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Surface dielectric constant, surface hydrophobicity and membrane fusion.

Membrane fusion induced by ions and its associated membrane property, surface dielectric constant, were studied with the use of acidic and neutral phospholipid vesicles. The fusion of vesicles was monitored by utilizing two fluorescence fusion assays: fluorescence content mixing method and fluorescence labelled membrane component dilution method. For the surface dielectric constant measurements, a fluorescence method was used which detected the environmental effect on the membrane surface upon the addition of various fusogenic cations. Also, the effects of poly-(ethylene glycol) on both fusion and surface dielectric properties were examined. It was found that the extent of fusion correlated well with the degree of lowering in the dielectric constant of the surface membrane, which corresponds to the increase in hydrophobicity of the membrane surface. This agrees with the previously obtained experimental results that the increase in interfacial tension of the membrane, which also corresponds to the increase in surface hydrophobicity, correlates with the extent of membrane fusion.

Calcium↗

[On the proof of MN-differentiation from blood samples (author's transl)].

1. The results of MN testing are--so far as the factor N is concerned--especially in the case of older samples to be used only with caution. 2. The provision for a reliable result demands several good sera that have been previously used in testing and found to be satisfactory. 3. It is especially necessary to work with two different methods. The mixed agglutination method is no longer reliable in cases of months-old or very dryly stored samples.

Blood Stains↗

GIS-based support tool system for decision-making regarding local forest protection: illustrations from Orissa, India.

A support tool system comprising risk and priority analyses was illustrated in a geographical information system environment and also tested with data from two forest protection areas for comparison of the system output. The system is recommended as a management monitoring tool for areas where village forest protection at a local level is taking place. The geographical area in the eastern part of India is subject to scarcity of forest resources and is representative in the context of widespread occurrence of local forest protection. Data used were topography, hectares protected, population census, distance to forest and other villages, degree of forest regeneration, presence of plantations, age of protection, surrounding forest resources, and population mix. Methods used were digitizing information for the systems' different layers, analyses of satellite information, field work, gathering of local information, and the application of five risk/priority analyses: erosion, ecological and institutional sustainability, conflict, and degree of dependency. Questions asked were how the different analyses should be interpreted and how the system could be kept updated. The results show that the system needs resource-demanding and field assistance to be kept dynamic. The system is also dependent on the interpretations of the analyses. The limits or levels of assistance for forest management depend on the resources available. The system illustrates how a tool can be utilized for decisions regarding input of resources. It can further be very useful in defining and comparing different areas in order to detect areas in need of assistance and the type of help needed.

Conservation of Natural Resources↗

A new approach to the solution of the linear mixing model for a single isotope: application to the case of an opportunistic predator.

Mixing models are used to determine diets where the number of prey items are greater than one, however, the limitation of the linear mixing method is the lack of a unique solution when the number of potential sources is greater than the number (n) of isotopic signatures +1. Using the IsoSource program all possible combinations of each source contribution (0-100%) in preselected small increments can be examined and a range of values produced for each sample analysed. We propose the use of a Moore Penrose (M-P) pseudoinverse, which involves the inverse of a 2x2 matrix. This is easily generalized to the case of a single isotope with (p) prey sources and produces a specific solution. The Antarctic leopard seal (Hydrurga leptonyx) was used as a model species to test this method. This seal is an opportunistic predator, which preys on a wide range of species including seals, penguins, fish and krill. The M-P method was used to determine the contribution to diet from each of the four prey types based on blood and fur samples collected over three consecutive austral summers. The advantage of the M-P method was the production of a vector of fractions f for each predator isotopic value, allowing us to identify the relative variation in dietary proportions. Comparison of the calculated fractions from this method with 'means' from IsoSource allowed confidence in the new approach for the case of a single isotope, N.

Animals↗

Benefit-finding among patients with rheumatoid arthritis: positive effects on interpersonal relationships.

This longitudinal study of patients with rheumatoid arthritis used mixed methods to identify and describe the positive effects of illness on relationships, examine correlates of benefit-finding, and test the relationship between benefit-finding and adjustment outcomes. When asked about interpersonal benefits of their illness, 71.3% of the respondents described interpersonal benefits, whereas 16.2% reported another type of benefit, and 12.5% reported no benefits. The most frequently described benefit was appreciation of support received from loved ones. Less pain, lower psychological distress, and perceiving fewer social constraints were related to finding interpersonal benefits in the illness experience. Interpersonal benefit-finding predicted lower levels of disability at a 12-month follow-up. Findings are discussed with regard to conceptual issues, methodological recommendations, and implications for interventions.

Arthritis, Rheumatoid↗

Neighborhood influences and intimate partner violence: does geographic setting matter?

Intimate partner violence is one health-related outcome that has received growing attention from those interested in the role of neighborhood context. A limitation of existing contextual health research is its' failure to look beyond urban settings. Because suburban and rural areas have received so little attention, it is not clear whether data generated from urban samples can be generalized to non-urban geographic settings. We began to explore this issue using concept mapping, a participatory, mixed method approach. Data from 37 urban and 24 suburban women are used to explore and compare perceptions of neighborhood characteristics related to intimate partner violence. While several similarities exist between the perceptions of participants residing in urban and suburban areas, some differences were uncovered. These results provide valuable information regarding the perceived relationship between neighborhood context and intimate partner violence and suggest future avenues for research interested in examining the role of geographic setting.

Adult↗

Tissue engineering heart valves: valve leaflet replacement study in a lamb model.

BACKGROUND: Valve replacements using either bioprosthetic or mechanical valves have the disadvantage that these structures are unable to grow, repair, or remodel and are both thrombogenic and susceptible to infection. These characteristics have significantly limited their durability and longevity. In an attempt to begin to overcome these shortcomings, we have tested the feasibility of constructing heart valve leaflets in lambs by seeding a synthetic polyglycolic acid fiber matrix in vitro with fibroblasts and endothelial cells. METHODS: Mixed cell populations of endothelial cells and fibroblasts were isolated from explanted ovine arteries. Endothelial cells were selectively labeled with an acetylated low-density lipoprotein marker and separated from the fibroblasts using a fluorescent activated cell sorter. A synthetic biodegradable scaffold constructed from polyglycolic acid fibers was seeded with fibroblasts, which grew to form a tissue-like sheet. This tissue was subsequently seeded with endothelial cells, which formed a cellular monolayer coating around the leaflet. Using these constructs, autologous (n = 3) and allogenic (n = 4) tissue engineered leaflets were implanted in 7 animals. In each animal the right posterior leaflet of the pulmonary valve was resected and replaced with an engineered valve leaflet. RESULTS: All animals survived the procedure. Postoperative echocardiography demonstrated no evidence of stenosis and trivial pulmonary regurgitation in the autografts and moderate regurgitation in the allogenic valves. Collagen analysis of the constructs showed development of an extracellular matrix. Histologic evaluation of the constructs demonstrated appropriate cellular architecture. CONCLUSIONS: This preliminary experiment showed that a tissue engineered valve leaflet constructed from its cellular components can function in the pulmonary valve position. Tissue engineering of a heart valve leaflet is feasible, and these preliminary studies suggest that autograft tissue will probably be superior to allogenic tissue.

Animals↗

Interactions of histones and histone peptides with DNA Thermal denaturation and solubility studies.

The interactions of DNA with the five histone components (H1, H2B, H2A, H3 and H4) and with a number of histone fragments (N-H1 (1--72), C-H1 (73--216), N-H2B (l--59), C-H2B, (63--125), N-H2A (1-39), C-H2A (58--129), N-H4 (1--84) and C-H4 (85--102) have been studied by using the techniques of thermal denaturation and solubility behaviour. Complexes in 10(-3) M phosphate buffer, 2 - 10(-5) M Na(2)-EDTA, pH 7.0 were prepared by the direct mixing method. For lysine-rich histones (H1 and H2B) it has been found that the main characteristics which governs the interaction with DNA are located in the very lysine-rich part of the molecules, i.e. in the C-H1 and N-H2B segments. These regions are also responsible for a cooperative distribution of the histone along the DNA molecules in the artificial complexes. It appears from our studies that the tertiary structure of the moderately, arginine-rich histone (H2A) is an essential feature for its interaction with DNA. The two arginine-rich histones (H3 and H4) complexed with DNA behave in a similar way, both in thermal denaturation and in DNA precipitation. In the case of C-H4, a marked shift of the melting profile has been observed which is correlated with the presence in the peptide of the hydrophilic cluster Lys-Arg-Gln-Gly-Arg-Thr. Our results suggest that large segments rich in lysine and basic clustering within histones give rise to different modes of electrostatic interaction with DNA.

Animals↗

Blood oxygen affinity in high- and low-altitude populations of the deer mouse.

There is little solid evidence for specific genetic adaptations in animal populations native to high altitude. There is also continuing debate over what oxygen transport characteristics are truly adaptive at high altitude. We have attempted to elucidate both problems through population genetic and physiological studies of the deer mouse, Peromyscus maniculatus. That species is noteworthy because it inhabits the widest range of altitudes of any North American mammal, and it shows a high degree of genetic variation in hemoglobins. Deer mice were collected from 35 populations representing ten nominal subspecies covering a broad geographical range of the United States. The mice were acclimated to low altitude (340 m); then a mixing method was used to determine P50 and other blood gas parameters on samples pooled from individuals of representative hemoglobin genotypes. When the data from all subspecies wee combined, there was a highly significant negative correlation between P50 and the native altitude of the population. Tests on progeny reared at low altitude indicated that the differences in P50 were primarily genetic. Part of the clinal variation in P50 could be attributed to 2,3-DPG effects; high-altitude populations showed lower baseline DPG/Hb ratios. Surprisingly, within those subspecies which inhabit a wide range of altitudes, there was no correlation between P50 and native altitude. Our tentative conclusion from these data and data presented elsewhere is that deer mouse populations do show genetic adaptations to high altitude. However, because of gene exchange between populations, the genetic characteristics of a population reflect the average altitude over a relatively broad geographic area.

2,3-Diphosphoglycerate↗

Adjusting planning guidelines for cardiac-care units.

The principal concern of this paper is the development of procedures for adjusting the criteria currently being used for federally-legislated health planning activities. These procedures would enable the planner to account for the demographic, geographic and health-system conditions which cause variations in the need for health-care services in local communities. A case-mix method, hospital chart abstract data and demographic, geographic and health-system data from New Jersey were used to: create a list of diagnoses eligible for treatment in a Cardiac-Care Unit (CCU): select a sample of hospitals for study, and conduct a step-wise regression analysis of CCU utilization in these hospitals. It was concluded that CCU utilization was affected by factors such as the in-hospital availability of CCu beds, the type of hospital, CCU-patients' clinical severity, and the availability of ambulances and mobile intensive care units. Procedure for adjusting planning criteria to account for local conditions have yet to be developed. However, a method for using the types of results presented in this paper to develop such adjustment procedures was presented and illustrated. It is recommended that this method be used to create such adjustment procedures for the planning criteria for all hospital services and hence to assist Health Systems Agencies in rationalizing the distribution of our hospital care.

Coronary Care Units↗

Correlation of immunoreactivity and polymer formation to DTPA modification of a monoclonal antibody.

The protocol used for coupling of monoclonal antibodies with mixed anhydride of DTPA for subsequent radiolabeling with indium-111 affects the integrity of the immunoreactivity of the antibody preparations. To analyze the effect of minor methodological variations on coupling characteristics, a two-step addition of DTPA to antimyosin antibody with gentle mixing was compared to a single addition with vigorous stirring. The molar ratios of DTPA to antibody were also varied. The polymer formation was assessed by SDS-PAGE and immunoreactivity was assessed by solid phase radioimmunoassay using human heart myosin as the antigen. The immunoreactivity was significantly decreased in the two-step, gentle-mixing method where polymer formation was evident. The one-step, vigorous-stirring method of DTPA incorporation produced no polymerization and no loss of immunoreactivity.

Antibodies, Monoclonal↗

Examining gaps in institutional policies for clinical genomic data sharing: A cross-jurisdictional study.

The sharing of data generated by clinical genetic and genomic testing without explicit consent is important for timely diagnosis and treatment. While many jurisdictions permit the sharing of identifiable data for direct clinical care, institutional policies vary in how clearly they specify key elements, including when sharing is permitted, what data are covered, and what safeguards apply. Greater clarity around these elements may support responsible data sharing while balancing timely care with transparency and appropriate protections. We conducted a mixed-methods content analysis of data-sharing and privacy policies from 33 clinical genomic institutions across 17 countries and regions. Using a predefined analytical framework, we assessed how policies document key governance elements relevant to sharing without explicit consent. Two independent reviewers extracted information about clinical contexts, data types, justifications, and protections. Although 70% of institutions described circumstances permitting data sharing without explicit consent, most policies did not clearly define the scope or governance of such sharing. Policies also rarely distinguished clinical from research or secondary use and inconsistently specified privacy and security safeguards. While sharing was commonly justified for clinical care (78.3%) or testing services (43.5%), data recipient roles and onward-sharing expectations were often left undefined. This uneven documentation could make it difficult for clinical teams and institutional decision-makers to identify and justify decisions about what is permitted and under what conditions. A guidance framework specifying core governance elements and corresponding protections could help institutions communicate their governance choices more clearly and support comparable baseline practices for responsible data sharing.

Information Dissemination↗

Evaluation of a community health promotion resource for primary care practices.

BACKGROUND: Primary care physicians' ability to provide effective health behavior change advice might be leveraged by linking to available community resources. This study evaluates tools to facilitate such a link. DESIGN: A mixed methods longitudinal pre-post-test study was conducted in 2004. SETTING/ PARTICIPANTS: Seven primary care practices in northeast Ohio and two longitudinal cohorts of patients (n=784). INTERVENTION: The practice-tailored intervention included two main components: (1) a web-based health behavior change resource including a database of community programs and patient education materials, and (2) a health behavior prescription pad. MAIN OUTCOME MEASURES: Rates of discussion of diet, exercise, weight management, and smoking cessation; and patient change in motivation to modify behaviors at 8 weeks post-visit. Qualitative field notes about practice routines, culture, and implementation efforts were analyzed to enhance understanding of the practice change process. RESULTS: The post-intervention cohort reported higher rates of discussion of diet (25.7% vs 20.2%), exercise (27.8% vs 16.9%), and weight management (23.2% vs 16.3%), and greater referral to patient education materials (24.2% vs 21.6%) and community programs for health behavior change (16.0% vs 13.6%) (p<0.05). No difference in change in patient motivation to modify behavior was observed between the pre- and post-intervention cohorts. Evaluation of the qualitative field notes suggests that for six of seven practices, the intervention was not appreciably implemented. CONCLUSIONS: The intervention tools show promise for increasing clinician discussion of health behaviors, information referral, and referral to community resources. Additional work to increase practice adoption of the tools is required to understand their potential to affect patient motivation to change behavior.

Adult↗

On-pump versus off-pump surgical revascularization for left main stem stenosis: risk adjusted outcomes.

BACKGROUND: Recent publications have shown coronary surgery is safe and effective in patients with critical left main stem stenosis when using off-pump coronary surgery techniques. However, these studies were small and did not adjust for differences in case mix. METHODS: Between April 1997 and March 2003, 1,197 consecutive patients with critical left main stem stenosis (> 50%) underwent coronary surgery. Two hundred and fifty-nine (21.6%) of these patients had off-pump coronary surgery, while 938 (78.4%) received on-pump coronary surgery. Multivariate logistic regression and Cox proportional hazards analysis were used to assess the effect of off-pump coronary surgery on outcomes, while adjusting for patient characteristics (treatment selection bias). Treatment selection bias was controlled by constructing a propensity score from core patient characteristics. The propensity score was the probability of receiving off-pump coronary surgery and was included along with the comparison variable in the multivariable analyses of outcome. RESULTS: After adjusting for the propensity score, the requirement for inotropic support (22.4% versus 35.3%; p < 0.001) or a prolonged length of stay (5.3% versus 9.3%; p = 0.034) were significantly reduced after receiving off-pump coronary surgery. There was a trend to suggest that off-pump patients had a lower incidence of stroke and chest infection. The adjusted freedom from death in off-pump patients at 2 years was 94.6% compared with 93.6% for on-pump patients (p = 0.54). CONCLUSIONS: After risk adjustment, patients with critical left main stem stenosis can undergo off-pump coronary surgery safely, with results comparable with on-pump coronary surgery.

Aged↗

Identification of new small non-coding RNAs from tobacco and Arabidopsis.

Small non-coding RNAs (ncRNAs) have typically been searched in fully sequenced genomes using one of two approaches-experimental or computational. We developed a mixed method, using both types of information, which has the advantage of applying bio-computing methods to actually expressed sequences. Our method allowed the identification of new small ncRNAs in Arabidopsis thaliana and in the unfinished genome of Nicotiana tabacum. We constructed a N. tabacum cDNA library from small RNAs ranging from 20 to 30 nucleotides (nt). The sequences from 73 unique clones were compared to the A. thaliana genome and to all plant sequences using a pattern-matching approach (program Patbank). Thus, we selected 15 clones from the library corresponding mostly to A. thaliana or N. tabacum non-coding sequences. By Northern blot analyses, we confirmed the presence of most RNA candidates in Arabidopsis and in Nicotiana sylvestris with a size range of 21-100 nt. To gain more insight into the possible genesis of 21-24 nt sequences, stable folding of sRNAs with their flanking regions were predicted with the software MIRFOLD dedicated to the folding of microRNAs (miRNA). Stable hairpins structures were observed for some putative miRNAs.

Arabidopsis↗

Microstructure and mechanical properties of plasma sprayed HA/YSZ/Ti-6Al-4V composite coatings.

Plasma sprayed hydroxyapatite (HA) coatings on titanium alloy substrate have been used extensively due to their excellent biocompatibility and osteoconductivity. However, the erratic bond strength between HA and Ti alloy has raised concern over the long-term reliability of the implant. In this paper, HA/yttria stabilized zirconia (YSZ)/Ti-6Al-4V composite coatings that possess superior mechanical properties to conventional plasma sprayed HA coatings were developed. Ti-6Al-4V powders coated with fine YSZ and HA particles were prepared through a unique ceramic slurry mixing method. The so-formed composite powder was employed as feedstock for plasma spraying of the HA/YSZ/Ti-6Al-4V coatings. The influence of net plasma energy, plasma spray standoff distance, and post-spray heat treatment on microstructure, phase composition and mechanical properties were investigated. Results showed that coatings prepared with the optimum plasma sprayed condition showed a well-defined splat structure. HA/YSZ/Ti-6Al-4V solid solution was formed during plasma spraying which was beneficial for the improvement of mechanical properties. There was no evidence of Ti oxidation from the successful processing of YSZ and HA coated Ti-6Al-4V composite powders. Small amount of CaO apart from HA, ZrO(2) and Ti was present in the composite coatings. The microhardness, Young's modulus, fracture toughness, and bond strength increased significantly with the addition of YSZ. Post-spray heat treatment at 600 degrees C and 700 degrees C for up to 12h was found to further improve the mechanical properties of coatings. After the post-spray heat treatment, 17.6% increment in Young's modulus (E) and 16.3% increment in Vicker's hardness were achieved. The strengthening mechanisms of HA/YSZ/Ti-6Al-4V composite coatings were related to the dispersion strengthening by homogeneous distribution of YSZ particles in the matrix, the good mechanical properties of Ti-6Al-4V and the formation of solid solution among HA, Ti alloy and YSZ components.

Aerosols↗

Discovery of galectin ligands in fully randomized combinatorial one-bead-one-compound (glyco)peptide libraries.

The involvement of human lectins (galectins) in disease progression accounts for the interest to design potent inhibitors. Three fully randomized hexa(glyco)peptide libraries were prepared using the portion mixing method combined with ladder synthesis. On-bead screening with fluorescently labelled galectin-1 and -3 yielded a series of lead structures, whose inhibitory activity on carbohydrate-dependent galectin binding was tested in solution by solid-phase and cell assays. The various data obtained define the library approach as a facile route for the discovery of selective (glyco)peptide-based galectin inhibitors.

Cell Line, Tumor↗

Complementary and alternative medicine whole systems research: beyond identification of inadequacies of the RCT.

Complementary and alternative medicine (CAM) often consists of whole systems of care (such as naturopathic medicine or traditional Chinese medicine (TCM)) that combine a wide range of modalities to provide individualised treatment. The complexity of these interventions and their potential synergistic effect requires innovative evaluative approaches. Model validity, which encompasses the need for research to adequately address the unique healing theory and therapeutic context of the intervention, is central to whole systems research (WSR). Classical randomised controlled trials (RCTs) are limited in their ability to address this need. Therefore, we propose a mixed methods approach that includes a range of relevant and holistic outcome measures. As the individual components of most whole systems are inseparable, complementary and synergistic, WSR must not focus only on the "active" ingredients of a system. An emerging WSR framework must be non-hierarchical, cyclical, flexible and adaptive, as knowledge creation is continuous, evolutionary and necessitates a continuous interplay between research methods and "phases" of knowledge. Finally, WSR must hold qualitative and quantitative research methods in equal esteem to realize their unique research contribution. Whole systems are complex and therefore no one method can adequately capture the meaning, process and outcomes of these interventions.

Complementary Therapies↗