Effects of controlled physical activity on immune cell phenotype in peripheral blood in prehypertension - studies in preclinical model and randomised crossover study.

Hypertension (HT) is a global public health issue. There are many behavioural risk factors including unhealthy diet, tobacco use and alcohol consumption as well physical inactivity that contribute to the development of high blood pressure (BP) and its complications. Favourable effect of regular physical activity on treatment or prevention of hypertension by improvement of endothelial function is widely accepted however little is known about its relationship with immune system. Thus, the aim of this study was to assess the role of moderate regular physical activity on immune cell phenotype. T cell and monocyte subsets were characterised in 31 subjects with prehypertension (130 - 139 mmHg systolic and 85 - 89 mmHg diastolic blood pressure) who participated in moderate training (3 times/week) on cyclometers for 3 months in crossover study design. Complementary study was performed in murine model of Ang II-induced hypertension and ten-week-old animals were trained on a treadmill (5 times/week, 1 hour) for 2 weeks before and 1.5 weeks after minipumps implantation. In the context of elevated blood pressure regular physical activity had modest influence on immune cell phenotype. Both in human study and murine model we did not observe effects of applied exercise that can explain the mechanism of BP reduction after short-term regular training. Twelve-weeks regular training did not affect the activation status of T lymphocytes measured as expression of CD69, CD25 and CCR5 in human study. Physical activity resulted in higher expression of adhesion molecule CD11c on CD16+ monocytes (especially CD14 high) without any changes in leukocytes subpopulation counts. Similar results were observed in murine model of hypertension after the training. However the training caused significant decrease of CCR5 and CD25 expressions (measured as a mean fluorescence intensity) on CD8+ T cells infiltrating perivascular adipose tissue. Our studies show modest regulatory influence of moderate training on inflammatory markers in prehypertensive subjects and murine model of Ang II induced hypertension.

Anti-atherosclerotic effect of the angiotensin 1-7 mimetic AVE0991 is mediated by inhibition of perivascular and plaque inflammation in early atherosclerosis.

BACKGROUND AND PURPOSE: Inflammation plays a key role in atherosclerosis. The protective role of angiotensin 1-7 (Ang-(1-7)) in vascular pathologies suggested the therapeutic use of low MW, non-peptide Ang-(1-7) mimetics, such as AVE0991. The mechanisms underlying the vaso-protective effects of AVE0991, a Mas receptor agonist, remain to be explored. EXPERIMENTAL APPROACH: We investigated the effects of AVE0991 on the spontaneous atherosclerosis in apolipoprotein E (ApoE)-/- mice, in the context of vascular inflammation and plaque stability. KEY RESULTS: AVE0991 has significant anti-atherosclerotic properties in ApoE-/- mice and increases plaque stability, by reducing plaque macrophage content, without effects on collagen. Using the descending aorta of chow-fed ApoE-/- mice, before significant atherosclerotic plaque develops, we gained insight to early events in atherosclerosis. Interestingly, perivascular adipose tissue (PVAT) and adventitial infiltration with macrophages and T-cells precedes atherosclerotic plaque or the impairment of endothelium-dependent NO bioavailability (a measure of endothelial function). AVE0991 inhibited perivascular inflammation, by reducing chemokine expression in PVAT and through direct actions on monocytes/macrophages inhibiting their activation, characterized by production of IL-1ß, TNF-α, CCL2 and CXCL10, and differentiation to M1 phenotype. Pretreatment with AVE0991 inhibited migration of THP-1 monocytes towards supernatants of activated adipocytes (SW872). Mas receptors were expressed in PVAT and in THP-1 cells in vitro, and the anti-inflammatory effects of AVE0991 were partly Mas dependent. CONCLUSIONS AND IMPLICATIONS: The selective Mas receptor agonist AVE0991 exhibited anti-atherosclerotic and anti-inflammatory actions, affecting monocyte/macrophage differentiation and recruitment to the perivascular space during early stages of atherosclerosis in ApoE-/- mice. LINKED ARTICLES: This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc.

Heterogeneity of peripheral blood monocytes, endothelial dysfunction and subclinical atherosclerosis in patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by increased cardiovascular morbidity and mortality. SLE patients have increased prevalence of subclinical atherosclerosis, although the mechanisms of this observation remain unclear. Considering the emerging role of monocytes in atherosclerosis, we aimed to investigate the relationship between subclinical atherosclerosis, endothelial dysfunction and the phenotype of peripheral blood monocytes in SLE patients. METHODS: We characterized the phenotype of monocyte subsets defined by the expression of CD14 and CD16 in 42 patients with SLE and 42 non-SLE controls. Using ultrasonography, intima-media thickness (IMT) of carotid arteries and brachial artery flow-mediated dilation (FMD) as well as nitroglycerin-induced dilation (NMD) were assessed. RESULTS: Patients with SLE had significantly, but only modestly, increased IMT when compared with non-SLE controls (median (25th/75th percentile) 0.65 (0.60/0.71) mm vs 0.60 (0.56/0.68) mm; p < 0.05). Importantly, in spite of early atherosclerotic complications in the studied SLE group, marked endothelial dysfunction was observed. CD14dimCD16+proinflammatory cell subpopulation was positively correlated with IMT in SLE patients. This phenomenon was not observed in control individuals. Interestingly, endothelial dysfunction assessed by FMD was not correlated with any of the studied monocyte subsets. CONCLUSIONS: Our observations suggest that CD14dimCD16+monocytes are associated with subclinical atherosclerosis in SLE, although the mechanism appears to be independent of endothelial dysfunction.

Characterization of the impairment of the uptake of apoptotic polymorphonuclear cells by monocyte subpopulations in systemic lupus erythematosus.

Efficient removal of apoptotic polymorphonuclear leukocytes (PMNs) is an important step in the resolution of inflammation, which protects tissues from the noxious contents of dying cells. While the impairment of apoptotic PMNs removal has been demonstrated for macrophages in systemic lupus erythematosus (SLE), recent studies show that monocytes are also capable of such phagocytosis, although their involvement in SLE is not clear. Therefore, we characterized phagocytosis of apoptotic PMNs by monocytes in 22 patients with SLE and 22 healthy controls. Using flow cytometry we demonstrate that in SLE peripheral blood monocytes show impaired phagocytosis of autologous apoptotic PMNs, while they efficiently engulf apoptotic PMNs isolated from healthy subjects. Monocytes CD14highCD16+ and CD14dimCD16+ more efficiently interacted with apoptotic neutrophils than CD16- cells both in SLE and healthy subjects. Monocytes in SLE showed modestly decreased expression of CD35 and CD91 and increased expression of T Cell Ig- and mucin-domain-containing molecule-3 (TIM-3); however, these differences were evident mainly in selected subsets of monocytes (CD16+) while defects in phagocytosis were observed in all monocyte subsets. Apoptotic cell-dependent induction of lipopolysaccharide (LPS) stimulated production of anti-inflammatory cytokine IL-10 by peripheral blood mononuclear cells (PBMC) was blunted in SLE while the production of pro-inflammatory cytokine TNF-α was unchanged.

Prognostic significance of serum antibodies to HPV-16 L1 virus-like particles in patients with invasive cervical cancer.

BACKGROUND: Persistent infection with high-risk human papilloma virus (HPV) is a prerequisite for the development of cervical cancer. The prognostic value of HPV-16 capsid antibodies in patients with invasive cervical cancer and its correlation with clinicopathological factors were investigated. PATIENTS AND METHODS: Serum samples from 150 patients with invasive cervical cancer and 40 healthy female control subjects were analyzed by ELISA for HPV-specific antibodies to HPV-16 L1 virus-like particles (VLPs). RESULTS: HPV-16 L1 antibodies were detectable in 65 out of 150 patients (43.3%) and in 12 out of 40 controls (30.0%). Seropositivity was correlated with prolonged, progression-free (p =0.012) and overall survival (p=0.043). Especially in the early FIGO-stages I and II antibodies to HPV-16 L1, VLPs predicted a better outcome. CONCLUSION: Antibodies to HPV-16 L1 capsid protein may be of prognostic value for patients with invasive cervical cancer and lack of HPV-16 L1 antibodies may indicate a group of patients with a poor prognosis.

Activity concentration of caesium-137 in seawater and plankton of the Pomeranian Bay (the Southern Baltic Sea) before and after flood in 1997.

Activity coefficients of 137Cs determined during culminating flood waters in August 1997 in the estuary of the Oder River, discharging to the Pomeranian Bay as well as in the coastal and open-seawaters of the Bay, did not show enhanced levels of the nuclide as compared to those measured before the flood. It is thus concluded that the flood did not contribute to releasing the nuclide from eroded soil particles. The bioconcentration factors of 137Cs in the riverine plankton has been found to be one to two orders of magnitude higher than those determined in the Pomeranian Bay plankton.

Benchmarking best practices in Web-based nursing courses.

This article describes the framework and process to determine best practices in online learning communities for Web-based nursing courses. The benchmarks for best practices were determined based on evidence-based research in higher education. These quality indicators were then used to develop and pilot test a benchmarking survey across three state schools of nursing. The results of the pilot test, as well as the applications and implications for benchmarking best practices, are discussed.

Health professionals' views of informatics education: findings from the AMIA 1999 spring conference.

Health care leaders emphasize the need to include information technology and informatics concepts in formal education programs, yet integration of informatics into health educational programs has progressed slowly. The AMIA 1999 Spring Congress was held to address informatics educational issues across health professions, including the educational needs in the various health professions, goals for health informatics education, and implementation strategies to achieve these goals. This paper presents the results from AMIA work groups focused on informatics education for non-informatics health professionals. In the categories of informatics needs, goals, and strategies, conference attendees suggested elements in these areas: educational responsibilities for faculty and students, organizational responsibilities, core computer skills and informatics knowledge, how to learn informatics skills, and resources required to implement educational strategies.

Case management and technology: a necessary fit for the future.

We now reside in a data-driven health care environment and methods for gathering, presenting, and evaluating relevant data about health care systems are paramount. This article expands on the importance of evaluating the outcomes of case management and how collecting relevant clinical and cost data can provide an infrastructure on which to base future decisions. Data-based decision making in case management is crucial for ensuring quality of care and the appropriate management of patient outcomes, and it underpins the viability of this delivery model of care.

An innovative curriculum plan for advanced practice in oncology nursing.

BACKGROUND: The Advanced Practice in Oncology Nursing Program was designed to prepare graduates to manage the cancer experience through the delivery of comprehensive, holistic, oncology-focused care to individuals, families, and communities in a variety of settings. METHODS: Theoretical course work and clinical practicum are required to complete the degree plan. Students are actively recruited from urban, rural, and underserved population settings. The program is committed to fostering a teaching-learning paradigm that facilitates self-directed learning. The program's basic tenet is that all course offerings will be designed in a distributed learning/distance learning method. Clinical experiences are accomplished in or near the student's home community. RESULTS: Development and implementation of the program are in process. Shaping a curriculum and learning environment to be consonant with a health care system in a constant state of reform flux is a challenging task. CONCLUSION: This program's long-term challenge is to remain flexible, collaborative, and futuristic while promoting the expansion of advanced practice in oncology nursing.

Nursing education to celebrate learning.

Institutions of higher education currently face a number of challenges, from the increasing diversity of students, a growing disparity between what society and what the university defines as its core mission, and society's transition from an industrial economy to an information economy. As part of such institutions, schools of nursing will need to consider a new "business design," which may include: new course formats that will keep groups of students together for several years in the same "learning communities"; use of Internet communications for projects and public exhibitions and defenses of results instead of the regular weekly scheduled class; offering programs for learning entrepreneurship, business practice, management, and leadership; and establishing programs for working professionals that promise, deliver, and certify specified competencies.

Intellectual property issues in the digital health care world.

The digitization of health care information presents a troublesome challenge to the two core principles of copyright: the expression of an idea should be rewarded and protected for a certain period and the user should be allowed the right to fair quotation during that period. The debate about intellectual property in a digital world will be a major focus over the next few years. Nursing administrators need to become copyright savvy to voice their concerns, protect nursing's works, and ensure that health care information is accessible for the public.

The learning collaboratory: a knowledge-building environment for nursing education.

As we approach the 21st century, higher education must face many challenges. One challenge is the transformation of education from a teacher-focused to a learner-centered model. To accomplish this learner-centered model, several learning strategies are proposed to create socially relevant, distributed, and modular courses. This project creates a Learning Collaboratory whose overall goals are to build a knowledge-building environment for students to learn about nursing and to serve as a future global model for nursing education and interdisciplinary coursework. To begin this transformation, the research sequence for the graduate program was selected as the first pilot. This paper describes the analysis, redesign and implementation of the existing research courses during the 1996-1997 academic year.

Computer mediated learning experiences spanning the globe: a pilot study between schools of nursing in the United States and the Netherlands.

The use of telecommunications in health care, education, and our daily lives has become a popular topic in both the professional and lay literature. The promise of the "Information Superhighway" and the expanded use of the Internet by other professionals have precipitated the examination of computer mediated communication as an instructional tool that transcends geographic boundaries and time barriers. This paper will discuss the development and implementation of a pilot project to foster collaborative learning experiences for nursing students between two schools of nursing in two different countries. The pilot is framed within the context of a Global Collaborative Learning Project in Nursing Informatics. A pilot project was initiated between the Schools of Nursing at the University of Colorado Health Sciences Center and the Hogeschool Holland during the 1994-95 academic year. Each school taught a nursing informatics course and assignments were designed to allow students from each school to participate in a collaborative learning experience. The presentation will highlight the outcomes of this pilot project and project future plans.

Combining telecommunications and interactive multimedia health information on the electronic superhighway.

This paper describes a unique system of providing health education in community-based settings. This project combines the structure of a telecommunications delivery system with the appeal of a colorful interactive educational program to produce a new type of "telemultimedia" program. Learners in two rural areas of Colorado can enter the electronic world of the information superhighway by way of the Denver Free-Net at The University Colorado Health Science Center in Denver; they can access The Healthy Touch Series of multimedia programs on maternal-infant health from The University of Texas Medical Branch in Galveston, Texas. This educational journey connects the learner with electronic devices in all three sites in a seamless interconnection of hardware and software. The journey was made possible by funding from The Colorado Trust and the W. K. Kellogg Foundation.