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Background

We have showed that secretory Apolipoprotein J/Clusterin (sCLU) is down-regulated in senescent, stressed or diseased red blood cells (RBCs). It was hypothesized that sCLU loss relates to RBCs vesiculation, a mechanism that removes erythrocyte membrane patches containing defective or potentially harmful components.

Methodology/Principal Findings

To investigate this issue we employed a combination of biochemical and microscopical approaches in freshly prepared RBCs or RBCs stored under standard blood bank conditions, an in vitro model system of cellular aging. We found that sCLU is effectively exocytosed in vivo during membrane vesiculation of freshly prepared RBCs. In support, the RBCs'' sCLU content was progressively reduced during RBCs ex vivo maturation and senescence under cold storage due to its selective exocytosis in membrane vesicles. A range of typical vesicular components, also involved in RBCs senescence, like Band 3, CD59, hemoglobin and carbonylated membrane proteins were found to physically interact with sCLU.

Conclusions/Significance

The maturation of RBCs is associated with a progressive loss of sCLU. We propose that sCLU is functionally involved in the disposal of oxidized/defected material through RBCs vesiculation. This process most probably takes place through sCLU interaction with RBCs membrane proteins that are implicit vesicular components. Therefore, sCLU represents a pro-survival factor acting for the postponement of the untimely clearance of RBCs.  相似文献   

4.

Introduction

Breast feeding has long term effects on the developing immune system which outlive passive immunization of the neonate. We have investigated the transfer of milk immune cells and examined the result of transfer once the recipients were adult.

Methods

Non-transgenic mouse pups were foster-nursed by green fluorescent protein (GFP) transgenic dams for 3 weeks and the fate of GFP+ cells was followed by FACS analysis, immunohistochemistry and RT-PCR for GFP and appropriate immune cell markers. Pups suckled by non-transgenic dams served as controls.

Results

Despite a preponderance of B cells and macrophages in the stomach contents of the pups, most cells undergoing trans-epithelial migration derived from the 3–4% of milk cells positive for T lymphocyte markers. These cells homed to the spleen and thymus, with maximal accumulation at 3–4 weeks. By sensitizing dams with an antigen which elicits a T cell-mediated delayed-type-hypersensitivity (DTH) response, we determined that nursing by a sensitized dam (compared to a non-sensitized dam) amplified a subsequent DTH response in females and yet suppressed one in males.

Discussion

These results suggest that clinical evaluation weighing the pros and cons of nursing male versus female children by mothers with genetically-linked hypersensitivity diseases, such as celiac disease and eczema, or those in regions of the world with endemic DTH-eliciting diseases, such as tuberculosis, may be warranted.  相似文献   

5.

Background

Epidemiological studies suggest an association between exposure to volatile organic compounds (VOCs) and adverse allergic and respiratory symptoms. However, whether VOCs exhibit a causal role as adjuvants in asthma development remains unclear.

Methods

To investigate the effect of VOC exposure on the development of allergic airway inflammation Balb/c mice were exposed to VOCs emitted by new polyvinylchloride (PVC) flooring, sensitized with ovalbumin (OVA) and characterized in acute and chronic murine asthma models. Furthermore, prevalent evaporated VOCs were analyzed and mice were exposed to selected single VOCs.

Results

Exposure of mice to PVC flooring increased eosinophilic lung inflammation and OVA-specific IgE serum levels compared to un-exposed control mice. The increased inflammation was associated with elevated levels of Th2-cytokines. Long-term exposure to PVC flooring exacerbated chronic airway inflammation. VOCs with the highest concentrations emitted by new PVC flooring were N-methyl-2-pyrrolidone (NMP) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB). Exposure to NMP or TXIB also increased the allergic immune response in OVA-sensitized mice. In vitro or in vivo exposure to NMP or TXIB reduced IL-12 production in maturing dendritic cells (DCs) and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. At higher concentrations both VOCs induced oxidative stress demonstrated by increased isoprostane and glutathione-S-transferase-pi1 protein levels in the lung of non-sensitized mice. Treatment of PVC flooring-exposed mice with N-acetylcysteine prevented the VOC-induced increase of airway inflammation.

Conclusions

Our results demonstrate that exposure to VOCs may increase the allergic immune response by interfering with DC function and by inducing oxidative stress and has therefore to be considerate as risk factor for the development of allergic diseases.  相似文献   

6.

Background

The essence of psychological support provided to oncology patients is to adjust its methods to the needs and expectations arising from the distressful experience of cancer and its treatment.

Aim

The aim of this study is to present methods of professional psychological support to be used in work with oncology patients during the treatment and follow-up stages.

Materials and methods

The article is a review of psychological and psychotherapy methods most often applied to oncology patients.

Conclusion

Methods of psychological support depend on the current condition of a patient. The support will be effective if provided in adequate time and place with the patient''s express consent and in line with their individual needs and expectations.  相似文献   

7.

Background

Increasing patient engagement in healthcare has become a health policy priority. However, there has been concern that promoting supported shared decision-making could increase health inequalities.

Objective

To evaluate the impact of SDM interventions on disadvantaged groups and health inequalities.

Design

Systematic review and meta-analysis of randomised controlled trials and observational studies.

Data Sources

CINAHL, the Cochrane Register of Controlled Trials, the Cochrane Database of Systematic Reviews, EMBASE, HMIC, MEDLINE, the NHS Economic Evaluation Database, Open SIGLE, PsycINFO and Web of Knowledge were searched from inception until June 2012.

Study Eligibility Criteria

We included all studies, without language restriction, that met the following two criteria: (1) assess the effect of shared decision-making interventions on disadvantaged groups and/or health inequalities, (2) include at least 50% of people from disadvantaged groups, except if a separate analysis was conducted for this group.

Results

We included 19 studies and pooled 10 in a meta-analysis. The meta-analyses showed a moderate positive effect of shared decision-making interventions on disadvantaged patients. The narrative synthesis suggested that, overall, SDM interventions increased knowledge, informed choice, participation in decision-making, decision self-efficacy, preference for collaborative decision making and reduced decisional conflict among disadvantaged patients. Further, 7 out of 19 studies compared the intervention''s effect between high and low literacy groups. Overall, SDM interventions seemed to benefit disadvantaged groups (e.g. lower literacy) more than those with higher literacy, education and socioeconomic status. Interventions that were tailored to disadvantaged groups'' needs appeared most effective.

Conclusion

Results indicate that shared decision-making interventions significantly improve outcomes for disadvantaged patients. According to the narrative synthesis, SDM interventions may be more beneficial to disadvantaged groups than higher literacy/socioeconomic status patients. However, given the small sample sizes and variety in the intervention types, study design and quality, those findings should be interpreted with caution.  相似文献   

8.

Background

Secretory Apolipoprotein J/Clusterin (sCLU) is a ubiquitously expressed chaperone that has been functionally implicated in several pathological conditions of increased oxidative injury, including aging. Nevertheless, the biological role of sCLU in red blood cells (RBCs) remained largely unknown. In the current study we identified sCLU as a component of human RBCs and we undertook a detailed analysis of its cellular topology. Moreover, we studied the erythrocytic membrane sCLU content during organismal aging, in conditions of increased organismal stress and accelerated RBCs senescence, as well as during physiological in vivo cellular senescence.

Methodology/Principal Findings

By using a combination of molecular, biochemical and high resolution microscopical methods we found that sCLU is a novel structural component of RBCs extra- and intracellular plasma membrane and cytosol. We observed that the RBCs membrane-associated sCLU decreases during organismal aging or exposure to acute stress (e.g. smoking), in patients with congenital hemolytic anemia, as well as during RBCs in vivo senescence. In all cases, sCLU reduction paralleled the expression of typical cellular senescence, redox imbalance and erythrophagocytosis markers which are also indicative of the senescence- and oxidative stress-mediated RBCs membrane vesiculation.

Conclusions/Significance

We propose that sCLU at the mature RBCs is not a silent remnant of the erythroid precursors, but an active component being functionally implicated in the signalling mechanisms of cellular senescence and oxidative stress-responses in both healthy and diseased organism. The reduced sCLU protein levels in the RBCs membrane following cell exposure to various endogenous or exogenous stressors closely correlates to the levels of cellular senescence and redox imbalance markers, suggesting the usefulness of sCLU as a sensitive biomarker of senescence and cellular stress.  相似文献   

9.
Source Partitioning Using Stable Isotopes: Coping with Too Much Variation   总被引:2,自引:0,他引:2  

Background

Stable isotope analysis is increasingly being utilised across broad areas of ecology and biology. Key to much of this work is the use of mixing models to estimate the proportion of sources contributing to a mixture such as in diet estimation.

Methodology

By accurately reflecting natural variation and uncertainty to generate robust probability estimates of source proportions, the application of Bayesian methods to stable isotope mixing models promises to enable researchers to address an array of new questions, and approach current questions with greater insight and honesty.

Conclusions

We outline a framework that builds on recently published Bayesian isotopic mixing models and present a new open source R package, SIAR. The formulation in R will allow for continued and rapid development of this core model into an all-encompassing single analysis suite for stable isotope research.  相似文献   

10.

Objectives

To quantify the proportion of adverse pregnancy outcome attributable to maternal obesity.

Design

Cross sectional analysis of routine obstetric dataset.

Setting

Guy’s and St Thomas’s NHS Foundation Trust (GSTFT).

Population

23,668 women who had singleton deliveries at GSTFT between 2004 and 2008.

Methods

Logistic regression was used to estimate the association between BMI and outcome in different ethnic groups. Adjusted odds ratios, and the proportions of obese women, were used to calculate population attributable risk fractions (PAFs).

Main Outcome Measures

(i) Maternal outcomes: diabetes, type of delivery, post-partum haemorrhage, and preterm delivery. (ii) Perinatal outcomes: macrosomia, low birth weight, admission to neonatal intensive care/special care baby unit, and perinatal death.

Results

The prevalence of maternal obesity was 14%. Increasing BMI was independently associated with increasing risk of adverse obstetric and neonatal outcome. At the individual level, the effect of obesity on diabetes was highest in Asian women compared to white women (p for interaction = 0.03). Calculation of population attributable risk fractions demonstrated that one third of diabetes cases and one in six Caesarean sections could be avoided in this population if all obese women were of normal BMI. At the population level, the contribution of obesity to diabetes was highest for Black women (42%), and lowest for oriental women (8%). Seven percent of neonatal macrosomia in all the population, and 13% in Black mothers, were attributable to obesity.

Conclusions

Preventing obesity prior to pregnancy will substantially reduce the burden of obstetric and neonatal morbidity in this population. This reduction will be higher in Black women.  相似文献   

11.

Background

DNA barcoding is a promising tool to facilitate a rapid and unambiguous identification of sponge species. Demosponges of the order Dictyoceratida are particularly challenging to identify, but are of ecological as well as biochemical importance.

Methodology/Principal Findings

Here we apply DNA barcoding with the standard CO1-barcoding marker on selected Indo-Pacific specimens of two genera, Ircinia and Psammocinia of the family Irciniidae. We show that the CO1 marker identifies several species new to science, reveals separate radiation patterns of deep-sea Ircinia sponges and indicates dispersal patterns of Psammocinia species. However, some species cannot be unambiguously barcoded by solely this marker due to low evolutionary rates.

Conclusions/Significance

We support previous suggestions for a combination of the standard CO1 fragment with an additional fragment for sponge DNA barcoding.  相似文献   

12.

Objective

Lack of social support is a strong predictor for poor mental health after disasters. Psychosocial post-disaster interventions may benefit from targeting survivors at risk of low support, yet it is unknown whether demographic and disaster exposure characteristics are associated with social support. This study assessed if age, gender, educational status, cohabitation, and disaster exposure severity predicted aspects of informal social support in a cohort of Swedish survivors from the 2004 Southeast Asian tsunami.

Methods

The participants were 3,536 disaster survivors who responded to a mail survey 14 months after the disaster (49% response rate). Their perceptions of present emotional support, contact with others, tangible support, negative support and overall satisfaction with informal support were assessed with the Crisis Support Scale and analysed in five separate ordinal regressions.

Results

Demographic factors and exposure severity explained variation in social supports although the effect size and predictive efficiency were modest. Cohabitation and female gender were associated with both more positive and more negative support. Single-household men were at risk for low emotional support and younger women were more likely to perceive negative support. Higher education was associated with more positive support, whereas no clear pattern was found regarding age as a predictor. Disaster exposure severity was associated with more negative support and less overall support satisfaction.

Conclusions

After a disaster that entailed little disruptions to the community the associations between demographic characteristics and social support concur with findings in the general population. The findings suggest that psychosocial disaster interventions may benefit from targeting specific groups of survivors.  相似文献   

13.

Background

The role of observational studies in informing clinical practice is debated, and high profile examples of discrepancies between the results of observational studies and randomised controlled trials (RCTs) have intensified that debate. We systematically reviewed findings from the Nurses’ Health Study (NHS), one of the longest and largest observational studies, to assess the number and strength of the associations reported and to determine if they have been confirmed in RCTs.

Methods

We reviewed NHS publication abstracts from 1978–2012, extracted information on associations tested, and graded the strength of the reported effect sizes. We searched PubMed for RCTs or systematic reviews for 3 health outcomes commonly reported in NHS publications: breast cancer, ischaemic heart disease (IHD) and osteoporosis. NHS results were compared with RCT results and deemed concordant when the difference in effect sizes between studies was ≤0.15.

Findings

2007 associations between health outcomes and independent variables were reported in 1053 abstracts. 58.0% (1165/2007) were statistically significant, and 22.2% (445/2007) were neutral (no association). Among the statistically significant results that reported a numeric odds ratio (OR) or relative risk (RR), 70.5% (706/1002) reported a weak association (OR/RR 0.5–2.0), 24.5% (246/1002) a moderate association (OR/RR 0.25–0.5 or 2.0–4.0) and 5.0% (50/1002) a strong association (OR/RR ≤0.25 or ≥4.0). 19 associations reported in NHS publications for breast cancer, IHD and osteoporosis have been tested in RCTs, and the concordance between NHS and RCT results was low (≤25%).

Conclusions

NHS publications contain a large number of analyses, the majority of which reported statistically significant but weak associations. Few of these associations have been tested in RCTs, and where they have, the agreement between NHS results and RCTs is poor.  相似文献   

14.

Background

Diagnosing peanut allergy properly is important and can be achieved by combining clinical history with various diagnostic methods such as IgE-antibody (IgE-ab) measurements, skin-prick test, basophil allergen threshold sensitivity (CD-sens) and food challenge. We aimed to evaluate CD-sens to peanut, Ara h 8 and Gly m 4 in relation to an oral peanut challenge in children IgE-sensitized to birch, peanut and Ara h 8 avoiding peanuts.

Methods

Twenty children IgE-sensitized to birch pollen and Ara h 8, but not to Ara h 1, Ara h 2 or Ara h 3 were challenged orally with roasted peanuts. Blood samples were drawn for IgE-ab and CD-sens analysis. To measure CD-sens, basophils were stimulated in vitro with decreasing doses of allergens until threshold sensitivity was reached.

Results

All children passed challenge without objective symptoms, but mild oral allergy syndrome (OAS) symptoms were reported in 6/20 children. Nineteen of twenty children were negative in CD-sens to peanut but 17/20 were positive to rAra h 8. Eleven of twenty children were positive in CD-sens to rGly m 4.

Conclusion

Positive CD-sens to rAra h 8 show that the Ara h 8 IgE-ab sensitized basophils can be activated by a rAra h 8 allergen and initiate an allergic inflammation despite a negative challenge. Hence, children sensitized to Ara h 8 but not to peanut storage proteins may be at risk for systemic allergic reaction when eating larger amounts of peanuts but most likely don’t have to fear smaller amounts.

Electronic supplementary material

The online version of this article (doi:10.1186/s12948-014-0007-3) contains supplementary material, which is available to authorized users.  相似文献   

15.

Objective

To determine whether microbial contamination of door handles in two busy intensive care units and one high dependency unit was related to their design, location, and usage.

Design

Observational study of the number of viable bacteria on existing door handles of different design at defined entry/exit points with simultaneous data collection of who used these doors and how often.

Setting

Two busy specialised intensive care units and one high dependency unit in a tertiary referral NHS neurological hospital.

Main outcome measures

Surface bacterial density on door handles with reference to design, location, and intensity of use.

Results

We found a significant correlation between the frequency of movements through a door and the degree to which it was contaminated (p = <0.01). We further found that the door''s location, design and mode of use all influenced contamination. When compared to push plate designs, pull handles revealed on average a five fold higher level of contamination; lever handles, however, displayed the highest levels of bacterial contamination when adjusted for frequency of use. We also observed differences in contamination levels at doors between clinical areas, particularly between the operating theatres and one of the ICUs.

Conclusions

Door handles in busy, “real life” high acuity clinical environments were variably contaminated with bacteria, and the number of bacteria found related to design, location, mode and frequency of operation. Largely ignored issues of handle and environmental design can support or undermine strategies designed to limit avoidable pathogen transmission, especially in locations designed to define “thresholds” and impose physical barriers to pathogen transmission between clinical areas. Developing a multidisciplinary approach beyond traditional boundaries for purposes of infection control may release hitherto unappreciated options and beneficial outcomes for the control of at least some hospital acquired infections.  相似文献   

16.

Objectives

Ti, which is biocompatible and resistant to corrosion, is widely used for dental implants, particularly in patients allergic to other materials. However, numerous studies have reported on Ti allergy and the in vitro corrosion of Ti. This study investigated the conditions that promote the elution of Ti ions from Ti implants.

Methods

Specimens of commercially pure Ti, pure nickel, a magnetic alloy, and a gold alloy were tested. Each specimen was immersed in a simulated body fluid (SBF) whose pH value was controlled (2.0, 3.0, 5.0, 7.4, and 9.0) using either hydrochloric or lactic acid. The parameters investigated were the following: duration of immersion, pH of the SBF, contact with a dissimilar metal, and mechanical stimulus. The amounts of Ti ions eluted were measured using a polarized Zeeman atomic absorption spectrophotometer.

Results

Eluted Ti ions were detected after 24 h (pH of 2.0 and 3.0) and after 48 h (pH of 9.0). However, even after 4 weeks, eluted Ti ions were not detected in SBF solutions with pH values of 5.0 and 7.4. Ti elution was affected by immersion time, pH, acid type, mechanical stimulus, and contact with a dissimilar metal. Elution of Ti ions in a Candida albicans culture medium was observed after 72 h.

Significance

Elution of Ti ions in the SBF was influenced by its pH and by crevice corrosion. The results of this study elucidate the conditions that lead to the elution of Ti ions in humans, which results in implant corrosion and Ti allergy.  相似文献   

17.

Purpose of the Study

To systematically review cost, cost-minimization and cost-effectiveness studies for assisted living technologies (ALTs) that specifically enable older people to ‘age in place’ and highlight what further research is needed to inform decisions regarding aging in place.

Design

People aged 65+ and their live-in carers (where applicable), using an ALT to age in place at home opposed to a community-dwelling arrangement.

Methods

Studies were identified using a predefined search strategy on two key economic and cost evaluation databases NHS EED, HEED. Studies were assessed using methods recommended by the Campbell and Cochrane Economic Methods Group and presented in a narrative synthesis style.

Results

Eight eligible studies were identified from North America spread over a diverse geographical range. The majority of studies reported the ALT intervention group as having lower resource use costs than the control group; though the low methodological quality and heterogeneity of the individual costs and outcomes reported across studies must be considered.

Implications

The studies suggest that in some cases ALTs may reduce costs, though little data were identified and what there were was of poor quality. Methods to capture quality of life gains were not used, therefore potential effects on health and wellbeing may be missed. Further research is required using newer developments such as the capabilities approach. High quality studies assessing the cost-effectiveness of ALTs for ageing in place are required before robust conclusion on their use can be drawn.  相似文献   

18.

Objectives

Paroxysmal nocturnal hemoglobinemia (PNH) is a rare but serious condition characterized by complement-mediated red blood cell (RBC) hemolysis and episodic thrombotic attack. It results from decay accelerating factor (CD55), and protectin (CD59), becoming attached to RBC and other cell surfaces. Absence of these protective proteins leaves such cells vulnerable to self attack at the C3 convertase and membrane attack complex (MAC) stages of complement activation. We have previously reported that aurin tricarboxylic acid (ATA) is an orally effective agent that selectively blocks complement activation at the C3 convertase stage as well as MAC formation at the C9 insertion stage.

Design and Methods

We used a CH50 assay method and western blot analysis to investigate the vulnerability to complement attack of PNH RBCs compared with normal RBCs. Zymosan was used as the activator of normal serum and PNH serum. ATA was added to the sera to determine the concentration necessary to protect the RBCs from lysis by the zymosan-activated sera.

Results

We found that erythrocytes from PNH patients on long term treatment with eculizumab were twice as vulnerable as normal erythrocytes to lysis induced by complement activated serum. Western blot data showed the presence of both C3 and C5 convertases on the PNH patient erythrocyte membranes. These data indicate persistent vulnerability of PNH erythrocytes to complement attack due to deficiencies in CD55 and CD59. ATA, when added to serum in vitro, protected PNH erythrocytes from complement attack, restoring their resistance to that of normal erythrocytes.

Conclusions

We conclude that ATA, by protecting PNH erythrocytes from their decay accelerating factor (CD55) and protectin (CD59) deficiencies, may be an effective oral treatment in this disorder.  相似文献   

19.

Background

In Africa, infant susceptibility to Plasmodium falciparum malaria increases substantially as fetal hemoglobin (HbF) and maternal immune IgG disappear from circulation. During the first few months of life, however, resistance to malaria is evidenced by extremely low parasitemias, the absence of fever, and the almost complete lack of severe disease. This resistance has previously been attributed in part to poor parasite growth in HbF-containing red blood cells (RBCs). A specific role for maternal immune IgG in infant resistance to malaria has been hypothesized but not yet identified.

Methods and Findings

We found that P. falciparum parasites invade and develop normally in fetal (cord blood, CB) RBCs, which contain up to 95% HbF. However, these parasitized CB RBCs are impaired in their binding to human microvascular endothelial cells (MVECs), monocytes, and nonparasitized RBCs – cytoadherence interactions that have been implicated in the development of high parasite densities and the symptoms of malaria. Abnormal display of the parasite''s cytoadherence antigen P. falciparum erythrocyte membrane protein-1 (PfEMP-1) on CB RBCs accounts for these findings and is reminiscent of that on HbC and HbS RBCs. IgG purified from the plasma of immune Malian adults almost completely abolishes the adherence of parasitized CB RBCs to MVECs.

Conclusions

Our data suggest a model of malaria protection in which HbF and maternal IgG act cooperatively to impair the cytoadherence of parasitized RBCs in the first few months of life. In highly malarious areas of Africa, an infant''s contemporaneous expression of HbC or HbS and development of an immune IgG repertoire may effectively reconstitute the waning protective effects of HbF and maternal immune IgG, thereby extending the malaria resistance of infancy into early childhood.  相似文献   

20.

Objective

The aim of the paper is to report the development and psychometric testing of Diabetes Attitude Scale.

Method

A prospective study was performed. The cultural equivalency and content validity of the Diabetes Attitude Scale were determined by panels of endocrinologists, physiologists, nurses and dieticians. An accurate and usable translation was obtained for each of five subscales examining attitudes on need for special training, the seriousness of type-2 diabetes, the need for controlling the condition, its psychosocial impact and the degree of autonomy given to patients in decision making. The validation was derived from 5961 patients with type-2 diabetes, recruited from 50 centers in 29 provinces throughout China between March 1st and September 30th, 2010.

Results

The modified Diabetes Attitude Scale showed an acceptable level of internal consistency. The strength of the inter-correlations among the domains of five subscales suggests that the instrument measures related but separate domains of patients'' attitudes toward diabetes. Moreover, the test-retest intraclass correlation coefficients were high enough to support the stability of the Chinese version of the third version of the scale.

Conclusions

The psychometric properties of the Chinese version of Diabetes Attitude Scale demonstrated satisfactory validity and reliability and appeared to effectively evaluate attitudes toward diabetes in patients with type-2 diabetes.  相似文献   

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