS patients (P < 0.0001; P = 0.0101, respectively) and HSs (P = 0.0071; P = 0.0122, respectively). PKM2 had a prevalent nuclear localization in T lymphocytes in NSTEMI (P = 0.0005 for nuclear vs. cytoplasm localization), while in CCS and HS, it was equally distributed in both compartments. In addition, the nuclear fraction of PKM2 was significantly higher in NSTEMI compared with HS (P = 0.0023). In NSTEMI patients, treatment with Shikonin and Fasentin, which inhibits PKM2 enzyme activity and GLUT-1-mediated glucose internalization, respectively, led to a significant reduction in GLUT-1 expression along with the down-regulation of pro-inflammatory cytokine expression. Conclusion NSTEMI patients exhibit dysregulation of the GLUT-1/PKM2 metabolic loop characterized by nuclear translocation of PKM2, where it acts as a transcription regulator of pro-inflammatory genes. This detrimental loop might represent a new therapeutic target for personalized medicine.

Hypertension and periodontitis are both highly prevalent co-morbidities worldwide, and their occurrence increases with age. Multiple observational epidemiological studies have shown that periodontitis is associated with an increased cardiovascular disease (CVD) occurrence. Large systematic reviews and metanalyses further show that periodontitis increases the risk of hypertension and is associated with increased systolic and diastolic blood pressure. Genetic and clinical evidence, utilizing mendelian randomization and randomized clinical trials, support the causal role of periodontitis in hypertension. The mechanisms of this link remain unclear. Critical components of immune and inflammatory pathogenesis of periodontitis considerably overlap with immune mechanisms of hypertension. Clinical studies support that both C-reactive protein (CRP) levels and white blood cell counts (WBC) mediate the relationship between periodontal disease and high blood pressure. In particular, activation of Th1, Th17, T regulatory cells, and proinflammatory monocytes has been shown to be essential in both conditions. Immunosenescent dysregulated CD28null T cells have been implicated, along with key effector cytokines such as interleukin 6 (IL-6), TNF-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin 17 (IL-17). A better understanding of the relationships between hypertension and periodontitis is essential not only for possible utilization of this knowledge for a non-pharmacological approach to improving blood pressure control. It may also provide valuable pathogenetic clues linking inflammation and hypertension, which has become particularly relevant in the light of links between hypertension and autoimmune disorders or, more recently, COVID-19.

Sphingosine kinase-1 (Sphk1) and its product, sphingosine-1-phosphate (S1P) are important regulators of cardiac growth and function. Numerous studies have reported that Sphk1/S1P signaling is essential for embryonic cardiac development and promotes pathological cardiac hypertrophy in adulthood. However, no studies have addressed the role of Sphk1 in postnatal cardiomyocyte (CM) development so far. The present study aimed to assess the molecular mechanism(s) by which Sphk1 silencing might influence CMs development and hypertrophy in vitro. Neonatal mouse CMs were transfected with siRNA against Sphk1 or negative control, and subsequently treated with 1 µM angiotensin II (AngII) or a control buffer for 24 h. The results of RNASeq analysis revealed that diminished expression of Sphk1 significantly accelerated neonatal CM maturation by inhibiting cell proliferation and inducing developmental pathways in the stress (AngII-induced) conditions. Importantly, similar effects were observed in the control conditions. Enhanced maturation of Sphk1-lacking CMs was further confirmed by the upregulation of the physiological hypertrophy-related signaling pathway involving Akt and downstream glycogen synthase kinase 3 beta (Gsk3β) downregulation. In summary, we demonstrated that the Sphk1 silencing in neonatal mouse CMs facilitated their postnatal maturation in both physiological and stress conditions.

Sphingosine kinase-1 (Sphk1) and its product, sphingosine-1-phosphate (S1P) are important regulators of cardiac growth and function. Numerous studies have reported that Sphk1/S1P signaling is essential for embryonic cardiac development and promotes pathological cardiac hypertrophy in adulthood. However, no studies have addressed the role of Sphk1 in postnatal cardiomyocyte (CM) development so far. The present study aimed to assess the molecular mechanism(s) by which Sphk1 silencing might influence CMs development and hypertrophy in vitro. Neonatal mouse CMs were transfected with siRNA against Sphk1 or negative control, and subsequently treated with 1 µM angiotensin II (AngII) or a control buffer for 24 h. The results of RNASeq analysis revealed that diminished expression of Sphk1 significantly accelerated neonatal CM maturation by inhibiting cell proliferation and inducing developmental pathways in the stress (AngII-induced) conditions. Importantly, similar effects were observed in the control conditions. Enhanced maturation of Sphk1-lacking CMs was further confirmed by the upregulation of the physiological hypertrophy-related signaling pathway involving Akt and downstream glycogen synthase kinase 3 beta (Gsk3β) downregulation. In summary, we demonstrated that the Sphk1 silencing in neonatal mouse CMs facilitated their postnatal maturation in both physiological and stress conditions.

The opioid system is well-known for its role in modulating nociception and addiction development. However, there are premises that the endogenous opioid system may also affect blood pressure. The main goal of the present study was to determine the impact of different endogenous opioid system activity and its pharmacological blockade on blood pressure. Moreover, we examined the vascular function in hyper- and hypoactive states of the opioid system and its pharmacological modification. In our study, we used two mouse lines which are divergently bred for high (HA) and low (LA) swim stress-induced analgesia. The obtained results indicated that individuals with low endogenous opioid system activity have higher basal blood pressure compared to those with a hyperactive opioid system. Additionally, naloxone administration only resulted in the elevation of blood pressure in HA mice. We also showed that the hypoactive opioid system contributes to impaired vascular relaxation independent of endothelium, which corresponded with decreased guanylyl cyclase levels in the aorta. Together, these data suggest that higher basal blood pressure in LA mice is a result of disturbed mechanisms in vascular relaxation in smooth muscle cells. We believe that a novel mechanism which involves endogenous opioid system activity in the regulation of blood pressure will be a promising target for further studies in hypertension development.

Atherosclerosis is a chronic nonresolving inflammatory disease of medium- and large-sized arteries causing heart attacks and strokes. As atherosclerotic plaques in the inner intimal layer and aortic media of these arteries lack nerve fibers, the impact of innervation on atherosclerosis remains unknown. However, nerves use the adventitia as their primary conduit to reach target tissues. We and others characterized artery tertiary lymphoid organs (ATLOs) in the aorta adventitia of apolipoprotein E knock-out mice and also found such aggregates in human diseased coronary arteries and other arterial tree segments. In view of these observations, we postulated that the peripheral nervous system may interact with diseased arteries via adventitial immune cells. We found in aged hyperlipidemic mice and in human atherosclerotic tissues that widespread neuro-immune-cardiovascular-interfaces (NICIs) establish atherosclerosis-brain circuits (ABCs) capable of sensing and affecting atherosclerosis: (i) ATLOs interact with the peripheral nervous system (PNS) by stimulating axon growth; (ii) the adventitia is innervated by the sensory and sympathetic NS but not by the parasympathetic NS system; (iii) the adventitia is wired directly to the brain stem through lower thoracic dorsal-root-ganglia and sympathetic perivascular ganglia; (iv) advanced atherosclerosis is associated with increased nerve activities in splenic and celiac vagus nerves; and (v) elimination of the sympathetic NS disrupts ATLOs, attenuates atherosclerosis progression, and reduces plaque vulnerability. Our data demonstrate the pathophysiological relevance of NICIs in atherosclerosis and that the PNS employs NICIs to assemble ABCs. We hypothesize that intervention into neural circuits creates multiple unexpected opportunities to treat atherosclerosis.

Supplemental Digital Content is available in the text., High blood pressure is a risk factor for cardiovascular diseases. Ang II (angiotensin II), a key pro-hypertensive hormone, mediates target organ consequences such as endothelial dysfunction and cardiac hypertrophy. S1P (sphingosine-1-phosphate), produced by Sphk1 (sphingosine kinase 1), plays a pivotal role in the pathogenesis of hypertension and downstream organ damage, as it controls vascular tone and regulates cardiac remodeling. Accordingly, we aimed to examine if pharmacological inhibition of Sphk1 using selective inhibitor PF543 can represent a useful vasoprotective and cardioprotective anti-hypertensive strategy in vivo. PF543 was administered intraperitoneally throughout a 14-day Ang II-infusion in C57BL6/J male mice. Pharmacological inhibition of Sphk1 improved endothelial function of arteries of hypertensive mice that could be mediated via decrease in eNOS (endothelial nitric oxide synthase) phosphorylation at T495. This effect was independent of blood pressure. Importantly, PF543 also reduced cardiac hypertrophy (heart to body weight ratio, 5.6±0.2 versus 6.4±0.1 versus 5.9±0.2 mg/g; P

Recent studies have emphasized the role of perivascular inflammation in cardiovascular disease. We studied mechanisms of perivascular leukocyte infiltration in angiotensin II (Ang II)-induced hypertension and their links to vascular dysfunction. Chronic Ang II infusion in mice increased immune cell content of T cells (255 ± 130 to 1664 ± 349 cells/mg; P < 0.01), M1 and M2 macrophages, and dendritic cells in perivascular adipose tissue. In particular, the content of T lymphocytes bearing CC chemokine receptor (CCR) 1, CCR3, and CCR5 receptors for RANTES chemokine was increased by Ang II (CCR1, 15.6 ± 1.5% vs. 31 ± 5%; P < 0.01). Hypertension was associated with an increase in perivascular adipose tissue expression of the chemokine RANTES (relative quantification, 1.2 ± 0.2 vs. 3.5 ± 1.1; P < 0.05), which induced T-cell chemotaxis and vascular accumulation of T cells expressing the chemokine receptors CCR1, CCR3, and CCR5. Mechanistically, RANTES−/− knockout protected against vascular leukocyte, and in particular T lymphocyte infiltration (26 ± 5% in wild type Ang II vs. 15 ± 4% in RANTES−/−), which was associated with protection from endothelial dysfunction induced by Ang II. This effect was linked with diminished infiltration of IFN-γ-producing CD8+ and double-negative CD3+CD4−CD8− T cells in perivascular space and reduced vascular oxidative stress while FoxP3+ T-regulatory cells were unaltered. IFN-γ ex vivo caused significant endothelial dysfunction, which was reduced by superoxide anion scavenging. In a human cohort, a significant inverse correlation was observed between circulating RANTES levels as a biomarker and vascular function measured as flow-mediated dilatation (R = −0.3, P < 0.01) or endothelial injury marker von Willebrand factor (R = +0.3; P < 0.01). Thus, chemokine RANTES is important in the regulation of vascular dysfunction through modulation of perivascular inflammation.—Mikolajczyk, T. P., Nosalski, R., Szczepaniak, P., Budzyn, K., Osmenda, G., Skiba, D., Sagan, A., Wu, J., Vinh, A., Marvar, P. J., Guzik, B., Podolec, J., Drummond, G., Lob, H. E., Harrison, D. G., Guzik, T. J. Role of chemokine RANTES in the regulation of perivascular inflammation, T-cell accumulation, and vascular dysfunction in hypertension.

The paper presents the way of estimating the wind force acting on straight or curved elements with circular cross-section. These elements can be positioned at any angle to the wind direction. They may also be bent into the form of a torus or a helix, laid horizontally or sloped. The first part of the article briefly presents the results of the air flow computer simulations. The second part of the work shows the analytical approach to the problem, solved by decomposition of the wind velocity vector to the normal, binormal and tangent components, estimation of the pressure distribution around the elements cross-section and finally integration of the pressure over the whole surface. Because there were observed significant differences between the data obtained from the analytical and numerical method, some empirical correction functions had to be attached to the analytical equations. The last part consists of the engineering applicable advices, presented in the form of a table of coefficients.

SummaryEndothelial dysfunction and inflammation are key mechanisms of vascular disease. We hypothesised that heterogeneity of monocyte subpopulations may be related to the development of vascular dysfunction in coronary artery disease (CAD). Therefore, we examined the relationships between monocyte subsets (CD14++CD16– “classical – Mon1”, CD14++CD16+ “intermediate – Mon2” and CD14+CD16++ “nonclassical – Mon3”), endothelial function and risk factor profiles in 130 patients with CAD undergoing coronary artery bypass grafting. This allowed for direct nitric oxide (NO) bioavailability assessment using isometric tension studies ex vivo (acetylcholine; ACh- and sodium- nitropruside; SNP-dependent) in segments of internal mammary arteries. The expression of CD14 and CD16 antigens and activation markers were determined in peripheral blood mononuclear cells using flow cytometry. Patients with high CD14+CD16++ “nonclassical” and low CD14++CD16- “classical” monocytes presented impaired endothelial function. High frequency of CD14+CD16++ “nonclassical” monocytes was associated with increased vascular superoxide production. Furthermore, endothelial dysfunction was associated with higher expression of activation marker CD11c selectively on CD14+CD16++ monocytes. Nonclassical and classical monocyte frequencies remained independent predictors of endothelial dysfunction when major risk factors for atherosclerosis were taken into account (β =0.18 p=0.04 and β =-0.19 p=0.03, respectively). In summary, our data indicate that CD14+CD16++ “nonclassical” monocytes are associated with more advanced vascular dysfunction measured as NO-bioavailability and vascular reactive oxygen species production.

Vascular dysfunction is an important phenomenon in hypertension. We hypothesized that angiotensin II (AngII) affects transcriptome in the vasculature in a region-specific manner, which may help to identify genes related to vascular dysfunction in AngII-induced hypertension. Mesenteric artery and aortic transcriptome was profiled using Illumina WG-6v2.0 chip in control and AngII infused (490 ng/kg/min) hypertensive mice. Gene set enrichment and leading edge analyses identified Sphingosine kinase 1 (Sphk1) in the highest number of pathways affected by AngII. Sphk1 mRNA, protein and activity were up-regulated in the hypertensive vasculature. Chronic sphingosine-1-phosphate (S1P) infusion resulted in a development of significantly increased vasoconstriction and endothelial dysfunction. AngII-induced hypertension was blunted in Sphk1−/− mice (systolic BP 167 ± 4.2 vs. 180 ± 3.3 mmHg, p Sphk1−/− mice. Pharmacological inhibition of S1P synthesis reduced vasoconstriction of mesenteric arteries. While Sphk1 is important in mediating vasoconstriction in hypertension, Sphk1−/− mice were characterized by enhanced endothelial dysfunction, suggesting a local protective role of Sphk1 in the endothelium. S1P serum level in humans was correlated with endothelial function (arterial tonometry). Thus, vascular transcriptome analysis shows that S1P pathway is critical in the regulation of vascular function in AngII-induced hypertension, although Sphk1 may have opposing roles in the regulation of vasoconstriction and endothelium-dependent vasorelaxation.

Endothelial dysfunction and inflammation are key mechanisms of vascular disease. We hypothesised that heterogeneity of monocyte subpopulations may be related to the development of vascular dysfunction in coronary artery disease (CAD). Therefore, we examined the relationships between monocyte subsets (CD14

Celem artykulu jest analiza sektorowego zroznicowania struktury kapitalowej, przeprowadzona z wykorzystaniem wybranych wskaźnikow finansowych, a takze proba ustalenia średniego dla sektorow kosztu kapitalu wlasnego z wykorzystaniem modelu CAPM. Do pomiaru rentowności finansowej wykorzystany zostal wskaźnik rentowności kapitalow wlasnych, a do oceny poziomu ryzyka finansowego zastosowano odchylenie standardowe indeksu tworzenia wartości, ktore wytypowalo sektory o najwiekszym i najmniejszym ryzyku finansowym. Poniewaz badania obejmują lata 2009-2011, ich wyniki pokazują rowniez zaleznośc liczonych wskaźnikow od faz cyklu koniunkturalnego.

The article briefly shows how to estimate the safety of recreational water slides by numerical analysis of motion of the users. There are presented: mathematical description of a typical water slides geometry, simplified model of a sliding person, model of contact between the user and the inner surface of the slide, equations of motion written for a rigid body with 6 degrees of freedom and finally some sample results compared to the limitations set by current European Standard.

Background Formation of compact and poorly lysable clots has been reported in thromboembolic disorders. Little is known about clot properties in bleeding disorders. Objectives We hypothesized that more permeable and lysis-sensitive fibrin clots can be detected in women with heavy menstrual bleeding (HMB). Methods We studied 52 women with HMB of unknown cause and 52 age-matched control women. Plasma clot permeability (Ks), turbidity and efficiency of fibrinolysis, together with coagulation factors, fibrinolysis proteins, and platelet aggregation were measured. Results Women with HMB formed looser plasma fibrin clots (+16% [95%CI 7–18%] Ks) that displayed lower maximum absorbancy (-7% [95%CI -9 – -1%] ΔAbsmax), and shorter clot lysis time (-17% [95%CI -23 – -11%] CLT). The HMB patients and controls did not differ with regard to coagulation factors, fibrinogen, von Willebrand antigen, thrombin generation markers and the proportion of subjects with defective platelet aggregation. The patients had lower platelet count (-12% [95%CI -19 – -2%]), tissue plasminogen activator antigen (-39% [95%CI -41 – -29%] tPA:Ag), and plasminogen activator inhibitor-1 antigen (-28% [95%CI -38 – -18%] PAI-1:Ag) compared with the controls. Multiple regression analysis upon adjustment for age, body mass index, glucose, and fibrinogen showed that decreased tPA:Ag and shortened CLT were the independent predictors of HMB. Conclusions Increased clot permeability and susceptibility to fibrinolysis are associated with HMB, suggesting that altered plasma fibrin clot properties might contribute to bleeding disorders of unknown origin.

Hypertension is associated with immune cells activation and their migration into the kidney, vasculature, heart and brain. These inflammatory mechanisms are critical for blood pressure regulation and mediate target organ damage, creating unique novel targets for pharmacological modulation. In response to angiotensin II and other pro-hypertensive stimuli, the expression of several inflammatory chemokines and their receptors is increased in the target organs, mediating homing of immune cells. In this review, we summarize the contribution of key inflammatory chemokines and their receptors to increased accumulation of immune cells in target organs and effects on vascular dysfunction, remodeling, oxidative stress and fibrosis, all of which contribute to blood pressure elevation. In particular, the role of CCL2, CCL5, CXCL8, CXCL9, CXCL10, CXCL11, CXCL16, CXCL1, CX3CL1, XCL1 and their receptors in the context of hypertension is discussed. Recent studies have tested the efficacy of pharmacological or genetic targeting of chemokines and their receptors on the development of hypertension. Promising results indicate that some of these pathways may serve as future therapeutic targets to improve blood pressure control and prevent target organ consequences including kidney failure, heart failure, atherosclerosis or cognitive impairment.