[Incidence of admissions due to pneumonia in children under 24 months old before and after the introduction of the 10-valent pneumococcal conjugate vaccine into the National Immunization Program of Chile]. / Incidencia de egresos por neumonía en niños menores de 24 meses antes y después de la implementación de la vacuna conjugada antineumocócica 10-valente en el Programa Nacional de Inmunizaciones de Chile.

INTRODUCTION: Streptococcus pneumoniae is the leading cause of bacterial pneumonia in children, especially in the hospitalized population. The 10-valent pneumococcal vaccine was included in the National Immunization Program of Chile in 2011. This study aims to evaluate the incidence of pneumonia in hospitalized children<24 months of age in the Luis Calvo Mackenna Hospital before and after the introduction of the pneumococcal vaccine into the National Immunization Program. PATIENTS AND METHODS: Passive surveillance study. Patients<24 months with discharge diagnosis of bacterial pneumonia from Luis Calvo Mackenna Hospital were studied between 2009 and 2013. Data were obtained from the Luis Calvo Mackenna Hospital's Statistical Service. The incidence of pneumonia was evaluated in the pre-vaccination period (2009-2010) and in the post-vaccination period (2012-2013). RESULTS: During the study period, an average of 4,321 discharges/year was observed in children<24 months (range: 3,587-4,702), with a significant decrease from pre- to post-vaccination vaccine period (4,644 vs 4,013, P<.001). The average incidence of pneumonia ranged from 3.4/100,000 to 1.5/100,000 in the pre- and post-vaccine period, respectively (P=.009), with an annual mean of 157 cases of pneumonia in the pre- vaccine period, and 62 cases in the postvaccine period (P<.001) and a decrease in incidence between the two periods of 56%. CONCLUSION: This study confirms information previously obtained in other countries, which show a decrease in the incidence of pneumonia associated with the implementation of a pneumococcal vaccine at the population level. Ongoing surveillance is required to evaluate if this effect is maintained over time and expands to older populations.

Probabilistic metrology attains macroscopic cloning of quantum clocks.

It has recently been shown that probabilistic protocols based on postselection boost the performances of the replication of quantum clocks and phase estimation. Here we demonstrate that the improvements in these two tasks have to match exactly in the macroscopic limit where the number of clones grows to infinity, preserving the equivalence between asymptotic cloning and state estimation for arbitrary values of the success probability. Remarkably, the cloning fidelity depends critically on the number of rationally independent eigenvalues of the clock Hamiltonian. We also prove that probabilistic metrology can simulate cloning in the macroscopic limit for arbitrary sets of states when the performance of the simulation is measured by testing small groups of clones.

Technology-driven dietary assessment: a software developer's perspective.

Dietary researchers need new software to improve nutrition data collection and analysis, although the creation of information technology is difficult. Software development projects may be unsuccessful as a result of an inadequate understanding of needs, management problems, technology barriers or legal hurdles. Cost over-runs and schedule delays are common. Barriers facing scientific researchers developing software include workflow, cost, schedule and team issues. Different methods of software development and the role that intellectual property rights play are discussed. A dietary researcher must carefully consider multiple issues to maximise the likelihood of success when creating new software.

Quantum metrology assisted by abstention.

The main goal of quantum metrology is to obtain accurate values of physical parameters using quantum probes. In this context, we show that abstention, i.e., the possibility of getting an inconclusive answer at readout, can drastically improve the measurement precision and even lead to a change in its asymptotic behavior, from the shot-noise to the Heisenberg scaling. We focus on phase estimation and quantify the required amount of abstention for a given precision. We also develop analytical tools to obtain the asymptotic behavior of the precision and required rate of abstention for arbitrary pure states.

A model of traumatic brain injury in rats is influenced by neuroprotection of diurnal variation which improves motor behavior and histopathology in white matter myelin.

Traumatic brain injury (TBI) represents a significant public health concern and has been associated with high rates of morbidity and mortality. TBI generates two types of brain damage: primary and secondary. Secondary damage originates a series of pathophysiological processes, which include metabolic crisis, excitotoxicity, and neuroinflammation, which have deleterious consequences for neuronal function. However, neuroprotective mechanisms are also activated. The balance among these tissue responses, and its variations throughout the day determines the fate of the damage tissue. We have demonstrated less behavioral and morphological damage when a rat model of TBI was induced during the light hours of the day. Moreover, here we show that rats subjected to TBI in the dark lost less body weight than those subjected to TBI in the light, despite no change in food intake. Besides, the rats subjected to TBI in the dark had better performance in the beam walking test and presented less histological damage in the corpus callosum and the cingulum bundle, as shown by the Klüver-Barrera staining. Our results suggest that the time of day when the injury occurs is important. Thus, this data should be used to evaluate the pathophysiological processes of TBI events and develop better therapies.

Solvent effects in ionic liquids: empirical linear energy-density relationships.

Multiparameter linear energy-density relationships to model solvent effects in room temperature ionic liquids (RTILs) are introduced and tested. The model incorporates two solvent dependent and two specific solute-solvent parameters represented by a set of electronic indexes derived from the conceptual density functional theory. The specific solute-solvent interactions are described in terms of the electronic chemical potential for proton migration between the anion or cation and the transition state structure of a specific reaction. These indexes provide a quantitative estimation of the hydrogen bond (HB) acceptor basicity and the hydrogen bond donor acidity of the ionic solvent, respectively. A sound quantitative scale of HB strength is thereby obtained. The solvent dependent contributions are described by the global electrophilicity of the cation and nucleophilicity of the anion forming the ionic liquid. The model is illustrated for the kinetics of cycloaddition of cyclopentadiene towards acrolein. In general, cation HB acidity outweighs the remaining parameters for this reaction.

[Improvement of insulin sensitivity after an intensive lifestyle program for youth's weight management in the primary care]. / Mejora en la sensibilidad a la insulina con un programa intensivo de cambio en el estilo de vida para control de obesidad en niños y adolescentes en el primer nivel de atención.

The aim of this study was to evaluate an intensive lifestyle intervention for weight management among youth in a primary care setting on insulin sensibility, compared to a control group. The study included 42 youths 9-17 years old (n=23 intensive lifestyle intervention, n=19 control group) who completed a randomized trial for weight management in a primary care setting which included an oral glucose tolerance test. The intensive lifestyle intervention included monthly consultations with the primary care physician, nutrition counseling with a registered dietitian (weekly first 3 months and then monthly) and 12 group sessions in a behavioral change protocol. The control group attended monthly consultations with the primary care physician. Insulin sensitivity was estimated by the Insulin Sensitivity Index ISI(0,120) at baseline and 6 months posttreatment. At 6 months, the mean +/- DE, increase in insulin sensitivity was greater in the intensive lifestyle intervention than the control group (+46.8 +/- 56 vs. +5.6 +/- 47, between-group difference 41.2 [CI 95%, 8.5, 73.9], p = 0.01): Sixty five percent of youths on the intensive lifestyle intervention increased insulin sensitivity over 9 units vs. 32% in the control group (p=0.03). This study shows preliminary evidence that an intensive lifestyle intervention program can be an alternative model to improve insulin sensitivity among youths in the primary care setting.

Chemical modulation of the metabolism of an endophytic fungal strain of Cophinforma mamane using epigenetic modifiers and amino-acids.

Endophytic fungi are capable of producing a great diversity of bioactive metabolites. However, the presence of silent and lowly expressed genes represents a main challenge for the discovery of novel secondary metabolites with different potential uses. Epigenetic modifiers have shown to perturb the production of fungal metabolites through the induction of silent biosynthetic pathways leading to an enhanced chemical diversity. Moreover, the addition of bioprecursors to the culture medium has been described as a useful strategy to induce specific biosynthetic pathways. The aim of this study was to assess the effects of different chemical modulators on the metabolic profiles of an endophytic fungal strain of Cophinforma mamane (Botryosphaeriaceae), known to produce 3 thiodiketopiperazine (TDKP) alkaloids (botryosulfuranols A-C), previously isolated and characterized by our team. Four epigenetic modifiers, 5-azacytidine (AZA), sodium butyrate (SB), nicotinamide (NIC), homoserine lactone (HSL) as well as 2 amino acids, l-phenylalanine and l-tryptophan, as bioprecursors of TDKPs, were used. The metabolic profiles were analysed by UHPLC-HRMS/MS under an untargeted metabolomics approach. Our results show that the addition of the two amino acids in C. mamane culture and the treatment with AZA significantly reduced the production of the TDKPs botryosulfuranols A, B and C. Interestingly, the treatment with HSL significantly induced the production of different classes of diketopiperazines (DKPs). The treatment with AZA resulted as the most effective epigenetic modifier for the alteration of the secondary metabolite profile of C. mamane by promoting the expression of cryptic genes.

Local discrimination of mixed States.

We provide rigorous, efficiently computable and tight bounds on the average error probability of multiple-copy discrimination between qubit mixed states by local operations assisted with classical communication (LOCC). In contrast with the pure-state case, these experimentally feasible protocols perform strictly worse than the general collective ones. Our numerical results indicate that the gap between LOCC and collective error rates persists in the asymptotic limit. In order for LOCC and collective protocols to achieve the same accuracy, the former can require up to twice the number of copies of the latter. Our techniques can be used to bound the power of LOCC strategies in other similar settings, which is still one of the most elusive questions in quantum communication.

First report of porcine respirovirus 1 in South America.

Porcine respirovirus 1 (PRV1) is an emerging virus in pigs that has been previously described in the USA and China. There are no reports of its presence in the rest of the world. The objective of this study was to determine the occurrence of PRV1 in Chile and to determine its phylogeny. Thus, we collected samples (oral fluids, nasal swabs, and lungs) from a swine influenza A virus (IAV) surveillance program, most of which belonged to pigs with respiratory disease. The samples were analyzed by RT-PCR, and the viral sequencing was obtained using RNA whole-genome sequencing approach. Maximum likelihood phylogeny was constructed with the available references. Thirty-one of 164 samples (18.9 %) were RT-PCR positive for PRV1: 62.5 % oral fluids, 19.0 % nasal swabs, and 8.6 % lungs. All 6 farms in this study had at least one positive sample, with 6-40 % of positive results per farm, which suggests that PRV1 is disseminated in Chilean swine farms. Twenty-one of 31 (677%) PRV1-positive samples were also positive for IAV, so the role of PRV1 as secondary pathogen in respiratory disease needs to be further evaluated. Near to complete genome of two PRV1s were obtained from two farms. The phylogenies, in general, showed low bootstrap support, except the concatenated genome and the L gene trees which showed clustering of the Chilean PRV1 with Asian sequences, suggesting a close genetic relationship. This is the first report of PRV1 in the Southern Hemisphere. Further studies are necessary to determine the genetic diversity of this virus in Chile.

Analysis of ten Brucella genomes reveals evidence for horizontal gene transfer despite a preferred intracellular lifestyle.

The facultative intracellular bacterial pathogen Brucella infects a wide range of warm-blooded land and marine vertebrates and causes brucellosis. Currently, there are nine recognized Brucella species based on host preferences and phenotypic differences. The availability of 10 different genomes consisting of two chromosomes and representing six of the species allowed for a detailed comparison among themselves and relatives in the order Rhizobiales. Phylogenomic analysis of ortholog families shows limited divergence but distinct radiations, producing four clades as follows: Brucella abortus-Brucella melitensis, Brucella suis-Brucella canis, Brucella ovis, and Brucella ceti. In addition, Brucella phylogeny does not appear to reflect the phylogeny of Brucella species' preferred hosts. About 4.6% of protein-coding genes seem to be pseudogenes, which is a relatively large fraction. Only B. suis 1330 appears to have an intact beta-ketoadipate pathway, responsible for utilization of plant-derived compounds. In contrast, this pathway in the other species is highly pseudogenized and consistent with the "domino theory" of gene death. There are distinct shared anomalous regions (SARs) found in both chromosomes as the result of horizontal gene transfer unique to Brucella and not shared with its closest relative Ochrobactrum, a soil bacterium, suggesting their acquisition occurred in spite of a predominantly intracellular lifestyle. In particular, SAR 2-5 appears to have been acquired by Brucella after it became intracellular. The SARs contain many genes, including those involved in O-polysaccharide synthesis and type IV secretion, which if mutated or absent significantly affect the ability of Brucella to survive intracellularly in the infected host.

Short-term intake of beta-carotene-supplemented diets enhances ovarian function and progesterone synthesis in goats.

The effect of beta-carotene supplementation upon luteal activity, measured as number (CLT) and volume (VLT) of corpus luteum, and P4 synthesis in goats, was evaluated. Goats (n = 22, 34 months) were randomly assigned to one of two experimental groups: (i) beta-carotene [Beta, n = 10; body weight (BW = 44.8 +/- 1.45 kg), body condition score (BCS = 3.25 +/- 0.07)], and (ii) Control (Control, n = 12; BW = 45.30 +/- 1.32 kg, BCS = 3.33 +/- 0.06). Upon oestrus synchronization, the Beta group received 50 mg of beta-carotene per day during 35 days pre- and 17 days post-ovulation. The day 4, 8, 12 and 16 post-ovulation, blood samples were collected for quantification of serum P4 concentrations by radioimmmunoassay, and transrectal ultrasonographic scanning was performed at day 18 for evaluating CLT and VLT. Overall, CLT and VLT mean were 3.10 and 2211.1 mm(3) respectively. The Beta-goats depicted both the largest values for CLT (p = 0.07) and serum P4 levels (p = 0.05), with no differences (p = 0.53) for VLT between treatments. Results suggest a higher efficiency within the cellular-enzymatic groups defining the steroidogenic pathways in the beta-carotene-supplemented goats, generating a larger P4 synthesis. The last is essential for ovulation of healthy oocytes, maintenance of uterine quiescence, nourishment and survival of the embryo around implantation; all of them of paramount significance during the maternal recognition of pregnancy process.

Semaphorin3a disrupts podocyte foot processes causing acute proteinuria.

Semaphorin3a was discovered as a secreted guidance protein that acts as a chemorepellent to migrating axons and endothelial cells. In the adult mouse kidney, it is expressed in podocytes and collecting tubules. Here, we show that exogenous semaphorin3a caused acute nephrotic range proteinuria associated with podocyte foot process effacement and fusion, endothelial cell damage, decreased vascular endothelial growth factor-A receptor expression, and downregulation of the slit-diaphragm proteins podocin, nephrin, and CD2-associated protein. When vascular endothelial growth factor 165 was administered at the same time as Semaphorin3a, no proteinuria or renal ultrastructural abnormalities occurred, suggesting that semaphorin3a effects may be mediated, in part, by downregulation of vascular endothelial growth factor receptor 2 signaling. Our findings indicate that a balance of semaphorin3a to vascular endothelial growth factor-A may be important for glomerular filtration barrier homeostasis.

Heating without heat: Thermodynamics of passive energy filters between finite systems.

Passive filters allowing the exchange of particles in a narrow band of energy are currently used in microrefrigerators and energy transducers. In this Rapid Communication, we analyze their thermal properties using linear irreversible thermodynamics and kinetic theory, and discuss a striking phenomenon: the possibility of simultaneously increasing or decreasing the temperatures of two systems without any supply of energy. This occurs when the filter induces a flow of particles whose energy is between the average energies of the two systems. Here we show that this selective transfer of particles does not need the action of any sort of Maxwell demon and can be carried out by passive filters without compromising the second law of thermodynamics. This phenomenon allows us to design cycles between two reservoirs at temperatures T_{1}

Antileishmanial activity of polycyclic derivatives.

33 polycyclic derivatives have been studied and tested on Leishmania donovani and L. major promastigotes. Their antileishmanial activity was assessed in vitro and an assay of their cytotoxicity was realized on human myelomonocytic cell line. The reference molecules used in the assays were amphotericin B and pentamidine. Among the compounds tested, 29 possess an antileishmanial activity; 25 of those were more active against L. donovani than amphotericin B, and nine were as effective as amphotericin B against L. major. Many synthesized derivatives were more active against L. donovani than against L. major. The cytotoxicity studies have shown that among the thirty-three derivatives tested, 12 molecules have an IC50 towards THP-1 cells about equal than that reference drugs, the 21 other derivatives are much less toxic. A 3D QSAR study was undertaken and has permitted to predict activity against L. donovani and L. major and to highlight critical area to optimize activity against the two species.

Effects of drugs on neurotransmitter release: experiments in vivo and in vitro.

Calcium ions play a fundamental role in the release of transmitters in the nervous system. Therefore, drugs capable of modifying Ca2+ transport are useful tools for studying the mechanisms of such release in vivo and in vitro. In this article the action of some of these drugs on motor behavior, as well as on Ca2+ uptake and neurotransmitter release in synaptosomes, is reviewed. Ruthenium red (RuR) inhibits Ca2+ uptake and transmitter release in synaptosomes, and produces flaccid paralysis when injected intraperitoneally (IP) and convulsions after intracranial administration. Drugs which stimulate the Ca2+-dependent transmitter release in synaptosomes, such as 4-aminopyridine, antagonize the paralysis produced by RuR. Lanthanum ions also inhibit Ca2+ uptake and neurotransmitter release in synaptosomes, but no paralysis was observed after La2+ IP injection. However, this cation blocks the binding of RuR to the presynaptic membrane, and prevents the RuR-induced paralysis. Veratridine and the Ca2+ chelator EGTA were used to demonstrate in synaptosomes that besides the Ca2+-dependent mechanism of release of the central inhibitory transmitter gamma-aminobutyric acid (GABA), there seems to be a strictly Na+-dependent process which is not shared by other transmitters such as acetylcholine or dopamine.

Seizures induced by intracerebral administration of pyridoxal-5'-phosphate: effect of GABAergic drugs and glutamate receptor antagonists.

Pyridoxal-5'-phosphate (PLP), the cofactor of glutamate decarboxylase, paradoxically induces convulsions when injected intracranially in adult mammals. We have tested the effect of some GABAergic and antiglutamatergic drugs on the behavioral and electroencephalographic (EEG) seizures produced by intracerebroventricular (i.c.v.) microinjection of 1 micromol PLP in the rat. PLP induced barrel turning, running fits and tonic-clonic convulsions, which started 5-10 min after recovery from the anesthesia (halothane), peaked at 20 min and disappeared at about 50 min. These symptoms were accompanied by frequent high amplitude EEG spike burst discharges. Pyridoxal, pyridoxamine-5'-phosphate or deoxypyridoxine were ineffective. The i.c.v. microinjection of the GABAergic compounds muscimol, isoguvacine, aminooxyacetic acid or GABA itself, significantly protected against PLP effects. In contrast, the NMDA receptor antagonists MK-801 and the non-NMDA receptor antagonist NBQX, failed to protect and induced motor alterations and mortality. We conclude that a temporary decrease of the GABA(A) receptor function is involved in the convulsant effect of PLP. This decrease might be due to the formation of a Schiff base between the carbonyl group of PLP and the epsilon-amino group of a functionally crucial lysine residue located in one extracellular loop of the GABA(A) receptor.

Paired pulse facilitation is turned into paired pulse depression in hippocampal slices after epilepsy induced by 4-aminopyridine in vivo.

Modifications in synaptic plasticity seem to play a key role in the origin and persistence of epilepsy. 4-Aminopyridine (4-AP) induces intense and long lasting epileptic seizures and neurodegeneration when applied into the hippocampus in vivo, effects that seem to be mediated by overactivation of glutamate receptors due to the enhancement of glutamate release from nerve endings. We have studied presynaptic modifications of CA1 responses, using the paired pulse paradigm, in hippocampal slices obtained from 4-AP-treated rats killed during epileptic activity (ex vivo). The paired pulse facilitation (PPF) observed in control slices with interstimulus intervals of 10-30 ms was changed into paired pulse depression (PPD) after 100 microM 4-AP added in vitro. A strikingly similar change was observed in the ex vivo slices even though 4-AP was no longer present in the tissue. We conclude that the facilitation of glutamate release induced by 4-AP becomes chronic after a transient exposure to the drug. This suggests that the facilitated neurotransmitter release induced by 4-AP triggers a more permanent plastic change that may be responsible for the persistence of epilepsy.

Seizures and neurodegeneration induced by 4-aminopyridine in rat hippocampus in vivo: role of glutamate- and GABA-mediated neurotransmission and of ion channels.

Infusion of the K(+) channel blocker 4-aminopyridine in the hippocampus induces the release of glutamate, as well as seizures and neurodegeneration. Since an imbalance between excitation and inhibition, as well as alterations of ion channels, may be involved in these effects of 4-aminopyridine, we have studied whether they are modified by drugs that block glutamatergic transmission or ion channels, or drugs that potentiate GABA-mediated transmission. The drugs were administered to anesthetized rats subjected to intrahippocampal infusion of 4-aminopyridine through microdialysis probes, with simultaneous collection of dialysis perfusates and recording of the electroencephalogram, and subsequent histological analysis. Ionotropic glutamate receptor antagonists clearly diminished the intensity of seizures and prevented the neuronal damage, but did not alter substantially the enhancement of extracellular glutamate induced by 4-aminopyridine. None of the drugs facilitating GABA-mediated transmission, including uptake blockers, GABA-transaminase inhibitors and agonists of the A-type receptor, was able to reduce the glutamate release, seizures or neuronal damage produced by 4-aminopyridine. In contrast, nipecotate, which notably increased extracellular levels of the amino acid, potentiated the intensity of seizures and the neurodegeneration. GABA(A) receptor antagonists partially reduced the extracellular accumulation of glutamate induced by 4-aminopyridine, but did not exert any protective action. Tetrodotoxin largely prevented the increase of extracellular glutamate, the electroencephalographic epileptic discharges and the neuronal death in the CA1 and CA3 hippocampal regions. Valproate and carbamazepine, also Na(+) channel blockers that possess general anticonvulsant action, failed to modify the three effects of 4-aminopyridine studied. The N-type Ca(2+) channel blocker omega-conotoxin, the K(+) channel opener diazoxide, and the non-specific ion channel blocker riluzole diminished the enhancement of extracellular glutamate and slightly protected against the neurodegeneration. However, the two former compounds did not antagonize the 4-aminopyridine-induced epileptiform discharges, and riluzole instead markedly increased the intensity and duration of the disharges. Moreover, at the highest dose tested (8mg/kg, i.p.), riluzole caused a 75% mortality of the rats. We conclude that 4-aminopyridine stimulates the release of glutamate from nerve endings and that the resultant augmented extracellular glutamate is directly related to the neurodegeneration and is involved in the generation of epileptiform discharges through the concomitant overactivation of glutamate receptors. Under these conditions, a facilitated GABA-mediated transmission may paradoxically boost neuronal hyperexcitation. Riluzole, a drug used to treat amyotrophic lateral sclerosis, seems to be toxic when combined with neuronal hyperexcitation.

2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline protects against both AMPA and kainate-induced lesions in rat striatum in vivo.

In the present work we have tested the neuroprotective effect of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) on the excitotoxic damage induced by the injection of several glutamate receptor agonists into the rat striatum. NBQX was co-injected with each of the agonists studied (1 microliter) in the striatum and damage was assessed by the determination of both glutamate decarboxylase and choline acetyltransferase activities in striatal homogenates, five days after the lesion. Additionally, animals were transcardially perfused with 0.9% saline/4% paraformaldehyde and brain coronal sections were stained with Cresyl Violet for histological analysis. Our results show that NBQX (25 nmol) did not protect against the damage induced by the intrastriatal injection of 200 nmol quinolinic acid monitored by either choline acetyltransferase or glutamate decarboxylase activity. In contrast, the same concentration of NBQX partially protected against 200 nmol N-methyl-D-aspartate induced damage; this protection was more notable as detected by changes in choline acetyltransferase activity. When non-N-methyl-D-aspartate receptor agonists were used as excitotoxins, coinjection of NBQX (25 nmol) resulted in a notable protection against both alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA, 40 nmol) and kainate (10 nmol) induced neurodegeneration. At this concentration, protection was slightly better in AMPA-injected animals (71% protection averaged from choline acetyltransferase and glutamate decarboxylase enzyme activities) as compared to kainate-injected animals (47.5% protection). When a higher concentration of NBQX was tested (40 nmol) the protection against kainate improved to 65% while that against AMPA remained constant (64% protection).(ABSTRACT TRUNCATED AT 250 WORDS)