Ferritins: furnishing proteins with iron

Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores and examine in detail how three selected ferritins oxidise Fe2+ in order to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins

Surface and Temporal Biosignatures

Recent discoveries of potentially habitable exoplanets have ignited the prospect of spectroscopic investigations of exoplanet surfaces and atmospheres for signs of life. This chapter provides an overview of potential surface and temporal exoplanet biosignatures, reviewing Earth analogues and proposed applications based on observations and models. The vegetation red-edge (VRE) remains the most well-studied surface biosignature. Extensions of the VRE, spectral "edges" produced in part by photosynthetic or nonphotosynthetic pigments, may likewise present potential evidence of life. Polarization signatures have the capacity to discriminate between biotic and abiotic "edge" features in the face of false positives from band-gap generating material. Temporal biosignatures -- modulations in measurable quantities such as gas abundances (e.g., CO2), surface features, or emission of light (e.g., fluorescence, bioluminescence) that can be directly linked to the actions of a biosphere -- are in general less well studied than surface or gaseous biosignatures. However, remote observations of Earth's biosphere nonetheless provide proofs of concept for these techniques and are reviewed here. Surface and temporal biosignatures provide complementary information to gaseous biosignatures, and while likely more challenging to observe, would contribute information inaccessible from study of the time-averaged atmospheric composition alone.Comment: 26 pages, 9 figures, review to appear in Handbook of Exoplanets. Fixed figure conversion error

Effect of tamoxifen on hepatic regeneration in male rats

A number of metabolic changes within the liver occur concurrent with hepatic regeneration. These processes suggest that the administration of an antiestrogen might alter the rate of hepatic regeneration. To examine this question, male Wistar rats were treated with tamoxifen (0.1 mg/rat/day or 1.0 mg/rat/day) or vehicle for three days prior to and after partial hepatectomy, and the anatomic and biochemical process of hepatic regeneration was assessed. Tamoxifen administration caused a dose-dependent decrease in the hepatic cytosolic estrogen receptor activity and, conversely, a dose-dependent increase in cytosolic androgen receptor activity. Despite these changes in baseline hepatic sex steroid receptor status, all receptor activities were comparable between the three groups within 24 hr of partial hepatectomy. Moreover, no differences in any of the the parameters assessing hepatic regeneration following partial hepatectomy were evident: liver-body ratio, ornithine decarboxylase activity, and thymidine kinase activity. This lack of effect of tamoxifen treatment on hepatic regeneration suggests either that estrogens do not play a role in the modulation of liver growth after partial hepatectomy or that, once initiated, the regenerative process per se determines a series of events that regulate hepatocellular sex hormone receptor status independent of extrahepatic stimuli. © 1989 Plenum Publishing Corporation

Enrichment of Sialylated IgG by Lectin Fractionation Does Not Enhance the Efficacy of Immunoglobulin G in a Murine Model of Immune Thrombocytopenia

Intravenous immunoglobulin G (IVIg) is widely used against a range of clinical symptoms. For its use in immune modulating therapies such as treatment of immune thrombocytopenic purpura high doses of IVIg are required. It has been suggested that only a fraction of IVIg causes this anti immune modulating effect. Recent studies indicated that this fraction is the Fc-sialylated IgG fraction. The aim of our study was to determine the efficacy of IVIg enriched for sialylated IgG (IVIg-SA (+)) in a murine model of passive immune thrombocytopenia (PIT). We enriched IVIg for sialylated IgG by Sambucus nigra agglutinin (SNA) lectin fractionation and determined the degree of sialylation. Analysis of IVIg-SA (+) using a lectin-based ELISA revealed that we enriched predominantly for Fab-sialylated IgG, whereas we did not find an increase in Fc-sialylated IgG. Mass spectrometric analysis confirmed that Fc sialylation did not change after SNA lectin fractionation. The efficacy of sialylated IgG was measured by administering IVIg or IVIg-SA (+) 24 hours prior to an injection of a rat anti-mouse platelet mAb. We found an 85% decrease in platelet count after injection of an anti-platelet mAb, which was reduced to a 70% decrease by injecting IVIg (p<0.01). In contrast, IVIg-SA (+) had no effect on the platelet count. Serum levels of IVIg and IVIg-SA (+) were similar, ruling out enhanced IgG clearance as a possible explanation. Our results indicate that SNA lectin fractionation is not a suitable method to enrich IVIg for Fc-sialylated IgG. The use of IVIg enriched for Fab-sialylated IgG abolishes the efficacy of IVIg in the murine PIT model

Perinatal Tobacco Smoke Exposure Increases Vascular Oxidative Stress and Mitochondrial Damage in Non-Human Primates

Epidemiological studies suggest that events occurring during fetal and early childhood development influence disease susceptibility. Similarly, molecular studies in mice have shown that in utero exposure to cardiovascular disease (CVD) risk factors such as environmental tobacco smoke (ETS) increased adult atherogenic susceptibility and mitochondrial damage; however, the molecular effects of similar exposures in primates are not yet known. To determine whether perinatal ETS exposure increased mitochondrial damage, dysfunction and oxidant stress in primates, archived tissues from the non-human primate model Macaca mulatta (M. mulatta) were utilized. M. mulatta were exposed to low levels of ETS (1 mg/m3 total suspended particulates) from gestation (day 40) to early childhood (1 year), and aortic tissues were assessed for oxidized proteins (protein carbonyls), antioxidant activity (SOD), mitochondrial function (cytochrome oxidase), and mitochondrial damage (mitochondrial DNA damage). Results revealed that perinatal ETS exposure resulted in significantly increased oxidative stress, mitochondrial dysfunction and damage which were accompanied by significantly decreased mitochondrial antioxidant capacity and mitochondrial copy number in vascular tissue. Increased mitochondrial damage was also detected in buffy coat tissues in exposed M. mulatta. These studies suggest that perinatal tobacco smoke exposure increases vascular oxidative stress and mitochondrial damage in primates, potentially increasing adult disease susceptibility

Development and preliminary validation of a Greek-language outpatient satisfaction questionnaire with principal components and multi-trait analyses

BACKGROUND: In the recent years there is a growing interest in Greece concerning the measurement of the satisfaction of patients who are visiting the outpatient clinics of National Health System (NHS) general acute hospitals. The aim of this study is therefore to develop a patient satisfaction questionnaire and provide its preliminary validation. METHODS: A questionnaire in Greek has been developed by literature review, researchers' on the spot observation and interviews. Pretesting has been followed by telephone surveys in two short-term general NHS hospitals in Macedonia, Greece. A proportional stratified random sample of 285 subjects and a second random sample of 100 outpatients, drawn on March 2004, have been employed for the analysis. These have resulted in scale creation via Principal Components Analysis and psychometric testing for internal consistency, test-retest and interrater reliability as well as construct validity. RESULTS: Four summated scales have emerged regarding the pure outpatient component of the patients' visits, namely medical examination, hospital environment, comfort and appointment time. Cronbach's alpha coefficients and Pearson, Spearman and intraclass correlations indicate a high degree of scale reliability and validity. Two other scales -lab appointment time and lab experience- capture the apparently distinct yet complementary visitor experience related to the radiographic and laboratory tests. Psychometric tests are equally promising, however, some discriminant validity differences lack statistical significance. CONCLUSION: The instrument appears to be reliable and valid regarding the pure outpatient experience, whereas more research employing larger samples is required in order to establish the apparent psychometric properties of the complementary radiographic and laboratory-testing process, which is only relevant to about 25% of the subjects analysed here

Patient satisfaction in an acute medicine department in Morocco

<p>Abstract</p> <p>Background</p> <p>Patients' satisfaction is an important indicator for quality of care. Measuring healthcare quality and improving patient satisfaction have become increasingly prevalent, especially among healthcare providers and purchasers of healthcare. This is mainly due to the fact that consumers are becoming increasingly more knowledgeable about healthcare. No studies of inpatients' satisfaction with hospital care have been conducted in Morocco. The first objective of the present study was to confirm the reliability and validity of the Arabic version of the EQS-H (Echelle de Qualité des Soins en Hospitalisation). The second objective was to evaluate patient satisfaction in an acute medicine department in Morocco by using the EQS-H questionnaire; and also to assess the influence of certain demographics, socioeconomics, and health characteristics in patient satisfaction.</p> <p>Methods</p> <p>it was a patient survey conducted in an acute medicine department of a Moroccan University Hospital. We surveyed their socio demographic status, and health characteristics at admission. We performed structured face to face interviews with patients who were discharged from hospital. The core of the EQS-H questionnaire was translated to Arabic, adapted to the present setting, and then used to measure patient satisfaction with quality of care. The internal consistency of the EQS-H scale was assessed by Chronbach's coefficient alpha. Validity was assessed by factor analysis. Factors influencing inpatients' satisfaction were identified using multiple linear regression.</p> <p>Results</p> <p>The Arabic version of EQS-H demonstrated an excellent internal consistency for the two dimensions studied (0.889 for 'quality of medical information' (MI) and 0.906 for 'Relationship with staff and daily routine' (RS)). The principal component analysis confirmed the bidimensional structure of the questionnaire and explained 60% of the total variance. In the univariate analysis, urban residence, higher income, better perceived health status compared to admission, better perceived health status compared to people of the same age, and satisfaction with life in general were related to MI dimension; Otherwise, mal gender, urban residence, higher income, staying in double room, better perceived health status compared to admission, and satisfaction with life in general were related to RS dimension. The multiple linear regression showed that four independent variables were associated with higher satisfaction in MI: More than 2 prior hospitalizations, a longer length of stay (10-14 days) (<it>P </it>= 0.002), staying in double room (<it>P </it>= 0.022), and better perceived health status compared to admission (<it>P </it>= 0.036). Three independent variables were associated with higher satisfaction in RS: a longer length of stay (10-14 days) (<it>P </it>= 0.017), better perceived health status compared to admission day (<it>P </it>= 0.013), and satisfaction with life in general (<it>P </it>= 0.006).</p> <p>Conclusions</p> <p>Our current data assessing patient satisfaction with acute health care by the Arabic version of the EQS-H showed that the satisfaction rate was average on MI dimension; and good on RS dimension of the questionnaire. The majority of participants were satisfied with the overall care. Demographic, socioeconomic, and health characteristics may influence in-patients satisfaction in Morocco, a low/middle income country. An appreciation and understanding of these factors is essential to develop socio culturally appropriate interventions in order to improve satisfaction of patients.</p

Mutation Accumulation May Be a Minor Force in Shaping Life History Traits

Is senescence the adaptive result of tradeoffs between younger and older ages or the nonadaptive burden of deleterious mutations that act at older ages? To shed new light on this unresolved question we combine adaptive and nonadaptive processes in a single model. Our model uses Penna's bit-strings to capture different age-specific mutational patterns. Each pattern represents a genotype and for each genotype we find the life history strategy that maximizes fitness. Genotypes compete with each other and are subject to selection and to new mutations over generations until equilibrium in gene-frequencies is reached. The mutation-selection equilibrium provides information about mutational load and the differential effects of mutations on a life history trait - the optimal age at maturity. We find that mutations accumulate only at ages with negligible impact on fitness and that mutation accumulation has very little effect on the optimal age at maturity. These results suggest that life histories are largely determined by adaptive processes. The non-adaptive process of mutation accumulation seems to be unimportant at evolutionarily relevant ages

A systematic review of economic analyses of telehealth services using real time video communication

Background: Telehealth is the delivery of health care at a distance, using information and communication technology. The major rationales for its introduction have been to decrease costs, improve efficiency and increase access in health care delivery. This systematic review assesses the economic value of one type of telehealth delivery - synchronous or real time video communication - rather than examining a heterogeneous range of delivery modes as has been the case with previous reviews in this area. Methods A systematic search was undertaken for economic analyses of the clinical use of telehealth, ending in June 2009. Studies with patient outcome data and a non-telehealth comparator were included. Cost analyses, non-comparative studies and those where patient satisfaction was the only health outcome were excluded. Results 36 articles met the inclusion criteria. 22(61%) of the studies found telehealth to be less costly than the non-telehealth alternative, 11(31%) found greater costs and 3 (9%) gave the same or mixed results. 23 of the studies took the perspective of the health services, 12 were societal, and one was from the patient perspective. In three studies of telehealth to rural areas, the health services paid more for telehealth, but due to savings in patient travel, the societal perspective demonstrated cost savings. In regard to health outcomes, 12 (33%) of studies found improved health outcomes, 21 (58%) found outcomes were not significantly different, 2(6%) found that telehealth was less effective, and 1 (3%) found outcomes differed according to patient group. The organisational model of care was more important in determining the value of the service than the clinical discipline, the type of technology, or the date of the study. Conclusion Delivery of health services by real time video communication was cost-effective for home care and access to on-call hospital specialists, showed mixed results for rural service delivery, and was not cost-effective for local delivery of services between hospitals and primary care