Prescripción de ejercicio físico saludable en Atención Primaria de Salud

La inactividad física predominante en las sociedades más desarrolladas, es la principal causa de muerte prematura y del espectacular incremento registrado a partir de la última parte del siglo XX en la incidencia de las modernas enfermedades crónicas. Sin duda, esa ausencia de actividad física está relacionada con el estilo de vida. Los datos de la última Encuesta Nacional de Salud (2006) indican que un 60,9% de la población española no realiza todo el ejercicio físico deseable, recomendado para mantener la salud. Por ello, fomentar el hábito de realizar ejercicio físico regular entre las personas que acuden a los Centros de Atención Primaria, probablemente sea una de las actuaciones que tengan un impacto más beneficioso en términos de salud para la población.A inactividade física predominante nas sociedades máis desenvolvidas, é a principal causa de morte prematura e do espectacular incremento rexistrado a partir da última parte do século XX na incidencia das modernas enfermidades crónicas. Sen dúbida, esa ausencia de actividade física está relacionada co estilo de vida. Os datos da última Enquisa Nacional de Saúde (2006) indican que un 60,9% da poboación española non realiza todo o exercicio físico desexable, recomendado para manter a saúde. Por iso, fomentar o hábito de realizar exercicio físico regular entre as persoas que acoden aos Centros de Atención Primaria, probablemente sexa unha das actuacións que teñan un impacto máis beneficioso en termos de saúde para a poboación

Chemically Programmed Vaccines: Iron Catalysis in Nanoparticles Enhances Combination Immunotherapy and Immunotherapy-Promoted Tumor Ferroptosis

Immunotherapy has yielded impressive results, but only for a minority of patients with cancer. Therefore, new approaches that potentiate immunotherapy are a pressing medical need. Ferroptosis is a newly described type of programmed cell death driven by iron-dependent phospholipid peroxidation via Fenton chemistry. Here, we developed iron oxide-loaded nanovaccines (IONVs), which, chemically programmed to integrate iron catalysis, drug delivery, and tracking exploiting the characteristics of the tumor microenvironment (TME), improves immunotherapy and activation of ferroptosis. The IONVs trigger danger signals and use molecular disassembly and reversible covalent bonds for targeted antigen delivery and improved immunostimulatory capacity and catalytic iron for targeting tumor cell ferroptosis. IONV- and antibody-mediated TME modulation interfaced with imaging was important toward achieving complete eradication of aggressive and established tumors, eliciting long-lived protective antitumor immunity with no toxicities. This work establishes the feasibility of using nanoparticle iron catalytic activity as a versatile and effective feature for enhancing immunotherapy

Selective turn-on fluorescence detection of cyanide in water using hydrophobic CdSe quantum dots

The ability of 2,2'-bipyridine-bound copper(II) ions to quench the photoluminescence of hydrophobic CdSe quantum dots is used to create a novel, selective turn-on fluorescence cyanide sensor

Catalytic zinc complexes for phosphate diester hydrolysis

Creating efficient artificial catalysts that can compete with biocatalysis has been an enduring challenge which has yet to be met. Reported herein is the synthesis and characterization of a series of zinc complexes designed to catalyze the hydrolysis of phosphate diesters. By introducing a hydrated aldehyde into the ligand we achieve turnover for DNA-like substrates which, combined with ligand methylation, increases reactivity by two orders of magnitude. In contrast to current orthodoxy and mechanistic explanations, we propose a mechanism where the nucleophile is not coordinated to the metal ion, but involves a tautomer with a more effective Lewis acid and more reactive nucleophile. This data suggests a new strategy for creating more efficient metal ion based catalysts, and highlights a possible mode of action for metalloenzymes

Cancer Immunotherapy of TLR4 Agonist-Antigen Constructs Enhanced with Pathogen-Mimicking Magnetite Nanoparticles and Checkpoint Blockade of PD-L1

Despite the tremendous potential of Toll-like receptor 4 (TLR4) agonists in vaccines, their efficacy as monotherapy to treat cancer has been limited. Only some lipopolysaccharides (LPS) isolated from particular bacterial strains or structures like monophosphoryl lipid A (MPLA) derived from lipooligosaccharide (LOS), avoid toxic overactivation of innate immune responses while retaining adequate immunogenicity to act as adjuvants. Here, different LOS structures are incorporated into nanoparticle-filled phospholipid micelles for efficient vaccine delivery and more potent cancer immunotherapy. The structurally unique LOS of the plant pathogen Xcc is incorporated into phospholipid micelles encapsulating iron oxide nanoparticles, producing stable pathogen-mimicking nanostructures suitable for targeting antigen presenting cells in the lymph nodes. The antigen is conjugated via a hydrazone bond, enabling rapid, easy-to-monitor and high-yield antigen ligation at low concentrations. The protective effect of these constructs is investigated against a highly aggressive model for tumor immunotherapy. The results show that the nanovaccines lead to a higher-level antigen-specific cytotoxic T lymphocyte (CTL) effector and memory responses, which when combined with abrogation of the immunosuppressive programmed death-ligand 1 (PD-L1), provide 100% long-term protection against repeated tumor challenge. This nanovaccine platform in combination with checkpoint inhibition of PD-L1 represents a promising approach to improve the cancer immunotherapy of TLR4 agonists

Highly fluorinated naphthalenes and bifurcated C–H⋯F–C hydrogen bonding

The synthesis and crystal structures of 1,2,4,5,6,8-hexafluoronaphthalene and 1,2,4,6,8-pentafluoronaphthalene are reported. Intermolecular interactions are dominated by offset stacking and by C–H⋯F–C hydrogen bonds. For hexafluoronaphthalene, molecules are linked in layers with (4,4) network topology via R12(6) C–H⋯(F–C)2 supramolecular synthons that are rationalised by consideration of the calculated electrostatic potential of the molecule. Such an arrangement is prevented by the additional hydrogen atom in pentafluoronaphthalene and molecules instead form tapes via an R12(8) (C–H⋯F)2 synthon. The geometric characteristics of C–H⋯(F–C)2 bifurcated hydrogen bonds have been analysed for crystal structures in the Cambridge Structural Database (6416 crystal structures; 9534 C–H⋯(F–C)2 bifurcated hydrogen bonds). A geometric analysis of these hydrogen bonds has enabled the extent of asymmetry of these hydrogen bonds to be assessed and indicates a preference for symmetrically bifurcated interactions

The role of Zn-OR and Zn-OH nucleophiles and the influence of para-substituents in the reactions of binuclear phosphatase mimetics

Analogues of the ligand 2,2'-(2-hydroxy-5-methyl-1,3-phenylene)bis(methylene)bis((pyridin-2-ylmethyl)azanediyl)diethanol (CH(3)H(3)L1) are described. Complexation of these analogues, 2,6-bis(((2-methoxyethyl)(pyridin-2-ylmethyl)amino)methyl)-4-methylphenol (CH(3)HL2), 4-bromo-2,6-bis(((2-methoxyethyl)(pyridin-2-ylmethyl)amino)methyl)phenol (BrHL2), 2,6-bis(((2-methoxyethyl)(pyridin-2-ylmethyl)amino)methyl)-4-nitrophenol (NO(2)HL2) and 4-methyl-2,6-bis(((2-phenoxyethyl)(pyridin-2-ylmethyl)amino)methyl)phenol (CH(3)HL3) with zinc(II) acetate afforded [Zn-2(CH(3)L2)(CH3COO)(2)](PF6), [Zn-2(NO(2)L2)(CH3COO)(2)](PF6), [Zn-2(BrL2)(CH3COO)(2)](PF6) and [Zn-2(CH(3)L3)(CH3COO)(2)](PF6), in addition to [Zn-4(CH(3)L2)(2)(NO2C6H5OPO3)(2)(H2O)(2)](PF6)(2) and [Zn-4(BrL2)(2)(PO3F)(2)(H2O)(2)](PF6)(2). The complexes were characterized using H-1 and C-13 NMR spectroscopy, mass spectrometry, microanalysis, and X-ray crystallography. The complexes contain either a coordinated methyl-(L2 ligands) or phenyl-(L3 ligand) ether, replacing the potentially nucleophilic coordinated alcohol in the previously reported complex [Zn-2(CH(3)HL1)(CH3COO)(H2O)](PF6). Functional studies of the zinc complexes with the substrate bis(2,4-dinitrophenyl) phosphate (BDNPP) showed them to be competent catalysts with, for example, [Zn-2(CH(3)L2)](+), k(cat) = 5.70 +/- 0.04 x 10(-3) s(-1) (K-m = 20.8 +/- 5.0 mM) and [Zn-2(CH(3)L3)](+), kcat = 3.60 +/- 0.04 x 10(-3) s(-1) (K-m = 18.9 +/- 3.5 mM). Catalytically relevant pK(a)s of 6.7 and 7.7 were observed for the zinc(II) complexes of CH(3)L2(-) and CH(3)L3(-), respectively. Electron donating para-substituents enhance the rate of hydrolysis of BDNPP such that k(cat) p-CH3 > p-Br > p-NO2. Use of a solvent mixture containing H2O18/H2O16 in the reaction with BDNPP showed that for [Zn-2(CH(3)L2)(CH3COO)(2)](PF6) and [Zn-2(NO(2)L2)(CH3COO)(2)](PF6), as well as [Zn-2(CH(3)HL1)(CH3COO)(H2O)](PF6), the O-18 label was incorporated in the product of the hydrolysis suggesting that the nucleophile involved in the hydrolysis reaction was a Zn-OH moiety. The results are discussed with respect to the potential nucleophilic species (coordinated deprotonated alcohol versus coordinated hydroxide)

Quantum dots decorated with pathogen associated molecular patterns as fluorescent synthetic pathogen models

We attached the pathogen associated molecular pattern Kdo2-Lipid A (the lipopolysaccharide (LPS) from Escherichia coli (E. coli)) to QDs by hydrophobic interactions to synthetically mimic the surface of E. coli. QD-LPS conjugates bind, are taken up and activate effectively macrophages in vitro and they have potent immunostimulatory activity in vivo