Bacterial RNA-free RNase P: Structural and functional characterization of multiple oligomeric forms of a minimal protein-only ribonuclease P.

tRNAs are typically transcribed with extended 5' and 3' ends that must be removed before they attain their active form. One of the first steps of tRNA processing in nearly every organism is the removal of the 5' leader sequence by ribonuclease P (RNase P). Here, we investigate a recently discovered class of RNase P enzymes, Homologs of Aquifex RNase P (HARPs). In contrast to other RNase Ps, HARPs consist only of a metallonuclease domain and lack the canonical substrate recognition domain essential in other classes of proteinaceous RNase P. We determined the cryo-EM structure of Aquifex aeolicus HARP (Aq880) and two crystal structures of Hydrogenobacter thermophilus HARP (Hth1307) to reveal that both enzymes form large ring-like assemblies: a dodecamer in Aq880 and a tetradecamer in Hth1307. In both oligomers, the enzyme active site is 42 Å away from a positively charged helical region, as seen in other protein-only RNase P enzymes, which likely serves to recognize and bind the elbow region of the pre-tRNA substrate. In addition, we use native mass spectrometry to confirm and characterize the previously unreported tetradecamer state. Notably, we find that multiple oligomeric states of Hth1307 are able to cleave pre-tRNAs. Furthermore, our single-turnover kinetic studies indicate that Hth1307 cleaves pre-tRNAs from multiple species with a preference for native substrates. These data provide a closer look at the nuanced similarities and differences in tRNA processing across disparate classes of RNase P.

Colonization With Antibiotic-Resistant Bacteria in a Hospital and Associated Communities in Guatemala: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: We estimated the prevalence of colonization with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) from a hospital and associated communities in western Guatemala. METHODS: Randomly selected infants, children, and adults (<1, 1-17, and ≥18 years, respectively) were enrolled from the hospital (n = 641) during the coronavirus disease 2019 (COVID-19) pandemic, March to September 2021. Community participants were enrolled using a 3-stage cluster design between November 2019 and March 2020 (phase 1, n = 381) and between July 2020 and May 2021 (phase 2, with COVID-19 pandemic restrictions, n = 538). Stool samples were streaked onto selective chromogenic agar, and a Vitek 2 instrument was used to verify ESCrE or CRE classification. Prevalence estimates were weighted to account for sampling design. RESULTS: The prevalence of colonization with ESCrE and CRE was higher among hospital patients compared to community participants (ESCrE: 67% vs 46%, P < .01; CRE: 37% vs 1%, P < .01). Hospital ESCrE colonization was higher for adults (72%) compared with children (65%) and infants (60%) (P < .05). Colonization was higher for adults (50%) than children (40%) in the community (P < .05). There was no difference in ESCrE colonization between phase 1 and 2 (45% and 47%, respectively, P > .05), although reported use of antibiotics among households declined (23% and 7%, respectively, P < .001). CONCLUSIONS: While hospitals remain foci for ESCrE and CRE colonization, consistent with the need for infection control programs, community prevalence of ESCrE in this study was high, potentially adding to colonization pressure and transmission in healthcare settings. Better understanding of transmission dynamics and age-related factors is needed.

Characterization of a Ferryl Flip in Electronically Tuned Nonheme Complexes. Consequences in Hydrogen Atom Transfer Reactivity.

Two oxoiron(IV) isomers (R 2a and R 2b) of general formula [FeIV (O)(R PyNMe3 )(CH3 CN)]2+ are obtained by reaction of their iron(II) precursor with NBu4 IO4 . The two isomers differ in the position of the oxo ligand, cis and trans to the pyridine donor. The mechanism of isomerization between R 2a and R 2b has been determined by kinetic and computational analyses uncovering an unprecedented path for interconversion of geometrical oxoiron(IV) isomers. The activity of the two oxoiron(IV) isomers in hydrogen atom transfer (HAT) reactions shows that R 2a reacts one order of magnitude faster than R 2b, which is explained by a repulsive noncovalent interaction between the ligand and the substrate in R 2b. Interestingly, the electronic properties of the R substituent in the ligand pyridine ring do not have a significant effect on reaction rates. Overall, the intrinsic structural aspects of each isomer define their relative HAT reactivity, overcoming changes in electronic properties of the ligand.

Biological Impacts of Reduced Graphene Oxide Affected by Protein Corona Formation.

Applications of reduced graphene oxide (rGO) in many different areas have been gradually increasing owing to its unique physicochemical characteristics, demanding more understanding of their biological impacts. Herein, we assessed the toxicological effects of rGO in mammary epithelial cells. Because the as-synthesized rGO was dissolved in sodium cholate to maintain a stable aqueous dispersion, we hypothesize that changing the cholate concentration in the dispersion may alter the surface property of rGO and subsequently affect its cellular toxicity. Thus, four types of rGO were prepared and compared: rGO dispersed in 4 and 2 mg/mL sodium cholate, labeled as rGO and concentrated-rGO (c-rGO), respectively, and rGO and c-rGO coated with a protein corona through 1 h incubation in culture media, correspondingly named pro-rGO and pro-c-rGO. Notably, c-rGO and pro-c-rGO exhibited higher toxicity than rGO and pro-rGO and also caused higher reactive oxygen species production, more lipid membrane peroxidation, and more significant disruption of mitochondrial-based ATP synthesis. In all toxicological assessments, pro-c-rGO induced more severe adverse impacts than c-rGO. Further examination of the material surface, protein adsorption, and cellular uptake showed that the surface of c-rGO was coated with a lower content of surfactant and adsorbed more proteins, which may result in the higher cellular uptake observed with pro-c-rGO than pro-rGO. Several proteins involved in cellular redox mediation were also more enriched in pro-c-rGO. These results support the strong correlation between dispersant coating and corona formation and their subsequent cellular impacts. Future studies in this direction could reveal a deeper understanding of the correlation and the specific cellular pathways involved and help gain knowledge on how the toxicity of rGO could be modulated through surface modification, guiding the sustainable applications of rGO.

Spin State Tunes Oxygen Atom Transfer towards FeIV O Formation in FeII Complexes.

Oxoiron(IV) complexes bearing tetradentate ligands have been extensively studied as models for the active oxidants in non-heme iron-dependent enzymes. These species are commonly generated by oxidation of their ferrous precursors. The mechanisms of these reactions have seldom been investigated. In this work, the reaction kinetics of complexes [FeII (CH3 CN)2 L](SbF6 )2 ([1](SbF6 )2 and [2](SbF6 )2 ) and [FeII (CF3 SO3 )2 L] ([1](OTf)2 and [2](OTf)2 (1, L=Me,H Pytacn; 2, L=nP,H Pytacn; R,R' Pytacn=1-[(6-R'-2-pyridyl)methyl]-4,7- di-R-1,4,7-triazacyclononane) with Bu4 NIO4 to form the corresponding [FeIV (O)(CH3 CN)L]2+ (3, L=Me,H Pytacn; 4, L=nP,H Pytacn) species was studied in acetonitrile/acetone at low temperatures. The reactions occur in a single kinetic step with activation parameters independent of the nature of the anion and similar to those obtained for the substitution reaction with Cl- as entering ligand, which indicates that formation of [FeIV (O)(CH3 CN)L]2+ is kinetically controlled by substitution in the starting complex to form [FeII (IO4 )(CH3 CN)L]+ intermediates that are converted rapidly to oxo complexes 3 and 4. The kinetics of the reaction is strongly dependent on the spin state of the starting complex. A detailed analysis of the magnetic susceptibility and kinetic data for the triflate complexes reveals that the experimental values of the activation parameters for both complexes are the result of partial compensation of the contributions from the thermodynamic parameters for the spin-crossover equilibrium and the activation parameters for substitution. The observation of these opposite and compensating effects by modifying the steric hindrance at the ligand illustrates so far unconsidered factors governing the mechanism of oxygen atom transfer leading to high-valent iron oxo species.

Chemical Composition and Antibacterial and Antioxidant Activity of a Citrus Essential Oil and Its Fractions.

Essential oils (EOs) from Citrus are the main by-product of Citrus-processing industries. In addition to food/beverage and cosmetic applications, citrus EOs could also potentially be used as an alternative to antibiotics in food-producing animals. A commercial citrus EO-Brazilian Orange Terpenes (BOT)-was fractionated by vacuum fractional distillation to separate BOT into various fractions: F1, F2, F3, and F4. Next, the chemical composition and biological activities of BOT and its fractions were characterized. Results showed the three first fractions had a high relative amount of limonene (≥10.86), even higher than the whole BOT. Conversely, F4 presented a larger relative amount of BOT's minor compounds (carvone, cis-carveol, trans-carveol, cis-p-Mentha-2,8-dien-1-ol, and trans-p-Mentha-2,8-dien-1-ol) and a very low relative amount of limonene (0.08-0.13). Antibacterial activity results showed F4 was the only fraction exhibiting this activity, which was selective and higher activity on a pathogenic bacterium (E. coli) than on a beneficial bacterium (Lactobacillus sp.). However, F4 activity was lower than BOT. Similarly, F4 displayed the highest antioxidant activity among fractions (equivalent to BOT). These results indicated that probably those minor compounds that detected in F4 would be more involved in conferring the biological activities for this fraction and consequently for the whole BOT, instead of the major compound, limonene, playing this role exclusively.

The Mechanism of the Intramolecular Hydrocarbyl Metathesis within a Planar Triruthenium Cluster: Combining Core Flexibility with Hydride Mobility.

The transition metal catalysed formation and cleavage of C-C bonds is of utmost importance in synthetic chemistry. While most of the existing homogeneous catalysts are mononuclear, knowledge of the behaviour of polynuclear species is much more limited. By using computational methods, here we shed light into the mechanistic details of the thermally-induced isomerization of Cp*3 Ru3 (µ-H)2 (µ3 -η2 -pentyne)(µ3 -pentylidyne) (2) into Cp*3 Ru3 (µ-H)2 (µ3 -η2 -octyne)(µ3 -ethylidyne) (3), a process that involves the migration of a C3 fragment between the hydrocarbyl ligands and across the plane formed by the three Ru centres. Our results show this to be a complex transformation that comprises of five individual rearrangements in an A→B→A→B→A order. Each so-called rearrangement A consists of the CH migration from the µ3 -η2 -alkyne into the µ3 -alkylidine ligand in the other side of the Ru3 plane. This process is facilitated by the cluster's ability to adopt open-core structures in which one Ru-Ru bond is broken and a new C-C bond is formed. In contrast, rearrangements B do not involve the formation or cleavage of C-C bonds, nor do they require the opening of the cluster core. Instead, they consist of the isomerization of the µ3 -η2 -alkyne and µ3 -alkylidyne ligands on each side of the triruthenium plane into µ3 -alkylidyne and µ3 -η2 -alkyne, respectively. Such transformation implies the migration of three H atoms within the hydrocarbyl ligands, and in this case, it is aided by the cluster's ability to behave as a H reservoir. All in all, this study highlights the plasticity of these Ru3 clusters, whereby Ru-Ru, Ru-C, Ru-H, C-C, and C-H bonds are formed and broken with surprising ease.

Sensory and hedonic impact of the replacement of synthetic antioxidant for pink pepper residue extract in chicken burger.

This study aimed to evaluate the sensory and hedonic perceptions of chicken burger manufactured with pink pepper residue extract (PPE) added to the meat and to the chitosan film. Five samples were manufactured: CT: control, without antioxidant; DP and FP: addition of PPE to the meat batter and to the film, respectively; C1 and C2: commercial brands of chicken burgers. Consumers characterized the samples using the overall liking test and Check-all-that-apply questions. The samples showed a medium-high level of acceptance and no significant differences were found between them. DP was the farthest sample from the ideal and FP showed positive results, since its characteristics were like the commercial samples. The direct extract application may lead to a reduction in the liking of chicken burgers, demonstrating that the technology of active films is a viable alternative to the use of natural antioxidant extracts in meat products.

Cobalt(II) Pentaaza-Macrocyclic Schiff Base Complex as Catalyst for Light-Driven Hydrogen Evolution in Water: Electrochemical Generation and Theoretical Investigation of the One-Electron Reduced Species.

We previously reported that the tetraazamacrocyclic Schiff base complex [CoIII(CR14)(X)2]n+ (CR14 = 2,12-dimethyl-3,7,11,17-tetraazabicyclo[11.3.1]heptadeca-1(17),2,11,13,15-pentaene, X = Cl (n = 1) (1-Cl2) or H2O (n = 3) (1-(H2O)2)) is a very efficient H2-evolving catalyst (HEC) in fully aqueous solutions at pH 4.0-4.5 when used in a photocatalytic system including a photosensitizer and ascorbate as sacrificial electron donor. The excellent H2-evolving activity of this complex, compared to other cobalt and rhodium catalysts studied in the same photocatalytic conditions, can be related to the high stability of its two-electron reduced form, the putative "Co(I)" state. These very interesting results led us to investigate the H2-evolving performances of a series of compounds from a close-related family, the pentaaza-macrocyclic cobalt [CoII(CR15)(H2O)2]Cl2 complex (2, CR15 = 2,13-dimethyl-3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),2,12,14,16-pentaene), which comprises a larger macrocycle with five nitrogen atoms instead of four. Electrochemical as well as spectroscopic investigations in CH3CN coupled to density functional theory (DFT) calculations point to decoordination of one of the amine upon reduction of Co(II) to the low-valent "Co(I)" form. The resulting unchelated amine could potentially act as a proton relay promoting the H2 formation via proton-coupled-electron transfer (PCET) reactions. Besides, the iron, manganese, and zinc analogues, [FeII(CR15)(X)2]n+ (X = Cl (n = 0) or H2O (n = 2)) (3), [MnII(CR15)(CH3CN)2](PF6)2 (4), and {[ZnII(CR15)Cl](PF6)}n (5) were also synthesized and investigated. The photocatalytic activity of 2-5 toward proton reduction was then evaluated in a tricomponent system containing the [RuII(bpy)3]Cl2 photosensitizer and ascorbate, in fully aqueous solution. The photocatalytic activity of 2 was also compared with that of 1 in the same experimental conditions. It was found that the number of catalytic cycles versus catalyst for 2 are slightly lower than that for 1, suggesting that if the amine released upon reduction of 2 plays a role in promoting the H2-evolving catalytic activity, other factors balance this effect. Finally, photophysical and nanosecond transient absorption spectroscopies were used to investigate the photocatalytic system.

Electrochemical Generation and Spectroscopic Characterization of the Key Rhodium(III) Hydride Intermediates of Rhodium Poly(bipyridyl) H2-Evolving Catalysts.

We previously reported that the [RhIII(dmbpy)2Cl2]+ (dmbpy = 4,4'-dimethyl-2,2'-bipyridine) complex is an efficient H2-evolving catalyst in water when used in a molecular homogeneous photocatalytic system for hydrogen production with [RuII(bpy)3]2+ (bpy = 2,2'-bipyridine) as photosensitizer and ascorbic acid as sacrificial electron donor. The catalysis is believed to proceed via a two-electron reduction of the Rh(III) catalyst into the square-planar [RhI(dmbpy)2]+, which reacts with protons to form a Rh(III) hydride intermediate that can, in turn, release H2 following different pathways. To improve the current knowledge of these key intermediate species for H2 production, we performed herein a detailed electrochemical investigation of the [RhIII(dmbpy)2Cl2]+ and [RhIII(dtBubpy)2Cl2]+ (dtBubpy = 4,4'-di- tert-butyl-2,2'-bipyridine) complexes in CH3CN, which is a more appropriate medium than water to obtain reliable electrochemical data. The low-valent [RhI(Rbpy)2]+ and, more importantly, the hydride [RhIII(Rbpy)2(H)Cl]+ species (R = dm or dtBu) were successfully electrogenerated by bulk electrolysis and unambiguously spectroscopically characterized. The quantitative formation of the hydrides was achieved in the presence of weak proton sources (HCOOH or CF3CO3H), owing to the fast reaction of the electrogenerated [RhI(Rbpy)2]+ species with protons. Interestingly, the hydrides are more difficult to reduce than the initial Rh(III) bis-chloro complexes by ∼310-340 mV. Besides, 0.5 equiv of H2 is generated through their electrochemical reduction, showing that Rh(III) hydrides are the initial catalytic molecular species for hydrogen evolution. Density functional theory calculations were also performed for the dmbpy derivative. The optimized structures and the theoretical absorption spectra were calculated for the initial bis-chloro complex and for the various rhodium intermediates involved in the H2 evolution process.

Permeability Characteristics of a New Antifungal Topical Amphotericin B Formulation with γ-Cyclodextrins.

Amphotericin B is a low soluble broad-spectrum antifungal agent. Cyclodextrins can be added to amphotericin formulations to enhance both their solubility and antifungal properties. Semisolid amphotericin formulations containing gamma cyclodextrin (AGCD) were prepared and compared with two reference formulations-one of them without any solubility enhancer (A) and the other with DMSO (ADMSO). Rheological, the permeability through hairless mouse skin and antifungal characteristics of the different formulations were evaluated. All three semisolid formulations show low thixotropy characteristics. ADMSO was the formulation with the least consistency, lowest viscosity, and greatest extensibility. The AGCD formulation had the opposite behavior and had both the greatest consistency and viscosity and the lowest extensibility. The lowest permeability was obtained with the reference A formulation while both AGCD and ADMSO had a similar permeability enhancement. According to the antimicrobial in vitro efficacy trials, the AGCD formulation showed 45⁻60% more activity than the reference A formulation. It can be concluded that γ-cyclodextrin is a useful excipient to improve the solubility, permeability, and antifungal activity of amphotericin B in semisolid topical formulations.

Optimization of lipid profile and hardness of low-fat mortadella following a sequential strategy of experimental design.

This study aims to optimize simultaneously the lipid profile and instrumental hardness of low-fat mortadella. For lipid mixture optimization, the overlapping of surface boundaries was used to select the quantities of canola, olive, and fish oils, in order to maximize PUFAs, specifically the long-chain n-3 fatty acids (eicosapentaenoic-EPA, docosahexaenoic acids-DHA) using the minimum content of fish oil. Increased quantities of canola oil were associated with higher PUFA/SFA ratios. The presence of fish oil, even in small amounts, was effective in improving the nutritional quality of the mixture, showing lower n-6/n-3 ratios and significant levels of EPA and DHA. Thus, the optimal lipid mixture comprised of 20, 30 and 50% fish, olive and canola oils, respectively, which present PUFA/SFA (2.28) and n-6/n-3 (2.30) ratios within the recommendations of a healthy diet. Once the lipid mixture was optimized, components of the pre-emulsion used as fat replacer in the mortadella, such as lipid mixture (LM), sodium alginate (SA), and milk protein concentrate (PC), were studied to optimize hardness and springiness to target ranges of 13-16 N and 0.86-0.87, respectively. Results showed that springiness was not significantly affected by these variables. However, as the concentration of the three components increased, hardness decreased. Through the desirability function, the optimal proportions were 30% LM, 0.5% SA, and 0.5% PC. This study showed that the pre-emulsion decreases hardness of mortadella. In addition, response surface methodology was efficient to model lipid mixture and hardness, resulting in a product with improved texture and lipid quality.

Iron(II) Complexes with Scorpiand-Like Macrocyclic Polyamines: Kinetico-Mechanistic Aspects of Complex Formation and Oxidative Dehydrogenation of Coordinated Amines.

The Fe(II) coordination chemistry of a pyridinophane tren-derived scorpiand type ligand containing a pyridine ring in the pendant arm is explored by potentiometry, X-ray, NMR, and kinetics methods. Equilibrium studies in water show the formation of a stable [FeL]2+ complex that converts to monoprotonated and monohydroxylated species when the pH is changed. A [Fe(H-2L)]2+ complex containing an hexacoordinated dehydrogenated ligand has been isolated, and its crystal structure shows the formation of an imine bond involving the aliphatic nitrogen of the pendant arm. This complex is low spin Fe(II) both in the solid state and in solution, as revealed by the Fe-N bond lengths and by the NMR spectra, respectively. The formation rate of [Fe(H-2L)]2+ in aqueous solutions containing Fe2+ and L (1:1 molar ratio) is strongly dependent on the pH, the process being completed in times that range from months in acid solutions to hours in basic conditions. However, detailed kinetic studies show that those differences are caused, at least in part, by the effect of pH on the rate of formation of the unoxidized [FeL]2+ complex. In this sense, the protonation of the donor atoms in the pendant arm of the scorpiand ligand leads to the formation of protonated species resistant to oxidative dehydrogenation. Complementary studies in acetonitrile solution indicate that the initial stage in the oxidative dehydrogenation process is the oxidation of the starting complex to form a [FeL]3+ complex, which then undergoes disproportionation into [Fe(H-2L)]2+ and [FeL]2+. Experiments starting with Fe(III) have allowed us to determine that disproportionation occurs with first order kinetics both in water and acetonitrile solutions. However, whereas a significant acceleration is observed in water when the pH is increased, no effect of the addition of acid or base on the rate of disproportionation is observed in acetonitrile. Oxidative dehydrogenation of the Fe(II) complex formed in experiments starting with an Fe(III) salt is slower than that occurring when an Fe(II) salt is used, an observation that can be explained in terms of the formation of two different Fe(III) complexes, one of them with a structure unable to evolve directly toward the product of oxidative dehydrogenation.

Molecular characterization and antibiotic resistance of Staphylococcus spp. isolated from cheese processing plants.

The aim of this research paper was to characterize coagulase-positive and coagulase-negative staphylococci from raw milk, Minas cheese, and production lines of Minas cheese processing. One hundred isolates from 3 different cheese producers were characterized using molecular approaches, such as PCR, molecular typing, and DNA sequencing. Staphylococcus aureus (88% of the isolates) was the most abundant followed by Staphylococcus epidermidis, Staphylococcus hyicus, and Staphylococcus warneri. Among the 22 enterotoxin genes tested, the most frequent was seh (62% of the isolates), followed by selx and ser. Hemolysin genes were widely distributed across isolates, and Panton-Valentine leukocidin and toxic shock syndrome toxin genes were also identified. Methicillin-resistant S. aureus were staphylococcal cassette chromosome mec III, IVa, IVd, and others nontypeable. In the phenotypic antibiotic resistance, multiresistant isolates were detected and resistance to penicillin was the most observed. Using spa typing, we identified several types and described a new one, t14969, isolated from cheese. These findings suggest that antibiotic resistance and potentially virulent strains from different sources can be found in the Brazilian dairy processing environment. Further research should be conducted with collaboration from regulatory agencies to develop programs of prevention of virulent and resistant strain dissemination in dairy products and the processing environment.

Using evidence-informed policies to tackle overweight and obesity in Chile.

Overweight and obesity are a global epidemic with rates having risen to alarming levels in both developed and developing countries. Chile has been no exemption, with sharp increases in obesity prevalence, especially among school-age children. This paper describes the policy actions and strategies implemented to tackle this major public health concern in Chile over the last 10 years, and highlights the main challenges and nuances of the process. Chile has taken policy action that includes front-of-package labelling, advertising regulations, and school-food restrictions. New policies focus on the social determinants of health as they relate to food environments and people's behavior. These actions are not only suitable to the current context in Chile, but are also supported by the best available scientific evidence. Moreover, the implementation of these policies has produced a broad debate involving public institutions and the food industry, with discussions issues ranging from property rights to trade barriers. Despite some differences among stakeholders, a valuable political consensus has been achieved, and several international organizations are eager to evaluate the impact of these pioneer initiatives in Latin America.

El sobrepeso y la obesidad son una epidemia mundial, en la que se registran tasas que han aumentado hasta niveles alarmantes tanto en los países desarrollados como en los países en desarrollo. Chile no ha sido una excepción, con aumentos pronunciados de la prevalencia de la obesidad, especialmente en los niños en edad escolar. En este documento se describen las políticas y estrategias aplicadas para luchar contra este grave problema de salud pública en Chile durante los 10 últimos años, y se resaltan los principales retos y matices del proceso. Chile ha tomado medidas de política que incluyen el etiquetado frontal de los envases, la reglamentación de la publicidad y restricciones en cuanto a la alimentación en las escuelas. Las nuevas políticas se centran en los determinantes sociales de la salud pues guardan relación con el entorno en cuanto a la alimentación y el comportamiento de las personas. Estas medidas no solo son apropiadas para el contexto actual de Chile, sino que también se basan en las mejores pruebas científicas de que se dispone. Por otro lado, la aplicación de estas políticas ha generado un amplio debate con las instituciones públicas y la industria alimentaria, cuyos temas de discusión abarcan desde derechos de propiedad hasta barreras comerciales. A pesar de algunas diferencias entre los interesados directos, se ha logrado un valioso consenso político y varias organizaciones internacionales están dispuestas a evaluar la repercusión de estas iniciativas pioneras en América Latina.

O sobrepeso e a obesidade constituem uma epidemia global atingindo níveis alarmantes nos países desenvolvidos e em desenvolvimento. O Chile não é exceção: o país tem registrado uma elevação acentuada da prevalência de obesidade, sobretudo em crianças em idade escolar. Este artigo descreve as medidas envolvendo políticas e estratégias implantadas no Chile na última década para combater este importante problema de saúde pública e destaca os principais desafios e as particularidades do processo. O país adotou políticas para rotulagem nutricional na parte da frente da embalagem dos produtos alimentícios, regulamentação da publicidade e restrições aos alimentos servidos em escolas. As novas políticas são direcionadas aos determinantes sociais da saúde por estarem associados aos ambientes e aos comportamentos alimentares da população. Além de serem adaptadas ao contexto atual do Chile, estas medidas se embasam nas melhores evidências científicas. A execução destas políticas deu início a um amplo debate entre as instituições públicas e a indústria de produtos alimentícios envolvendo de questões sobre direitos de propriedade às barreiras comerciais. Apesar das suas posições divergentes sobre alguns aspectos, os interessados diretos chegaram a um consenso político importante. As organizações internacionais esperam agora conhecer o resultado da avaliação do impacto dessas iniciativas pioneiras na América Latina.

Synthesis, Characterization, and Photocatalytic H2-Evolving Activity of a Family of [Co(N4Py)(X)](n+) Complexes in Aqueous Solution.

A series of [Co(III)(N4Py)(X)](ClO4)n (X = Cl(-), Br(-), OH(-), N3(-), NCS(-)-κN, n = 2: X = OH2, NCMe, DMSO-κO, n = 3) complexes containing the tetrapyridyl N5 ligand N4Py (N4Py = 1,1-di(pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine) has been prepared and fully characterized by infrared (IR), UV-visible, and NMR spectroscopies, high-resolution electrospray ionization mass spectrometry (HRESI-MS), elemental analysis, X-ray crystallography, and electrochemistry. The reduced Co(II) and Co(I) species of these complexes have been also generated by bulk electrolyses in MeCN and characterized by UV-visible and EPR spectroscopies. All tested complexes are catalysts for the photocatalytic production of H2 from water at pH 4.0 in the presence of ascorbic acid/ascorbate, using [Ru(bpy)3](2+) as a photosensitizer, and all display similar H2-evolving activities. Detailed mechanistic studies show that while the complexes retain the monodentate X ligand upon electrochemical reduction to Co(II) species in MeCN solution, in aqueous solution, upon reduction by ascorbate (photocatalytic conditions), [Co(II)(N4Py)(HA)](+) is formed in all cases and is the precursor to the Co(I) species which presumably reacts with a proton. These results are in accordance with the fact that the H2-evolving activity does not depend on the chemical nature of the monodentate ligand and differ from those previously reported for similar complexes. The catalytic activity of this series of complexes in terms of turnover number versus catalyst (TONCat) was also found to be dependent on the catalyst concentration, with the highest value of 230 TONCat at 5 × 10(-6) M. As revealed by nanosecond transient absorption spectroscopy measurements, the first electron-transfer steps of the photocatalytic mechanism involve a reductive quenching of the excited state of [Ru(bpy)3](2+) by ascorbate followed by an electron transfer from [Ru(II)(bpy)2(bpy(•-))](+) to the [Co(II)(N4Py)(HA)](+) catalyst. The reduced catalyst then enters into the H2-evolution cycle.

Calcitriol prevents inflammatory gene expression in macrovascular endothelial cells.

BACKGROUND: Calcitriol (vitamin D) supplementation has been proposed for therapeutical use in vascular diseases due to its immunomodulatory activity, preventing inflammation and promoting angiogenesis. In the present study, we hypothesised whether calcitriol downregulates pro-inflammatory gene expression without affecting angiogenesis and anti-inflammatory gene expression in LPS-induced endothelial cells. METHOD: In order to evaluate the effect of calcitriol in suppressing inflammatory gene expression in the endothelium, endothelial cells were exposed to the physiological concentration of calcitriol followed by stimulation with lipopolysaccharide (LPS). Gene expression of interleukin (IL)-1ß, Transforming Growth Factor (TGF)-ß, Human ß-defensin (HBD)-2, angiogenin (ANG) and cathelicidin (LL-37) were quantified by quantitative polymerase chain reaction. RESULTS: The results from six independent experiments conducted in duplicate, showed that calcitriol decreased IL-1ß (p < 0.01) and HBD-2 expression (p < 0.01) when compared to non-treated cells. However, calcitriol treatment had no effect on TGF-ß, ANG and LL-37 gene expression. CONCLUSION: Calcitriol prevents inflammatory gene expression, but does not affect expression of angiogenic genes in endothelial cells, which suggest the potential use of calcitriol to prevent endothelial activation through the downregulation of IL-1ß and HBD-2.

The effects of (-)-epicatechin on endothelial cells involve the G protein-coupled estrogen receptor (GPER).

We have provided evidence that the stimulatory effects of (-)-epicatechin ((-)-EPI) on endothelial cell nitric oxide (NO) production may involve the participation of a cell-surface receptor. Thus far, such entity(ies) has not been fully elucidated. The G protein-coupled estrogen receptor (GPER) is a cell-surface receptor that has been linked to protective effects on the cardiovascular system and activation of intracellular signaling pathways (including NO production) similar to those reported with (-)-EPI. In bovine coronary artery endothelial cells (BCAEC) by the use of confocal imaging, we evidence the presence of GPER at the cell-surface and on F-actin filaments. Using in silico studies we document the favorable binding mode between (-)-EPI and GPER. Such binding is comparable to that of the GPER agonist, G1. By the use of selective blockers, we demonstrate that the activation of ERK 1/2 and CaMKII by (-)-EPI is dependent on the GPER/c-SRC/EGFR axis mimicking those effects noted with G1. We also evidence by the use of siRNA the role that GPER has on mediating ERK1/2 activation by (-)-EPI. GPER appears to be coupled to a non Gαi/o or Gαs, protein subtype. To extrapolate our findings to an ex vivo model, we employed phenylephrine pre-contracted aortic rings evidencing that (-)-EPI can mediate vasodilation through GPER activation. In conclusion, we provide evidence that suggests the GPER as a potential mediator of (-)-EPI effects and highlights the important role that GPER may have on cardiovascular system protection.

Nonlinear relationship between waist to hip ratio, weight and strength in elders: is gender the key?

Visceral fat has a high metabolic activity with deleterious effects on health contributing to the risk for the frailty syndrome. We studied the association between waist to hip ratio (an indirect measure of visceral fat stores) on upper and lower extremities strength. 1741 individuals aged ≥65 participated in this study. The data was obtained from the Toledo Study for Healthy Aging. For each gender, we studied the relationship between the waist-to-hip ratio (WHR), body mass index (BMI) and regional muscle strength (grip, shoulder, knee and hip) using multivariate linear regression and kernel regression statistical models. WHR was higher in men than in women (0.98 ± 0.07 vs. 0.91 ± 0.08, respectively, P < 0.05). In women with high WHR, we observed a decrease in strength especially in those with a normal BMI. As the WHR lowered, the strength increased regardless of the BMI. In men, lower strength was generally related to the lowest and highest WHR's. Maximum strength in men corresponded at a WHR around 1 and the highest BMI. Muscle strength depends on the joined distribution of WHR and BMI according to gender. In consequence, sex, WHR and BMI should be analyzed conjointly to study the relationship among fat distribution, weight and muscle strength.

Assessing Health Literacy in Urban Patients With Implantable Cardioverter Defibrillators and Pacemakers.

Functional health literacy (FHL) has become an increasingly prevalent topic of discussion in patient health and well-being. Although FHL has been studied in a variety of populations, it has not been investigated in patients with pacemakers and implantable cardioverter defibrillators (ICDs).The purpose of this study was to evaluate FHL in a primarily older, urban-dwelling ICD/pacemaker population. A secondary objective was to compare 2 commonly used instruments for assessing FHL.A convenience sample of 116 patients was recruited from an urban ICD/pacemaker clinic. Participants were asked to complete the Short Test of Functional Health Literacy in Adults (STOFHLA) followed by the Test of Functional Health Literacy in Adults to assess reading comprehension and numeracy. Logistic regression was used to assess the association between FHL and patient descriptors.The population was 68 ± 13 years of age, and 62.7% were men. The sample was ethnically diverse: 37.1% white, 39.7% Hispanic, and 22.4% African American; 77.4% of the population reported finishing high school. Of the 109 completing the Test of Functional Health Literacy in Adults, 60.6% had adequate FHL, 10.1% had marginal FHL, and 29.4% had inadequate FHL. The presence of coexisting chronic conditions such as diabetes mellitus, hyperlipidemia, and hypertension was associated with inadequate/marginal FHL (P = .007, P = .004, and P = .02, respectively). Of the 113 completing STOFHLA, 67.3% had adequate FHL, 7.1% had marginal FHL, and 25.7% had inadequate FHL. The presence of diabetes mellitus, hyperlipidemia, and hypertension was also associated with inadequate/marginal FHL as assessed by STOFHLA (P = .009, P = .02, and P = .004, respectively).In this older, urban, ICD/pacemaker population, approximately 40% had inadequate/marginal FHL. These results warrant further investigation of FHL in other cardiovascular populations.