[Increase in severe acute respiratory infections in children during the last phase of the COVID-19 pandemic]. / Incremento de infecciones respiratorias agudas graves en niños durante la última etapa de la pandemia COVID-19.

OBJECTIVE: The COVID-19 pandemic has caused a variation in the circulation of respiratory pathogens. Our aim was to analyze the epidemiology of severe acute respiratory infections (SARI) in children during 3 years of the COVID-19 pandemic, in comparison with a previous period. METHODS: An observational study was conducted in a tertiary hospital in Spain, which analyzed the frequency and characteristics of patients admitted for SARI in the Pediatric Intensive Care Unit (PICU) during the COVID-19 pandemic (1 March 2020 to 28 February 2023), compared to pre-pandemic period (1 March 2017 to 29 February 2020). RESULTS: A total of 268 patients were included (59.6% males). The median age was 9.6 months (IQR 1.7 - 37). In the pre-pandemic period, there were 126 admissions with an average of 42 admissions/year. During the pandemic, there were 142 admissions, observing a significant reduction in admissions in the first year (12 admissions/year), in contrast to 82 admissions during the third year, which represented an increase of 95% compared to the average of admissions/year in pre-pandemic. In addition, in the last year there was evidence of an increase in viral coinfections in relation to pre-pandemic period (54.9% vs 39.7%; p=0.032). There were no differences in length of hospital stay or PICU stay. CONCLUSIONS: During the last year, coinciding with low rates of hospitalization for COVID in Spain, we observed a notable increase in admissions to the PICU for SARI. Probably, the prolonged period of low exposure to pathogens due to the measures adopted during the pandemic might have caused a decrease in population immunity with a rise in severe respiratory infections.

Bulky, electron-rich, renewable: analogues of Beller's phosphine for cross-couplings.

In recent years, considerable progress has been made in the conversion of biomass into renewable chemicals, yet the range of value-added products that can be formed from biomass remains relatively small. Herein, we demonstrate that molecules available from biomass serve as viable starting materials for the synthesis of phosphine ligands, which can be used in homogeneous catalysis. Specifically, we prepared renewable analogues of Beller's ligand (di(1-adamantyl)-n-butylphosphine, cataCXium® A), which is widely used in homogeneous catalysis. Our new renewable phosphine ligands facilitate Pd-catalysed Suzuki-Miyaura, Stille, and Buchwald-Hartwig coupling reactions with high yields, and our catalytic results can be rationalized based on the stereoelectronic properties of the ligands. The new phosphine ligands generate catalytic systems that can be applied for the late-stage functionalization of commercial drugs.

Morphological Plasticity of LiCl Clusters Interacting with Grignard Reagent in Tetrahydrofuran.

Ab initio molecular dynamics simulations are used to explore tetrahydrofuran (THF) solutions containing pure LiCl and LiCl with CH3MgCl, as model constituents of the turbo Grignard reagent. LiCl aggregates as Li4Cl4, which preferentially assumes compact cubane-like conformations. In particular, an open-edge pseudotetrahedral frame is promoted by solvent-assisted Li-Cl bond cleavage. Among the Grignard species involved in the Schlenk equilibrium, LiCl prefers to coordinate MgCl2 through µ2-Cl bridges. Using a 1:1 Li:Mg ratio, the plastic tetranuclear LiCl cluster decomposes to a highly solvated mixed LiCl·MgCl2 aggregate with prevalent Li-(µ2-Cl)2-Mg rings and linear LiCl entities. The MgCl2-assisted disaggregation of Li4Cl4 occurs through transient structures analogous to those detected for pure LiCl in THF, also corresponding to moieties observed in the solid state. This study identifies a synergistic role of LiCl for the determination of the compounds present in turbo Grignard solutions. LiCl shifts the Schlenk equilibrium promoting a higher concentration of dialkylmagnesium, while decomposing into smaller, more soluble, mixed Li:Mg:Cl clusters.

Exploring the Parameters Controlling Product Selectivity in Electrochemical CO2 Reduction in Competition with Hydrogen Evolution Employing Manganese Bipyridine Complexes.

Selective reduction of CO2 is an efficient solution for producing nonfossil-based chemical feedstocks and simultaneously alleviating the increasing atmospheric concentration of this greenhouse gas. With this aim, molecular electrocatalysts are being extensively studied, although selectivity remains an issue. In this work, a combined experimental-computational study explores how the molecular structure of Mn-based complexes determines the dominant product in the reduction of CO2 to HCOOH, CO, and H2. In contrast to previous Mn(bpy-R)(CO)3Br catalysts containing alkyl amines in the vicinity of the Br ligand, here, we report that bpy-based macrocycles locking these amines at the side opposite to the Br ligand change the product selectivity from HCOOH to H2. Ab initio molecular dynamics simulations of the active species showed that free rotation of the Mn(CO)3 moiety allows for the approach of the protonated amine to the reactive center yielding a Mn-hydride intermediate, which is the key in the formation of H2 and HCOOH. Additional studies with DFT methods showed that the macrocyclic moiety hinders the insertion of CO2 to the metal hydride favoring the formation of H2 over HCOOH. Further, our results suggest that the minor CO product observed experimentally is formed when CO2 adds to Mn on the side opposite to the amine ligand before protonation. These results show how product selectivity can be modulated by ligand design in Mn-based catalysts, providing atomistic details that can be leveraged in the development of a fully selective system.

Solid-State 19F NMR Chemical Shift in Square-Planar Nickel-Fluoride Complexes Linked by Halogen Bonds.

The halogen bond (XB) is a highly directional class of noncovalent interactions widely explored by experimental and computational studies. However, the NMR signature of the XB has attracted limited attention. The prediction and analysis of the solid-state NMR (SSNMR) chemical shift tensor provide useful strategies to better understand XB interactions. In this work, we employ a computational protocol for modeling and analyzing the 19F SSNMR chemical shifts previously measured in a family of square-planar trans NiII-L2-iodoaryl-fluoride (L = PEt3) complexes capable of forming self-complementary networks held by a NiF···I(C) halogen bond [Thangavadivale, V.; Chem. Sci. 2018, 9, 3767-3781]. To understand how the 19F NMR resonances of the nickel-bonded fluoride are affected by the XB, we investigate the origin of the shielding in trans-[NiF(2,3,5,6-C6F4I)(PEt3)2], trans-[NiF(2,3,4,5-C6F4I)(PEt3)2], and trans-[NiF(C6F5)(PEt3)2] in the solid state, where a XB is present in the two former systems but not in the last. We perform the 19F NMR chemical shift calculations both in periodic and molecular models. The results show that the crystal packing has little influence on the NMR signatures of the XB, and the NMR can be modeled successfully with a pair of molecules interacting via the XB. Thus, the observed difference in chemical shift between solid-state and solution NMR can be essentially attributed to the XB interaction. The very high shielding of the fluoride and its driving contributor, the most shielded component of the chemical shift tensor, are well reproduced at the 2c-ZORA level. Analysis of the factors controlling the shielding shows how the highest occupied Ni/F orbitals shield the fluoride in the directions perpendicular to the Ni-F bond and specifically perpendicular to the coordination plane. This shielding arises from the magnetic coupling of the Ni(3d)/F(2p lone pair) orbitals with the vacant σNi-F* orbital, thereby rationalizing the very highly upfield (shielded) resonance of the component (δ33) along this direction. We show that these features are characteristic of square-planar nickel-fluoride complexes. The deshielding of the fluoride in the halogen-bonded systems is attributed to an increase in the energy gap between the occupied and vacant orbitals that are mostly responsible for the paramagnetic terms, notably along the most shielded direction.

Supramolecular Coronation of Platinum(II) Complexes by Macrocycles: Structure, Relativistic DFT Calculations, and Biological Effects.

Platinum-based anticancer drugs are actively developed utilizing lipophilic ligands or drug carriers for the efficient penetration of biomembranes, reduction of side effects, and tumor targeting. We report the development of a supramolecular host-guest system built on cationic platinum(II) compounds bearing ligands anchored in the cavity of the macrocyclic host. The host-guest binding and hydrolysis process on the platinum core were investigated in detail by using NMR, MS, X-ray diffraction, and relativistic DFT calculations. The encapsulation process in cucurbit[7]uril unequivocally promotes the stability of hydrolyzed dicationic cis-[PtII(NH3)2(H2O)(NH2-R)]2+ compared to its trans isomer. Biological screening on the ovarian cancer lines A2780 and A2780/CP shows time-dependent toxicity. Notably, the reported complex and its ß-cyclodextrin (ß-CD) assembly achieve the same cellular uptake as cisplatin and cisplatin@ß-CD, respectively, while maintaining a significantly lower toxicity profile.

First-Principles Calculation of 1H NMR Chemical Shifts of Complex Metal Polyhydrides: The Essential Inclusion of Relativity and Dynamics.

1H NMR spectroscopy has become an important technique for the characterization of transition-metal hydride complexes, whose metal-bound hydrides are often difficult to locate by X-ray diffraction. In this regard, the accurate prediction of 1H NMR chemical shifts provides a useful, but challenging, strategy to help in the interpretation of the experimental spectra. In this work, we establish a density-functional-theory protocol that includes relativistic, solvent, and dynamic effects at a high level of theory, allowing us to report an accurate and reliable interpretation of 1H NMR hydride chemical shifts of iridium polyhydride complexes. In particular, we have studied in detail the hydride chemical shifts of the [Ir6(IMe)8(CO)2H14]2+ complex in order to validate previous assignments. The computed 1H NMR chemical shifts are strongly dependent on the relativistic treatment, the choice of the DFT exchange-correlation functional, and the conformational dynamics. By combining a fully relativistic four-component electronic-structure treatment with ab initio molecular dynamics, we were able to reliably model both the terminal and bridging hydride chemical shifts and to show that two NMR hydride signals were inversely assigned in the experiment.

Computational NMR Spectra of o-Benzyne and Stable Guests and Their Hemicarceplexes.

The incarceration of o-benzyne and 27 other guest molecules within hemicarcerand 1, as reported experimentally by Warmuth, and Cram and co-workers, has been studied by density functional theory (DFT). The 1 H NMR chemical shifts, rotational mobility, and conformational preference of the guests within the supramolecular cage were determined, which showed intriguing correlations of the chemical shifts with structural parameters of the host-guest system. Furthermore, based on the computed chemical shifts reassignments of some NMR signals are proposed. This affects, in particular, the putative characterization of the volatile benzyne molecule inside a hemicarcerand, for which our CCSD(T) and KT2 results indicate that the experimentally observed signals are most likely not resulting from an isolated o-benzyne within the supramolecular host. Instead, it is shown that the guest reacted with an aromatic ring of the host, and this adduct is responsible for the experimentally observed signals.

Spontaneous trans-Selective Transfer Hydrogenation of Apolar Boron-Boron Double Bonds.

The transfer hydrogenation of N-heterocyclic carbene (NHC)-supported diborenes with dimethylamine borane proceeds with high selectivity for the trans-1,2-dihydrodiboranes. DFT calculations, supported by kinetic studies and deuteration experiments, suggest a stepwise proton-first-hydride-second reaction mechanism via an intermediate µ-hydrodiboronium dimethylaminoborate ion pair.

Four-component relativistic 31P NMR calculations for trans-platinum(ii) complexes: importance of the solvent and dynamics in spectral simulations.

We report a combined experimental-theoretical study on the 31P NMR chemical shift for a number of trans-platinum(ii) complexes. Validity and reliability of the 31P NMR chemical shift calculations are examined by comparing with the experimental data. A successful computational protocol for the accurate prediction of the 31P NMR chemical shifts was established for trans-[PtCl2(dma)PPh3] (dma = dimethylamine) complexes. The reliability of the computed values is shown to be critically dependent on the level of relativistic effects (two-component vs. four component), choice of density functionals, dynamical averaging, and solvation effects. Snapshots obtained from ab initio molecular dynamics simulations were used to identify those solvent molecules which show the largest interactions with the platinum complex, through inspection by using the non-covalent interaction program. We observe satisfactory accuracy from the full four-component matrix Dirac-Kohn-Sham method (mDKS) based on the Dirac-Coulomb Hamiltonian, in conjunction with the KT2 density functional, and dynamical averaging with explicit solvent molecules.

Diagnostic response to a cross-border challenge for the Swiss caprine arthritis encephalitis virus eradication program.

INTRODUCTION: Animal trading between countries with different small ruminant lentivirus infectious status is a potential danger for the reintroduction of eradicated genotypes. This was the case in 2017 with the importation of a large flock of seropositive goats into Switzerland. The handling of this case permitted us to test the preventive measures in place. The coordination between the local veterinarian and the cantonal and federal veterinary authorities worked efficiently and rapidly involved the national reference center in the investigations. This case posed a challenge for the reference center and enabled scrutiny of the applied diagnostic tests. ELISA and western blot provided consistent results and pointed to an unusually high infection rate in the flock. This was confirmed by the isolation of several viruses from different organs and cells, demonstrating that the spleen is particularly well suited for isolation of small ruminant lentiviruses. The SU5-ELISA, designed to predict the subtype of the infecting virus, correctly pointed to a B1 subtype as the infectious agent. We confirmed that with this test it is necessary to analyze a representative number of samples from a flock and not just individual sera to obtain reliable results. This analysis permitted us to identify particular amino acid residues in the SU5 peptides that may be crucial in determining the subtype specificity of antibody binding. Different gag-pol and env regions were amplified by PCR using primers designed for this purpose. The phylogenetic analysis revealed a surprisingly high heterogeneity of the sequences, pointing to multiple infections within single animals and the entire flock. In conclusion, this case showed that the defense of the CAEV negative status of the Swiss goat population with respect to the virulent, prototypic B1 subtype of small ruminant lentiviruses, requires, among other measures, a diagnostic facility capable of performing a thorough analysis of the collected samples.

INTRODUCTION: Le commerce d'animaux entre pays où le statut infectieux des lentivirus des petits ruminants est différent constitue un danger potentiel pour la réintroduction de génotypes éradiqués. Ce fut le cas en 2017 avec l'importation d'un grand troupeau de chèvres séropositives en Suisse. Le traitement de cette affaire nous a permis de tester les mesures préventives mises en place. La coordination entre le vétérinaire local et les autorités vétérinaires cantonales et fédérales a été efficace et a impliqué rapidement le centre de référence national dans les enquêtes. Ce cas a constitué un défi pour le centre de référence et a permis d'examiner de près les tests de diagnostic appliqués. Les tests ELISA et Western blot ont fourni des résultats cohérents et ont mis en évidence un taux d'infection anormalement élevé dans le troupeau. Cela a été confirmé par l'isolement de plusieurs virus provenant d'organes et de cellules différents, démontrant que la rate est particulièrement bien adaptée à l'isolement des lentivirus des petits ruminants. Le SU5-ELISA, conçu pour prédire le sous-type du virus infectant, désignait correctement un sous-type B1 en tant qu'agent infectieux. Nous avons confirmé qu'avec ce test, il était nécessaire d'analyser un nombre représentatif d'échantillons d'un troupeau et pas seulement des sérums individuels pour obtenir des résultats fiables. Cette analyse nous a permis d'identifier des résidus d'acides aminés particuliers dans les peptides SU5 qui pourraient jouer un rôle crucial dans la détermination de la spécificité de sous-type de la liaison à l'anticorps. Différentes régions gag-pol et env ont été amplifiées par PCR en utilisant des amorces conçues à cet effet. L'analyse phylogénétique a révélé une hétérogénéité étonnamment élevée des séquences, indiquant de multiples infections chez les animaux isolés et dans l'ensemble du troupeau. En conclusion, cette affaire a montré que la défense du statut négatif CAEV de la population de chèvres suisses vis-à-vis du virus virulent, sous-type B1 des lentivirus des petits ruminants, nécessite, entre autres mesures, un système de diagnostic capable d'effectuer une analyse approfondie des échantillons collectés.

The influence of substituents and the environment on the NMR shielding constants of supramolecular complexes based on A-T and A-U base pairs.

In the present study, we have theoretically analyzed supramolecular complexes based on the Watson-Crick A-T and A-U base pairs using dispersion-corrected density functional theory (DFT). Hydrogen atoms H8 and/or H6 in the natural adenine and thymine/uracil bases were replaced, respectively, by substituents X8, Y6 = NH-, NH2, NH3+ (N series), O-, OH, OH2+ (O series), F, Cl or Br (halogen series). We examined the effect of the substituents on the hydrogen-bond lengths, strength and bonding mechanism, and the NMR shielding constants of the C2-adenine and C2-thymine/uracil atoms in the base pairs. The general belief in the literature that there is a direct connection between changes in the hydrogen-bond strength and the C2-adenine shielding constant is conclusively rejected by our computations.

Exploring the potential energy surface of E2P4 clusters (E=Group 13 element): the quest for inverse carbon-free sandwiches.

Inverse carbon-free sandwich structures with formula E2P4 (E=Al, Ga, In, Tl) have been proposed as a promising new target in main-group chemistry. Our computational exploration of their corresponding potential-energy surfaces at the S12h/TZ2P level shows that indeed stable carbon-free inverse-sandwiches can be obtained if one chooses an appropriate Group 13 element for E. The boron analogue B2P4 does not form the D(4h)-symmetric inverse-sandwich structure, but instead prefers a D(2d) structure of two perpendicular BP2 units with the formation of a double B-B bond. For the other elements of Group 13, Al-Tl, the most favorable isomer is the D(4h) inverse-sandwich structure. The preference for the D(2d) isomer for B2P4 and D(4h) for their heavier analogues has been rationalized in terms of an isomerization-energy decomposition analysis, and further corroborated by determination of aromaticity of these species.

[Elbow dislocation and lateral epicondyle fracture in a five year-old girl. Case report]. / Luxación del codo y fractura del epicóndilo lateral en una niña de 5 años. Reporte de caso.

Traumatic elbow dislocation in the pediatric population is a particularly unusual injury. It was first described by Stimson in 1900 and almost 100 years later revisited by Tachdjian in 1990. Three percent of cases are associated with lateral epicondyle fracture, so this is an infrequent injury that has been described in only a few papers as case reports. The mechanism of injury is not clearly known, nor is the best type of treatment or its complications. We report herein the case of a five year-old girl with fracture dislocation of the lateral epicondyle who was managed with closed reduction and percutaneous fixation with Kirschner nails, with good functional results.

Chemical bonding in supermolecular flowers.

We report here a systematic study on the ability of molecular cages to bind (transition) metals. Starting from the superferrocenophane we investigate the incorporation of first-row transition metal (Sc-Zn) and alkaline-earth metal (Mg, Ca) double cations into these supermetallocenophane (super[5]phane) cages, and compare them with the corresponding metallocenes (Inorg. Chim. Acta, 2007, 360, 179). Moreover, we also investigate the binding of neutral and double-cationic metals inside supermetallocyclophane (super[6]phane) cages. The heterolytic and homolytic associations show preferences for different metals, and new metal-containing cages are proposed that should be viable candidates for synthesis.

CBe5E- (E = Al, Ga, In, Tl): planar pentacoordinate carbon in heptaatomic clusters.

A series of clusters with the general formula CBe(5)E(-) (E = Al, Ga, In, Tl) are theoretically shown to have a planar pentacoordinate carbon atom. The structures show a simple and rigid topological framework-a planar EBe(4) ring surrounding a C center, with one of the ring Be-Be bonds capped in-plane by a fifth Be atom. The system is stabilized by a network of multicenter σ bonds in which the central C atom is the acceptor, and π systems as well by which the C atom donates charge to the Be and E atoms that encircle it.

The distribution of E-cadherin expression in listeric rhombencephalitis of ruminants indicates its involvement in Listeria monocytogenes neuroinvasion.

AIM: To investigate the expression of E-cadherin, a major host cell receptor for Listeria monocytogenes (LM) internalin A, in the ruminant nervous system and its putative role in brainstem invasion and intracerebral spread of LM in the natural disease. METHODS: Immunohistochemistry and double immunofluorescence was performed on brains, cranial nerves and ganglia of ruminants with and without natural LM rhombencephalitis using antibodies against E-cadherin, protein gene product 9.5, myelin-associated glycoprotein and LM. RESULTS: In the ruminant brain, E-cadherin is expressed in choroid plexus epithelium, meningothelium and restricted neuropil areas of the medulla, but not in the endothelium. In cranial nerves and ganglia, E-cadherin is expressed in satellite cells and myelinating Schwann cells. Expression does not differ between ruminants with or without listeriosis and does not overlap with the presence of microabscesses in the medulla. LM is observed in phagocytes, axons, Schwann cells, satellite cells and ganglionic neurones. CONCLUSION: Our results support the view that the specific ligand-receptor interaction between LM and host E-cadherin is involved in the neuropathogenesis of ruminant listeriosis. They suggest that oral epithelium and Schwann cells expressing E-cadherin provide a port of entry for free bacteria offering a site of primary intracellular replication, from where the bacterium may invade the axonal compartment by cell-to-cell spread. As E-cadherin expression in the ruminant central nervous system is weak, only very locally restricted and not related to the presence of microabscesses, it is likely that further intracerebral spread is independent of E-cadherin and relies primarily on axonal spread.

Retrospective study on necrotizing enteritis in piglets in Switzerland.

The re-emergence of necrotizing enteritis (NE) in Swiss pig breeding farms raised concern that, besides C. perfringens type C strains, additional C. perfringens toxinotypes might cause this disease. Therefore we retrospectively investigated the association of NE with C. perfringens type C or different C. perfringens toxinotypes. We evaluated pathological lesions, routine diagnostic bacteriology results, and multiplex real-time PCR analyses from DNA extracts of archived intestinal samples of 199 piglets from our diagnostic case load. 96.5% of NE cases and 100% of herds affected by NE were positive for C. perfringens type C genotypes. Animals without necrotizing enteritis revealed a significantly lower detection rate of type C genotypes. Non affected piglets showed a high prevalence for beta-2-toxin positive C. perfringens type A strains. Collectively, our data indicate that outbreaks of NE in piglets in Switzerland cannot be attributed to newly emerging pathogenic toxinotypes, but are due to a spread of pathogenic C. perfringens type C strains.

Stenotrophomonas maltophilia isolated from the airways of animals with chronic respiratory disease.

Stenotrophomonas maltophilia (S. maltophilia) is a nonfermentative bacterium, which is naturally resistant against a panel of commonly-used antibiotics. It is frequently isolated from humans with chronic respiratory disease, e.g. cystic fibrosis or chronic obstructive pulmonary disease. In veterinary medicine S. maltophilia is perceived to be a mere coloniser. We herewith report 7 strains of S. maltophilia isolated from animals, of which 5 strains were harvested from 3 horses, a dog and a cat with chronic respiratory disease. The dog isolate showed resistance to trimethoprim / sulphamethoxazole, which was confirmed by detection of the sul 1 gene. Analysis with pulsed field gel electrophoresis revealed that 2 horses, which were boarded in the same clinic but two years apart, harboured the same strain of S. maltophilia. This is indicative of a hospital acquired colonisation / infection, which contradicts involvement in the pre-existing chronic disease.

Novel identification and differentiation of Brucella melitensis, B. abortus, B. suis, B. ovis, B. canis, and B. neotomae suitable for both conventional and real-time PCR systems.

We describe the development of a novel PCR assay for the rapid detection of members of the Brucella genus, and the differentiation between six recognized Brucella species. The assay has proven to be highly specific with the additional advantage of being suitable for use with both conventional and real-time PCR.