Half-sandwich Ni(II) complexes bearing enantiopure bidentate NHC-carboxylate ligands: efficient catalysts for the hydrosilylative reduction of acetophenones.

Chiral nickel complexes containing NHC-carboxylate chelate ligands derived from the (S)-isomeric form of amino acids have been synthesised from the corresponding imidazolium salt and nickelocene. The presence of the carboxylate on the N-side arm of the heterocycle results in the competing formation of mixtures of mono- and bis-NHC complexes (i.e., [Ni(η5-Cp)(κ2-C,O-NHC)] and [Ni(κ2-C,O-NHC)2]), both of which retain the (S)-configuration of the stereogenic center and which can be separated by chromatography. Both the 18e- and 16e- complexes are found to be very stable and cannot be interconverted. The composition of the resulting mixtures depends mainly on the entity of the amino acid residue and, of more practical interest, on the reaction conditions. Thus, microwave heating and MeCN as a solvent favor the formation of the half-sandwich nickel complexes, rather than the bis-NHC compounds. Some of the [Ni(η5-Cp)(κ2-C,O-NHC)] complexes turn out to be among the best nickel catalysts for the hydrosilylative reduction of p-acetophenones described to date, although without chiral induction, in the absence of activating additives and under mild catalytic conditions.

Severe respiratory disease caused by human respiratory syncytial virus impairs language learning during early infancy.

Human respiratory syncytial virus infection is a leading cause of pediatric morbidity and mortality. A previous murine study showed that during severe acute respiratory infections the virus invades the central nervous system, and that infected animals evolve with long-lasting learning difficulties associated with long-term potentiation impairment in their hippocampus. We hypothesized here that human infants who presented a severe episode of respiratory syncytial virus infection before 6 months of age would develop long-term learning difficulties. We measured the acquisition of the native phoneme repertoire during the first year, a milestone in early human development, comprising a reduction in the sensitivity to the irrelevant nonnative phonetic information and an increase in the sensitivity to the information relevant for the native one. We found that infants with a history of severe respiratory infection by the human respiratory syncytial virus presented poor distinction of native and nonnative phonetic contrasts at 6 months of age, and remained atypically sensitive to nonnative contrasts at 12 months, which associated with weak communicative abilities. Our results uncover previously unknown long-term language learning difficulties associated with a single episode of severe respiratory infection by the human respiratory syncytial virus, which could relate to memory impairments.

Contraception and post abortion services: qualitative analysis of users' perspectives and experiences following Zika epidemic in Honduras.

BACKGROUND: Zika virus (ZIKV) infection during pregnancy has severe consequences on the new-born. The World Health Organization declared the Zika outbreak to be a Public Health Emergency of International Concern (PHEIC) in 2016. Health facilities in the regions most affected by Zika lacked the capacity to respond to the increased demand for contraception. The objectives were to explore healthcare users' perceptions regarding contraception, Zika prevention during pregnancy and post-abortion care (PAC) services in the context of a Zika outbreak in Tegucigalpa, Honduras, and to follow these services over time. METHODS: This study was part of a broader implementation research study. We used qualitative research consistent with grounded theory approach. Semi-structured interviews and focus groups were performed with women and their partners who used contraceptive services or received PAC services. Data were collected in two stages from December 2017 to July 2018. Themes explored included contraception, Zika and PAC services. RESULTS: Participants had positive attitude towards the use of contraceptive methods and demanded more information on safety, efficacy and on side effects. Health care services were inconsistent in the provision of information on Zika and contraception services. ZIKV vector transmission was known but fewer participants were aware of risk of sexual transmission of Zika. Barriers to access healthcare services included contraceptive and PAC services included distance to healthcare facilities, disorganized admission process, long waiting times and out-of-pocket expenditure to purchase medicines. Furthermore, poor quality, mistreatment and abuse of women seeking PAC was prevalent. Some positive changes were noted over time, such as improvements in infrastructure including improved privacy and cleanliness, removal of fees, requisite to bring clean water to hospital. CONCLUSIONS: Our results highlight the challenges and areas for improvement in policy and practice related to contraceptive services and PAC in the context of ZIKV infection. Public policies to prevent epidemics should focus more on providing proper sanitation; removing barriers to access and use of effective contraception as human rights priority. Zika epidemic has highlighted weaknesses in health systems that obstruct access to and use of sexual and reproductive health services. The study results call for increased efforts to improve access, especially for women of low socio-economic status and intervene at different levels to eradicate discrimination and improve equity in the provision of health care. Qualitative methods can capture the community perspectives and can provide useful information to develop interventions to improve services.

Molecular Mechanisms of Non-ionotropic NMDA Receptor Signaling in Dendritic Spine Shrinkage.

Structural plasticity of dendritic spines is a key component of the refinement of synaptic connections during learning. Recent studies highlight a novel role for the NMDA receptor (NMDAR), independent of ion flow, in driving spine shrinkage and LTD. Yet little is known about the molecular mechanisms that link conformational changes in the NMDAR to changes in spine size and synaptic strength. Here, using two-photon glutamate uncaging to induce plasticity at individual dendritic spines on hippocampal CA1 neurons from mice and rats of both sexes, we demonstrate that p38 MAPK is generally required downstream of non-ionotropic NMDAR signaling to drive both spine shrinkage and LTD. In a series of pharmacological and molecular genetic experiments, we identify key components of the non-ionotropic NMDAR signaling pathway driving dendritic spine shrinkage, including the interaction between NOS1AP (nitric oxide synthase 1 adaptor protein) and neuronal nitric oxide synthase (nNOS), nNOS enzymatic activity, activation of MK2 (MAPK-activated protein kinase 2) and cofilin, and signaling through CaMKII. Our results represent a large step forward in delineating the molecular mechanisms of non-ionotropic NMDAR signaling that can drive shrinkage and elimination of dendritic spines during synaptic plasticity.SIGNIFICANCE STATEMENT Signaling through the NMDA receptor (NMDAR) is vitally important for the synaptic plasticity that underlies learning. Recent studies highlight a novel role for the NMDAR, independent of ion flow, in driving synaptic weakening and dendritic spine shrinkage during synaptic plasticity. Here, we delineate several key components of the molecular pathway that links conformational signaling through the NMDAR to dendritic spine shrinkage during synaptic plasticity.

Synergistic Effect of Covalent Bonding and Physical Encapsulation of Sulfur in the Pores of a Microporous COF to Improve Cycling Performance in Li-S Batteries.

Lithium-sulfur batteries stands out as a promising technology for energy storage owing to a combination of favorable characteristics including a high theoretical gravimetric capacity, energy density, inexpensive character, and environmental benignity. Covalent organic frameworks (COFs) are a rapidly developing family of functional nanostructures which combine porosity and crystallinity, and which have been already used in these kinds of batteries to build sulfur electrodes, by embedding sulfur into porous COFs in order to enhance cycle lifetimes. In this contribution, this is taken one step forward and a COF endowed with vinyl groups is used, in order to graft sulfur to the COF skeleton through inverse vulcanization. The main aim of the article is to show the synergistic effect of covalent bonding and physical encapsulation of sulfur in the pores of the COF in order to alleviate the fatal redox shuttling process, to improve the cycling performance, and to provide faster ion diffusion pathways. In addition, it is shown how the material with covalently-bound S provides better electrochemical performance under demanding and/or changeable charge conditions than a parent analogue material with sulfur physically confined, but without covalent linkage.

Water-soluble platinum nanoparticles stabilized by sulfonated N-heterocyclic carbenes: influence of the synthetic approach.

The synthesis of metal nanoparticles (NPs) under controlled conditions in water remains a challenge in nanochemistry. Two different approaches to obtain platinum NPs, which involve the treatment of aqueous solutions of preformed sulfonated (NHC)Pt(ii) dimethyl complexes with carbon monoxide, and of (NHC)Pt(0) diolefin complexes with dihydrogen (NHC = N-heterocyclic carbene), are disclosed here. The resulting NPs were found to be highly stable in water under air for an indefinite time period. Coordination of the NHC ligands to the platinum surface via the carbenic carbon was monitored by solid-state NMR spectroscopy, and the presence of a platinum-carbon bond was unambiguously evidenced by the determination of a 13C-195Pt coupling constant (1106 and 1050 Hz for NPs containing 13C labeled-NHC ligands and prepared under CO and H2, respectively). The coordination of CO to the (NHC)Pt(ii) precursors prior to formation of the NPs was confirmed by NMR spectroscopy. When using a disulfonated NHC ligand, a second coordination sphere containing bis(NHC)Pt(ii) complexes is described. Under CO, the formation of NPs was found to be slower than in a previously reported thermal method (Angew. Chem., Int. Ed., 2014, 53, 13220-13224), but led to NPs of similar sizes, whereas under H2, the synthesis of platinum NPs progressed even more slowly and produced larger NPs. In addition to the influence of the synthetic approach, the present study highlights the importance of ligand design for NP stabilization.

Monitoring of nanoparticle reactivity in solution: interaction of l-lysine and Ru nanoparticles probed by chemical shift perturbation parallels regioselective H/D exchange.

Thanks to new water-soluble Ru nanoparticles (NPs) stabilized by sulfonated NHC ligands, we demonstrate that it is possible to monitor the catalyst/substrate interaction using NMR chemical shift perturbations (CSPs), under conditions that closely resemble those applied during the enantiospecific C-H deuteration of l-lysine. Correlating the pH dependence of the interaction of l-lysine with the surface of the RuNPs and its subsequent deuteration, our study underscores the importance of oriented binding to the surface as a critical factor for H/D exchange.

Magnetically recoverable catalysts based on mono- or bis-(NHC) complexes of palladium for the Suzuki-Miyaura reaction in aqueous media: two NHC-Pd linkages are better than one.

Pre-synthesized mono- and bis(NHC) palladium complexes have been grafted onto magnetic core/shell γ-Fe2O3/silica particles and tested as catalysts in model Suzuki-Miyaura coupling reactions. The bis(NHC) immobilized complex was found to be a robust catalyst that can operate under mild conditions in aqueous media, even for the activation of chloroarene, whereas the mono(NHC) counterpart rapidly deactivates. Moreover, it can be readily recovered by magnetic separation and reused many times, providing very high productivities, and with so low leaching of palladium that the crude products obtained contain ≤10 ppm Pd.

Poly(benzyl ether) Dendrimers Functionalized at the Core with Palladium Bis(N-Heterocyclic Carbene) Complexes as Catalysts for the Heck Coupling Reaction.

Bis(imidazolylidene)palladium complexes 9-12 containing a sterically hindered aryl group (mesityl or 2,6-diisopropylphenyl) and a poly(benzyl ether) dendron as N-substituents of the NHC ligand are accessible up to the third generation by transmetalation of the corresponding silver complexes. Complexes 9-12 are soluble, active, and very stable catalysts under Heck reaction conditions. The NHC ligand appears to be stably coordinated to the Pd during catalysis. The catalytic activity increases with generation number, although irregularly. The palladium site is not significantly congested in the reaction solvent by the increasing size of the dendritic substituents, as corroborated by X-ray diffraction, fluorescence and DOSY-NMR spectroscopy, and MD simulation studies. This is a consequence of the conformational semiflexibility of the poly(benzyl ether) dendrons and the benzylic link between these dendrons and the N-heterocyclic ligands.

Synthesis and behavior of novel sulfonated water-soluble N-heterocyclic carbene (η(4)-diene) platinum(0) complexes.

A series of water-soluble (NHC)Pt(0)(dvtms) and (NHC)Pt(0)(AE) complexes containing different sulfonated NHC ligands (dvtms = divinyltetramethyldisiloxane and AE = diallyl ether) are reported. The dvtms compounds have been found to be quite robust and to display some conformational rigidity, whereas their AE counterparts are less stable and more flexible. The catalytic evaluation of these complexes in the hydrosilylation of alkynes in water revealed no benefits in favor of the complexes containing the more labile spectator diene (AE), and a fairly regular catalytic behavior for all complexes that restricts the location of the sulfonate group to the proximity of the metal site.

[Higher risk for health care associated infections in hospitalized children with special health needs]. / Mayor riesgo de infecciones asociadas a atención en salud en niños con necesidades especiales hospitalizados.

BACKGROUND: Nosocomial infections (NIs) represent an important public health issue, being associated with high morbidity, mortality and costs. OBJECTIVES: To identify risk factors of NIs in a cohort of hospitalized pediatric patients, with emphasis in children with special health care needs (CSHCN). PATIENTS AND METHODS: We studied patients hospitalized in Sótero del Río Pediatric Hospital at Santiago-Chile, between September and December, 2009. Relative Risk (RR) was calculated between CSHCN-3 (children attended by three or more health care professionals) versus non CSHCN-3, and between children with medical complexity (CMC) versus non CMC, using log-binomial models. RESULTS: 920 patients were included. Prevalence of NIs was 12.7%. The most frequent diagnoses were gastrointestinal and respiratory viral infections. Both crude and adjusted by confounders (age and sex), CSHCN-3 and CMC presented significantly higher risk of NIs compared to patients without these conditions (RR 2.91 and RR 2.16, respectively). CONCLUSION: CSHCN-3 and CMC represent independent conditions associated to a 2-3 fold risk of NIs.

Mayor riesgo de infecciones asociadas a atención en salud en niños con necesidades especiales hospitalizados / Higher risk for health care associated infections in hospitalized children with special health needs

Background: Nosocomial infections (NIs) represent an important public health issue, being associated with high morbidity, mortality and costs. Objectives: To identify risk factors of NIs in a cohort of hospitalized pediatric patients, with emphasis in children with special health care needs (CSHCN). Patients and Methods: We studied patients hospitalized in Sótero del Río Pediatric Hospital at Santiago-Chile, between September and December, 2009. Relative Risk (RR) was calculated between CSHCN-3 (children attended by three or more health care professionals) versus non CSHCN-3, and between children with medical complexity (CMC) versus non CMC, using log-binomial models. Results: 920 patients were included. Prevalence of NIs was 12.7%. The most frequent diagnoses were gastrointestinal and respiratory viral infections. Both crude and adjusted by confounders (age and sex), CSHCN-3 and CMC presented significantly higher risk of NIs compared to patients without these conditions (RR 2.91 and RR 2.16, respectively). Conclusion: CSHCN-3 and CMC represent independent conditions associated to a 2-3 fold risk of NIs.

Introducción: Las infecciones asociadas a atención en salud (IAAS) representan un problema frecuente, el cual se asocia a una mayor morbimortalidad y costos. Objetivos: Evaluar factores de riesgo de IAAS en una cohorte de niños hospitalizados, con énfasis en el grupo de niños y adolescentes con necesidades especiales de atención en salud (NANEAS). Materiales y Métodos: Estudio realizado en el Hospital Sótero del Río, Santiago-Chile, entre septiembre y diciembre de 2009. Se calculó riesgo relativo (RR) de IAAS entre pacientes NANEAS-3 (niños controlados por tres o más profesionales de la salud) versus no NANEAS-3, y entre niños con complejidad médica (NCM) versus no NCM, a través de modelos log-binomial. Resultados: Se obtuvo información de 920 pacientes. Un 12,7% presentó IAAS; las más frecuentes fueron infecciones virales gastrointestinales y respiratorias. Tanto en forma cruda como ajustada por variables confundentes (edad y sexo), los pacientes NANEAS-3 y NCM presentaron significativamente mayor riesgo de IAAS versus aquellos que no cumplían estas definiciones (RR 2,91 y RR 2,16, respectivamente). Conclusiones: Los pacientes NANEAS-3 y NCM representan condiciones independientes asociadas a un riesgo dos a tres veces mayor de IAAS.

Mechanical ventilation in pediatric intensive care units during the season for acute lower respiratory infection: a multicenter study.

OBJECTIVE: To describe the characteristics and outcomes of mechanical ventilation in pediatric intensive care units during the season of acute lower respiratory infections. DESIGN: Prospective cohort of infants and children receiving mechanical ventilation for at least 12 hrs. SETTING: Sixty medical-surgical pediatric intensive care units. PATIENTS: All consecutive patients admitted to participating pediatric intensive care units during a 28-day period. MEASUREMENTS AND MAIN RESULTS: Of 2,156 patients admitted to pediatric intensive care units, 1185 (55%) received mechanical ventilation for a median of 5 days (interquartile range 2-8). Median age was 7 months (interquartile range 2-25). Main indications for mechanical ventilation were acute respiratory failure in 78% of the patients, altered mental status in 15%, and acute on chronic pulmonary disease in 6%. Median length of stay in the pediatric intensive care units was 10 days (interquartile range 6-18). Overall mortality rate in pediatric intensive care units was 13% (95% confidence interval: 11-15) for the entire population, and 39% (95% confidence interval: 23 - 58) in patients with acute respiratory distress syndrome. Of 1150 attempts at liberation from mechanical ventilation, 62% (95% confidence interval: 60-65) used the spontaneous breathing trial, and 37% (95% confidence interval: 35-40) used gradual reduction of ventilatory support. Noninvasive mechanical ventilation was used initially in 173 patients (15%, 95% confidence interval: 13-17). CONCLUSION: In the season of acute lower respiratory infections, one of every two children admitted to pediatric intensive care units requires mechanical ventilation. Acute respiratory failure was the most common reason for mechanical ventilation. The spontaneous breathing trial was the most commonly used method for liberation from mechanical ventilation.

[Clinical guidelines on identification, management and complications of chronic kidney disease]. / Enfermedad renal crónica: clasificación, identificación, manejo y complicaciones.

The key messages of these guidelines on chronic kidney disease are: Chronic kidney disease (CKD) is a public health problem due to its wide distribution, high rate of complications and cost. CKD is a common condition, its prevalence being about 10%, and is treatable if it is detected on time. A patient with CKD has a higher risk of cardiovascular mortality than of progression of its underlying renal disease. A new definition of CKD, based on estimated Glomerular Filtration Rate (eGFR) and kidney damage, facilitates its detection and management. CKD is detected with three simple tests: 1) Blood pressure measurement, 2) Detection of proteinuria or albuminuria in an isolated urine sample, and 3) Estimation of renal function (eGFR), based on serum creatinine, age, gender and race. The CKD risk groups are individuals with diabetes, hypertension and a family history of renal disease. The most cost-effective measures are to detect and treat diabetic and hypertensive patients in the community. Therapy must emphasize the maximal reduction of cardiovascular risk. The complications of CKD such as anemia and renal osteodystrophy can be identified and treated on time. Most patients with chronic kidney disease are detected in the community, therefore their initial care must be organized at the level of primary care, along with programs for hypertension and diabetes.

Deposition of silver nanoshell and reactivity of silver nanoparticles with surface silanols of submicrospherical silica.

We describe in this report the production of a smooth and uniform silver outer nanoshell with thickness -15 nm on submicrospherical silica, using a rapid and simple one pot chemical route. The reaction mechanism proposed for the formation of the silver nanoshell is the reactivity of silver nanoparticles with surface silanols at high pH, without added coupling agent or surface modification of silica, leading to the formation of the continuous and homogeneous silver nanoshell on the silica spheres.

Enfermedad renal crónica: Clasificación, identificación, manejo y complicaciones / Clinical guidelines on identitication, management and complications of chronic kidney disease

The key messages of these guidel ines on chronic kidney disease are: • Chronic kidney disease (CKD) is a public health problem due to its wide distribution, high rate of complications and cost. • CKD is a common condition, its prevalence being about 10 percent, and is treatable if it is detected on time. • A patient with CKD has a higher risk of cardiovascular mortality than of progression of its underlying renal disease. • A new definition of CKD, based on estimated Glomerular Filtration Rate (eGFR) and kidney damage, facilitates its detection and management. • CKD is detected with three simple tests: 1) Blood pressure measurement, 2) Detection of proteinuria or albuminuria in an isolated urine sample, and 3) Estimation of renal function (eGFR), based on serum creatinine, age, gender and race. • The CKD risk groups are individuáis with diabetes, hypertension and a family history of renal disease. • The most cost-effective measures are to detect and treat diabetic and hypertensive patients in the community. • Therapy must emphasize the maximal reduction of cardiovascular risk. • The complications of CKD such as anemia and renal osteodystrophy can be identified and treated on time. • Most patients with chronic kidney disease are detected in the community, therefore their initial care must be organized at the level of primary care, along with programs for hypertension and diabetes.

Dendronized scorpionate complexes of molybdenum in low and high oxidation states.

Tridentate (L(3)) and bidentate (L(2)) poly(pyrazolyl)methane ligands (Gn-dend)OCH(2)C(pz)(3) (1-4) and (Gn-dend)CH(3,5-Me(2)pz)(2) (pz = pyrazol-1-yl) have been used to synthesize the molybdenum(0) complexes [Mo(CO)(3)(L(3))] (G0-G3, 5-8), [Mo(CO)(4)(L(2))] (G0-G1, 13-14), and [Mo(CO)(3)(NCMe)(L(2))] (G0, 15), and the molybdenum(VI) complexes [MoCl(2)O(2)(L(2))] (9-12). The G0-G3 prefixes represent the generation of poly(aryl ether) dendrons in which the metal complexes are embedded. The molecular structures of compounds 13 and 15 have been determined by X-ray diffraction studies and the hydrodynamic radii of tricarbonyl complexes 5-8 calculated by diffusion-ordered NMR spectroscopy (DOSY). Molybdenum(VI) compounds 9-12 have also been evaluated as catalysts for olefin epoxidation, showing comparable but inferior performances than ligand-free MoCl(2)O(2), probably because of the labile coordination of L(2).

Crystal structures of poly(aryl ether) dendrons with palladium scorpionate complexes at their focal point.

Novel palladium(II) complexes with bis(pyrazol-1-yl)methane ligands at the focal point of G0-G3 poly(aryl ether) Fréchet-type dendrons are reported. The molecular structures of the metallodendrimer series G0, G1, and G2 [(dend)CH(3,5-Me2pz)2(PdCl2)] have been determined by X-ray diffraction methods. The three structures show a similar three-dimensional organization of the metal complex, which is progressively engulfed by the branches with increasing dendrimer generation.

Synthesis and 1H NMR studies of paramagnetic nickel(II) complexes containing bis(pyrazolyl)methane ligands with dendritic substituents.

The substituted bis(pyrazolyl)methane ligands RCH(3,5-Me2pz)2(R=SiMe3, CH2Ph, G1, G2, and G3; Gn=Fréchet-type dendritic wedges of generation n) have been prepared starting from H2C(3,5-Me2pz)2. Reaction of these didentate ligands with [NiBr2(DME)] is a straightforward procedure that allows the synthesis of the nickel(II) complexes [NiBr2{RCH(3,5-Me2pz)2}]. The molecular structure of compound (R=CH2Ph) has been determined by X-ray diffraction studies. The nickel centre coordinates two bromine and two nitrogen atoms in a tetrahedral environment, and the metallacycle Ni(NN)2C adopts a boat conformation with the benzyl group in an axial position. 1H NMR studies have been carried out to characterize these paramagnetic nickel compounds in solution. Valuable information about the disposition of the ligands and dendritic wedges in solution has been obtained thanks to the influence of the paramagnetic centre on the proton resonances.

Activation of a CNXylyl ancillary ligand in the reaction of electron-deficient alkynes with a phosphido niobocene complex.

The niobium phosphido complex [Nb(eta5-C5H4SiMe3)2-(CNXylyl)(PPh2)] (2) undergoes an unusual cycloaddition reaction with electron-deficient alkynes to give the novel five-membered heteroniobacycles [Nb(eta5-C5H4SiMe3)2(kappaC-C(=N(Xylyl))C(CO2Me)=C(R)PPh2-kappaP)] (R = H 3 and R = Me 4).