Objectives and Methods of Iron Chelation Therapy

Recent developments in the understanding of the molecular control of iron homeostasis provided novel insights into the mechanisms responsible for normal iron balance. However in chronic anemias associated with iron overload, such mechanisms are no longer sufficient to offer protection from iron toxicity, and iron chelating therapy is the only method available for preventing early death caused mainly by myocardial and hepatic damage. Today, long-term deferoxamine (DFO) therapy is an integral part of the management of thalassemia and other transfusion-dependent anemias, with a major impact on well-being and survival. However, the high cost and rigorous requirements of DFO therapy, and the significant toxicity of deferiprone underline the need for the continued development of new and improved orally effective iron chelators. Within recent years more than one thousand candidate compounds have been screened in animal models. The most outstanding of these compounds include deferiprone (L1); pyridoxal isonicotinoyl hydrazone (PIH) and; bishydroxy- phenyl thiazole. Deferiprone has been used extensively as a substitute for DFO in clinical trials involving hundreds of patients. However, L1 treatment alone fails to achieve a negative iron balance in a substantial proportion of subjects. Deferiprone is less effective than DFO and its potential hepatotoxicity is an issue of current controversy. A new orally effective iron chelator should not necessarily be regarded as one displacing the presently accepted and highly effective parenteral drug DFO. Rather, it could be employed to extend the scope of iron chelating strategies in a manner analogous with the combined use of medications in the management of other conditions such as hypertension or diabetes. Coadministration or alternating use of DFO and a suitable oral chelator may allow a decrease in dosage of both drugs and improve compliance by decreasing the demand on tedious parenteral drug administration. Combined use of DFO and L1 has already been shown to result in successful depletion of iron stores in patients previously failing to respond to single drug therapy, and to lead to improved compliance with treatment. It may also result in a “shuttle effect” between weak intracellular chelators and powerful extracellular chelators or exploit the entero-hepatic cycle to promote fecal iron excretion. All of these innovative ways of chelator usage are now awaiting evaluation in experimental models and in the clinical setting

Show your best self(ie):An exploratory study on selfie-related motivations and behavior in emerging adulthood

Although self-presentation has been studied for decades, social networking sites (SNS) such as Facebook have produced novel opportunities for visual online self-presentation. Posting selfies is currently a popular mode of consciously constructing visual online self-presentations, yet most prior research is limited to selfie-posting alone. This study aimed to profile selfie-makers’ motivations and behavior, and examine the extent to which underlying mechanisms preceding selfie-posting are interconnected. Results of a survey (N = 224; 79.9% females; Mage = 21.66, SDage = 2.08) regarding selfie-behavior on SNS (e.g., Facebook and Instagram) characterized selfie-makers in emerging adulthood as mainly concerned with the social aspects of selfies. Entertainment and moment-retention were identified as main motivations for selfie-making. Findings supported the proposed Selfie-Stadium Model, representing various steps of selfie-taking and underlying motives as well as selection and editing before actual posting. This study on profiling selfie-makers and their self-presentation taps into a fairly new media use research domain

Me, My Selfie, and I:The Relations Between Selfie Behaviors, Body Image, Self-Objectification, and Self-Esteem in Young Women

Due to the enormous popularity of social networking sites (SNSs), online and offline social lives seem inextricably linked, which raises concerns for how SNS use relates to psychological health. Similarly, the omnipresence of selfies on SNSs-a form of appearance-related exposure-raises concerns regarding psychological health. This study aimed to investigate the relationships between body image, self-objectification, self-esteem, and various selfie behaviors among young women (N = 179). We hypothesized that a worsened body image (i.e., higher body dissatisfaction or lower body appreciation), higher levels of self-objectification, and lower self-esteem would precede greater engagement in selfie behaviors. Structural equation modeling showed that body appreciation is associated with greater engagement in selfie selection and deliberate posting, and that self-objectification is related to greater engagement in all selfie behaviors assessed. In support of our proposed model, a reversed model was also tested that showed poorer results. These findings suggest that body image may serve not only as an outcome of SNS use but also as a motive preceding selfie behaviors

Possibilistic KNN regression using tolerance intervals

International audienceBy employing regression methods minimizing predictive risk, we are usually looking for precise values which tends to their true response value. However, in some situations, it may be more reasonable to predict intervals rather than precise values. In this paper, we focus to find such intervals for the K-nearest neighbors (KNN) method with precise values for inputs and output. In KNN, the prediction intervals are usually built by considering the local probability distribution of the neighborhood. In situations where we do not dispose of enough data in the neighborhood to obtain statistically significant distributions, we would rather wish to build intervals which takes into account such distribution uncertainties. For this latter we suggest to use tolerance intervals to build the maximal specific possibility distribution that bounds each population quantiles of the true distribution (with a fixed confidence level) that might have generated our sample set. Next we propose a new interval regression method based on KNN which take advantage of our possibility distribution in order to choose, for each instance, the value of K which will be a good trade-off between precision and uncertainty due to the limited sample size. Finally we apply our method on an aircraft trajectory prediction problem

3':5'-Cyclic AMP-dependent 3'

Suspensions of 3':5'-cyclic AMP (cAMP)-sensitive cells of Dictyostelium discoideum responded to a cAMP pulse with increased 3':5'-cyclic GMP (cGMP) levels. Under the assay conditions used (2 × 10^8 cells per ml in 10 mM phosphate buffer, pH 6.0) cAMP (5 × 10-8 M final concentration) increased cGMP levels from 1 pmol per 10^7 cells to 7 pmol per 10^7 cells in 10 sec and basal levels were recovered in 20-25 sec. cGMP accumulation did not occur when cells were in the cAMP-insensitive stage. cAMP-sensitive cells responded with increased cGMP levels when triggered by 5 × 10-8 M 5'-CH2-cAMP or 10-5 M adenosine-5'-methylmonophosphate (5'-AMPMe) but not after addition of 5 × 10-8 M 3':5'-cyclic IMP (cIMP) or 5 × 10-8 M 5'-AMP. As agonists of cAMP, 5'-CH2-cAMP and 5'-AMPMe have, respectively, more than 10% and 1% the chemotactic activity of cAMP, while cIMP has 0.01% the activity of cAMP and 5-AMP is inactive up to a concentration of 10-3 M. cAMP-mediated cGMP formation was dependent upon cAMP concentration, with a half-maximal cAMP concentration of about 10-8 M. This cAMP concentration agrees closely with that necessary for half-maximal receptor occupation. cAMP-mediated cGMP formation was independent of the presence of extracellular Ca2+; cell aggregation and chemotaxis were also independent of the presence of external Ca2+. Therefore, cAMP action does not depend on stimulation of the Ca2+ influx. cAMP was found to mediate desensitization of cAMP-dependent cGMP formation. Additon of 5 × 10-8 M cAMP to sensitive cells induced a desensitization period that lasted 1-5 min. Desensitization was dependent on the cAMP concentration. Finally, we propose that the translation of a chemotactic signal from the cell surface to pseudopod formation in Dictyostelium involves changes in the levels of cGMP

Development of atypical parental behavior during an inpatient family preservation intervention program

Since failed reunification is a detrimental outcome for children, particularly infants and toddlers, the aim of this study was to gain insight into support to families in multiple-problem situations to help them achieve sustainable good-enough parenting. Therefore, we examined outcomes of an assessment-based inpatient family preservation program. We prepared a thorough target-population description (n = 70) using file analysis. Next, we examined atypical parental behavior during the intervention using the Atypical Maternal Behavior Instrument for Assessment and Classification with a repeated measures design (n = 30). The family files revealed a great number of issues at the family, parent, and child levels, such as practical matters, problems in parent functioning and between parents, and difficulties in the broader environment. We found a significant decline in three dimensions of atypical parental behavior over time. This program has great potential in supporting vulnerable families in their pursuit of family preservation

Driving pressure during general anesthesia for open abdominal surgery (DESIGNATION) : study protocol of a randomized clinical trial

Background Intraoperative driving pressure (Delta P) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (V-T) is kept constant, Delta P may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. Delta P may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery. Methods The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged >= 18 years and with a body mass index <= 40 kg/m(2), scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5 cm H2O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which Delta P is lowest. In both groups of the trial, V-T is kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events. Discussion DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery

Dendritic Cell Migration to Skin-Draining Lymph Nodes Is Controlled by Dermatan Sulfate and Determines Adaptive Immunity Magnitude

Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease