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Find video protocols related to scientific articles indexed in Pubmed.
A straightforward alkynylation of Li and Mg metalated heterocycles with sulfonylacetylenes.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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Coupling of alkynyl moieties to heterocyclic rings, without using transition metals, can be easily performed by the reaction of aryl or heteroaryl sulfonylacetylenes with heteroaryl-Li compounds or their corresponding less reactive magnesium derivatives.
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Whole-exome sequencing reveals defective CYP3A4 variants predictive of paclitaxel dose-limiting neuropathy.
Clin. Cancer Res.
PUBLISHED: 11-16-2014
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Purpose: Paclitaxel, a widely-used chemotherapeutic drug, can cause peripheral neuropathies leading to dose reductions and treatment suspensions and decreasing the quality of life of patients. It has been suggested that genetic variants altering paclitaxel pharmacokinetics increase neuropathy risk, but the major causes of inter-individual differences in susceptibility to paclitaxel toxicity remain unexplained. We carried out a whole-exome sequencing (WES) study to identify genetic susceptibility variants associated with paclitaxel neuropathy. Experimental Design: Blood samples from eight patients with severe paclitaxel-induced peripheral neuropathy were selected for WES. An independent cohort of 228 cancer patients with complete paclitaxel neuropathy data was used for variant screening by DHPLC and association analysis. HEK293 cells were used for heterologous expression and characterization of two novel CYP3A4 enzymes. Results: WES revealed two patients with rare CYP3A4 variants, a premature stop codon (CYP3A4*20 allele) and a novel missense variant (CYP3A4*25, p.P389S) causing reduced enzyme expression. Screening for CYP3A4 variants in the independent cohort revealed three additional CYP3A4*20 carriers, and two missense variants exhibiting diminished enzyme activity (CYP3A4*8 and the novel CYP3A4*27 allele, p.L475V). Relative to CYP3A4 wild-type patients, those carrying CYP3A4 variants had more severe neuropathy (2- and 1.3-fold higher risk of neuropathy for loss-of-function and missense variants, respectively, P=0.045) and higher probability of neuropathy-induced paclitaxel treatment modifications (7- and 3-fold higher risk for loss-of-function and missense variants, respectively, P=5.9x10-5). Conclusion: This is the first description of a genetic marker associated with paclitaxel treatment modifications caused by neuropathy. CYP3A4 defective variants may provide a basis for paclitaxel treatment individualization.
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Structural Properties and Singular Phase Transitions of Metallic Pr0.50Sr0.50CoO3 Cobaltite.
Inorg Chem
PUBLISHED: 11-11-2014
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The Pr0.50Sr0.50CoO3 perovskite exhibits unique magnetostructural properties among the rest of the ferromagnetic/metallic Ln0.50Sr0.50CoO3 compounds. Existing reports are largely controversial. We have determined and described its structural evolution, which follows the Pm3?m ? R3?c ? Imma ? I4/mcm transformations. The structural changes have been thoroughly described. The results are confronted with distinct nonconventional properties and spin-lattice coupling effects in another half-doped cobaltite based on praseodymium, Pr0.50Ca0.50CoO3. The Imma ? ?I4/mcm symmetry change is responsible for the unexpected second magnetic transition.
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Pterygodermatites (Paucipectines) baiomydis n. sp. (Nematoda: Rictulariidae), a parasite of Baiomys taylori (Cricetidae).
Parasite
PUBLISHED: 11-07-2014
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Pterygodermatites (Paucipectines) baiomydis n. sp., an intestinal parasite of the northern pygmy mouse, Baiomys taylori (Cricetidae), collected in La Yerbabuena, Colima, Mexico, is described herein. Specimens were studied using light and scanning electronic microscopy. This is the 19th species of the subgenus Paucipectines described worldwide and the fourth collected in Mexico. It is differentiated from the remaining species in the subgenus by having 25 perioral denticles, arranged in a triangle (seven on each lateroventral margin, and eleven on the dorsal margin), and 10 pairs of caudal papillae.
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Efficacy of a Tetravalent Dengue Vaccine in Children in Latin America.
N. Engl. J. Med.
PUBLISHED: 11-04-2014
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Background In light of the increasing rate of dengue infections throughout the world despite vector-control measures, several dengue vaccine candidates are in development. Methods In a phase 3 efficacy trial of a tetravalent dengue vaccine in five Latin American countries where dengue is endemic, we randomly assigned healthy children between the ages of 9 and 16 years in a 2:1 ratio to receive three injections of recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) or placebo at months 0, 6, and 12 under blinded conditions. The children were then followed for 25 months. The primary outcome was vaccine efficacy against symptomatic, virologically confirmed dengue (VCD), regardless of disease severity or serotype, occurring more than 28 days after the third injection. Results A total of 20,869 healthy children received either vaccine or placebo. At baseline, 79.4% of an immunogenicity subgroup of 1944 children had seropositive status for one or more dengue serotypes. In the per-protocol population, there were 176 VCD cases (with 11,793 person-years at risk) in the vaccine group and 221 VCD cases (with 5809 person-years at risk) in the control group, for a vaccine efficacy of 60.8% (95% confidence interval [CI], 52.0 to 68.0). In the intention-to-treat population (those who received at least one injection), vaccine efficacy was 64.7% (95% CI, 58.7 to 69.8). Serotype-specific vaccine efficacy was 50.3% for serotype 1, 42.3% for serotype 2, 74.0% for serotype 3, and 77.7% for serotype 4. Among the severe VCD cases, 1 of 12 was in the vaccine group, for an intention-to-treat vaccine efficacy of 95.5%. Vaccine efficacy against hospitalization for dengue was 80.3%. The safety profile for the CYD-TDV vaccine was similar to that for placebo, with no marked difference in rates of adverse events. Conclusions The CYD-TDV dengue vaccine was efficacious against VCD and severe VCD and led to fewer hospitalizations for VCD in five Latin American countries where dengue is endemic. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01374516 .).
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Hypoxia-induced Deoxycytidine Kinase Contributes to Epithelial Proliferation in Pulmonary Fibrosis.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 10-31-2014
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Rationale: Idiopathic Pulmonary Fibrosis (IPF) is a deadly lung disease with few therapeutic options. Apoptosis of alveolar epithelial cells, followed by abnormal tissue repair characterized by hyperplastic epithelial cell formation, is a pathogenic process that contributes to the progression of pulmonary fibrosis. However, the signaling pathways responsible for increased proliferation of epithelial cells remain poorly understood. Objectives: To investigate the role of deoxycytidine kinase (DCK), an important enzyme for the salvage of deoxynucleotides, in the progression of pulmonary fibrosis. Methods: DCK expression was examined in the lungs of IPF patients and mice exposed to bleomycin. The regulation of DCK expression by hypoxia was studied in vitro and the importance of DCK in experimental pulmonary fibrosis was examined using a DCK inhibitor and alveolar epithelial cell specific knockout mice. Measurements and Main Results: DCK was elevated in hyperplastic alveolar epithelial cells of IPF patients and in mice exposed to bleomycin. Increased DCK was localized to cells associated with hypoxia, and hypoxia directly induced DCK in alveolar epithelial cells in vitro. Hypoxia-induced DCK expression was abolished by silencing hypoxia-inducible factor 1 alpha (Hif-1a) and treatment of bleomycin-exposed mice with a DCK inhibitor attenuated pulmonary fibrosis in association with decreased epithelial cell proliferation. Furthermore, DCK expression, as well as proliferation of epithelial cells and pulmonary fibrosis, were attenuated in mice with conditional deletion of Hif-1a in the alveolar epithelium. Conclusions: Our findings suggest that the induction of DCK following hypoxia plays a role in the progression of pulmonary fibrosis by contributing to alveolar epithelial cell proliferation.
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Copper-catalyzed diastereo- and enantioselective desymmetrization of cyclopropenes: synthesis of cyclopropylboronates.
J. Am. Chem. Soc.
PUBLISHED: 10-31-2014
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A novel Cu-catalyzed diastereo- and enantioselective desymmetrization of cyclopropenes to afford nonracemic cyclopropylboronates is described. Trapping the cyclopropylcopper intermediate with electrophilic amines allows for the synthesis of cyclopropylaminoboronic esters and demonstrates the potential of the approach for the synthesis of functionalized cyclopropanes.
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[Myxoid liposarcoma of the anterior mediastinum. A case report and bibliography review].
Cir Cir
PUBLISHED: 10-15-2014
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Five cases per year. Of those cases 50% are located in the extremities and 40% are located in the trunk and retroperitoneum. Primary mediastinal liposarcomas represent less than 1% of mediastinal tumors.
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Ionic liquids entrapped in reverse micelles as nanoreactors for bimolecular nucleophilic substitution reaction. Effect of the confinement on the chloride ion availability.
Langmuir
PUBLISHED: 10-10-2014
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In this work was explored how the confinement of two ionic liquids (ILs), 1-butyl-3-methylimidazolium chloride (bmimCl) and 1-butyl-3-methylimidazolium tetrafluoroborate (bmimBF4), inside toluene/benzyl-n-hexadecyldimethylammonium chloride (BHDC) reverse micelles (RMs) affects the Cl(-) nucleophilicity on the bimolecular nucleophilic substitution (SN2) reaction between this anion and dimethyl-4-nitrophenylsulfonium trifluoromethanesulfonate. The results obtained show that, upon confinement, the ionic interactions between the ILs with the cationic surfactant polar head group and the surfactant counterion modify substantially the performance of both ILs as solvents. In toluene/BHDC/bmimCl RMs, the Cl(-) interacts strongly with bmim(+) (and/or BHD(+)) in such a way that its nucleophilicity is reduced in comparison with neat IL. In toluene/BHDC/bmimBF4 RMs, an ionic exchange equilibrium produces segregation of bmim(+) and BF4(-) ions, changing the composition of the RMs interface and affecting dramatically the Cl(-) availability. These results show the versatility of this kind of organized system to alter the ionic organization and influence on reaction rate when used as nanoreactors.
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Control of the Dual Reactivity (Iminium-Dienamine) of ?-Arylmethyl ?,?-Unsaturated Aldehydes in Organocatalytic 1,3-Dipolar Cycloadditions with N-Benzoyl C,N-Cyclic Azomethine Imines.
J. Org. Chem.
PUBLISHED: 10-09-2014
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1,3-Dipolar cycloadditions of C,N-cyclic azomethine imines with ?,?-unsaturated aldehydes can be performed with complete control of the regio-, exo-, and enantioselectivity under aminocatalytic conditions. The so far never studied competence of the iminium-dienamine reactivity inherent to ?-alkyl ?,?-unsaturated aldehydes was studied, which was possible by allowing achievement of complete control of the chemoselectivity in reactions of the ?-arylmethyl derivatives with azomethine imines by using different additives and organocatalysts, whose role has been rationalized by DFT calculations and chemical proofs. Thus, it has been possible to selectively obtain the pyrazolidines resulting from both the attack to the C2-C3 (via iminium) and the C3-C4 (via dienamine) bonds at the starting enals, which can be used as precursors of interesting tetrahydroisoquinolinic compounds.
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In Vivo [(18)F] FDG PET Imaging Reveals that p-Chloroamphetamine Neurotoxicity is Associated with Long-Term Cortical and Hippocampal Hypometabolism.
Mol Imaging Biol
PUBLISHED: 10-01-2014
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p-Chloroamphetamine (PCA) is a neurotoxin that selectively degenerates the serotonin (5-HT) axon terminals. In order to study the brain metabolic consequences induced by serotonergic denervation, a single dose of PCA (2.5 or 10 mg/kg i.p.) was administered to male adult rats.
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Blockade of IL-6 Trans signaling attenuates pulmonary fibrosis.
J. Immunol.
PUBLISHED: 08-29-2014
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Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with progressive fibrosis and death within 2-3 y of diagnosis. IPF incidence and prevalence rates are increasing annually with few effective treatments available. Inhibition of IL-6 results in the attenuation of pulmonary fibrosis in mice. It is unclear whether this is due to blockade of classical signaling, mediated by membrane-bound IL-6R?, or trans signaling, mediated by soluble IL-6R? (sIL-6R?). Our study assessed the role of sIL-6R? in IPF. We demonstrated elevations of sIL-6R? in IPF patients and in mice during the onset and progression of fibrosis. We demonstrated that protease-mediated cleavage from lung macrophages was important in production of sIL-6R?. In vivo neutralization of sIL-6R? attenuated pulmonary fibrosis in mice as seen by reductions in myofibroblasts, fibronectin, and collagen in the lung. In vitro activation of IL-6 trans signaling enhanced fibroblast proliferation and extracellular matrix protein production, effects relevant in the progression of pulmonary fibrosis. Taken together, these findings demonstrate that the production of sIL-6R? from macrophages in the diseased lung contributes to IL-6 trans signaling that in turn influences events crucial in pulmonary fibrosis.
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Sinus Mucosal Thickening in Bisphosphonate-Related Osteonecrosis of the Jaws: A Case-Control Study.
ORL J. Otorhinolaryngol. Relat. Spec.
PUBLISHED: 08-28-2014
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Osteonecrosis of the jaws is a clinically significant complication of bisphosphonate (BP) medications. Otherwise, the effects of BPs on oral soft tissue or cells remain unknown. The main objective of the present study was to determine whether the presence of sinus mucosal thickening was significantly related to BP-related osteonecrosis of the jaw (BRONJ). A case-control study was conducted on 32 patients who underwent treatment of BRONJ with conventional radiological investigations (panoramic radiographs) and computed tomography. The results indicated that patients with BRONJ had a 5.57-fold greater probability of presenting sinus mucosal thickening than controls. Although the existence of this thickening was more common in patients with advanced-stage disease or low levels of C-telopeptide-cross-linked type I collagen, no significant difference was observed between cases and controls. While considering the limitations inherent in the design and number of cases analyzed in our study, patients with osteonecrosis of the jaw were found to have a 5.57-fold greater probability of presenting sinus mucosal thickening (>3 mm) than healthy subjects. © 2014 S. Karger AG, Basel.
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Effects of aging on Laser Evoked Potentials.
Muscle Nerve
PUBLISHED: 08-27-2014
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Introduction: Aging has been reported to reduce the amplitude of laser evoked potentials. However, it is unknown whether this effect depends on the length of the sensory fibers. This is an important issue, since most painful neuropathies are length-dependant. Methods: We conducted a study of 40 healthy subjects, half of whom were older than age 50 years. Nociceptive stimuli were delivered to the feet and thighs using a CO2 laser stimulator. Results: Detection and pain perception thresholds did not correlate with age. Latencies of N1, N2, and P2 correlated positively with age on the feet but not on the thighs, whereas the amplitude of N2P2 decreased with age for both areas. Discussion: The effects of aging on latencies may reflect a distal loss of peripheral inputs and a length-dependent de-synchronization of the ascending nociceptive volley. Additional changes in peripheral and central processes may explain the diffuse decrease of N2P2 amplitudes observed with aging. © 2014 Wiley Periodicals, Inc.
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Towards a comprehensive global approach to prevention and control of NCDs.
Global Health
PUBLISHED: 08-26-2014
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BackgroundThe ¿25x25¿ strategy to tackle the global challenge of non-communicable diseases takes a traditional approach, concentrating on a few diseases and their immediate risk factors. Discussion: We propose elements of a comprehensive strategy to address NCDs that takes account of the evolving social, economic, environmental and health care contexts, while developing mechanisms to respond effectively to local patterns of disease. Principles that underpin the comprehensive strategy include: (a) a balance between measures that address health at the individual and population level; (b) the need to identify evidence-based feasible and effective approaches tailored to low and middle income countries rather than exporting questionable strategies developed in high income countries; (c) developing primary health care as a universal framework to support prevention and treatment; (d) ensuring the ability to respond in real time to the complex adaptive behaviours of the global food, tobacco, alcohol and transport industries; (e) integrating evidence-based, cost-effective, and affordable approaches within the post-2015 sustainable development agenda; (f) determination of a set of priorities based on the NCD burden within each country, taking account of what it can afford, including the level of available development assistance; and (g) change from a universal ¿one-size fits all¿ approach of relatively simple prevention oriented approaches to more comprehensive multi-sectoral and development-oriented approaches which address both health systems and the determinants of NCD risk factors.SummaryThe 25x25 is approach is absolutely necessary but insufficient to tackle the the NCD disease burden of mortality and morbidity. A more comprehensive approach is recommended.
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Foleyellides rhinellae sp. nov. (Nematoda, Onchocercidae) a new filaria parasitizing Rhinella marina (Anura, Bufonidae) in Mexico.
Acta Parasitol.
PUBLISHED: 08-15-2014
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A new nematode species, Foleyellides rhinellae sp. nov. (Onchocercidae), is described from specimens found in the body cavity of the cane toad, Rhinella marina (Linnaeus) (Anura, Bufonidae), in the Laguna de Coyuca, Guerrero, in the Pacific slope of Mexico. The new species differs from the other nine species of Foleyellides by infecting bufonid anurans and by the number and arrangement of caudal papillae. Other distinguishing feature of the new species is the size of the left spicule (0.16-0.23 long), the smallest recorded among the species included in the genus. Foleyellides rhinellae sp. nov. is the second known species of the genus recorded from amphibians of Mexico.
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Stability of the cationic oxidation states in Pr(0.50)Sr(0.50)CoO? across the magnetostructural transition by X-ray absorption spectroscopy.
Inorg Chem
PUBLISHED: 08-11-2014
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The possible hybridization between Pr 4f and O 2p states in Pr(0.50)Sr(0.50)CoO3 at low temperatures was investigated by different techniques. First, using neutron diffraction we observed a strong contraction of some Pr-O bonds across the magnetostructural transition at T(S) ? 120 K. In contrast to the Pr-O bond contraction in Pr(0.50)Sr(0.50)CoO3, this transition is not accompanied by the appearance of Pr(4+) at low temperatures, as revealed by X-ray absorption spectroscopy at Pr edges. Despite the fact that a Pr valence change is not the mechanism that drives this transition, we point out an active participation of Pr ions across T(S). Moreover, Co L(2,3)-edge and O K edge X-ray absorption spectra did not reveal any spin-state variation and showed the stability of the average formal valence of cobalt ions. The large density of empty t(2g) symmetry states in the studied thermal range does not suggest the occurrence of Co(3+) in a pure low-spin state. The overall metallic behavior agrees with our findings. We propose a mixture of Co(3+) ions in the intermediate-spin or high-spin configuration together with Co(4+) ions in a low- or intermediate-spin state.
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Host-guest chemistry of a water-soluble pillar[5]arene: evidence for an ionic-exchange recognition process and different complexation modes.
Chemistry
PUBLISHED: 08-08-2014
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The complexation of an anionic guest by a cationic water-soluble pillararene is reported. Isothermal titration calorimetry (ITC), (1)H?NMR, (1)H and (19)F DOSY, and STD NMR experiments were performed to characterize the complex formed under aqueous neutral conditions. The results of ITC and (1)H?NMR analyses showed the inclusion of the guest inside the cavity of the pillar[5]arene, with the binding constant and thermodynamic parameters influenced by the counter ion of the macrocycle. NMR diffusion experiments showed that although a fraction of the counter ions are expelled from the host cavity by exchange with the guest, a complex with both counter ions and the guest inside the pillararene is formed. The results also showed that at higher concentrations of guest in solution, in addition to the inclusion of one guest molecule in the cavity, the pillararene can also form an external complex with a second guest molecule.
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Correlations between major risk factors and closely related Mycobacterium tuberculosis isolates grouped by three current enotyping procedures: a population-based study in northeast Mexico.
Mem. Inst. Oswaldo Cruz
PUBLISHED: 08-06-2014
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The characteristics of tuberculosis (TB) patients related to a chain of recent TB transmissions were investigated. Mycobacterium tuberculosis (MTB) isolates (120) were genotyped using the restriction fragment length polymorphism-IS6110 (R), spacer oligotyping (S) and mycobacterial interspersed repetitive units-variable number of tandem repeats (M) methods. The MTB isolates were clustered and the clusters were grouped according to the similarities of their genotypes. Spearman's rank correlation coefficients between the groups of MTB isolates with similar genotypes and those patient characteristics indicating a risk for a pulmonary TB (PTB) chain transmission were ana- lysed. The isolates showing similar genotypes were distributed as follows: SMR (5%), SM (12.5%), SR (1.67%), MR (0%), S (46.67%), M (5%) and R (0%). The remaining 35 cases were orphans. SMR exhibited a significant correlation (p < 0.05) with visits to clinics, municipalities and comorbidities (primarily diabetes mellitus). S correlated with drug consumption and M with comorbidities. SMR is needed to identify a social network in metropolitan areas for PTB transmission and S and M are able to detect risk factors as secondary components of a transmission chain of TB.
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Intraoperative surgical sealant application during cardiac defect repair.
Tex Heart Inst J
PUBLISHED: 08-01-2014
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Bleeding can occur as a sequela to cardiac surgery. Surgical products-such as conventional sutures and clips, and somewhat less conventional sealants-have been developed to prevent this event. Among these, CoSeal is a sealant used at our institution; here we report the cases of 2 patients in whom CoSeal was used successfully as either a supplement or an alternative to suture repair. This sealant was found to be useful in attaining hemostasis both in high-pressure ventricular repair and in the rupture of a friable coronary sinus adjacent to vital structures (in this instance, a left circumflex coronary artery).
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Interobserver variance in myelodysplastic syndromes with less than 5 % bone marrow blasts: unilineage vs. multilineage dysplasia and reproducibility of the threshold of 2 % blasts.
Ann. Hematol.
PUBLISHED: 07-27-2014
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Previous studies have shown the reproducibility of the 2008 World Health Organization (WHO) classification in myelodysplastic syndromes (MDS), especially when multilineage dysplasia or excess of blasts are present. However, there are few data regarding the reproducibility of MDS with unilineage dysplasia. The revised International Prognostic Scoring System R-IPSS described two new morphological categories, distinguishing bone marrow (BM) blast cell count between 0-2 % and >2-?
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N-(4-[(18)F]-fluoropyridin-2-yl)-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}carboxamides as analogs of WAY100635. New PET tracers of serotonin 5-HT(1A) receptors.
Eur J Med Chem
PUBLISHED: 07-26-2014
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N-(4-[(18)F]-Fluoropyridin-2-yl)-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-carboxamides were prepared by labeling their 4-nitropyridin-2-yl precursors through nitro substitution by the (18)F anion. In vitro and in vivo tests showed that the cyclohexanecarboxamide derivative is a reversible, selective and high affinity 5-HT1A receptor antagonist (IC50 = 0.29 nM, ki = 0.18 nM) with high brain uptake, slow brain clearance and stability to defluorination when compared with conventional standards. This PET radioligand is a promising candidate for an improved in vivo quantification of 5-HT1A receptors in neuropsychiatric disorders.
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Does migration affect asthma, rhinoconjunctivitis and eczema prevalence? Global findings from the international study of asthma and allergies in childhood.
Int J Epidemiol
PUBLISHED: 07-25-2014
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Immigrants to Westernized countries adopt the prevalence of allergic diseases of native populations, yet no data are available on immigrants to low-income or low-disease prevalence countries. We investigated these questions using data from the International Study of Asthma and Allergies in Childhood.
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Asymmetric nucleophilic monofluorobenzylation of allyl and propargyl halides mediated by a remote sulfinyl group: synthesis of homoallylic and homopropargylic fluorides.
J. Org. Chem.
PUBLISHED: 07-14-2014
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Fluorinated 2-(p-tolylsulfinyl)benzyl carbanions react with allyl and propargyl halides in a highly stereoselective way, providing homoallylic and homopropargylic fluorides, respectively, with high optical purity. Theoretical calculations found transition states for these transformations whose relative stabilities are consistent with the experimentally observed stereoselectivity.
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Big thistle eats the little thistle: does unidirectional introgressive hybridization endanger the conservation of Onopordum hinojense?
New Phytol.
PUBLISHED: 07-09-2014
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Hybridization is known to have a creative role in plant evolution. However, it can also have negative effects on parental species. Onopordum is a large genus whose species frequently hybridize. In the Southwest Iberian Peninsula, the rare O. hinojense co-occurs with the widely distributed O. nervosum, and hybrids between these two taxa have been described as O. × onubense. In this study we determine the extinction risk in a hybrid zone, both for hybrids and parentals, using analyses of morphological and cytogenetic traits as well as genetic markers and demographic models. To investigate the introgression process we used amplified fragment length polymorphism (AFLP) markers, Bayesian analyses and genome scan methods. Morphology, genome size and molecular markers confirmed homoploid hybridization and also indicated unidirectional backcrossing of F1 hybrids with O. nervosum, which is likely to swamp O. hinojense, the parental with lower pollen size and a very low fruit set (8%). Genome scan methods revealed several loci significantly deviating from neutrality. Finally, our demographic modeling indicated that the higher fitness of O. nervosum threats the survival of O. hinojense by demographic swamping. Our study provides strong new evidence for a scenario of rapid extinction by unidirectional introgression and demographic swamping. The multifaceted approach used here sheds new light on the role of introgression in plant extinctions.
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Adaptation in human somatosensory cortex as a model of sensory memory construction: a study using high-density EEG.
Brain Struct Funct
PUBLISHED: 06-26-2014
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Adaptation in sensory cortices has been seen as a mechanism allowing the creation of transient memory representations. Here we tested the adapting properties of early responses in human somatosensory areas SI and SII by analysing somatosensory-evoked potentials over the very first repetitions of a stimulus. SI and SII generators were identified by well-defined scalp potentials and source localisation from high-density 128-channel EEG. Earliest responses (~20 ms) from area 3b in the depth of the post-central gyrus did not show significant adaptation to stimuli repeated at 300 ms intervals. In contrast, responses around 45 ms from the crown of the gyrus (areas 1 and 2) rapidly lessened to a plateau and abated at the 20th stimulation, and activities from SII in the parietal operculum at ~100 ms displayed strong adaptation with a steady amplitude decrease from the first repetition. Although responses in both SI (1-2) and SII areas showed adapting properties and hence sensory memory capacities, evidence of sensory mismatch detection has been demonstrated only for responses reflecting SII activation. This may index the passage from an early form of sensory storage in SI to more operational memory codes in SII, allowing the prediction of forthcoming input and the triggering of a specific signal when such input differs from the previous sequence. This is consistent with a model whereby the length of temporal receptive windows increases with progression in the cortical hierarchy, in parallel with the complexity and abstraction of neural representations.
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Two Streptomyces Species Producing Antibiotic, Antitumor, and Anti-Inflammatory Compounds Are Widespread Among Intertidal Macroalgae and Deep-Sea Coral Reef Invertebrates from the Central Cantabrian Sea.
Microb. Ecol.
PUBLISHED: 06-26-2014
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Streptomycetes are widely distributed in the marine environment, although only a few studies on their associations to algae and coral ecosystems have been reported. Using a culture-dependent approach, we have isolated antibiotic-active Streptomyces species associated to diverse intertidal marine macroalgae (Phyllum Heterokontophyta, Rhodophyta, and Chlorophyta), from the central Cantabrian Sea. Two strains, with diverse antibiotic and cytotoxic activities, were found to inhabit these coastal environments, being widespread and persistent over a 3-year observation time frame. Based on 16S rRNA sequence analysis, the strains were identified as Streptomyces cyaneofuscatus M-27 and Streptomyces carnosus M-40. Similar isolates to these two strains were also associated to corals and other invertebrates from deep-sea coral reef ecosystem (Phyllum Cnidaria, Echinodermata, Arthropoda, Sipuncula, and Anelida) living up to 4.700-m depth in the submarine Avilés Canyon, thus revealing their barotolerant feature. These two strains were also found to colonize terrestrial lichens and have been repeatedly isolated from precipitations from tropospheric clouds. Compounds with antibiotic and cytotoxic activities produced by these strains were identified by high-performance liquid chromatography (HPLC) and database comparison. Antitumor compounds with antibacterial activities and members of the anthracycline family (daunomycin, cosmomycin B, galtamycin B), antifungals (maltophilins), anti-inflamatory molecules also with antituberculosis properties (lobophorins) were identified in this work. Many other compounds produced by the studied strains still remain unidentified, suggesting that Streptomyces associated to algae and coral ecosystems might represent an underexplored promising source for pharmaceutical drug discovery.
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Role of radiotherapy in the chemotherapy-containing multidisciplinary management of patients with resected pancreatic adenocarcinoma.
Strahlenther Onkol
PUBLISHED: 06-06-2014
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To analyze prognostic factors associated with long-term outcomes in patients with resected pancreatic cancer treated with chemotherapy (CT) and surgery with or without external beam radiotherapy (EBRT).
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Interaction of bolaform surfactants with p-sulfonatocalix[4]arene: the role of two positive charges in the binding.
Langmuir
PUBLISHED: 06-06-2014
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The inclusion binding manners of bolaform surfactants of type C(n)R6(2+) 2Br(-) with different spacer lengths (n = 6, 12) and terminal headgroup volumes (R = methyl, ethyl) by p-sulfonatocalix[4]arene were studied. The combination of ITC parameters (binding constants and complexation enthalpy and entropy) and NMR chemical shifts and NOE cross-peaks obtained upon complexation allows us to propose different binding modes. The results point out that the spacer length has an influence on the binding stoichiometry. The bolaforms with larger spacer lengths between polar head groups enable the formation of 2:1 complexes in addition to 1:1, while with the shorter spacer they form only 1:1 complexes. On the other hand, the formation of 1:1 complexes is not affected by the headgroup volume or the spacer length of the bolaform. Unexpectedly, a complex binding mode was observed where both positive charged terminal groups of the bolaform are accommodated in the cavity of the calixarene. The inclusion of both terminal groups of the guests can be related to its own structure but also evidence the high flexibility of the calixarene.
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Epidemiology, pharmacology and clinical characterization of bisphosphonate-related osteonecrosis of the jaw. A retrospective study of 70 cases.
Acta Otorrinolaringol Esp
PUBLISHED: 05-29-2014
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Bisphosphonates are widely prescribed drugs whose principal capacity is inhibiting the osteoclast function. In 2003 a complication related to their administration, bisphosphonate-related osteonecrosis of the jaw (BRONJ), was described. The objectives of this study were to identify diagnosed cases of BRONJ in a third-level hospital over 8years, evaluating the main features in relation to the disease, the bisphosphonate and the presence of local or general risk factors that could trigger the BRONJ.
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Can parent training for parents with high levels of expressed emotion have a positive effect on their child's social anxiety improvement?
J Anxiety Disord
PUBLISHED: 05-28-2014
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The role that parents' involvement may play in improving their child's social anxiety is still under debate. This paper aimed to investigate whether training parents with high expressed emotion (EE) could improve outcomes for adolescent social anxiety intervention. Fifty-two socially anxious adolescents (aged 13-18 years), whose parents exhibited high levels of expressed emotion, were assigned to either (a) a school-based intervention with an added parent training component, or (b) a school-based program focused solely on intervening with the adolescent (no parental involvement). Post-treatment and 12-month follow-up findings showed that school-based intervention with parent training was superior to the adolescent-specific program, yielding significant reductions in diagnosis remission, social and depressive symptomatology, particularly when the EE status of parents changed. Overall, the findings suggest that high-EE parents of children with social anxiety need to be involved in their child's therapy.
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Emergency contraceptive pill safety profile. Comparison of the results of a follow-up study to those coming from spontaneous reporting.
Pharmacoepidemiol Drug Saf
PUBLISHED: 05-20-2014
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The emergency contraceptive pill (ECP) containing levonorgestrel is dispensed without a prescription in Spain since 2009. An easy access could diminish unwanted pregnancies; however, there is a risk of misuse and, in any case, of developing some adverse events. The aim of the present study is to further learn the adverse effects of this ECP.
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Bisphosphonate-related osteonecrosis associated with dental implants: a microcomputed tomography study.
Implant Dent
PUBLISHED: 05-14-2014
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The aims of this study were to quantify bone mineral density (BMD) and trabecular architecture of sequestra in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) associated with dental implants and to assess if there are differences between trabecular bone in "implant loading-triggered" and "implant surgery-triggered" BRONJ.
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Gryporhynchidae (Cestoda: Cyclophyllidea) in Mexico: species list, hosts, distribution and new records.
Zootaxa
PUBLISHED: 05-09-2014
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As a result of this study, 8 new host (Botaurus lentiginosus for Glossocercus caribaensis and Valipora mutabilis; Egretta caerulea for Valipora minuta; Egretta thula for Glossocercus cyprinodontis; Egretta tricolor and Nycticorax nycticorax for Glossocercus caribaensis; Pelecanus occidentalis and Platalea ajaja for Paradilepis caballeroi) and 31 new locality records for gryporhynchid cestode species in Mexico are presented. With these data, the total number of species of this group of helminths in Mexico becomes 25 (19 named species and 6 unidentified taxa), which have been registered as parasites of fishes (47 host species) and (or) birds (20 host species). This information comes from 102 localities, pertaining to 20 of 32 Mexican states. Five of the 25 taxa have been exclusivelly collected in fishes, 7 in fish-eating birds, and 13 in both groups of hosts. The most frequent metacestodes found in Mexican fishes are the merocercoids of Cyclustera ralli, Valipora mutabilis, Parvitaenia cochlearii and Valipora campylancristrota; in adult stage, Glossocercus caribaensis was the species with the largest host spectrum, while Paradilepis caballeroi has the widest distribution range. The work includes parasite/host lists, as well as habitat, distribution, references and information on specimens' deposition.
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Birthweight and the risk of atopic diseases: the ISAAC Phase III study.
Pediatr Allergy Immunol
PUBLISHED: 04-23-2014
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The association between birthweight and asthma, eczema and rhinoconjunctivitisis conflicting.
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Ionic exchange in p-sulfonatocalix[4]arene-mediated formation of metal-ligand complexes.
J Phys Chem B
PUBLISHED: 04-22-2014
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The effect of alkali and transition metal cations in the formation of host-guest complexes with the water-soluble p-sulfonatocalix[4]arene (SC4) was studied using 2-chloropyridine and Na(+) and Cu(2+) as model guest and model cations, respectively. The results obtained from isothermal titration calorimetry and NMR experiments provide evidence for the formation of 1:1:1 ternary complexes for both cations with Cu(2+) showing positive cooperativity and Na(+) negative cooperativity. The formation of ternary complexes comprising transition metal cations has been scarcely explored but present high potential for devising catalytic systems/models or for enhancing the stability and selectivity of SC4 complexes. Because transition metal cations are usually present in solution together with other SC4 countercations (e.g., Na(+)), a general binding model that considers the dynamic formation of all possible complexes (including ionic exchange between ternary complexes) is presented. This model allows the optimization of the conditions required to selectively form target complexes.
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Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS).
Clin Neurophysiol
PUBLISHED: 04-09-2014
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A group of European experts was commissioned to establish guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS) from evidence published up until March 2014, regarding pain, movement disorders, stroke, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, consciousness disorders, tinnitus, depression, anxiety disorders, obsessive-compulsive disorder, schizophrenia, craving/addiction, and conversion. Despite unavoidable inhomogeneities, there is a sufficient body of evidence to accept with level A (definite efficacy) the analgesic effect of high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC). A Level B recommendation (probable efficacy) is proposed for the antidepressant effect of low-frequency (LF) rTMS of the right DLPFC, HF-rTMS of the left DLPFC for the negative symptoms of schizophrenia, and LF-rTMS of contralesional M1 in chronic motor stroke. The effects of rTMS in a number of indications reach level C (possible efficacy), including LF-rTMS of the left temporoparietal cortex in tinnitus and auditory hallucinations. It remains to determine how to optimize rTMS protocols and techniques to give them relevance in routine clinical practice. In addition, professionals carrying out rTMS protocols should undergo rigorous training to ensure the quality of the technical realization, guarantee the proper care of patients, and maximize the chances of success. Under these conditions, the therapeutic use of rTMS should be able to develop in the coming years.
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Post-chemoradiation intraoperative electron-beam radiation therapy boost in resected locally advanced rectal cancer: long-term results focused on topographic pattern of locoregional relapse.
Radiother Oncol
PUBLISHED: 03-25-2014
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Patients with locally advanced rectal cancer (LARC) have a dismal prognosis. We investigated outcomes and risk factors for locoregional recurrence (LRR) in patients treated with preoperative chemoradiotherapy (CRT), surgery and IOERT.
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Activation and silencing of secondary metabolites in Streptomyces albus and Streptomyces lividans after transformation with cosmids containing the thienamycin gene cluster from Streptomyces cattleya.
Arch. Microbiol.
PUBLISHED: 03-04-2014
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Activation and silencing of antibiotic production was achieved in Streptomyces albus J1074 and Streptomyces lividans TK21 after introduction of genes within the thienamycin cluster from S. cattleya. Dramatic phenotypic and metabolic changes, involving activation of multiple silent secondary metabolites and silencing of others normally produced, were found in recombinant strains harbouring the thienamycin cluster in comparison to the parental strains. In S. albus, ultra-performance liquid chromatography purification and NMR structural elucidation revealed the identity of four structurally related activated compounds: the antibiotics paulomycins A, B and the paulomenols A and B. Four volatile compounds whose biosynthesis was switched off were identified by gas chromatography-mass spectrometry analyses and databases comparison as pyrazines; including tetramethylpyrazine, a compound with important clinical applications to our knowledge never reported to be produced by Streptomyces. In addition, this work revealed the potential of S. albus to produce many others secondary metabolites normally obtained from plants, including compounds of medical relevance as dihydro-?-agarofuran and of interest in perfume industry as ?-patchoulene, suggesting that it might be an alternative model for their industrial production. In S. lividans, actinorhodins production was strongly activated in the recombinant strains whereas undecylprodigiosins were significantly reduced. Activation of cryptic metabolites in Streptomyces species might represent an alternative approach for pharmaceutical drug discovery.
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Longitudinal assessment of a transgenic animal model of tauopathy by FDG-PET imaging.
J. Alzheimers Dis.
PUBLISHED: 03-01-2014
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Abnormal levels and hyperphosphorylation of tau protein have been proposed as the underlying cause of a group of neurodegenerative disorders collectively known as 'tauopathies'. The detrimental consequence is the loss of affinity between this protein and the microtubules, increased production of fibrillary aggregates, and the accumulation of insoluble intracellular neurofibrillary tangles. A similar phenotype can be observed in various preclinical models, which have been generated to study the role of tau protein in neurodegenerative disorders. In this study, we have analyzed the brain metabolic activity in an animal model of tauopathy (tauVLW transgenic mice), which has been previously reported to mimic some of the phenotypic features of these disorders. By using a non-invasive technique, positron emission tomography (PET), a longitudinal non-clinical follow up study was carried out during most of the lifespan of these transgenic mice, from the youth to the senescence stages. The results obtained point out to an aging-dependent decrease in 18F-fluoro-deoxyglucose (FDG) uptake in the cerebral areas analyzed, which was already significant at the adult age, i.e., 11 months, and became much more prominent in the oldest animals (19 months old). This observation correlates well with the histopathological observation of neurodegeneration in brain areas where there is overexpression of tau protein.
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Multidisciplinary therapy for patients with locally oligo-recurrent pelvic malignancies.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 02-27-2014
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To analyze prognostic factors and long-term outcomes in patients with locally recurrent pelvic cancer (LRPC) treated with a multidisciplinary approach.
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Classification and pharmacological treatment of preschool wheezing: changes since 2008.
Eur. Respir. J.
PUBLISHED: 02-13-2014
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Since the publication of the European Respiratory Society Task Force report in 2008, significant new evidence has become available on the classification and management of preschool wheezing disorders. In this report, an international consensus group reviews this new evidence and proposes some modifications to the recommendations made in 2008. Specifically, the consensus group acknowledges that wheeze patterns in young children vary over time and with treatment, rendering the distinction between episodic viral wheeze and multiple-trigger wheeze unclear in many patients. Inhaled corticosteroids remain first-line treatment for multiple-trigger wheeze, but may also be considered in patients with episodic viral wheeze with frequent or severe episodes, or when the clinician suspects that interval symptoms are being under reported. Any controller therapy should be viewed as a treatment trial, with scheduled close follow-up to monitor treatment effect. The group recommends discontinuing treatment if there is no benefit and taking favourable natural history into account when making decisions about long-term therapy. Oral corticosteroids are not indicated in mild-to-moderate acute wheeze episodes and should be reserved for severe exacerbations in hospitalised patients. Future research should focus on better clinical and genetic markers, as well as biomarkers, of disease severity.
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Pillar[5]arene-mediated synthesis of gold nanoparticles: size control and sensing capabilities.
Chemistry
PUBLISHED: 02-07-2014
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We present a simple procedure for the synthesis of quasi-spherical Au nanoparticles in a wide size range mediated by macrocyclic host molecules, ammonium pillar[5]arene (AP[5]A). The strategy is based on a seeded growth process in which the water-soluble pillar[5]arene undergoes complexation of the Au salt through the ammonium groups, thereby avoiding Au nucleation, while acting as a stabilizer. The presence of the pillar[5]arene onto the Au nanoparticle particle surface is demonstrated by surface-enhanced Raman scattering (SERS) spectroscopy, and the most probable conformation of the molecule when adsorbed on the Au nanoparticles surface is suggested on the basis of theoretical calculations. In addition, we analyze the host-guest interactions of the AP[5]A with 2-naphthoic acid (2NA) by using (1)H?NMR spectroscopy and the results are compared with theoretical calculations. Finally, the promising synergetic effects of combining supramolecular chemistry and metal nanoparticles are demonstrated through SERS detection in water of 2NA and a polycyclic aromatic hydrocarbon, pyrene (PYR).
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Alternative treatments for oral bisphosphonate-related osteonecrosis of the jaws: a pilot study comparing fibrin rich in growth factors and teriparatide.
Med Oral Patol Oral Cir Bucal
PUBLISHED: 01-24-2014
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The aim of this study is to describe and compare the evolution of recurrent bisphosphonate-related osteonecrosis of the jaws (BRONJ) in patients treated with plasma rich in growth factors or teriparatide.
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Is Life better after motor cortex stimulation for pain control? Results at long-term and their prediction by preoperative rTMS.
Pain Physician
PUBLISHED: 01-24-2014
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A positive effect of motor cortex stimulation (MCS) (defined as subjective estimations of pain relief ? 30%) has been reported in 55 - 64% of patients. Repetitive magnetic cortical stimulation (rTMS) is considered a predictor of MCS effect. These figures are, however, mostly based on subjective reports of pain intensity, and have not been confirmed in the long-term.
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Asleep but aware?
Brain Cogn
PUBLISHED: 01-18-2014
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Despite sleep-induced drastic decrease of self-awareness, human sleep allows some cognitive processing of external stimuli. Here we report the fortuitous observation in a patient who, while being recorded with intra-cerebral electrodes, was able, during paradoxical sleep, to reproduce a motor behaviour previously performed at wake to consciously indicate her perception of nociceptive stimulation. Noxious stimuli induced behavioural responses only if they reached the cortex during periods when mid-frontal networks (pre-SMA, pre-motor cortex) were pre-activated. Sensory responses in the opercular cortex and insula were identical whether the noxious stimulus was to evoke or not a motor behaviour; conversely, the responses in mid-anterior cingulate were specifically enhanced for stimuli yielding motor responses. Neuronal networks implicated in the voluntary preparation of movements may be reactivated during paradoxical sleep, but only if behavioural-relevant stimuli reach the cortex during specific periods of "motor awareness". These local activation appeared without any global sleep stage change. This observation opens the way to further studies on the currently unknown capacity of the sleeping brain to interact meaningfully with its environment.
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Lung function in wheezing infants.
Front Biosci (Elite Ed)
PUBLISHED: 01-07-2014
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Recurrent wheeze is a very frequent disease during infancy. In many cases, this condition is a transient one, but some infants who suffer from this illness, have a persistent recurrent wheeze. During the past decades different international cohorts have been designed to answer what are the risk factors to develop recurrent wheeze and to make the conditon persistent even into the adulthood. Infant lung function could explain some aspects of this pathophysiology. The aim of this article is to review the current knowledge on the relationships of recurrent wheeze with an eventual impairment in lung function, the beginning of this impairment early in life, its relationship with asthma later in life and what risk factors are related with low lung function.
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Influence of controlled inoculation of malolactic fermentation on the sensory properties of industrial cider.
J. Ind. Microbiol. Biotechnol.
PUBLISHED: 01-06-2014
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Given the lack of research in the traditional cider making field when compared to the efforts devoted to winemaking, this work focused on the effects of controlled inoculation of the malolactic fermentation (MLF) on the sensory properties of cider. MLF develops spontaneously in cider making at industrial level. In this work, industrial cider samples were inoculated with selected indigenous Oenococcus oeni strains and the benefits on the aroma and flavour in cider production compared to non-inoculated ciders were evaluated. Randomly amplified polymorphic DNA PCR was used to monitor strain colonization ability, outnumbering the indigenous microbiota, after completion of the alcoholic fermentation at industrial scale (20,000 l). Aroma-active compounds of experimentally inoculated ciders were analysed by HPLC and GC-MS, and sensory profiles were determined by fractioning aroma extracts using reversed-phase HPLC. Principal component analysis allowed the identification of relationships and differences among ciders with or without inoculation, including several highly appreciated commercial ones obtained under spontaneous conditions. Under controlled inoculation conditions, not only could MLF be shortened by half but, interestingly, enhancement of aroma complexity and flavour resulted in ciders enriched with a higher fruity note. In addition, important aromatic groups analysed here had not been previously described, thus affording deeper knowledge on aroma characterization of apple cider.
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Direct application of Padé approximant for solving nonlinear differential equations.
Springerplus
PUBLISHED: 01-01-2014
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This work presents a direct procedure to apply Padé method to find approximate solutions for nonlinear differential equations. Moreover, we present some cases study showing the strength of the method to generate highly accurate rational approximate solutions compared to other semi-analytical methods. The type of tested nonlinear equations are: a highly nonlinear boundary value problem, a differential-algebraic oscillator problem, and an asymptotic problem. The high accurate handy approximations obtained by the direct application of Padé method shows the high potential if the proposed scheme to approximate a wide variety of problems. What is more, the direct application of the Padé approximant aids to avoid the previous application of an approximative method like Taylor series method, homotopy perturbation method, Adomian Decomposition method, homotopy analysis method, variational iteration method, among others, as tools to obtain a power series solutions to post-treat with the Padé approximant.
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Interleukin-1 receptor antagonist gene polymorphism increases susceptibility to septic shock in children with acute lymphoblastic leukemia.
Pediatr. Infect. Dis. J.
PUBLISHED: 10-22-2013
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Interleukin-1 receptor antagonist polymorphism (ILRN) 2 (ILRN*2) has been associated with a poor outcome in septic patients because of an elevated production of anti-inflammatory cytokines. In >70% of patients, morbidity and mortality in childhood acute lymphoblastic leukemia is caused by infections. The aim of this study was to determine the association between this polymorphism and the frequency of septic shock from the time of diagnosis until completion of treatment.
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Organocatalytic Michael addition/intramolecular Julia-Kocienski olefination for the preparation of nitrocyclohexenes.
J. Org. Chem.
PUBLISHED: 10-18-2013
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An asymmetric organocatalytic [3 + 3] annulation strategy based on a Michael addition/intramolecular Julia-Kocienski olefination sequence has been developed for the synthesis of 4-substituted-5-nitrocyclohex-1-ene compounds. The strategy is an alternative to the direct reluctant enantioselective Diels-Alder approach. The potential of the methodology has been demonstrated with a concise enantioselective formal synthesis of trandolapril.
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Safety and immunogenicity of a recombinant tetravalent dengue vaccine in 9-16 year olds: a randomized, controlled, phase II trial in Latin America.
Pediatr. Infect. Dis. J.
PUBLISHED: 09-27-2013
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The dengue virus is a member of the Flavivirus (FV) genus, which also includes the yellow fever virus. Dengue disease is caused by any 1 of 4 dengue virus serotypes and is a serious public health concern in Latin America. This study evaluated the safety and immunogenicity of a candidate recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) in 9-16 year olds in Latin America.
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Cooperative assembly of discrete stacked aggregates driven by supramolecular host-guest complexation.
J. Org. Chem.
PUBLISHED: 09-12-2013
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p-Sulfonatocalix[4]arene (SC4) interacts with the aromatic dye crystal violet (CV) to form complexes with stoichiometries ranging from SC4:CV = 1:1 up to 1:5 both in solution and in the gas phase. While the 1:1 complex is of the inclusion type, as frequently observed for other guests, in the higher-order complexes the CV molecules interact with SC4 in a peripheral manner. The formation of such complexes is driven by ionic interactions established between the dye and the calixarene and by CV-CV stacking interactions. The application of an advanced fitting procedure made possible a quantitative analysis of the UV-vis data and allowed the determination of the stepwise binding constants. This unprecedented approach provides evidence that the formation of the highest-order complexes occurs through a cooperative mechanism. Moreover, the development of a quantitative analytical model enables the possibility of using this type of system for water-soluble sensing assays, as is also exemplified in the present work.
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Reappraising neuropathic pain in humans--how symptoms help disclose mechanisms.
Nat Rev Neurol
PUBLISHED: 09-10-2013
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Neuropathic pain--that is, pain arising directly from a lesion or disease that affects the somatosensory system--is a common clinical problem, and typically causes patients intense distress. Patients with neuropathic pain have sensory abnormalities on clinical examination and experience pain of diverse types, some spontaneous and others provoked. Spontaneous pain typically manifests as ongoing burning pain or paroxysmal electric shock-like sensations. Provoked pain includes pain induced by various stimuli or even gentle brushing (dynamic mechanical allodynia). Recent clinical and neurophysiological studies suggest that the various pain types arise through distinct pathophysiological mechanisms. Ongoing burning pain primarily reflects spontaneous hyperactivity in nociceptive-fibre pathways, originating from irritable nociceptors, regenerating nerve sprouts or denervated central neurons. Paroxysmal sensations can be caused by several mechanisms; for example, electric shock-like sensations probably arise from high-frequency bursts generated in demyelinated non-nociceptive A? fibres. Most human and animal findings suggest that brush-evoked allodynia originates from A? fibres projecting onto previously sensitized nociceptive neurons in the dorsal horn, with additional contributions from plastic changes in the brainstem and thalamus. Here, we propose that the emerging mechanism-based approach to the study of neuropathic pain might aid the tailoring of therapy to the individual patient, and could be useful for drug development.
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Pediatricians attitudes and costs of bronchiolitis in the emergency department: A prospective multicentre study.
Pediatr. Pulmonol.
PUBLISHED: 09-05-2013
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How pediatricians manage bronchiolitis and the derived total costs (direct and indirect) in the emergency department (ED) have not been fully characterized. The aim of the present study is to calculate those costs in a European country.
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Polymeric premicelles as efficient lipophilic nanocarriers: extending drug uptake to the submicellar regime.
Langmuir
PUBLISHED: 08-26-2013
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A multitechnique investigation on the self-assembly behavior of a biocompatible polymer in the high dilution regime is reported herein. The obtained results unambiguously reveal the existence of premicellar structures that may further extend the efficiency of traditional polymeric micelles as drug-delivery vehicles. Such an expansion in the excipient capacity arises from (i) the increased drug retention of submicellar assemblies due to their higher resistance to dilution and therefore to their improved circulation time and (ii) the superior carrier permeability of these premicellar aggregates as a result of their smaller size, which makes these drug vehicles more effectively targeted to the tumors through the so-called enhanced permeability and retention effect. The uptake ability of the polymeric premicelles described in this work has been tested through the use of Nile Red as drug model given its intermediate lipophilicity (log P ? 3-5) similar to that of potent chemotherapy agents and its microenvironment-sensitive fluorescence properties relevant for localization purposes. Thus, it has been found that an efficient drug encapsulation can be achieved under conditions well below the normally required critical micelle concentration. These results may constitute a promising strategy in order to develop new and more efficient polymeric formulations in drug delivery technology.
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The Impact of Atmospheric Pollutants on the Prevalence of Atopic Eczema in 6-7-Year-Old Schoolchildren in Spain; ISAAC Phase III.
Iran J Allergy Asthma Immunol
PUBLISHED: 07-30-2013
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Atopic Eczema (AE) is a chronic inflammatory skin disease that affects children and adults, and alters quality of life with a high morbidity rate and severe economic burden. The objective of the present work was to analyse specific atmospheric pollutants (O3, NO, PM10 and SO2) affecting the prevalence of diagnosed AE and its symptoms among 6-7-year-old schoolchildren.The participants included 21311 schoolchildren aged 6-7 years from 8 Spanish regions, whose parents completed the ISAAC Phase III questionnaire to ascertain AE diagnosis and symptoms. The mean levels (µg/m3) of O3, NO, PM10 (particles 10 micrometers or less in diameter) and SO2 were determined in each geographical area. Participating in this study.According to these mean levels, three levels of exposure to each pollutant were considered: level 1 (percentiles 0-25); level 2 (percentiles 26-74); level 3 (percentiles 75-100). Exposure to O3 was associated with increased prevalence of rashes (exposure level 2, Odds Ratio (OR): 1.22, 95% Confidence Interval (95%CI): 1.02-1.45; level 3 OR: 1.33, 95%CI: 1.10-1.61) and diagnosed AE (level 2, OR: 1.27, 95%CI: 1.17-1.39; level 3 OR: 1.27, 95%CI: 1.15-1.41). An association was found between the level of NO and a drop in the prevalence of diagnosed AE (exposure level 2, OR: 0.88, 95%CI: 0.81-0.95; level 3 OR: 0.85, 95%CI: 0.74-0.97). There was also an association between the highest exposure level to PM10 and a reduced prevalence of rashes (level 3 OR: 0.42, 95%CI: 0.22-0.81) and diagnosed AE (level 3 OR: 0.53, 95%CI: 0.38-0.75). Future studies into exposure to O3 and its relationship with allergic diseases may be conducted in order to prevent this association.
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Adenosine A2B Receptor and Hyaluronan Modulate Pulmonary Hypertension Associated with Chronic Obstructive Pulmonary Disease.
Am. J. Respir. Cell Mol. Biol.
PUBLISHED: 07-17-2013
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Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide. The development of pulmonary hypertension (PH) in patients with COPD is strongly associated with increased mortality. Chronic inflammation and changes to the lung extracellular matrix (ECM) have been implicated in the pathogenesis of COPD, yet the mechanisms that lead to PH secondary to COPD remain unknown. Our experiments using human lung tissue show increased expression levels of the adenosine A2B receptor (ADORA2B) and a heightened deposition of hyaluronan (HA; a component of the ECM) in remodeled vessels of patients with PH associated with COPD. We also demonstrate that the expression of HA synthase 2 correlates with mean pulmonary arterial pressures in patients with COPD, with and without a secondary diagnosis of PH. Using an animal model of airspace enlargement and PH, we show that the blockade of ADORA2B is able to attenuate the development of a PH phenotype that correlates with reduced levels of HA deposition in the vessels and the down-regulation of genes involved in the synthesis of HA.
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Chemoradiation for resected pancreatic adenocarcinoma with or without intraoperative radiation therapy boost: Long-term outcomes.
Pancreatology
PUBLISHED: 07-07-2013
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To analyze prognostic factors associated with long-term outcomes in patients with pancreatic cancer treated with chemoradiation therapy (CRT) and surgery with or without intraoperative electron beam radiotherapy (IOERT).
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Postchemoradiation laparoscopic resection and intraoperative electron-beam radiation boost in locally advanced rectal cancer: long-term outcomes.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 07-07-2013
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In selected patients with rectal cancer, laparoscopic surgery is as safe as open surgery, with similar resection margins and completeness of resection. In addition, recovery is faster after laparoscopic surgery. We analyzed long-term outcomes in a group of patients with locally advanced rectal cancer (LARC) treated with preoperative therapy followed by laparoscopic surgery and intraoperative electron-beam radiotherapy (IOERT).
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Morphological and molecular differentiation of Parastrigea (Trematoda: Strigeidae) from Mexico, with the description of a new species.
Parasitol. Int.
PUBLISHED: 06-25-2013
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Parastrigea plataleae n. sp. (Digenea: Strigeidae) is described from the intestine of the roseate spoonbill Platalea ajaja (Threskiornithidae) from four localities on the Pacific coast of Mexico. The new species is mainly distinguished from the other 18 described species of Parastrigea based on the ratio of its hindbody length to forebody length. A principal component analysis (PCA) of 16 morphometric traits for 15 specimens of P. plataleae n. sp., five of Parastrigea cincta and 11 of Parastrigea diovadena previously recorded in Mexico, clearly shows three clusters, which correspond to the three species. DNA sequences of the internal transcribed spacers (ITSs) of ribosomal DNA and the mitochondrial gene cytochrome c oxidase subunit I (cox 1) were used to corroborate this morphological distinction. The genetic divergence estimated among P. plataleae n. sp., P. cincta and P. diovadena ranged from 0.5 to 1.48% for ITSs and from 9.31 to 11.47% for cox 1. Maximum parsimony (MP) and maximum likelihood (ML) analyses were performed on the combined datasets (ITSs+cox 1) and on each dataset alone. All of the phylogenetic analyses indicated that the specimens from the roseate spoonbill represent a clade with strong bootstrap support. The morphological evidence and the genetic divergence in combination with the reciprocal monophyly in all of the phylogenetic trees support the hypothesis that the digeneans found in the intestines of roseate spoonbills represent a new species.
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The "True" Affinities of Metal Cations to p-Sulfonatocalix[4]arene: A Thermodynamic Study at Neutral pH Reveals a Pitfall Due to Salt Effects in Microcalorimetry.
Chemistry
PUBLISHED: 06-20-2013
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A microcalorimetric study on the inclusion of monovalent and divalent metal cations by p-sulfonatocalix[4]arene was performed. The thermodynamic parameters for the complexation of alkali metal cations and Ag(+) were obtained for the first time at neutral pH. The Na(+) cation is routinely present as counterion of the calixarene in neutral aqueous solution, and this must be taken into account in the determination of the thermodynamic parameters for the complexation of Na(+) and the other cations by considering a sequential or a competitive binding scheme. The ?H° and ?S° values show that the inclusion process is entropically driven, although an influence of the temperature on the complexation reaction indicates that the enthalpic term is also an important contributor. The results also reveal that enthalpy/entropy compensation balances the gain in one contribution against a corresponding loss in the other. The obtained thermodynamic data are in contrast to the results from previous microcalorimetric studies, which showed binding constants that were orders of magnitude smaller and complexations, which were in part enthalpically driven but which neglected the influence of the alkali metal counterions.
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Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy.
J. Med. Genet.
PUBLISHED: 06-17-2013
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Peripheral neuropathy is the dose limiting toxicity of paclitaxel, a chemotherapeutic drug widely used to treat solid tumours. This toxicity exhibits great inter-individual variability of unknown origin. The present study aimed to identify genetic variants associated with paclitaxel induced neuropathy via a whole genome approach.
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Is acetaminophen use associated with atopic eczema and other allergic diseases in adolescents?
Iran J Allergy Asthma Immunol
PUBLISHED: 06-12-2013
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Atopic Eczema (AE) is a chronic inflammatory skin disease that affects children and adults, and alters quality of life. Previous studies have suggested several socio-demographic and environmental factors related to the prevalence of AE and other allergic diseases, including acetaminophen use. In the present study, we report the rates of isolated AE, AE associated with asthma and AE associated with rhinitis among 13- to 14-year-old Spanish adolescents and the level of association of these conditions with the use of acetaminophen. We analyzed Spanish data from a cross-sectional Phase 3 study within ISAAC. A total of 28,717 adolescents completed the Phase 3 written questionnaire by answering questions for acetaminophen use and on asthma, rhinitis and AE symptoms.We observed an association between acetaminophen use and AE among the adolescents who had used acetaminophen in the previous month. Furthermore, the prevalence rate increased with the number of allergic processes: for AE alone, the adjusted Prevalence Ratio (aPR) was 1.81 and for AE associated with rhinitis or with asthma, aPRs were 2.20 and 3.03, respectively.We conclude that acetaminophen use in childhood may be an important factor associated with development and/or maintenance of AE and other allergic diseases.
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Brain opioid receptor density predicts motor cortex stimulation efficacy for chronic pain.
Pain
PUBLISHED: 05-12-2013
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The clinical effects of motor cortex stimulation (MCS) for neuropathic pain (NP) is thought to be mediated primarily by the secretion of endogenous opioids in humans and in animal models. Because opioid receptor density is itself decreased in patients with NP, we investigated whether the magnitude and distribution of the remaining opioid receptors in patients with NP could be biological predictors of the pain-relieving effects of MCS. Using (11)C-diprenorphine positron emission tomography scans, opioid receptor availability was assessed in 15 patients suffering refractory NP, who subsequently received chronically implanted MCS. All patients underwent 2 preoperative baseline scans at 2-wk intervals and were clinically assessed after 7mo of chronic MCS. The levels of preoperative opioid-binding in the insula, thalamus, periaqueductal gray, anterior cingulate, and orbitofrontal cortex were significantly and positively correlated with postoperative pain relief at 7mo. Patients with receptor density values below the lower limits in age-matched controls in the thalamus, periaqueductal gray and contralateral insula were the least likely to benefit from MCS. Opioid-receptor availability as shown in preoperative positron emission tomography scans appears to be related to the efficacy of MCS in NP and may help clinicians to select the candidates most likely to benefit from this procedure.
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Nitrofurantoin, phenazopyridine, and the superoxide-response regulon soxRS of Escherichia coli.
J. Infect. Chemother.
PUBLISHED: 05-06-2013
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Nitrofurantoin and phenazopyridine are two drugs commonly used against urinary tract infections. Both compounds exert oxidative damage in patients deficient in glucose-6-phosphate dehydrogenase. This study was done to assess the interactions of these drugs with the soxRS regulon of Escherichia coli, a superoxide-defense system (that includes a nitroreductase that yields the active metabolite of nitrofurantoin) involved in antibiotic multi-resistance. The effects of either nitrofurantoin or phenazopyridine, upon strains with different soxRS genotypes, were measured as minimum inhibitory concentrations (MICs) and growth curves. Also, the ability of these drugs to induce the expression of a soxS::lacZ gene fusion was assessed. The effect of antibiotics in the presence of phenazopyridine, paraquat (a known soxRS inducer), or an efflux inhibitor, was measured using the disk diffusion method. A strain constitutively expressing the soxRS regulon was slightly more susceptible to nitrofurantoin, and more resistant to phenazopyridine, compared to wild-type and soxRS-deleted strains, during early treatment, but 24-h MICs were the same (8 mg/l nitrofurantoin, 1,000 mg/l phenazopyridine) for all strains. Both compounds were capable of inducing the expression of a soxS::lacZ fusion, but less than paraquat. Subinhibitory concentrations of phenazopyridine increased the antimicrobial effect of ampicillin, chloramphenicol, tetracycline, and nitrofurantoin. The induction or constitutive expression of the soxRS regulon seems to be a disadvantage for E. coli during nitrofurantoin exposure; but might be an advantage during phenazopyridine exposure, indicating that the latter compound could act as a selective pressure for mutations related to virulence and antibiotic multi-resistance.
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Mechanism of the deprotonation reaction of alkyl benzyl ethers with n-butyllithium.
Chemistry
PUBLISHED: 04-15-2013
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Kinetic study of the ?-lithiation of benzyl methyl ether (BME) by nBuLi has revealed that increasing the concentration of the organolithium compound does not necessarily increase the reactivity, and this is a consequence of the reactivities of the different nBuLi aggregates present in solution. We propose a dimer-based mechanism, in which a pre-complexation step is a key process for substrates bearing a donor oxygen atom that can interact with the lithium cation to form mixed dimers. For these studies, we have developed a system based on UV/Vis spectroscopy that allows kinetic measurements to be conducted at -80 °C under argon.
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The association between acetaminophen and asthma: should its pediatric use be banned?
Expert Rev Respir Med
PUBLISHED: 04-04-2013
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During the last few decades, a huge epidemiological effort has been made all over the world in order to cast some light on the origin of asthma (or wheezing disorders as a general term) and its recent increase in prevalence. The focus on genetic factors has failed to show any genetic signal strong enough to be seriously considered, and the tiny genetic signals found have never been appropriately replicated. The focus on environmental factors has provided some variable signals on the role of infections, allergens and bacterial substances, the direction of which have curiously varied from protecting to inducing asthma. The only environmental factor that has launched a large and consistent epidemiological signal, found in almost every epidemiological study addressing the issue, is previous acetaminophen exposure, which consistently increases the prevalence and clinical manifestations of every wheezing disorder under study. Is acetaminophen a real asthma promoter or an innocent bystander?
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Pain matrices and neuropathic pain matrices: a review.
Pain
PUBLISHED: 03-29-2013
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The pain matrix is conceptualised here as a fluid system composed of several interacting networks. A nociceptive matrix receiving spinothalamic projections (mainly posterior operculoinsular areas) ensures the bodily specificity of pain and is the only one whose destruction entails selective pain deficits. Transition from cortical nociception to conscious pain relies on a second-order network, including posterior parietal, prefrontal and anterior insular areas. Second-order regions are not nociceptive-specific; focal stimulation does not evoke pain, and focal destruction does not produce analgesia, but their joint activation is necessary for conscious perception, attentional modulation and control of vegetative reactions. The ensuing pain experience can still be modified as a function of beliefs, emotions and expectations through activity of third-order areas, including the orbitofrontal and perigenual/limbic networks. The pain we remember results from continuous interaction of these subsystems, and substantial changes in the pain experience can be achieved by acting on each of them. Neuropathic pain (NP) is associated with changes in each of these levels of integration. The most robust abnormality in NP is a functional depression of thalamic activity, reversible with therapeutic manoeuvres and associated with rhythmic neural bursting. Neuropathic allodynia has been associated with enhancement of ipsilateral over contralateral insular activation and lack of reactivity in orbitofrontal/perigenual areas. Although lack of response of perigenual cortices may be an epiphenomenon of chronic pain, the enhancement of ipsilateral activity may reflect disinhibition of ipsilateral spinothalamic pathways due to depression of their contralateral counterpart. This in turn may bias perceptual networks and contribute to the subjective painful experience.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.