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Charge-altering releasable transporters (CARTs) are a class of oligonucleotide delivery vehicles shown to be effective for delivery of messenger RNA (mRNA) both in vitro and in vivo. Here, we exploited the chemical versatility of the CART synthesis to generate CARTs containing the small-molecule drug fingolimod (FTY720) as a strategy to increase mRNA delivery and expression in lymphocytes through a specific ligand−receptor interaction. Fingolimod is an FDA-approved small-molecule drug that, upon in vivo phosphorylation, binds to the sphingosine-1-phosphate receptor 1 (S1P1), which is highly expressed on lymphocytes. Compared to its non-fingolimod-conjugated analogue, the fingolimod-conjugated CART achieved superior transfection of activated human and murine T and B lymphocytes in vitro. The higher transfection of the fingolimod-conjugated CARTs was lost when cells were exposed to a free fingolimod before transfection. In vivo, the fingolimod-conjugated CART showed increased mRNA delivery to marginal zone B cells and NK cells in the spleen, relative to CARTs lacking fingolimod. Moreover, fingolimod-CART-mediated mRNA delivery induces peripheral blood T-cell depletion similar to free fingolimod. Thus, we show that functionalization of CARTs with a pharmacologically validated small molecule can increase transfection of a cellular population of interest while conferring some of the targeting properties of the conjugated small molecule to the CARTs.

Hallux valgus is a high frequency disorder, affecting the first ray. Operative correction techniques have grown popularity lately. One of them is the Reverdin-Isham technique (first metatarsal medial incomplete osteotomy). Recently, a protection and osteotomy cutting guide has been developed: the BARU system.To test the usefulness of the BARU system as a protective factor for soft structures adjacent to the surgical site and guidance for osteotomy.Experimental cadaveric study. Six cadaveric feet (two fresh-frozen and four in formaldehyde solution), unapproached. Feet were numbered and intervened with RI technique, three of them with BARU system and three without it. Afterwards, dissection by two dissectors who did not know whether the BARU system had been used or not, establishing a single-blinded model. 13 structures were evaluated in each foot. Data was recovered into Microsoft Office Excel and processed with SPSS. 2 test (significative if p value0.05) and relative risk were calculated.Approach using BARU system was satisfactory, with usual-size operation-ports. BARU system colocation was simple and radiological control showed adequate spatial location. The device contributed as reference for cutting direction and depth. 65 out of the 78 searched structures were found (83.3%). Six injuries were found among the assessed structures: plantar medial nerve (one injury), plantar medial artery (one injury), flexor brevis muscle (three injuries), abductor muscle (one injury). Five of these injuries occurred in non-utilizing BARU system feet.Promising results in terms of protection of nearby structures, cutting guide, and ease of intervention. Avoids X-rays exposure. Not significant statistical calculations, the sample should be enlarged.El hallux valgus es una patología con alta prevalencia en la población. Técnicas de corrección quirúrgica han crecido en popularidad últimamente. Una de ellas es la de Reverdin-Isham (RI: osteotomía incompleta medial en primer metatarsiano), se desarrolló un dispositivo de protección y guía de corte para dicho procedimiento: el sistema BARU.Probar la utilidad del sistema BARU como factor protector de estructuras blandas adyacentes al sitio de abordaje y guía para osteotomía.Estudio cadavérico; seis pies (dos frescos y cuatro formolados) sin abordajes previos. Tres con el sistema BARU y tres sin éste. Posteriormente disección por dos disectores con enmascaramiento simple ciego. Se evaluaron 13 estructuras en cada pie. Los datos fueron recabados con Microsoft Office Excel y procesados en SPSS. Se realizó test de 2 (valor p0.05 significativo) y se calculó el riesgo relativo.El sistema BARU fue satisfactorio. Su colocación fue sencilla y el control radiológico mostró adecuada ubicación espacial. Ayudó como referencia para la dirección y profundidad del corte. Se encontraron 65 de las 78 estructuras buscadas (83.3%). En las estructuras evaluadas hubo seis lesiones: nervio plantar medial (uno dañado), arteria plantar medial (uno dañado), músculo flexor corto (tres dañados), músculo abductor (uno dañado). Cinco de estas lesiones ocurrieron en pies donde no se utilizó el sistema BARU.Resultados prometedores en cuanto a protección de estructuras cercanas, guía de corte y facilidad para la intervención. Cálculos estadísticos no significativos, la muestra debería ampliarse.

In 2016, the WHO included haemoglobin values within normal ranges as a diagnostic criterion for Polycythaemia Vera (PV). Since then, concerns have arisen that a large number of patients are undergoing unnecessary screening for PV. To address this issue, we estimated the prevalence of JAK2 p.V617F in individuals with elevated haemoglobin or haematocrit and developed and validated a screening algorithm for PV. A total of 15,366 blood counts performed in seven non-consecutive days were reviewed, of which 1001 were selected for subsequent JAK2 p.V617F mutation screening. Eight (0.8%) new JAK2 p.V617F-mutated cases were detected. From ROC curves, a two-step algorithm was developed based on the optimal cut-off for the detection of the JAK2 p.V617F mutation. The algorithm was prospectively validated in an independent cohort of 15,298 blood counts. A total of 1595 (10.4%) cases met the criterion for haemoglobin or haematocrit, of whom 581 passed to step 2 (3.8% of the total). The JAK2 p.V617F mutation was detected in 7 of the 501 patients tested, which accounts for 0.04% of the total cohort and 0.4% of patients with erythrocytosis. In conclusion, this data show that our two-step algorithm improves the selection of candidates for JAK2 p.V617F testing.

Sternoclavicular epiphysiolysis is a rare lesion, the posterior variant being even less common. Its clinical presentation may be subtle, or it may compromise mediastinal structures, either initially or during evolution, which is a serious and potentially fatal picture. This case report documents sternoclavicular dissociation in a patient with an immature skeleton, given by a Salter and Harris 1-type injury, which was surgically treated by open reduction and internal fixation with transosseous configuration with non-reabsorbable suture. With a 10-month follow-up and excellent results. This technique seems to be a good option for the treatment of sternoclavicular dislocation in the schematically immature patient, regaining function and avoiding complications.La epifisiólisis esternoclavicular es una lesión rara, siendo la variante posterior aún menos frecuente. Su presentación clínica puede ser sutil o puede comprometer estructuras mediastinales, ya sea inicialmente o durante la evolución, lo que constituye un cuadro grave y potencialmente fatal. Este reporte de caso documenta una disociación esternoclavicular en un paciente con esqueleto inmaduro, dada por una lesión fisaria tipo Salter y Harris 1, la que se trató quirúrgicamente mediante reducción abierta y fijación interna con lazadas en ocho transóseas con sutura no reabsorbible. Con un seguimiento de 10 meses y resultados excelentes. Esta técnica parece ser una buena opción para el tratamiento de luxación esternoclavicular en el paciente esquemáticamente inmaduro, recuperando la función y evitando complicaciones.

Ce3+ single-doped, Ce3+-Tb3+, Ce3+-Eu3+ and Tb3+-Eu3+ co-doped, and Ce3+-Tb3+-Eu3+ triply-doped nano-glass-ceramics (nGCs), containing cubic 10 nm size BaGdF5 nanocrystals, were synthesized by thermal treatment of precursor sol-gel glasses. The structural characterization was carried out by X-ray diffraction, transmission electron microscopy and energy dispersive X-ray spectroscopy, while the spectroscopic study was performed by excitation and emission spectra, along with lifetime measurements. In the Ce3+ single-doped, and Ce3+-Tb3+, Ce3+-Eu3+ co-doped nGCs, the emission spectra by exciting in the maximum of the UV excitation band of Ce3+ ions (∼ 300 nm) show a UV-violet broad band corresponding to the emission of Ce3+ ions. Additionally, Gd3+ UV, Tb3+ green and Eu3+ red emission peaks are also observed respectively, revealing an energy transfer mechanism from the Ce3+ to these ions. For the Tb3+-Eu3+ co-doped nGCs, efficient energy transfer from Gd3+ host to Tb3+ and Eu3+, and from Tb3+ to Eu3+ ions were also evidenced. Moreover, taking advantage of the Eu3+ properties as structural probe ion, it was found that an important fraction of dopant ions were incorporated to the BaGdF5 nanocrystalline environments. In the Ce3+-Tb3+-Eu3+ triply-doped nGCs, intense and simultaneous UV-violet, green and red emissions were observed under Ce3+ excitation. Moreover, it was shown that the emitted colour can be tuned by varying the Eu3+ doping level and/or the excitation wavelength. After the analysis of nGCs luminescent features, the energy transfer and metal-metal charge transfer mechanisms, responsible of these emissions, are proposed. Results suggest these materials have potential applications as efficient UV to VIS converters.

Sol-gel derived nano-glass-ceramics with composition 95SiO2-5BaY0.78-xGdxYb0.2Tm0.02F5, where x = 0, 0.2, 0.4, 0.6 and 0.78, were obtained after adequate thermal treatments of precursor glasses. X-ray diffraction, transmission electron microscope and energy dispersive X-ray spectroscopy, confirmed the precipitation and distribution of nanocrystals, with sizes around 10–13 nm, in an amorphous silica network. Under excitation at 980 nm, along with blue, red and NIR characteristic up-conversion emissions of Tm3+ ions, intense UV up-conversion emissions coming from 1I6 and 1D2 levels of Tm3+ ions were also observed in all the studied samples. Additionally, when substituting Y3+ by Gd3+ ions, UV up-conversion emissions coming from Gd3+ ions, along with a reduction of the UV up-conversion emissions of Tm3+ ions, were observed, involving an energy transfer process from Yb3+/Tm3+ systems to Gd3+ ions. UC mechanisms and energy transfer processes were confirmed by transient emission and pump power measurements. Moreover, power dependence analysis revealed saturation effects in all up-conversion emissions, even at low pump power. Results suggest that these highly efficient up-conversion nano-glass-ceramics present potential applications as UV-blue solid state laser materials and solid state lighting.

Substrate selectivity in reductive multielectron/proton catalysis with small molecules such as N2, CO2, and O2 is a major challenge for catalyst design, especially where the competing hydrogen evolution reaction (HER) is thermodynamically and kinetically competent. In this study, we investigate how the selectivity of a tris(phosphine)borane iron(I) catalyst, P3BFe+, for catalyzing the nitrogen reduction reaction (N2RR, N2-to-NH3 conversion) versus HER changes as a function of acid p Ka. We find that there is a strong correlation between p Ka and N2RR efficiency. Stoichiometric studies indicate that the anilinium triflate acids employed are only compatible with the formation of early stage intermediates of N2 reduction (e.g., Fe(NNH) or Fe(NNH2)) in the presence of the metallocene reductant Cp*2Co. This suggests that the interaction of acid and reductant is playing a critical role in N-H bond-forming reactions. DFT studies identify a protonated metallocene species as a strong PCET donor and suggest that it should be capable of forming the early stage N-H bonds critical for N2RR. Furthermore, DFT studies also suggest that the observed p Ka effect on N2RR efficiency is attributable to the rate and thermodynamics of Cp*2Co protonation by the different anilinium acids. Inclusion of Cp*2Co+ as a cocatalyst in controlled potential electrolysis experiments leads to improved yields of NH3. The data presented provide what is to our knowledge the first unambiguous demonstration of electrocatalytic nitrogen fixation by a molecular catalyst (up to 6.7 equiv of NH3 per Fe at -2.1 V vs Fc+/0).

Spectral conversion of light is an emerging route for enhancing the efficiency of solar energy harvesting schemes. We present high intense UV-blue up-conversion emissions in Sr2YbF7:Tm3+@Sr2YF7 core-shell nanocrystals successfully obtained by solvothermal method. Photocatalytic degradation of organic dye methylene blue (MB), as a pollutant model, has been successfully achieved under NIR radiation, by means of upconversion luminescence coming from core-shell nanocrystals. Thus, we probe a solely upconversion photonic effect to degrade the organic pollutant, converting the incident NIR radiation before its interaction with titanium dioxide photocatalyst.

RE-doped (Yb3+, Er3+ and Tm3+) nano-glass-ceramics (nGCs) comprising BaGdF5 nanocrystals have been developed under thermal treatment of precursor sol-gel glasses. Structural analysis by means of X-ray diffraction patterns, high-resolution transmission electron microscopy images, and energy dispersive X-ray spectroscopy measurements, confirmed the precipitation and distribution of cubic BaGdF5 nanocrystals (around 10 nm in size) in the silica glass matrix. Under near-IR excitation at 980 nm, up-conversion (UC) emissions have been studied as a function of selected dopants, the doping level and the pump power. In addition to the characteristic NIR, vis and UV UC emissions of Er3+ and Tm3+ dopant ions, the studied nGCs present intense UV UC emissions of the host fluoride nanocrystal, Gd3+. It was also observed that the relative Yb3+ content tended to improve the UC emission intensities. Corresponding UC mechanisms and energy transfer processes were analysed in terms of their energy level diagrams and confirmed by transient emission and pump power measurements. Moreover, power dependence analysis revealed that these emissions present saturation effects with the increase of Yb3+ content, even at low pump power. Results suggest that these high-efficiency UC nGCs have potential applications in UV solid state laser materials, solid state lighting and photovoltaics.

This report focuses on Cu(I) catalyzed cycloaddition reactions between organic azides and the platinum diacetylide complexes trans-(PR3)2Pt(C≡CR′)2 (where PR3 = P(OEt)3, PEt3, PnBu3, PPhMe2, PPh3, and PBn3; and R′ = H, Ph, and p-PhNO2). Pt(II)-Diacetylides supported by P(OEt)3, PEt3, PnBu3, and PPhMe2 react with benzyl azide to provide syn/anti isomers of double cycloaddition products. In contrast, Pt(II)-diacetylide complexes supported by PPh3 and PBn3 afford single cycloaddition products, exclusively. Steric congestion enforced by the larger phosphines PPh3 and PBn3 prevent the second cycloaddition. Ground state DFT computations provide some insight into the divergent reactivity and indicate that the π-acidity of the phosphine ligands is a variable in the single vs double cycloaddition outcome.

RE3+ (Ce3+, Gd3+, Tb3+, Eu3+)-doped LaF3 silica nano-glass-ceramics (nGCs) were obtained by thermal treatment of precursor sol-gel glasses. The precipitation and distribution of spherical LaF3 nanocrystals (NCs) with sizes around 8.5 nm in the silica matrix were confirmed by X-ray diffraction patterns, transmission electron microscope images and energy dispersive X-ray spectroscopy measurements. Very efficient energy transfer mechanisms from Ce3+ to Tb3+ or Eu3+ ions, mediated by Gd3+ ions through the Ce3+→(Gd3+)n→(Tb3+/Eu3+) scheme, were observed in Ce3+-Gd3+-Tb3+ and Ce3+-Gd3+-Eu3+ co-doped nGCs, yielding intense green and red emissions, respectively. Moreover, simultaneous and tuneable Ce3+ sensitized Tb3+ and Eu3+ emissions were obtained in Ce3+-Gd3+-Tb3+-Eu3+ co-doped nGCs by varying the content of Tb3+ and Eu3+ ions, and the corresponding energy transfer mechanisms were analysed. Results suggest these nGCs as potential UV to VIS converters in the field of lighting and display.

RE-doped (Yb3+, Er3+ and Tm3+) nano-glass-ceramics (nGCs) comprising BaGdF5 nanocrystals have been developed under thermal treatment of precursor sol-gel glasses. Structural analysis by means of X-ray diffraction patterns, high-resolution transmission electron microscopy images, and energy dispersive X-ray spectroscopy measurements, confirmed the precipitation and distribution of cubic BaGdF5 nanocrystals (around 10 nm in size) in the silica glass matrix. Under near-IR excitation at 980 nm, up-conversion (UC) emissions have been studied as a function of selected dopants, the doping level and the pump power. In addition to the characteristic NIR, vis and UV UC emissions of Er3+ and Tm3+ dopant ions, the studied nGCs present intense UV UC emissions of the host fluoride nanocrystal, Gd3+. It was also observed that the relative Yb3+ content tended to improve the UC emission intensities. Corresponding UC mechanisms and energy transfer processes were analysed in terms of their energy level diagrams and confirmed by transient emission and pump power measurements. Moreover, power dependence analysis revealed that these emissions present saturation effects with the increase of Yb3+ content, even at low pump power. Results suggest that these high-efficiency UC nGCs have potential applications in UV solid state laser materials, solid state lighting and photovoltaics.

Well-defined molecular catalysts for the reduction of N2 to NH3 with protons and electrons remain very rare despite decades of interest and are currently limited to systems featuring molybdenum or iron. This report details the synthesis of a molecular cobalt complex that generates superstoichiometric yields of NH3 (200% NH3 per Co-N2 precursor) via the direct reduction of N2 with protons and electrons. While the NH3 yields reported herein are modest by comparison to those of previously described iron and molybdenum systems, they intimate that other metals are likely to be viable as molecular N2 reduction catalysts. Additionally, a comparison of the featured tris(phosphine)borane Co-N2 complex with structurally related Co-N2 and Fe-N2 species shows how remarkably sensitive the N2 reduction performance of potential precatalysts is. These studies enable consideration of the structural and electronic effects that are likely relevant to N2 conversion activity, including the π basicity, charge state, and geometric flexibility.

PRPS1 encodes isoform I of phosphoribosylpyrophosphate synthetase (PRS-I), a key enzyme in nucleotide biosynthesis. Different missense mutations in PRPS1 cause a variety of disorders that include PRS-I superactivity, nonsyndromic sensorineural hearing impairment, Charcot-Marie-Tooth disease, and Arts syndrome. It has been proposed that each mutation would result in a specific phenotype, depending on its effects on the structure and function of the enzyme.Thirteen Spanish unrelated families segregating X-linked hearing impairment were screened for PRPS1 mutations by Sanger sequencing. In two positive pedigrees, segregation of mutations was studied, and clinical data from affected subjects were compared.We report two novel missense mutations in PRPS1, p.Ile275Thr and p.Gly306Glu, which were found in the propositi of two unrelated Spanish families, both subjects presenting with nonsyndromic hearing impairment. Further investigation revealed syndromic features in other hemizygous carriers from one of the pedigrees. Sequencing of genes that are functionally related to PRPS1 did not reveal any candidate variant that might act as a phenotype modifier.This case of intrafamilial phenotypic variation associated with a single PRPS1 mutation complicates the genotype-phenotype correlations, which makes genetic counseling of mutation carriers difficult because of the wide spectrum of severity of the associated disorders.

The inner ear is a very complex sensory organ whose development and function depend on finely balanced interactions among diverse cell types. The many different kinds of inner ear supporting cells play the essential roles of providing physical and physiological support to sensory hair cells and of maintaining cochlear homeostasis. Appropriately enough, the gene most commonly mutated among subjects with hereditary hearing impairment (HI), GJB2, encodes the connexin-26 (Cx26) gap-junction channel protein that underlies both intercellular communication among supporting cells and homeostasis of the cochlear fluids, endolymph and perilymph. GJB2 lies at the DFNB1 locus on 13q12. The specific kind of HI associated with this locus is caused by recessively-inherited mutations that inactivate the two alleles of the GJB2 gene, either in homozygous or compound heterozygous states. We describe the many diverse classes of genetic alterations that result in DFNB1 HI, such as large deletions that either destroy the GJB2 gene or remove a regulatory element essential for GJB2 expression, point mutations that interfere with promoter function or splicing, and small insertions or deletions and nucleotide substitutions that target the GJB2 coding sequence. We focus on how these alterations disrupt GJB2 and Cx26 functions and on their different effects on cochlear development and physiology. We finally discuss the diversity of clinical features of DFNB1 HI as regards severity, age of onset, inner ear malformations and vestibular dysfunction, highlighting the areas where future research should be concentrated.

We have recently reported on several Fe catalysts for N_2-to-NH_3 conversion that operate at low temperature (−78 °C) and atmospheric pressure while relying on a very strong reductant (KC_8) and acid ([H(OEt_2)_2][BArF_4]). Here we show that our original catalyst system, P_3^BFe, achieves both significantly improved efficiency for NH_3 formation (up to 72% for e^– delivery) and a comparatively high turnover number for a synthetic molecular Fe catalyst (84 equiv of NH_3 per Fe site), when employing a significantly weaker combination of reductant (Cp*_2Co) and acid ([Ph_2NH_2][OTf] or [PhNH_3][OTf]). Relative to the previously reported catalysis, freeze-quench Mössbauer spectroscopy under turnover conditions suggests a change in the rate of key elementary steps; formation of a previously characterized off-path borohydrido–hydrido resting state is also suppressed. Theoretical and experimental studies are presented that highlight the possibility of protonated metallocenes as discrete PCET reagents under the present (and related) catalytic conditions, offering a plausible rationale for the increased efficiency at reduced driving force of this Fe catalyst system.

Resumen: Objetivos: Analizar si el estado de gravedad previo, el láctico, la creatinina y el índice inotrópico se relacionan con la mortalidad de la parada cardiaca (PC) intrahospitalaria en niños y si un índice de predicción pronóstica diseñado para adultos tiene utilidad en pediatría. Métodos: Se estudió a 44 niños de edades entre un mes y 18 años de edad que presentaron una PC en el hospital durante un período de 2 años. Se analizaron la relación entre las puntuaciones de gravedad PRIMS y PELOD, el láctico, la creatinina, el tratamiento previo con fármacos vasoactivos, el índice inotrópico con la recuperación de la circulación espontánea (RCE) y la supervivencia. Resultados: Un 90,3% de los pacientes recuperaron la circulación espontánea y un 59% sobrevivió al alta del hospital. Un 68,2% de los pacientes recibían inotrópicos previos a la PCR. Los pacientes fallecidos presentaban valores de lactato previos a la parada más elevados (3,4 mmol/L) que los supervivientes (1,4 mmol/L), p = 0,04. No existieron diferencias en las puntuaciones de PRISM, PELOD, los valores de creatinina, el tratamiento con inotrópicos, con adrenalina, el número de inotrópicos, o el índice inotrópico antes de la PCR entre fallecidos y supervivientes. Conclusión: La elevación de ácido láctico previa a la parada cardiaca puede ser un indicador de mal pronóstico en la PC en los niños. Abstract: Objectives: To analyze the relationship between previous severity of illness, lactic acid, creatinine and inotropic index with mortality of in-hospital cardiac arrest (CA) in children, and the value of a prognostic index designed for adults. Methods: The study included total of 44 children aged from 1 month to 18 years old who suffered a cardiac arrest while in hospital. The relationship between previous severity of illness scores (PRIMS and PELOD), lactic acid, creatinine, treatment with vasoactive drugs, inotropic index with return of spontaneous circulation and survival at hospital discharge was analyzed. Results: The large majority (90.3%) of patients had a return of spontaneous circulation, and 59% survived at hospital discharge. More than two-thirds (68.2%) were treated with inotropic drugs at the time of the CA. The patients who died had a higher lactic acid before the CA (3.4 mmol/L) than survivors (1.4 mmol/L), P=.04. There were no significant differences in PRIMS, PELOD, creatinine, inotropic drugs, and inotropic index before CA between patients who died and survivors. Conclusion: A high lactic acid previous to cardiac arrest could be a prognostic factor of in-hospital cardiac arrest in children.

The use of hydrogen to feed Fuel Cells emerges as an attractive renewable solution to meet the terawatt carbon-neutral energy demand challenge. Rare-earth doped nano-glass-ceramics, presenting outstanding high intense UV-blue up-conversion processes, appear as an interesting approach to assist long wavelength light harvesting of solar irradiation, extending the photo-catalytic response to the red and near-infrared region to overcome the drawback of large band-gap materials used in the splitting of water into oxygen and hydrogen in a photo-electrochemical cell.

Transparent nano-glass-ceramics containing KYF4 nanocrystals were successfully obtained by the sol–gel method, doped with Eu3+ and co-doped with Yb3+ and Tm3+ ions. Precipitation of cubic KYF4 nanocrystals was confirmed by X-ray diffraction and high-resolution transmission electron microscope images. Excitation and emission spectra let us to discern between ions into KYF4 nanocrystals and those remaining in a glassy environment, supplemented with time-resolved photoluminescence decays, that also clearly reveal differences between local environments. Unusual high-energy up-conversion emissions in the UV range were obtained in Yb3+–Tm3+ co-doped samples, and involved mechanisms were discussed. The intensity of these high-energy emissions was analyzed as a function of Yb3+ concentration, heat treatment temperature of precursor sol–gel glasses and pump power, determining the optimum values for potential optical applications as highly efficient UV up-conversion materials in UV solid-state lasers.

The interpolating spline or trigonometric polynomial to a function at equally spaced points approximates the Dirichlet partial sums of its Fourier series with accuracy depending only on the neglected coefficients. We show that the Fejer mean of the Dirichlet sums can be approximated by the arithmetic mean of two Fejer trigonometric interpolants, one at the points with even indexes and one at the points with odd indexes, with an error depending only on the neglected Fourier coefficients and it is positive for positive functions. We also consider the case of Fejer spline interpolants and a constructive relation between Hermite and Fejer interpolants.

Resumen: Introducción: Los pacientes críticos frecuentemente presentan inestabilidad hemodinámica que puede verse empeorada por la administración de algunos fármacos. El omeprazol es un fármaco muy empleado en la profilaxis de la hemorragia digestiva en estos pacientes, pero se desconocen sus efectos cardiovasculares. El objetivo fue estudiar los cambios hemodinámicos producidos por la administración de omeprazol por vía intravenosa en niños críticos y analizar si existen diferencias entre 2 dosis diferentes de omeprazol. Material y métodos: Se realizó un estudio prospectivo observacional aleatorizado, que incluyó niños críticos entre un mes y 14 años de edad, que precisaban profilaxis de hemorragia digestiva. La muestra aleatoria fue de 37 pacientes de los cuales, 19 recibieron omeprazol por vía intravenosa 0,5 mg/kg cada 12 h y 18 omeprazol por vía intravenosa 1 mg/kg cada 12 h. La dosis correspondiente se administró en 20 min mediante bomba de infusión continua. Se recogieron la frecuencia cardiaca, presión arterial sistólica, media y diastólica, presión venosa central y el electrocardiograma basal, a los 15, 30, 60 y 120 min de la infusión. Resultados: La edad media fue de 27,7 ± 33,3 meses. Todos los pacientes recibieron dopamina y 14, adrenalina. No se produjeron modificaciones significativas en ninguna de las variables estudiadas. Ningún paciente precisó modificación del tratamiento inotrópico. No se objetivaron diferencias entre las 2 dosis de omeprazol. Conclusiones: El omeprazol por vía intravenosa es un fármaco hemodinámicamente seguro en niños críticos, a cualquiera de las 2 dosis utilizadas. Abstract: Introduction: Critical patients usually have hemodynamic disturbances which may become worse by the administration of some drugs. Omeprazole is a drug used in the prophylaxis of the gastrointestinal bleeding in these patients, but its cardiovascular effects are unknown. The objective was to study the hemodynamic changes produced by intravenous omeprazole in critically ill children and to find out if there are differences between two different doses of omeprazole. Material and methods: A randomized prospective observational study was performed on 37 critically ill children aged from 1 month to 14 years of age who required prophylaxis for gastrointestinal bleeding. Of these, 19 received intravenous omeprazole 0.5 mg/kg every 12 hours, and 18 received intravenous omeprazole 1 mg/kg every 12 hours. Intravenous omeprazole was administered in 20 minutes by continuous infusion pump. Heart rate, systolic, diastolic and mean arterial blood pressure, central venous pressure and ECG were recorded at baseline, and at 15, 30, 60 and 120 minutes of the infusion. Results: There were no significant changes in the electrocardiogram, heart rate, blood pressure and central venous pressure. No patients required inotropic therapy modification. There were no differences between the two doses of omeprazole. Conclusions: Intravenous omeprazole administration of 0.5 mg/kg and 1 mg/kg is a hemodynamically safe drug in critically ill children.

We have recently reported on several Fe catalysts for N2-to-NH3 conversion that operate at low temperature (−78 °C) and atmospheric pressure while relying on a very strong reductant (KC8) and acid ([H(OEt2)2][BArF4]). Here we show that our original catalyst system, P3BFe, achieves both significantly improved efficiency for NH3 formation (up to 72% for e– delivery) and a comparatively high turnover number for a synthetic molecular Fe catalyst (84 equiv of NH3 per Fe site), when employing a significantly weaker combination of reductant (Cp*2Co) and acid ([Ph2NH2][OTf] or [PhNH3][OTf]). Relative to the previously reported catalysis, freeze-quench Mössbauer spectroscopy under turnover conditions suggests a change in the rate of key elementary steps; formation of a previously characterized off-path borohydrido–hydrido resting state is also suppressed. Theoretical and experimental studies are presented that highlight the possibility of protonated metallocenes as discrete PCET reagents under the present (and related) catalytic conditions, offering a plausible rationale for the increased efficiency at reduced driving force of this Fe catalyst system., A synthetic Fe complex catalyzes nitrogen fixation at lower driving force increasing its relevance as a functional model of nitrogenase. Theory and experiment lead to the proposal that protonated cobaltocenes may play a role as PCET reagents.