Charge Radii of

Nuclear charge radii of ^{55,56}Ni were measured by collinear laser spectroscopy. The obtained information completes the behavior of the charge radii at the shell closure of the doubly magic nucleus ^{56}Ni. The trend of charge radii across the shell closures in calcium and nickel is surprisingly similar despite the fact that the ^{56}Ni core is supposed to be much softer than the ^{48}Ca core. The very low magnetic moment µ(^{55}Ni)=-1.108(20) µ_{N} indicates the impact of M1 excitations between spin-orbit partners across the N,Z=28 shell gaps. Our charge-radii results are compared to ab initio and nuclear density functional theory calculations, showing good agreement within theoretical uncertainties.

Influence of Metal Salts Addition on Physical and Electrochemical Properties of Ethyl and Propylammonium Nitrate.

In this work, we deepen in the characterization of two protic ionic liquids (PILs), ethylammonium nitrate (EAN) and propylammonium nitrate (PAN). With this aim, we determined the influence of inorganic nitrate salts addition on their physical properties and their electrochemical potential window (EPW). Thus, experimental measurements of electrical conductivity, density, viscosity, refractive index and surface tension of mixtures of {EAN or PAN + LiNO3, Ca(NO3)2, Mg(NO3)2 or Al(NO3)3} at a temperature range between 5 and 95 °C are presented first, except for the last two properties which were measured at 25 °C. In the second part, the corresponding EPWs were determined at 25 °C by linear sweep voltammetry using three different electrochemical cells. Effect of the salt addition was associated mainly with the metal cation characteristics, so, generally, LiNO3 showed the lower influence, followed by Ca(NO3)2, Mg(NO3)2 or Al(NO3)3. The results obtained for the EAN + LiNO3 mixtures, along with those from a previous work, allowed us to develop novel predictive equations for most of the presented physical properties as functions of the lithium salt concentration, the temperature and the water content. Electrochemical results showed that a general order of EPW can be established for both PILs, although exceptions related to measurement conditions and the properties of the mixtures were found.

Aberrant Alternative Splicing in U2af1/Tet2 Double Mutant Mice Contributes to Major Hematological Phenotypes.

Mutations in splicing factors are recurrent somatic alterations identified in myelodysplastic syndromes (MDS) and they frequently coincide with mutations in epigenetic factors. About 25% of patients present concurrent mutations in such pathways, suggesting a cooperative role in the pathogenesis of MDS. We focused on the splicing factor U2AF1 involved in the recognition of the 3' splice site during pre-mRNA splicing. Using a CRISPR/Cas9 system, we created heterozygous mice with a carboxy-terminal truncated U2af1 allele (U2af1mut/+), studied the U2af1mut/+ hematopoietic system, and did not observe any gross differences in both young (12-13 weeks) and old (23 months) U2af1mut/+ mice, except for a reduction in size of approximately 20%. However, hematopoietic stem/progenitor cells lacked reconstitution capacity in transplantation assays and displayed an aberrant RNA splicing by RNA sequencing. We also evaluated U2af1mut/+ in conjunction with Tet2-deficiency. Novel double mutant U2af1mut/+Tet2-/- mice showed increased monogranulocytic precursors. Hematopoietic stem/progenitor cells were also enhanced and presented functional and transcriptomic alterations. Nonetheless, U2af1mut/+Tet2-/- mice did not succumb to MDS disease over a 6-month observation period. Collectively, our data suggest that cooperation between mutant U2af1 and Tet2 loss is not sufficient for MDS initiation in mice.

CRISPR to fix bad blood: a new tool in basic and clinical hematology.

Advances in genome engineering in the last decade, particularly in the development of programmable nucleases, have made it possible to edit the genomes of most cell types precisely and efficiently. Chief among these advances, the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system is a novel, versatile and easy-to-use tool to edit genomes irrespective of their complexity, with multiple and broad applications in biomedicine. In this review, we focus on the use of CRISPR/Cas9 genome editing in the context of hematologic diseases and appraise the major achievements and challenges in this rapidly moving field to gain a clearer perspective on the potential of this technology to move from the laboratory to the clinic. Accordingly, we discuss data from studies editing hematopoietic cells to understand and model blood diseases, and to develop novel therapies for hematologic malignancies. We provide an overview of the applications of gene editing in experimental, preclinical and clinical hematology including interrogation of gene function, target identification and drug discovery and chimeric antigen receptor T-cell engineering. We also highlight current limitations of CRISPR/Cas9 and the possible strategies to overcome them. Finally, we consider what advances in CRISPR/Cas9 are needed to move the hematology field forward.

[Cervical paraspinal chordoma, a condition we should know. A case report]. / Cordoma cervical paravertebral, entidad que debemos conocer. A propósito de un caso.

Chordoma is a rare, slow-growing tumour arising from remnants of the notochord. It is most often located in the base of the skull and the sacrococcygeal region, being located in the cervical region in only 6% of cases. A rare case is presented of a left para-spinal chordoma, of which less than 10 cases have been reported in literature. It was located at C2-C4 level in a young male with no personal history of interest. Radiographic findings suggested that this was a slow-growing tumour, of cystic dominance, which eroded the bone structures and encompassed the left vertebral artery. Surgical excision was performed, and in the analysis of the surgical piece, cell proliferation was observed, with a stromal myxoid-chondroid appearance, epithelioid and physaliphorous (PAS+) cells, all of them compatible with chordoma.

[Drug prescriptions study in the outpatient setting: assessment of off-label uses in children]. / Estudio de las prescripciones farmacológicas en niños a nivel de atención primaria: evaluación de los usos off-label o fuera de ficha técnica.

OBJECTIVE: to evaluate the prescription profile and to assess the off-label and unlicensed uses of medicines among non-hospitalised pediatric patients. DESIGN: cross-sectional study. SETTING: pediatric units in two urban health centers and general emergency room (Hospital Materno-Infantil, Málaga). MAIN MEASUREMENTS: sociodemographics variables, reasons for consultation and information about therapeutic medications. The classification of prescriptions was established according to information requirements contained in the Summary of Products Characteristics (SPC). RESULTS: A total of 388 children were included (a subsample of 105 treated in the emergency room). Four hundred sixty-two prescriptions (involving 74 different active ingredients) were evaluated. Each infant received and average of 1,7 drugs (95% CI: 1,6-1,9). The most prescribed medicines were ibuprofen, paracetamol, amoxicillin-clavulanate and budesonide. The therapeutic group with the greatest variety of drugs was the respiratory group. 27,4% (95% CI: 23,5-31) of prescriptions were off-label and the main cause was different age (60%; 95% CI: 54,1-63), followed by different dose (21,5%; 95% CI: 18-25), different indication (12%; 95% CI: 9,2-15) and different route of administration (7%; 95% CI: 5,4-10). CONCLUSIONS: The rate of off-label uses presents intermediate figures. Around one third of the paediatric outpatients in our sample are exposed to at least one off-label or unlicensed prescription. We should, however, point out that such usage is based on scant official, quality information, although it is not necessarily incorrect. Evidence-based medicine should be encouraged to improve drug therapy in children, as well as following the rules on drugs in special situations.

Academic Burnout, Personality, and Academic Variables in University Students.

This study examines academic burnout syndrome and its relation to personal and academic variables among university students in nursing and early childhood education programs in Spain. A total of 606 university students (primary education: 49.7%; nursing: 49.7%) of both sexes (71.5% female) with an average age of 20.68 years (SD = 1.65) participated. An ex post facto retrospective single-group design was planned. The instruments used were the Maslach Burnout Inventory-Student Survey (MBI-SS) and the NEO Five-Factor Inventory (NEO-FFI). Nursing students, who reported more study hours, less sleep, and lower grades, had higher academic burnout scores. Linear regression models were proposed to analyze the relationship between academic burnout, personality, and sociodemographic variables. Nursing students scored higher in emotional exhaustion and lower in cynicism, and they scored higher in neuroticism and openness. Furthermore, 16.1% of the variance in academic burnout was explained by personality variables as well as the degree studied, course year, and study hours. These findings suggest the importance of considering both academic and personality variables in understanding academic burnout in university students.

Real-World Effectiveness and Safety of SDZ ETN, an Etanercept Biosimilar, in Patients with Rheumatic Diseases: Final Results from Multi-Country COMPACT Study.

INTRODUCTION: COMPACT, a non-interventional study, evaluated the persistence, effectiveness, safety and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA), axial-spondyloarthritis (axSpA) or psoriatic arthritis (PsA) treated with SDZ ETN (etanercept [ETN] biosimilar) in Europe and Canada. METHODS: Patients (aged ≥ 18 years) who have been treated with SDZ ETN were categorised on the basis of prior treatment status (groups A-D): patients in clinical remission or with low disease activity under treatment with reference ETN or biosimilar ETN and switched to SDZ ETN; patients who received non-ETN targeted therapies and switched to SDZ ETN; biologic-naïve patients who started SDZ ETN after conventional therapy failure; or disease-modifying anti-rheumatic drug (DMARD)-naïve patients with RA considered suitable for treatment initiation with a biologic and started on treatment with SDZ ETN. The primary endpoint was drug persistence, defined as time from study enrolment until discontinuation of SDZ ETN treatment. RESULTS: Of the 1466 patients recruited, 844 (57.6%) had RA, 334 (22.8%) had axSpA and 288 (19.6%) had PsA. Patients had an ongoing SDZ ETN treatment at the time of enrolment for an observed average of 138 days (range 1-841); 22.7% of patients discontinued SDZ ETN through 12 months of study observation. Overall, all the patients receiving SDZ ETN showed good treatment persistence at 12 months with discontinuation rates of 15.2%, 25.7% and 27.8% in groups A, B and C, respectively. Across all patient groups, no major differences were observed in the disease activity and PRO scores between baseline and month 12. Injection-site reactions were low across the treatment groups. CONCLUSION: These results support the effectiveness and safety of SDZ ETN treatment in patients with RA, axSpA or PsA in real-life conditions. The treatment persistence rates observed were consistent with previously published reports of patients treated with reference or other biosimilar ETN. No new safety signals were identified.

A Carbon Paste Electrode Modified by Bentonite and l-Cysteine for Simultaneous Determination of Ascorbic and Uric Acids: Application in Biological Fluids.

A novel modification of a paste carbon electrode by Bentonite (Bent) and l-Cysteine (l-Cyst) was carried out for uric acid (UA) and ascorbic acid (AA) detection and quantification. Morphological and compositional characterization of the electrode surface were carried out using electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopic analysis (EDS). Cyclic voltammetry (CV) and square wave voltammetry (SWV) techniques were used to analyze UA and AA. The obtained sensor shows a good stability, sensibility, selectivity, and regeneration ability. Accordingly, the limit of detection (LOD) is found to be 0.031 µm and 9.6 µm for UA and AA, respectively. A good linearity in the range of 0.1 to 100 µm for UA and 10 to 1000 µm for AA was obtained. The peak-to-peak separation of UA-AA (ΔEUA-AA ) was determined to be 330 mV. In addition, the sensor is applied successfully to monitor UA and AA in serum samples.

PCR-Based Strategy for Introducing CRISPR/Cas9 Machinery into Hematopoietic Cell Lines.

Acute myeloid leukemia is a complex heterogeneous disease characterized by the clonal expansion of undifferentiated myeloid precursors. Due to the difficulty in the transfection of blood cells, several hematological models have recently been developed with CRISPR/Cas9, using viral vectors. In this study, we developed an alternative strategy in order to generate CRISPR constructs by fusion PCR, which any lab equipped with basic equipment can implement. Our PCR-generated constructs were easily introduced into hard-to-transfect leukemic cells, and their function was dually validated with the addition of MYBL2 and IDH2 genes into HEK293 cells. We then successfully modified the MYBL2 gene and introduced the R172 mutation into the IDH2 gene within NB4 and HL60 cells that constitutively expressed the Cas9 nuclease. The efficiency of mutation introduction with our methodology was similar to that of ribonucleoprotein strategies, and no off-target events were detected. Overall, our strategy represents a valid and intuitive alternative for introducing desired mutations into hard-to-transfect leukemic cells without viral transduction.

Complete genome sequence of a potyvirus infecting yam beans (Pachyrhizus spp.) in Peru.

In 2010, yam beans in a field trial in Peru showed viral disease symptoms. Graft-transmission and positive ELISA results using potyvirus-specific antibodies suggested that the symptoms could be the result of a potyviral infection. Small interfering RNA (siRNA) were extracted from one of the samples and sent for high-throughput sequencing. The full genome of a new potyvirus could be assembled from the resulting siRNA sequences, and it was sufficiently different from other sequences to be considered a member of a new species, which we have designated Yam bean mosaic virus (YBMV). Sequence similarity suggests that YBMV has also been detected in yam beans in Indonesia.

Effects of dietary cadmium exposure on osmoregulation and urine concentration mechanisms of the semi-desert rodent Meriones shawi.

Contamination by cadmium in the environment is of great concern because of its toxicity and threats to human and animal health. The current study was conducted to investigate the effects of a cadmium contaminated diet on the osmoregulation and urine concentration mechanisms of the semi-desert rodent Meriones shawi and eventual accumulation of this metal in vital organs such as the kidneys, which are directly implicated in water regulation. Originally, we used Differential Pulse Anodic Stripping Voltammetry (DPASV) to avoid the matrix interference due to the highly organic content in the biological samples. Our results show that Meriones shawi successfully maintained a homeostasis state and presented a special adaptation to regulate urine volume during cadmium exposure by decreasing diuresis and increasing urinary osmolality. The plasma osmolality and hematocrit remained constant throughout the experiment. The stripping signals of cadmium are linear up to 0.3-100 µg L(-1) range, with a detection limit of 0.28 µg L(-1). The DPASV technique was useful for easy, fast, selective and sensitive determination of Cd, which permits working at cellular concentration. This gives us more information about the chemical form in which Cd is introduced into the organ, as well as the intracellular Cd quantities. This study has potential importance if this valuable novel animal model, imitating human and animal environmental chronic exposure to Cd, could serve as an appropriate terrestrial biomonitor for Cd contaminated sites. These results are encouraging in the context of developing a low-cost and fast technology for the detection of pollutants and for studying the impairment caused by their effects.

Novel Pyridazin-3(2H)-one-Based Guanidine Derivatives as Potential DNA Minor Groove Binders with Anticancer Activity.

Novel aryl guanidinium analogues containing the pyridazin-3(2H)-one core were proposed as minor groove binders (MGBs) with the support of molecular docking studies. The target dicationic or monocationic compounds, which show the guanidium group at different positions of the pyridazinone moiety, were synthesized using the corresponding silyl-protected pyridazinones as key intermediates. Pyridazinone scaffolds were converted into the adequate bromoalkyl derivatives, which by reaction with N,N'-di-Boc-protected guanidine followed by acid hydrolysis provided the hydrochloride salts 1-14 in good yields. The ability of new pyridazin-3(2H)-one-based guanidines as DNA binders was studied by means of DNA UV-thermal denaturation experiments. Their antiproliferative activity was also explored in three cancer cell lines (NCI-H460, A2780, and MCF-7). Compounds 1-4 with a bis-guanidinium structure display a weak DNA binding affinity and exhibit a reasonable cellular viability inhibition percentage in the three cancer cell lines studied.

High efficiency laser resonance ionization of plutonium.

Three-step resonance photoionization spectra of plutonium have been studied with Ti:Sapphire lasers for the development of efficient laser ionization schemes for ultra-trace analysis of Pu isotopes by resonance ionization mass spectrometry. We observed eighteen intermediate excited states of even parity in the energy range 35568-36701 [Formula: see text], thirteen of them have not been previously documented, and a larger number of high-lying excited states and autoionizing states of odd-parity between 48238 and 49510 [Formula: see text]. Three-color, three-photon ionization schemes via six intermediate states were evaluated under similar ion source operating conditions. This led to a highly efficient three-step scheme with an overall ionization efficiency of [Formula: see text], which is an order of magnitude improvement over the previously reported ionization efficiency for Pu.

The Quantity and Quality of Anxiety Are Mediating Variables between Motivation, Burnout and Fear of Failing in Sport.

The purpose of this study was to examine the effect mediated by self-determined motivation on an athlete's burnout, anxiety and fear of failure. To this end, the sample group consisting of 235 semi-professional yachtsmen and women was asked to answer four questionnaires which set out to assess each of the study's variables: Behavioural Regulation in Sport Questionnaire, Performance Failure Appraisal Inventory, Sport Anxiety Scale-2 and Athlete Burnout Questionnaire. The ex-post facto research was designed to analyse a single group based on structural equation modelling (SEM) between the constructs under analysis. The results illustrate that behavioural regulation could be used to positively predict burnout and fear of failure mediated by sport anxiety. Moreover, behavioural regulation has a significant, positive and moderate bearing on burnout and is wholly mediated by sport anxiety. It concludes by underscoring the point that there is no relationship either between behavioural regulation and burnout or between behavioural regulation and fear of failure, unless the athlete in question experiences anxiety.

A Single-Run Next-Generation Sequencing (NGS) Assay for the Simultaneous Detection of Both Gene Mutations and Large Chromosomal Abnormalities in Patients with Myelodysplastic Syndromes (MDS) and Related Myeloid Neoplasms.

Myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms are clonal disorders that share most of their cytogenetic and molecular alterations. Despite the increased knowledge of the prognostic importance of genetics in these malignancies, next-generation sequencing (NGS) has not been incorporated into clinical practice in a validated manner, and the conventional karyotype remains mandatory in the evaluation of suspected cases. However, non-informative cytogenetics might lead to an inadequate estimation of the prognostic risk. Here, we present a novel targeted NGS-based assay for the simultaneous detection of all the clinically relevant genetic alterations associated with these disorders. We validated this platform in a large cohort of patients by performing a one-to-one comparison with the lesions from karyotype and single-nucleotide polymorphism (SNP) arrays. Our strategy demonstrated an approximately 97% concordance with standard clinical assays, showing sensitivity at least equivalent to that of SNP arrays and higher than that of conventional cytogenetics. In addition, this NGS assay was able to identify both copy-neutral loss of heterozygosity events distributed genome-wide and copy number alterations, as well as somatic mutations within significant driver genes. In summary, we show a novel NGS platform that represents a significant improvement to current strategies in defining diagnosis and risk stratification of patients with MDS and myeloid-related disorders.

Screen-printed electrodes-based technology: Environmental application to real time monitoring of phenolic degradation by phytoremediation with horseradish roots.

The following is a description of a simple strategy for monitoring phenolic pollutants from highly-contaminated water samples. These phenolic compounds are removed from tap water using horseradish roots (Raphanus sativus) that contain peroxidase as catalyst and H2O2 to generate hydroxyl radicals. The later (•OH) acts on the aromatic structure, causing them to degrade to non-toxic by-products. The tool used to follow up the evolution of the process is based on screen-printed carbon electrodes (SPCEs) as electrochemical sensor for simultaneous detection of hydroquinone (Epa at 0.047 V), m-cresol (Epa at 0.506 V) and 4-nitrophenol (Epa at 0.696 V) by differential pulse voltammetry (DPV). This electroanalytical methodology enables close monitoring of the situation and rapid sensor response time. Furthermore, this direct methodology works for opaque and heterogeneous samples, as tap water with chopped horseradish roots, without any treatment of samples previously to the analysis. For better knowledge of the electrodic-transfer process, the electrochemical behavior of these phenolic compounds by cyclic voltammetry (CV) is also included. This simple methodology shows a low detection limit (below to 5 µM) and an excellent selectivity (peak potential separation between them up to 200 mV or greater) in a linear range of three orders of concentration (from 1-5 µM to 1 mM) for all of the analytes studied. The DPV responses of the phenolic compounds during the phytoremediation process are simultaneously monitored by this direct, cheap, reproducible (RSD < 2.3%) and rapid DPV-SPCE electroanalytical methodology. Portable device as electrochemical sensor with this optimized and validated technology can be applied for decentralized analysis, on-site assays and rapid screening purposes. The use of the horseradish roots achieves the total elimination of phenolic pollutants in concentrations 1000 times higher than the legal limits in less than 1 h.

Basic Psychological Needs, Burnout and Engagement in Sport: The Mediating Role of Motivation Regulation.

The purpose of the present research was to analyze the mediating role of motivational regulation between the satisfaction of basic psychological needs and burnout and engagement in athletes. From different sports 1011 young Spanish athletes participated in the study. Participants completed several measurement instruments concerning: the Basic Needs Satisfaction in Sport Scale, Behavioral Regulation in Sport Questionnaire, Athlete Burnout Questionnaire and Athlete Engagement Questionnaire. The results of structural equation modeling showed that the satisfaction of basic psychological needs has direct effects on burnout and engagement: a negative effect on athlete burnout (-0.49, p < 0.001) and a positive effect on engagement (0.54, p < 0.001). In addition, the satisfaction of basic psychological needs has a partial indirect effect over these variables in the same direction mediated by the self-determined degree of motivation. Thus, low levels of self-regulated motivation are positively related to burnout, but high levels of self-determined motivation are not. The same was observed with engagement, but vice versa: high levels of self-determined motivation are positively related to athlete engagement, but low levels of self-determined motivation are not. The proposed model explained 37% of the variance of burnout and 51% of the variance of engagement.

Systematic Observation of the Verbal Behavior of Families of Youth Athletes in Grassroots and Team Sports.

Some of the more protective and favorable factors for the development and health in children and teenagers are family and sport, so family involvement in the children's sports activities is vital in their sports process. The purpose of this study was to analyze the verbal behavior (positive, negative, and neutral comments) of family spectators of school-age athletes regarding sociodemographic and sporting variables. The sample consisted of 190 family spectators of 215 male and female (Mage = 11.66; SD = 1.60) football, basketball, and volleyball players. The Parents' Observation Instrument at Sport Events (POISE) was used for the observation and LINCE was used to codify the verbal comments made. After registering 38,829 comments, the results showed statistically significant differences in relation to the comments made and the gender of athletes, geographical area, kind of sport, and the sporting category. The findings highlight that in a competitive environment, the comments made by spectators related to athletes do not seem to be initiators of potentially violent situations but rather are dependent on the atmosphere in question. Further research is required in this area to foster positive conduct relating to grassroots sports.

Analysis of SNP Array Abnormalities in Patients with DE NOVO Acute Myeloid Leukemia with Normal Karyotype.

Nearly 50% of patients with de novo acute myeloid leukemia (AML) harbor an apparently normal karyotype (NK) by conventional cytogenetic techniques showing a very heterogeneous prognosis. This could be related to the presence of cryptic cytogenetic abnormalities (CCA) not detectable by conventional methods. The study of copy number alterations (CNA) and loss of heterozygozity (LOH) in hematological malignancies is possible using a high resolution SNP-array. Recently, in clinical practice the karyotype study has been complemented with the identification of point mutations in an increasing number of genes. We analyzed 252 de novo NK-AML patients from Hospital La Fe (n = 44) and from previously reported cohorts (n = 208) to identify CCA by SNP-array, and to integrate the analysis of CCA with molecular alterations detected by Next-Generation-sequencing. CCA were detected in 58% of patients. In addition, 49% of them harbored CNA or LOH and point mutations, simultaneously. Patients were grouped in 3 sets by their abnormalities: patients carrying several CCA simultaneously, patients with mutations in FLT3, NPM1 and/or DNMT3A and patients with an amalgam of mutations. We found a negative correlation between the number of CCA and the outcome of the patients. This study outlines that CCA are present in up to 50% of NK-AML patients and have a negative impact on the outcome. CCA may contribute to the heterogeneous prognosis.