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Acute myeloid leukemia (AML) is a complex disease, and its treatment needs to be adjusted to the risk, which is conferred by cytogenetics and molecular markers. Cytarabine is the main drug to treat AML, and it has been suggested that the genotype of cytarabine metabolizing enzymes may have a prognostic relevance in AML. Here we report the association between the 5'-nucleotidase, cytosolic II (NT5C2) rs10883841, cytidine deaminase (CDA) rs2072671 and rs532545 genotypes and the clinical outcome of 477 intermediate-risk cytogenetic AML patients receiving cytarabine-based chemotherapy. Patients younger than 50 years old with the NT5C2 rs10883841 AA genotype had lower overall survival (OS) (p: .003; HR 2.16, 95% CI 1.29-3.61) and lower disease-free survival (DFS) (p: .002; HR 2.45, 95% CI 1.41-4.27), associated to a higher relapse incidence (p: .010; HR 2.23, 95% CI 1.21-4.12). Interestingly, subgroup analysis showed that the negative effect of the NT5C2 rs10883841 AA genotype was detected in all subgroups except in patients with nucleophosmin mutation without high ratio FLT-3 internal tandem duplication. CDA polymorphisms were associated with the complete remission rate after induction chemotherapy, without influencing OS. Further studies are warranted to determine whether this pharmacogenomic approach may be helpful to individualize AML treatment.

Extracorporeal photopheresis (ECP) has been shown to be an effective treatment for graft-versus-host disease (GvHD). However, information regarding lymphocyte collection for ECP in children is limited. The aim of this study was to analyse and compare lymphocyte collection for ECP in children using different devices and protocols. Moreover, we have studied both safety and variables of the infused product related to treatment efficacy.This was a retrospective study of 91 patients who underwent 1524 apheresis procedures with either the COBE Spectra or Spectra Optia system. The comparison study between the Optia protocols (MNC and CMNC) was prioritized. We analysed 578 procedures using the Optia blood cell separator: 204 and 374 using the MNC and the CMNC protocol, respectively.The Optia CMNC protocol showed better collection efficiency, with increased lymphocyte collection per kg of body weight (p 0.001). On multivariate analysis, the type of protocol showed no relationship with haematocrit or platelet loss. Most procedures were well-tolerated, with the most frequent adverse events related to venous access (21.7%). Seventy-one percent of patients had either partial or complete clinical GvHD response. In the multivariate model, only two variables were associated with a better response to ECP, younger age and a greater increase of B lymphocytes after treatment.Lymphocyte collection for ECP is well-tolerated in most children, achieving complete or partial response in more than half of GvHD patients. CMNC is the optimal software to perform lymphocyte collection in children.

Background and Aims Transient elastography (TE) to estimate liver stiffness has proved to be very useful in the diagnosis of chronic liver disease. Here, we intend to evaluate its use in a large Spanish cohort. Method Nested study within the PREVHEP‐ETHON (Epidemiological sTudy of Hepatic infectiONs; NCT02749864) population‐based, cross‐sectional study performed between July 2015 and April 2017. An epidemiological questionnaire, laboratory tests and TE and anthropometric measurements were obtained. Results Data from 11,440 subjects were analyzed. Mean age was 50.3 (SD 12.4), of which 58.1% were women. 15.4% showed metabolic syndrome (NCEP ATP‐III), 1.3% were positive for hepatitis C antibodies, 0.8% positive for HBsAg, 9.1% reported harmful use of alcohol. The prevalence of significant fibrosis (LSM > 8 kPa), suggestive compensated advanced chronic liver disease (cACLD) (LSM ≥ 10 kPa) and highly suggestive cACLD (LSM > 15 kPa) was 5.6%, 2.9%, and 1.2% respectively. Risk factors associated with significant fibrosis were age (OR 1.03 [1.02–1.04; p

BACKGROUND The diagnosis of photoallergic contact dermatitis (PACD) is confirmed by photopatch testing (PPT). In Spain, the latest recommendation on which allergens to test in PPT dates from 1995. METHODS In the last 4 years, we studied 455 patients with epicutaneous tests and performed PPT on 33 of those patients (7.3%). RESULTS The most prevalent allergens in PPT were as follows: non-steroidal anti-inflammatory drugs (NSAIDs) (46%), fragrances (21%), and solar filters (18%). DISCUSSION In our country, the most common photoallergens continue to be NSAIDs (ketoprofen). The increasingly common use of sunscreens has led to a growing involvement of solar filters in PACD, which can be also contained in other cosmetics. In our experience, PACD due to fragrances is nonetheless at least similar in frequency. CONCLUSIONS The PPT battery must adapt to the prescription, use, and exposure habits of each country. We propose a diagnostic model to guide which allergens to test in PPT, which in our experience should also include fragrances.

INTRODUCTION In order to propose risk-adapted mobilization algorithms, several authors have tried to look for predictive factors of the CD34+ yield in healthy pediatric donors. Donor recipient body weight ratio (D/R ratio) was identified as one of the main variables related with the success to achieve the target cell dose for transplantation. According to this variable we modified the mobilization schedule. MATERIAL AND METHODS We report the results of 46 mobilizations and apheresis procedures performed in our center with unfavorable D/R ratio. Mobilization was attempted by the standard regime of G-CSF (10 mcg/kg/24 hours) in 28 cases (60.9%), with high dose G-CSF (10 mcg/kg/12 hours) in 9 cases (19.6%), and with plerixafor and G-CSF single dose regime in 9 cases (19.6%). RESULTS CD34+ cell quantification before apheresis is closely related to CD34+ yield, being the only factor related to collected CD34+ cells (beta .71; P

The loss of noradrenergic neurons and subsequent reduction of brain noradrenaline (NA) levels are associated with the progression of Alzheimer's disease (AD). This seems to be due mainly to the ability of NA to reduce the activation of microglial cells. We previously observed that NA induces the production of the chemokine Fractalkine/CX3CL1 in neurons. The activation of microglial CX3CR1, sole receptor for CX3CL1, reduces the activation of microglia, which is known to largely contribute to the neuronal damage characteristic of AD. Therefore, alterations of CX3CR1 production in microglia could translate into the enhancement or inhibition of CX3CL1 anti-inflammatory effects. In order to determine if microglial CX3CR1 production is altered in AD and if NA can control it, CX3CR1 expression and synthesis were analyzed in 5xFAD mice and human AD brain samples. In addition, the effects of NA and its reuptake inhibitor reboxetine were analyzed in microglial cultures and mice respectively. Our results indicate that in AD CX3CR1 production is increased in the brain cortex and that reboxetine administration further increases it and enhances microglial reactivity toward amyloid beta plaques. However, direct administration of NA to primary rat microglia or human HMC3 cells inhibits CX3CR1 production, suggesting that microglia responses to NA may be altered in the absence of CX3CL1-producing neurons or other nonmicroglial external factors.

Online language teaching has become a reality for many foreign language programs that have been forced to teach remotely. When developing an online language teaching curriculum (beyond a simple emergency teaching patch), it is important to uphold the same rigor and base our curriculum in methodological and pedagogic choices based on second language acquisition and educational research, and keep in mind that interaction is critical to developing second language skills. This article advocates that, through collaborative technology‐mediated tasks, we can promote productive language output (spoken and written) and the type of interaction that facilitates language learning and motivates students to continue improving their language skills

Childhood cancer patients are at risk of developing important adverse effects, mortality and disease relapse after treatments, which has a substantial economic impact on healthcare systems. The objective of this study was to determine the effects of supervised inhospital exercise on clinical endpoints during childhood cancer treatment. 169 children with a new diagnosis of cancer were divided into an exercise intervention (n = 68, 11 ± 4 years) or a control group (n = 101, 11 ± 3 years). The cohort was followed up from the start of treatment for up to five years. Supervised inhospital exercise intervention was performed during the neoadjuvant (for solid tumors) or intensive chemotherapy treatment period (for leukemias). The median duration of the intervention was 22 (interquartile range, 14‐28) weeks. We assessed survival, risk of disease relapse or metastasis, and days of hospitalization (primary outcomes), and cardiovascular function, anthropometry and blood variables (secondary outcomes). No exercise‐related adverse events were noted. The exercise group had significantly less days of hospitalization than the control group (P = .031), resulting in a lower (~−17%) mean total economic cost of hospitalization in the former. Moreover, echocardiography‐determined left ventricular function (ejection fraction and fractional shortening) was significantly impaired in the control group after treatment compared with baseline, whereas it was maintained in the exercise group (P = .024 and .021 for the between‐group differences, respectively). In conclusion, supervised inhospital exercise intervention is safe and plays a cardioprotective role, at least in the short term, in children with cancer, also reducing hospitalization time, and therefore alleviating the economic burden. Sin financiación 4.221 JCR (2020) Q1, 18/88 Sport Sciences 1.575 SJR (2020) Q1, 27/288 Orthopedics and Sports Medicine No data IDR 2019 UEM

BACKGROUND: Defibrotide is approved in European Union for the treatment of severe sinusoidal obstruction syndrome (SOS) after HSCT. However, it has also been used for SOS prophylaxis, moderate SOS and in other complications such as transplant-associated thrombotic microangiopathy (TAM). The objective of this study was to evaluate current uses, effectiveness and safety of defibrotide in patients with HSCT. METHODS: This multicenter, retrospective study included patients treated with defibrotide for any indication at 28 HSCT centers of the Grupo Español de Trasplante Hematopoyetico (GETH) including the pediatric subgroup Grupo Español de Trasplante de Medula en Niños (GETMON). RESULTS: Three hundred and eighty eight patients treated with defibrotide between January 2011 and December 2018 were included. 253 patients were children, and 135 patients were adults. In total, 332 transplants were allogeneic, and the remainder were autologous. Main indications for defibrotide use were severe/very severe SOS in 173 patients, SOS prophylaxis in 135 patients, moderate SOS in 41 patients, TAM in six patients and suspected SOS in 33 patients. Overall survival (OS) at day +100 in the SOS prophylaxis group was 89% (95% CI, 87%-91%). In the group of patients with moderate and severe/very severe SOS, the OS at day +100 was 80% (95% CI, 74%-86%) and 62% (95% CI, 59%-65%), respectively (P = .0015). With a longer follow-up, median of 2 years (4 months-7 years), OS was 63% (95% CI, 59%-67%) in the SOS prophylaxis patients. OS for patients with moderate and severe/very severe SOS groups was 53% (95% CI, 47%-61%) and 26% (95% CI, 22%-30%), respectively (P = .006). 191 patients died, and SOS was the main cause of death in 23 patients (12%). CONCLUSIONS: Defibrotide has an acceptable safety profile with an improved response in severe/very severe SOS compared with historical controls, mainly in pediatric patients. Use of defibrotide for prophylaxis may improve prognosis of patients at high risk of complications due to endothelial damage such as those who receive a second transplant. SOS has an important impact on the HSCT long-term survival, as can be concluded from our study.

We read with great interest the article by Piccolo et al1. describing chilblain‐like lesions (CLL) on feet and hands during the COVID‐19 Pandemic. They mention the rate of association to autoimmune conditions was very low, which led the to exclude a note autoimmune disorder as main cause of CLL. Here, we hypothesize the possible relationship between the development of these lesions and immune‐chained phenomena following viral infection in a certain group of patients.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Aims Unavailability and lack of appropriate, effective and safe formulations are common problems in paediatric therapeutics. Key factors such as swallowing abilities, organoleptic preferences and dosage requirements determine the need for optimization of formulations. The provisional Biopharmaceutics Classification System (BCS) can be used in paediatric formulation design as a risk analysis and optimization tool. The objective of this study was to classify six neglected tropical disease drugs following a provisional paediatric BCS (pBCS) classification adapted to three paediatric subpopulations (neonates, infants and children). Methods Albendazole, benznidazole, ivermectin, nifurtimox, praziquantel and proguanil were selected from the 5th edition of the Model List of Essential Medicines for Children from the World Health Organization. Paediatric drug solubility classification was based on dose number calculation. Provisional permeability classification was based on log P comparison versus metoprolol log P value, assuming passive diffusion absorption mechanisms and no changes in passive membrane permeability between paediatric patients and adults. pBCS classes were estimated for each drug, according to different doses and volumes adapted for each age stage and were compared to the adult classification. Results All six drugs were classified into provisional pBCS in the three paediatric subpopulations. Three drugs maintained the same classification as for adults, ivermectin and benznidazole changed solubility class from low to high in neonates and proguanil changed from low to high solubility in all age stages. Conclusion Provisional pBCS classification of these six drugs shows potential changes in the limiting factors in oral absorption in paediatrics, depending on age stage, compared to the adult population. This valuable information will aid the optimization of paediatric dosing and formulations and can identify bioinequivalence risks when comparing different formulations and paediatric populations.

The state-of-the art in the design and the manufacture methods of the different electromagnetic shielding materials has been reviewed. This topic has become a mainstream field of research because of the electromagnetic pollution generated by telecommunication technology development. The review is centred in absorbent materials and shows a general overview of how the absorption properties of such composites can be tailored through changes in geometry, composition, morphology, and the filler particles content. Although different types of materials are explained, the text is mainly focused on carbon materials such as graphene and carbon nanotubes. In this way, the importance of the dispersion of the conductive fillers in different polymer matrices is discussed. In addition, an extensive study on new complex architectures such as foam-based materials is presented. Finally, the combination of carbon fillers with other constituents such as metallic nanoparticles is mentioned. In all these studies, the efficiency of the composites as absorbent or reflective of electromagnetic radiation is discussed.

The Cu-mediated skeletal rearrangement of O-propargyl oximes features a mechanistic manifold that yields different compounds. Strategic modification of the substituent at the oxime moiety (R3) allows the selection of a preferred mechanistic route that leads to azete oxides/amidodienes (if R3 is an electron-poor/-rich aryl group) or to pyridine N-oxides (if R3 is an olefin). In the present work, we explore the mechanism that leads to each product. All the computed mechanisms have in common an initial stepwise 2,3-rearrangement that generates the key N-allenylnitrone intermediate the further reactivity of which will depend on the nature of the R3 substituent. Our calculations reveal the subtle details that govern the different behavior of this reaction with each of the aforementioned substituents and disclose a complex and multistep pathway to different aminodienes.

The recently developed nitrene transfer reaction onto gold-activated alkynes provides a route to safe and accessible synthons of α-diazo imides. This reaction is rather unique in that it requires AuI in catalytic amounts; however, this promiscuous metal is only used to activate the alkyne moiety. After such activation is obtained, the nitrene-transfer process occurs through an outer-sphere mechanism, in which the metal acts only as a spectator. Density functional theory was applied to elucidate this peculiar reaction and to provide a mechanistic explanation for the experimentally observed isomers at the double bond and imine sites.

Background Ruxolitinib is a promising treatment for steroid refractory graft-versus-host disease (GvHD). However, data concerning effects on T cells are probably involved in increased risk of opportunistic infections. We analyzed clinical and immunological changes in children with GvHD taking ruxolitinib. Patients and Methods Twenty-two children that underwent transplantation and received ruxolitinib were included. Ruxolitinib indication was acute and chronic GvHD in 13 and 9 patients, respectively. Results Overall response rate in acute GvHD and chronic GvHD was high, of 77% and 89%, respectively. Ruxolitinib was associated with an increase in CD4 effector memory, and decrease of CD4 central memory percentage (Figure 1). CD4 regulatory T cells percentage decreased significantly (Figure 2). Patients who achieved complete response to ruxolitinib had higher natural killer cells before ruxolitinib that patients who did not respond. Also there was increase of CD4 lymphocytes percentage, with decrease of CD8 and natural killer cells percentage in responders against non-responders. There were 54%, 18% and 13% infections caused by virus, bacteria and fungi, respectively. Cumulative incidence of relapse and non relapse mortality was 19±9%and 28±10%, respectively. Overall survival and disease free survival rate at 2 years were 62±11% and 58±11%, respectively. Conclusions Ruxolitinib is a promising treatment for GvHD with a high overall response rate of 77% and 89%, respectively. It produces important changes in immune system, such as increase of CD4 effector memory cells and decrease in natural killer and regulatory T cells. Now we need pharmacokinetic studies to determine ruxolitinib dose in children and close surveillance and antimicrobial prophylaxis. Keywords Ruxolitinib, GvHD, children, immune reconstitution

The feasibility of using plantation-grown biomass to fuel bioenergy plants is in part dependent on the ability to predict the capacity of surrounding forests to maintain a sustainable supply. In this study, the potential productivity of Eucalyptus nitens (Deane and Maiden) Maiden plantations grown for bioenergy in a region of north-west Spain was quantified using the 3-PG process-based model. The model was calibrated using detailed measurements from five permanent sample plots and validated using data from thirty-five additional permanent sample plots; both sets represented the variability of climate and soils of the region. Plot scale analysis showed that the model was able to reasonably estimate above-ground biomass and water use when compared with the observed data. Using a representative loam soil characteristic, a spatial analysis was then carried out to predict the potential productivity of E. nitens for bioenergy across a potential area for plantation establishment of 2550 km2 and to evaluate different management scenarios related to rotation length and stocking. An increase of only 1.9% in mean annual increment (MAI) of above-ground biomass (WAGB) was found between stockings of 3000 and 5000 trees ha−1; for the lower stocking, MAI of WAGB increased 4% for rotation lengths between 6 and 8 years. Production was reduced by low summer rainfall and to a lesser extent by high summer and low winter temperatures, and vapour pressure deficit. Above-ground biomass production was higher by around 12% when average rather than actual climate data were applied. The information from this study can be used to optimize forest management, determine regional relative potential productivity and contribute to decision-making for bioenergy production from E. nitens plantations in north-west Spain.

Bisphenol-A, a chemical used in the production of the plastic lining of food and beverage containers, can be found in significant levels in human fluids. Recently, bisphenol-A has been associated with low-grade albuminuria in adults as well as in children. Since glomerular epithelial cells (podocytes) are commonly affected in proteinuric conditions, herein we explored the effects of bisphenol-A on podocytes in vitro and in vivo. On cultured podocytes we first observed that bisphenol-A?at low or high concentrations?(10?nM and 100?nM, respectively) was able to induce hypertrophy, diminish viability, and promote apoptosis. We also found an increase in the protein expression of TGF-?1 and its receptor, the cyclin-dependent kinase inhibitor p27Kip1, as well as collagen-IV, while observing a diminished expression of the slit diaphragm proteins nephrin and podocin. Furthermore, mice intraperitoneally injected with bisphenol-A (50?mg/Kg for 5 weeks) displayed an increase in urinary albumin excretion and endogenous creatinine clearance. Renal histology showed mesangial expansion. At ultrastructural level, podocytes displayed an enlargement of both cytoplasm and foot processes as well as the presence of condensed chromatin, suggesting apoptosis. Furthermore, immunohistochemistry for WT-1 (specific podocyte marker) and the TUNEL technique showed podocytopenia as well as the presence of apoptosis, respectively. In conclusion, our data demonstrate that Bisphenol-A exposure promotes a podocytopathy with proteinuria, glomerular hyperfiltration and podocytopenia. Further studies are needed to clarify the potential role of bisphenol-A in the pathogenesis as well as in the progression of renal diseases., Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III, The Eugenio Rodríguez Pascual Foundation

Bisphenol A (BPA) is found in human urine and fat tissue. Higher urinary BPA concentrations are associated with arterial hypertension. To shed light on the underlying mechanism, we orally administered BPA (4 nM to 400 μM in drinking water) to 8-wk-old CD11 mice over 30 d. Mice developed dosage-dependent high blood pressure (systolic 130 ± 12 vs. 170 ± 12 mmHg; EC50 0.4 μM), impairment of acetylcholine (AcH)-induced carotid relaxation (0.66 ± 0.08 vs. 0.44 ± 0.1 mm), a 1.7-fold increase in arterial angiotensin II (AngII), an 8.7-fold increase in eNOS mRNA and protein, and significant eNOS-dependent superoxide and peroxynitrite accumulation. AngII inhibition with 0.5 mg/ml losartan reduced oxidative stress and normalized blood pressure and endothelium-dependent relaxation, which suggests that AngII uncouples eNOS and contributes to the BPA-induced endothelial dysfunction by promoting oxidative and nitrosative stress. Microarray analysis of mouse aortic endothelial cells revealed a 2.5-fold increase in expression of calcium/calmodulin-dependent protein kinase II-α (CaMKII-α) in response to 10 nM BPA, with increased expression of phosphorylated-CaMKII-α in carotid rings of BPA-exposed mice, whereas CaMKII-α inhibition with 100 nM autocamptide-2-related inhibitor peptide (AIP) reduced BPA-mediated increase of superoxide. Administration of CaMKII-α inhibitor KN 93 reduced BPA-induced blood pressure and carotid blood velocity in mice, and reverted BPA-mediated carotid constriction in response to treatment with AcH. Given that CaMKII-α inhibition prevents BPA-mediated high blood pressure, our data suggest that BPA regulates blood pressure by inducing AngII/CaMKII-α uncoupling of eNOS.

In two preliminary control checks it was shown that affective attitudes presented greaterabstraction than cognitive attitudes. Three further studies explored how construal levelmoderated the role of affective and cognitive attitudes in predicting one health-promoting behaviour (exercising) and two risk behaviours (sleep debt and binge drinking). There was astronger influence of affective attitudes both when participants were in abstract (vs.concrete) mindsets induced by a priming task in Studies 1a and 1b, and when behaviouralintentions were formed for the distant (vs. near) future in Study 2. In the case of concretemindsets, the results were inconclusive; the interaction between construal level andcognitive attitudes was only marginally significant in Study 1b. The present researchsupports the assertion that in abstract mindsets (vs. concrete mindsets) people use moreaffective attitudes to construe their behavioural intentions. Practical implications forhealth promotion are discussed in the framework of construal-level theory, This research was supported by grant PSI 2011-28720.

In this in vitro study, we have investigated the ability of Taraxacum officinale (dandelion) to inhibit adipocyte differentiation and lipogenesis in 3T3-L1 preadipocytes. HPLC analysis of the three plant extracts used in this study—leaf and root extracts and a commercial root powder—identified caffeic and chlorogenic acids as the main phenolic constituents. Oil Red O staining and triglyceride levels analysis showed decreased lipid and triglyceride accumulation, respectively. Cytotoxicity was assessed with the MTT assay showing non-toxic effect among the concentrations tested. DNA microarray analysis showed that the extracts regulated the expression of a number of genes and long non-coding RNAs that play a major role in the control of adipogenesis. Taken together, our results indicate that the dandelion extracts used in this study may play a significant role during adipogenesis and lipid metabolism, and thus, supporting their therapeutic interest as potential candidates for the treatment of obesity. Copyright © 2013 John Wiley & Sons, Ltd.

New approaches are needed to the therapy of advanced prostate cancer. This study determined the effect of growth hormone-releasing hormone (GHRH) antagonists, JMR-132 and JV-1-38 on growth of PC3 tumors as well as on angiogenesis and metastasis through the evaluation of various factors that contribute largely to the progression of prostate cancer. Human PC3 androgen-independent prostate cancer cells were injected subcutaneously into nude mice. The treatment with JMR-132 (10 μg/day) or JV-1-38 (20 μg/day) lasted 41 days. We also evaluated the effects of JMR-132 and JV-1-38 on proliferation, cell adhesion and migration in PC-3 cells in vitro. Several techniques (Western blot, reverse transcription polymerase chain reaction, immunohistochemistry, ELISA and zymography) were used to evaluate the expression levels of GHRH receptors and its splice variants, GHRH, vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF)-1α, metalloproteinases (MMPs) -2 and -9, β-catenin and E-cadherin. GHRH antagonists suppressed the proliferation of PC-3 cells in vitro and significantly inhibited growth of PC3 tumors. After treatment with these analogues, we found an increase in expression of GHRH receptor accompanied by a decrease of GHRH levels, a reduction in both VEGF and HIF-1α expression and in active forms of MMP-2 and MMP-9, a significant increase in levels of membrane-associated β-catenin and a significant decline in E-cadherin. These results support that the blockade of GHRH receptors can modulate elements involved in angiogenesis and metastasis. Consequently, GHRH antagonists could be considered as suitable candidates for therapeutic trials in the management of androgen-independent prostate cancer.

Childhood and adult obesity have been widely associated with FTO genetic variability in different populations. This study aimed to investigate the linkage disequilibrium (LD) block structure of a region surrounding the candidate rs9939609 SNP and determine the best single nucleotide polymorphism (SNP) combination that explains the higher proportion of variability observed in children with severe obesity, including obese subjects from families with a very high occurrence of obesity. A sliding window approach pointed to a block containing the rs1477196/rs17817449/rs9939609 haplotype (P value 3.1 × 10(-8)). Carriers of the GGA combination had an increased risk of obesity (odds ratio (OR) 2.07, 95% confidence interval (CI) 1.41-3.04, P = 2.0 × 10(-4)) with respect to those individuals with the reference ATT haplotype. A further SNP, rs9921255, also showed association with obesity (P = 8.3 × 10(-4), OR 1.77; 95% CI 1.15-2.74 and OR 5.78; 95% CI 1.22-27.49 for heterozygotes and homozygotes, respectively) and did not segregate with the previously described risk haplotype. The calculation of risk score based on the GGA haplotype combined with the rs9921255 variant showed a much greater effect of the FTO gene on high BMI. This score yields an attributable risk of 34% for severe obesity, and the increased risk per risk allele was 1.71 (P = 1.0 × 10(-6)). We conclude that the description of this polymorphic combination in the FTO gene could be useful for the early identification of inherited susceptibility to weight-gain since childhood, with a higher sensitivity than considering the effect of a single marker.

Questions Do Mediterranean riparian guilds show distinct responses to stream water declines? If observed, which are the most sensitive and resilient guilds and their most affected attributes? Location Tietar river below the Rosarito dam, central-western Spain. Methods We identified riparian guilds based on key woody species features and species distribution within this Mediterranean river corridor, and evaluated similarity of their responses to long-term flow alteration (i.e. stream water declines since dam construction in 1959). Hierarchical cluster analysis was used to group surveyed vegetation bands according to species composition. The groups were designated as riparian guilds where each vegetation group comprising a guild: (1) contains species sharing similar features (using PCA); and (2) shares a similar environment (using DCA). Changes in several guild attributes (i.e. dominance and species composition, diversity and establishment patterns) during the regulated period were compared statistically. We used pre- and post-dam established vegetation bands identified based on old (1956) and modern (2006) aerial photographs and field measurements of woody species diameter. Results Responses to flow alterations varied between guilds according to ecological requirements of their species. The ability to survive water stress (i.e. ‘Xeric’ guilds) and drag forces caused by floods (‘Torrential’ guilds) allowed certain pioneer shrub-dominated guilds (e.g. Flueggea tinctoria and Salix salviifolia) to spread on newly emerged surfaces downward to the main channel after flow alterations, although new shrubland had less species diversity than pre-dam shrubland. In contrast, new hydromorphological conditions following damming limited recruitment of native late-successional tree guilds sensitive to floods (to drag forces, inundation and anoxia; i.e. ‘Slow-water’ and ‘Flood-sensitive’, respectively) and those with greater water requirements (i.e. ‘Hydric’) (e.g. Alnus glutinosa and Celtis australis), although species diversity increased in this mature forest through co-existence of remaining riparian species and new arrival of upland species. Conclusions Changes in several riparian attributes after flow alterations differed between guilds. Stream water declines after damming caused shifts in species-poor pioneer shrubland downwards to the watered channel, resulting in severe declines of mature native forest. Understanding vegetation guild responses provides information about general trends in plant populations and assemblage structures expected to occur during river development and flow regulation, increasing our capacity to detect and synthesize complex flow alteration–riparian ecosystem response relationships, and anticipate irreversible impacts.

We retrospectively analyzed outcomes in 67 children with acute leukemia who received hematopoietic stem cell transplantation from alternative allogeneic donors: 29 received a haploidentical family donor and 38, an unrelated cord blood donor. All transplantations were performed from 1996 through 2010 in our center. Neutrophil and platelet engraftment were significantly delayed after cord blood transplantation. The median times to neutrophil and platelet recovery were 13 d (7-34) and 11 d (5-70) after haploidentical transplant and 20 d (9-125) and 56 d (12-200) after cord blood (P < 0.001). All supportive care measures included red blood cell, and platelet transfusions were significantly increased in cord blood transplantation group.Transplant-related mortality rates was lower with haplo donors (25 ± 9%) than with cord blood donors (47 ± 9%) (P < 0.05). Acute graft-versus-host disease (GVHD) more than grade II was also lower in haploidentical transplants (19 ± 7%) than in cord blood transplants (44 ± 10%) (P < 0.03). Relapse and chronic GVHD incidence were not significantly different in the two groups. Leukemia-free survival was higher after haploidentical transplants (44 ± 10%) than after cord blood transplants (33 ± 7%) (P < 0.03). Main differences were observed in patients diagnosed with acute lymphoblastic leukemia: haplo, 41 ± 13%; cord blood, 26 ± 9% (P < 0.03) and in advanced phase of disease: haplo, 37 ± 14%; cord blood, 21 ± 8% (P < 0.05). In conclusion, haploidentical transplants are a good and promising alternative option for patients with childhood leukemia who lack an human leukocyte antigen-matched donor (sibling or unrelated donor).

This paper analyses a participatory process related to the plan to construct an offshore wind farm in the Sea of Trafalgar, off the coast of Cadiz, in Andalucia (southern Spain). This case study shows the complexities of public participation in energy development, indicating the vital importance of context. The stakeholders' values and attitudes in the controversy are highly dependent on the specific situation, including the concrete characteristics of the project proposal. In fact, they may diverge sharply from the stakeholders' core beliefs. It is important for decision making to take account of this contextual and dynamic element in stakeholder behavior, contrary to suppositions of static and predetermined behavior. Copyright © 2010 John Wiley & Sons, Ltd.

1. Flow dynamics is a major determinant of riparian plant communities. Therefore, flowregulation may heavily affect riparian ecosystems. Despite the large number of damsworldwide, little specific i ...

The use of children as haematopoietic stem cell donors represents an ethical dilemma. For some investigators, this is even more questionable if the children underwent peripheral blood progenitor cell (PBPC) collection. Due to these controversies, information related to adverse events (AE) in paediatric donors and variables related to the collection is scanty. We analysed 152 PBPC collections, and compared the complications and results between young children, older children and adults. The pattern of AE was shown to vary according to the age of the donor. Older paediatric donors and adults had a higher incidence of complaints related to PBPC priming (54.3% vs. 79.7%, respectively) than the youngest children (12%). On the other hand, these donors had a lower incidence of AE during PBPC collection (19.6% older children, 37.3% adults) mainly related to hypocalcaemia, than the youngest donors, who suffered mainly cardiovascular complications due to hypovolaemia (51.7%). The only variables related to collected cell dose were total blood volume processed per donor body weight, and CD34(+) cell count before apheresis. The donor/recipient body weight ratio predicted the outcome of collection in a single large volume leukapheresis. Donors with body weight ratio >or=0.75 had 4.69 times higher likelihood to reach the minimum target cell dose.

Rationale and aims Total hip and knee replacements, usually, have long waiting lists. There are several prioritization tools for these kind of patients. A new tool should undergo a standardized validation process. The aim of the present study was to validate a new prioritization tool for primary hip and knee replacements. Methods We carried out a prospective study. Consecutive patients placed on the waiting list were eligible for the study. Patients included were mailed a questionnaire which included, among other questions, the seven items of the priority tool and the Western Ontario and McMasters Universities Arthritis Index (WOMAC) specific questionnaire. The priority tool gives a score from 0 to 100 points, and three categories (urgent, preferent and ordinary). We studied the content and construct validity. We used Student's t-test or one-way analysis of variance. Correlational analysis was used to evaluate convergent and discriminate validity. Results The sample consisted of 838 patients (62.3% were female), with mean age of 70.2 years (SD 8.4). A total of 55.5% patients underwent knee replacement. Given that the tool was elaborated by patients and orthopaedic surgeons, it shows a good content validity. The priority score was statistically different (P

The work presented here describes the synthesis of new copper(II) complexes derived from 2-amino-5-(pyridin-2-yl)-1,3,4-oxadiazole (L1) and 2-methylamino-5-(pyridin-2-yl)-1,3,4-oxadiazole (L2) which also incorporate azido (N3 -), thiocyanato (NCS-), cyanato (NCO-), dicyanamido [N(CN)2 -, dca] and malonato (C3H2O4 2-, mal) coligands. Structures of the [Cu(L2)(mal)(H2O)]·2H 2O(1), [{Cu(L2)(mal)}2] (2), [Cu(L 2)2-(NCS)2] (3), [Cu(L1)(NCS) 2]n (4) and [{Cu(L2)}2(dca) 2](ClO4)2·2H2O (5) compounds show the dependence of the dimensionality on parameters such as the type of oxadiazole and coligand utilised, solvents or reaction times. In this sense, 1 and 3 are mononuclear complexes, 2 contains centrosymmetric dinuclear entities, 4 is a 1D compound in which thiocyanato groups act as end-to-end bridges and 5 shows a 2D arrangement of dinuclear motifs linked through dicyanamido spacers. The copper(II) ions acquire distorted octahedral (3 and 4), square-pyramidal (1 and 2) and trigonal bipyramidal (5) geometries. Stacking π-π interactions and hydrogen bonds stabilise the crystal frameworks. Water tetramers are present in 1. Spectroscopic (infrared, UV/Vis absorption and electron spin resonance) studies have also been developed for 1-5 and for the Cu(L2)(dca) 2(H2O) (6), Cu(L2)(NCO)2 (7) and Cu(L2)2(N3)2(H2O) 2 (8) complexes. The studies suggest the coordination of oxadiazole and coligands in all cases. Magnetic measurements show antiferromagnetic coupling for compound 5, ferromagnetic interactions for compound 2 and paramagnetic behaviour in compound 4. The susceptibility data were fitted by using the Bleaney-Bowers' equation for the copper(II) dimers derived from H = -2JS1S2. The resultant J/k values are +2.15 and -38.3 K for compounds 2 and 5, respectively. Magneto-structural correlations are discussed and extended to more than 30 published dinuclear Cu(NN) 2Cu′ diazole-only bridged compounds. All these systems show J values close to or greater than those given by the expression J ≈ -90 + 3 Δβ (where Δβ is the difference between the Cu-N-N and Cu-N′-N′ angles). The artificial nuclease activity of 1, 2, 3 and 5 in the presence of mercaptopropionic acid or glutathione has also been analysed and compared with that exhibited by [Cu(L2)2(H 2O)2](NO3)2 and CuSO4. © Wiley-VCH Verlag GmbH & Co. KGaA, 2009., We thank Dr. J. J. Delgado (SCAI, Universidad de Burgos, Spain) for the elemental analyses and Prof. R. Olazcuaga and Dr. F. Guillen (CNRS, Pessac, France) for the reflectance measurements. This work was financially supported by the Junta de Castilla y Leon (BU033A06) and Ministerio de Ciencia y Tecnologia (MCYT) [CTQ2007-63690 (ERDF(EU)-DGI-MCYT)]. P. G.-S. thanks the Universidad de Burgos for a Doctoral Fellowship.