Unexpected Coexisting Solid Solutions in the Quasi-Binary Ag(II) F2 /Cu(II) F2 Phase Diagram.

High-temperature solid-state reaction between orthorhombic AgF2 and monoclinic CuF2 (y=0.15, 0.3, 0.4, 0.5) in a fluorine atmosphere resulted in coexisting solid solutions of Cu-poor orthorhombic and Cu-rich monoclinic phases with stoichiometry Ag1-x Cux F2 . Based on X-ray powder diffraction analyses, the mutual solubility in the orthorhombic phase (AgF2 : Cu) appears to be at an upper limit of Cu concentration of 30 mol % (Ag0.7 Cu0.3 F2 ), while the monoclinic phase (CuF2 : Ag) can form a nearly stoichiometric Cu : Ag=1 : 1 solid solution (Cu0.56 Ag0.44 F2 ), preserving the CuF2 crystal structure. Experimental data and DFT calculations showed that AgF2 : Cu and CuF2 : Ag solid solutions deviate from the classical Vegard's law. Magnetic measurements of Ag1-x Cux F2 showed that the Néel temperature (TN ) decreases with increasing Cu content in both phases. Likewise, theoretical DFT+U calculations for Ag1-x Cux F2 showed that the progressive substitution of Ag by Cu decreases the magnetic interaction strength |J2D | in both structures. Electrical conductivity measurements of Ag0.85 Cu0.15 F2 showed a modest increase in specific ionic conductivity (3.71 ⋅ 10-13 ±2.6 ⋅ 10-15  S/cm) as compared to pure AgF2 (1.85 ⋅ 10-13± 1.2 ⋅ 10-15  S/cm), indicating the formation of a vacancy- or F adatom-free metal difluoride sample.

The activation of complement system in different types of renal replacement therapy.

The complement cascade is a part of innate immune system that responds rapidly to defend the host against invading microorganisms and complete the action of immune cells. The activation of the complement system leads to increased inflammatory response, fibrosis of tubulointestinal tissue and progression of chronic kidney disease (CKD). The purpose of this study was to determine whether the type of renal replacement therapy has an effect on activation of the complement system. The study included 79 patients with CKD stages 4 - 5 according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines on conservative treatment (CKD4-5) (n = 28), on peritoneal dialysis (PD) (n = 21) and undergoing chronic haemodialysis (HD) (n = 30). The concentrations of complement components C3a, C5a and C5b-9 were determined in plasma using the ELISA method. The highest concentration of C3a was found in PD group and differed significantly from HD group, both before and after haemodialysis treatment and CKD4-5 patients (P = 0.00001). The C5a concentration in HD patients was significantly higher than in PD patients and CKD4-5 group (P = 0.0001). The C5a and C5b-9 concentrations significantly increased during the haemodialysis session (P = 0.027 and P = 0.01, respectively). The values of C5b-9 observed in PD and CKD4-5 groups were significantly lower, than in HD patients (P = 0.0005). In HD patients the negative correlations were found between the time of haemodialysis treatment and C5b-9 concentration, both before and after haemodialysis session (Rs = -0.436, P = 0.016 and Rs = -0.365, P = 0.046, respectively). The type of renal replacement therapy influences the complement activation, which is the most intense during the haemodialysis treatment and correlates negatively with the haemodialysis vintage. The promising therapeutic intervention may be an improvement of HD biocompatibility.

Dynamic cell adhesion and migration on nanoscale grooved substrates.

Organised nanotopography mimicking the natural extracellular matrix can be used to control morphology, cell motility, and differentiation. However, it is still unknown how specific cell types react with specific patterns. Both initial adhesion and preferential cell migration may be important to initiate and increase cell locomotion and coverage with cells, and thus achieve an enhanced wound healing response around an implantable material. Therefore, the aim of this study was to evaluate how MC3T3-E1 osteoblast initial adhesion and directional migration are influenced by nanogrooves with pitches ranging from 150 nm up to 1000 nm. In this study, we used a multi-patterned substrate with five different groove patterns and a smooth area with either a concentric or radial orientation. Initial cell adhesion measurements after 10 s were performed using atomic force spectroscopy-assisted single-cell force spectroscopy, and demonstrated that nascent cell adhesion was highly induced by a 600 nm pitch and reduced by a 150 nm pitch. Addition of RGD peptide significantly reduced adhesion, indicating that integrins and cell adhesive proteins (e.g. fibronectin or vitronectin) are key factors in specific cell adhesion on nanogrooved substrates. Also, cell migration was highly dependent on the groove pitch; the highest directional migration parallel to the grooves was observed on a 600 nm pitch, whereas a 150 nm pitch restrained directional cell migration. From this study, we conclude that grooves with a pitch of 600 nm may be favourable to enhance fast wound closure, thereby promoting tissue regeneration.

Submicron-patterning of bulk titanium by nanoimprint lithography and reactive ion etching.

Nanopatterns on titanium may enhance endosseous implant biofunctionality. To enable biological studies to prove this hypothesis, we developed a scalable method of fabricating nanogrooved titanium substrates. We defined nanogrooves by nanoimprint lithography (NIL) and a subsequent pattern transfer to the surface of ASTM grade 2 bulk titanium applying a soft-mask for chlorine-based reactive ion etching (RIE). With respect to direct write lithographic techniques the method introduced here is fast and capable of delivering uniformly patterned areas of at least 4 cm(2). A dedicated silicon nanostamp process has been designed to generate the required thickness of the soft-mask for the NIL-RIE pattern transfer. Stamps with pitch sizes from 1000 nm down to 300 nm were fabricated using laser interference lithography (LIL) and deep cryogenic silicon RIE. Although silicon nanomachining was proven to produce smaller pitch sizes of 200 nm and 150 nm respectively, successful pattern transfer to titanium was only possible down to a pitch of 300 nm. Hence, the smallest nanogrooves have a width of 140 nm. An x-ray photoelectron spectroscopy study showed that only very few contaminations arise from the fabrication process and a cytotoxicity assay on the nanopatterned surfaces confirmed that the obtained nanogrooved titanium specimens are suitable for in vivo studies in implantology research.

Oxidative stress and renal interstitial fibrosis in patients after renal transplantation: current state of knowledge.

Long-term outcomes in renal transplantation has represented a major challenge for transplantologists and nephrologists for many years. The use of a new generation of immunosuppressive drugs has contributed to reducing the incidence of acute rejection episodes, but chronic allograft nephropathy is the cause of renal allograft loss in ∼50% of recipients. Organ fibrosis is the main histopathologic finding in those cases. Many researchers have focused on mechanisms leading to fibrosis. It is thought that an explanation of the pathologic mechanism of this phenomenon may improve long-term effects of therapy for kidney transplant recipients.

Hypoxanthine as a graft ischemia marker stimulates catalase activity in the renal vein during reperfusion in humans.

BACKGROUND: The impairment of organ function derived from ischemia-reperfusion injury is still an important problem in solid organ transplantation. Cell alterations induced by ischemia prime the tissue for subsequent damage occurring during the reperfusion phase. Purine nucleotides and oxypurines are products of adenine nucleotide degradation. Reperfusion and reoxygenation are characterized by great production of reactive oxygen species and free radicals. On the contrary, superoxide dismutase, catalase, glutathione, and glutathione peroxidase are involved in protecting against free radicals. The aim of the study was to examine the correlation between concentrations of ischemia markers (hypoxanthine or inosine) and the activity of erythrocyte superoxide dismutase, catalase, or glutathione peroxidase. PATIENTS AND METHODS: The study included 40 renal transplant recipients. Before anastomosis of the kidney vessels with the recipient's iliac vessels, a "0" blood sample was taken from the iliac vein. Then, after anastomosis, the renal vein of the graft was cannulated and blood samples I, II, and III were obtained. The reperfusion of the transplanted kidney was measured with a thermovision camera ThermaCAM SC500. RESULTS: The plasma concentrations of hypoxanthine and inosine increased in statistically significant fashion immediately after total tissue reperfusion (P < .0001). Catalase activity at 4 minutes after total tissue reperfusion correlated positively with hypoxanthine concentrations immediately after total tissue reperfusion (Rs = +0.49), 2 minutes after total tissue reperfusion (Rs = +0.47), and 4 minutes after total tissue reperfusion (Rs = +0.46). There were no statistically significant correlations between hypoxanthine or inosine concentrations or superoxide dismutase or glutathione peroxidase activities. CONCLUSIONS: The results of the present study suggest that catalase activity may correlate with the concentration of hypoxanthine in the graft renal vein and other mediators of oxidative stress.

Activity of CuZn-superoxide dismutase, catalase and glutathione peroxidase in erythrocytes in kidney allografts during reperfusion in patients with and without delayed graft function.

BACKGROUND: Generation of reactive oxygen species (ROS) is the main mechanism involved in the ischemic/reperfusion damage of the transplanted organ. Oxygen burst is a trigger for complex biochemical events leading to generation of oxygenated lipids and changes in microcirculation. Many markers have been researched to prove the presence of ROS in the transplanted tissue. Some of them, like superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) are considered to play a major role in graft protection against oxygen stress during reperfusion. METHODS: The aim of this study was to examine the changes of SOD1, CAT and GPx activity in erythrocytes during the first minutes after total graft reperfusion. Forty patients undergoing kidney transplantation at our center were assigned to two groups: with or without delayed graft function (DGF). Before anastomosing kidney vessels with recipient's iliac vessels, the '0' blood sample was taken from the iliac vein. Next blood samples I, II and III were taken from the graft's renal vein. The reperfusion of the transplanted kidney was evaluated precisely with the thermovision camera. Erythrocyte SOD1, CAT and GPx activity was measured with a spectrophotometric method. RESULTS: We did not observe statistically significant changes in SOD1, CAT and GPx activity in erythrocytes during the early phase of reperfusion in patients with and without DGF. CONCLUSIONS: Erythrocyte-antioxidative system in graft's vein remain stable during the early phase of reperfusion. The results of the study suggest that further studies on extracellular enzymes are required for the assessment of antioxidant system in the conditions of ischemia/reperfusion.

The effect of gender on outcome in digitalis-treated heart failure patients.

BACKGROUND: The use of digitalis is recommended for the treatment of heart failure to reduce hospitalization. Recent data suggest that digitalis treatment may adversely affect survival in women but not in men. We studied patients with left ventricular dysfunction enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) to determine whether there was a gender-based survival difference in patients treated with digitalis. METHODS AND RESULTS: Symptomatic (n = 2569) and asymptomatic (n = 4228) patients with left ventricular ejection fraction < or = 0.35 were studied. Digitalis use was assessed at baseline and baseline demographic variables were catalogued and compared. A multivariate analysis, incorporating known covariates of risk for adverse cardiovascular events, was used to examine the association of digitalis with all-cause mortality, cardiovascular death, death from heart failure, and arrhythmic death, with, or without, worsening heart failure in women compared with men. Analysis for an interaction between digitalis and gender on mortality was also performed. No interaction between gender and digitalis treatment on survival was found, and there was no significant difference in the hazard ratios for men and women on digitalis either with respect to all-cause mortality, cardiovascular mortality, heart failure mortality, or arrhythmic death with worsening heart failure. When mortality for arrhythmic death without worsening heart failure was adjusted for the probability of being treated with digitalis (propensity analysis), women fared better than men. CONCLUSION: Data from the SOLVD trials suggest that digitalis treatment of heart failure does not result in a difference in survival between men and women. Because a randomized trial to definitively answer the question is unlikely, and perhaps inappropriate, examination of other heart failure populations for a gender-digitalis interaction is indicated.

Effect of baseline or changes in adrenergic activity on clinical outcomes in the beta-blocker evaluation of survival trial.

BACKGROUND: Adrenergic activation is thought to be an important determinant of outcome in subjects with chronic heart failure (CHF), but baseline or serial changes in adrenergic activity have not been previously investigated in a large patient sample treated with a powerful antiadrenergic agent. METHODS AND RESULTS: Systemic venous norepinephrine was measured at baseline, 3 months, and 12 months in the beta-Blocker Evaluation of Survival Trial (BEST), which compared placebo treatment with the beta-blocker/sympatholytic agent bucindolol. Baseline norepinephrine level was associated with a progressive increase in rates of death or death plus CHF hospitalization that was independent of treatment group. On multivariate analysis, baseline norepinephrine was also a highly significant (P<0.001) independent predictor of death. In contrast, the relation of the change in norepinephrine at 3 months to subsequent clinical outcomes was complex and treatment group-dependent. In the placebo-treated group but not in the bucindolol-treated group, marked norepinephrine increase at 3 months was associated with increased subsequent risks of death or death plus CHF hospitalization. In the bucindolol-treated group but not in the placebo-treated group, the 1st quartile of marked norepinephrine reduction was associated with an increased mortality risk. A likelihood-based method indicated that 18% of the bucindolol group but only 1% of the placebo group were at an increased risk for death related to marked reduction in norepinephrine at 3 months. CONCLUSIONS: In BEST, a subset of patients treated with bucindolol had an increased risk of death as the result of sympatholysis, which compromised the efficacy of this third-generation beta-blocker.

A comparison of rate control and rhythm control in patients with atrial fibrillation.

BACKGROUND: There are two approaches to the treatment of atrial fibrillation: one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm, and the other is the use of rate-controlling drugs, allowing atrial fibrillation to persist. In both approaches, the use of anticoagulant drugs is recommended. METHODS: We conducted a randomized, multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death. The primary end point was overall mortality. RESULTS: A total of 4060 patients (mean [+/-SD] age, 69.7+/-9.0 years) were enrolled in the study; 70.8 percent had a history of hypertension, and 38.2 percent had coronary artery disease. Of the 3311 patients with echocardiograms, the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent. There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy (mortality at five years, 23.8 percent and 21.3 percent, respectively; hazard ratio, 1.15 [95 percent confidence interval, 0.99 to 1.34]; P=0.08). More patients in the rhythm-control group than in the rate-control group were hospitalized, and there were more adverse drug effects in the rhythm-control group as well. In both groups, the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic. CONCLUSIONS: Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy, and there are potential advantages, such as a lower risk of adverse drug effects, with the rate-control strategy. Anticoagulation should be continued in this group of high-risk patients.

Cardiovascular risk assessment using pulse pressure in the first national health and nutrition examination survey (NHANES I).

Increased stiffness of the conduit arteries has been associated with increased risk of death and cardiovascular death in a number of populations. None of these populations, however, are fully representative of the US population. The cohort examined in the First National Health and Nutrition Examination Survey (NHANES I) that was free of overt cardiovascular disease was selected to be representative of the US population. We assessed and quantified the increased risk of death associated with elevated pulse pressure in this population. A cohort of 5771 subjects from NHANES I was used to determine the value of adding pulse pressure to standard cardiovascular disease risk factors for assessment of the risk of death during a mean follow-up period of 16.5 years. Analyses were performed by use of the SUDAAN statistical package for performing Cox proportional regression, logistic regression, and other standard methods in complex, weighted samples. Pulse pressure increased with increasing age, body mass index, cholesterol level, and mean arterial pressure. With increasing pulse pressure, the percentage of cigarette smokers decreased and the percentage of diabetics increased. Despite these associations with known risk factors, pulse pressure was independently predictive of an increased risk of death from cardiovascular disease, coronary heart disease, and all-cause mortality. It provides independent prognostic information beyond that provided by known risk factors that were evaluated in this study, including the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure hypertension classification. A 10 mm Hg increase in pulse pressure in persons 25 to 45 of age was associated with a 26% increase in risk of cardiovascular death (95% confidence interval [CI], 5 to 50) and with an 10% increase (95% CI, 2 to 19) in persons 46 to 77 years of age. In a cohort designed to be representative of the US population, elevated pulse pressure has been shown to provide independent prognostic information. This variable may be a marker for the extent of vascular disease and may contribute to the occurrence of clinical events.

Antiarrhythmic drug use in the implantable defibrillator arm of the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study.

BACKGROUND: Previous retrospective or observational series suggest that many patients with an implantable cardioverter-defibrillator (ICD) will be treated with antiarrhythmic drugs (AADs) to modify the frequency or manifestation of recurrent ventricular arrhythmias. The relative clinical benefit, however, is uncertain, and deleterious interactions can occur. The objective of this clinical investigation was to study the need for, and effects of, concomitant AAD use with the ICD in a prospectively defined cohort. METHODS: All patients randomly assigned to the ICD arm of the Antiarrhythmics Versus Implantable Defibrillators (AVID) study were followed for the addition of class I or III AADs ("crossover") after hospital discharge. Addition of AADs was strictly regulated by AVID protocol. The timing and reasons for crossover and the effects on ventricular arrhythmia recurrence were analyzed. Patients were excluded if they required AADs before hospital discharge after index arrhythmias or if they had no ventricular arrhythmia before initiation of AADs. RESULTS: After a median follow-up of 135 days, 81 (18%) of the 461 eligible patients required AADs and formed the crossover group. The primary reason for crossover was frequent ICD shocks in 64% of patients. The most common AAD selected was amiodarone (in 42%). Independent predictors of crossover were lower ejection fraction, absence of ventricular fibrillation, or presence of nonsyncopal ventricular tachycardia at presentation, prior unexplained syncope, female sex, and history of cigarette smoking. Before AAD use, the 1-year arrhythmia event rate was 90%; after AAD, the event rate was only 64% (P =.0001). The time to first event was extended from 3.9 +/- 0.7 months to 11.2 +/- 1.8 months. There were 1.4 +/- 3.7 fewer ICD therapy events (P =.005) after crossover, predominantly accounted for by reduction in shocks rather than antitachycardia pacing therapies. CONCLUSIONS: The majority of patients who receive ICDs for sustained ventricular tachycardia or ventricular fibrillation can be treated without AADs. Most commonly, AADs are added to combat frequent ICD shocks, which are successfully reduced by AAD therapy.

Central clinical research issues in electrophysiology: report of the NASPE Committee.

This article contains the results of an attempt by appointed members of the North American Society of Pacing and Electrophysiology to define the research frontier in electrophysiology and suggest areas of study as an aid in setting the research agenda.

Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction.

BACKGROUND: Black patients with heart failure have a poorer prognosis than white patients, a difference that has not been adequately explained. Whether racial differences in the response to drug treatment contribute to differences in outcome is unclear. To address this issue, we pooled and analyzed data from the Studies of Left Ventricular Dysfunction (SOLVD) prevention and treatment trials, two large, randomized trials comparing enalapril with placebo in patients with left ventricular dysfunction. METHODS: We used a matched-cohort design in which up to four white patients were matched with each black patient according to trial, treatment assignment, sex, left ventricular ejection fraction, and age. A total of 1196 white patients (580 from the prevention trial and 616 from the treatment trial) were matched with 800 black patients (404 from the prevention trial and 396 from the treatment trial). The average duration of follow-up was 35 months in the prevention trial and 33 months in the treatment trial. RESULTS: The black patients and the matched white patients had similar demographic and clinical characteristics, but the black patients had higher rates of death from any cause (12.2 vs. 9.7 per 100 person-years) and of hospitalization for heart failure (13.2 vs. 7.7 per 100 person-years). Despite similar doses of drug in the two groups, enalapril therapy, as compared with placebo, was associated with a 44 percent reduction (95 percent confidence interval, 27 to 57 percent) in the risk of hospitalization for heart failure among the white patients (P<0.001) but with no significant reduction among black patients (P=0.74). At one year, enalapril therapy was associated with significant reductions from base line in systolic blood pressure (by a mean [+/-SD] of 5.0+/-17.1 mm Hg) and diastolic blood pressure (3.6+/-10.6 mm Hg) among the white patients, but not among the black patients. No significant change in the risk of death was observed in association with enalapril therapy in either group. CONCLUSIONS: Enalapril therapy is associated with a significant reduction in the risk of hospitalization for heart failure among white patients with left ventricular dysfunction, but not among similar black patients. This finding underscores the need for additional research on the efficacy of therapies for heart failure in black patients.

Determinants and prognostic information provided by pulse pressure in patients with coronary artery disease undergoing revascularization. The Balloon Angioplasty Revascularization Investigation (BARI).

Arterial stiffness, as evidenced by increased pulse pressure (PP), is associated with adverse cardiovascular events. However, the prognostic importance of PP in patients who have undergone revascularization is unknown. We examined the prognostic importance of PP and predictors of increased PP in patients entered into the Balloon Angioplasty Revascularization Investigation (BARI). Estimated correlation and standardized regression coefficients were reported, indicating the relative magnitude of independent effects of baseline characteristics on PP. The independent association of PP and outcome over 5 years was determined. Baseline characteristics independently associated with PP were higher mean arterial pressure, older age, female sex, noncoronary vascular disease, history of diabetes mellitus, and history of hypertension (p <0.001 for all). Cox regression covariates significantly associated with time to death were age, smoking, male gender, diabetes history, congestive heart failure, and baseline use of angiotensin-converting enzyme inhibitors, diuretic, or digitalis. When PP was added to the model, it was found to be an independent predictor of time to death (p = 0.008). When PP and mean arterial pressure were added to the model, PP remained significantly associated with time to death (p = 0.033). When renal disease and noncoronary vascular disease were added to the model, the relative risk declined from 1.07 to 1.04 and the association was no longer statistically significant. Thus, increased PP is directly and independently associated with mean arterial pressure, hypertension, age > or =65 years, diabetes mellitus, and the presence of noncoronary vascular disease, and inversely associated with a history of myocardial infarction. After coronary revascularization, PP, reflecting arterial stiffness, is independently associated with total mortality.

Lessons from the post coronary artery bypass graft study in evaluating and controlling technical variability in angiographic trials. Post CABG Investigators.

Although many investigators have evaluated the technical variability of quantitative angiographic techniques used to study atherosclerosis regression in native coronary arteries, few have studied the variability inherent in repeated studies of atherosclerotic saphenous vein grafts. This study describes 2 studies performed during the course of the Post Coronary Artery Bypass Graft (CABG) Clinical Trial that were designed to assess the reproducibility of: (1) repeated angiographic views within a short time period; and (2) reproducibility of the total process of quantitative analysis of saphenous vein graft angiograms. Statistical methods are described that provide a more meaningful assessment of the impact of measurement variability in the analytic process versus the variability related to changes induced by pharmacologic interventions. One such method, the increase in standard deviation (SD) among patients (ISDP), showed that repeated angiographic views increased the variability of calculation of lesion minimal diameter by 1.5%, whereas the ISDP for repetition of the entire process of quantitative angiographic readings increased variability 6.4%. These data from the Post CABG trial reveal that technical variability is small and has negligible impact on the conclusions of the study.