QRDR mutations, efflux system & antimicrobial resistance genes in enterotoxigenic Escherichia coli isolated from an outbreak of diarrhoea in Ahmedabad, India

Background & objectives: Diverse mechanisms have been identified in enteric bacteria for their adaptation and survival against multiple classes of antimicrobial agents. Resistance of bacteria to the most effective fluoroquinolones have increasingly been reported in many countries. We have identified that most of the enterotoxigenic Escherichia coli (ETEC) were resistant to several antimicrobials in a diarrhoea outbreak at Ahmedabad during 2000. The present study was done to identify several genes responsible for antimicrobial resistance and mobile genetic elements in the ETEC strains. Methods: Seventeen ETEC strains isolated from diarrhoeal patients were included in this study. The antimicrobial resistance was confirmed by conventional disc diffusion method. PCR and DNA sequencing were performed for the identification of mutation in the quinolone resistance-determining regions (QRDRs). Efflux pump was tested by inhibiting the proton-motive force. DNA hybridization assay was made for the detection of integrase genes and the resistance gene cassettes were identified by direct sequencing of the PCR amplicons. Results: Majority of the ETEC had GyrA mutations at codons 83 and 87 and in ParC at codon 80. Six strains had an additional mutation in ParC at codon 108 and two had at position 84. Plasmid-borne qnr gene alleles that encode quinolone resistance were not detected but the newly described aac(6')-Ib-cr gene encoding a fluoroquinolne-modifying enzyme was detected in 64.7 per cent of the ETEC. Class 1 (intI1) and class 2 (intI2) integrons were detected in six (35.3%) and three (17.6%) strains, respectively. Four strains (23.5%) had both the classes of integrons. Sequence analysis revealed presence of dfrA17, aadA1, aadA5 in class 1, and dfrA1, sat1, aadA1 in class 2 integrons. In addition, the other resistance genes such as tet gene alleles (94.1%), catAI (70.6%), strA (58.8%), bla TEM-1 (35.2%), and aphA1-Ia (29.4%) were detected in most of the strains. Interpretation & Conclusions: Innate gene mutations and acquisition of multidrug resistance genes through mobile genetic elements might have contributed to the emergence of multidrug resistance (MDR) in ETEC. This study reinforces the necessity of utilizing molecular techniques in the epidemiological studies to understand the nature of resistance responsible for antimicrobial resistance in different species of pathogenic bacteria

(Nitrato-κO)oxido(5,10,15,20-tetra­phenyl­porphyrinato-κ4 N)molybdenum(V) benzene solvate

In the title compound, [Mo(C44H28N4)(NO3)O]·C6H6, the porphyrin ring is centrosymmetric. The Mo atom, oxide ion and nitrate ion are equally disordered over two sites, such that the Mo atom is displaced by 0.366 (1) Å towards the oxide ion from the 24-atom mean plane of the porphyrin, and also makes a long Mo—O bond to a nitrate O atom. A centrosymmetric benzene solvent mol­ecule is situated between adjacent porphyrin mol­ecules

The investigation of acute optic neuritis: a review and proposed protocol

Optic neuritis is an inflammatory optic neuropathy that affects many patients with multiple sclerosis (MS) at some point during their disease course. Differentiation of acute episodes of MS-associated optic neuritis from other autoimmune and inflammatory optic neuropathies is vital for treatment choice and further patient management, but is not always straightforward. Over the past decade, a number of new imaging, laboratory and electrophysiological techniques have entered the clinical arena. To date, however, no consensus guidelines have been devised to specify how and when these techniques can be most rationally applied for the diagnostic work-up of patients with acute optic neuritis. In this article, we review the literature and attempt to formulate a consensus for the investigation of patients with acute optic neuritis, both in standard care and in research with relevance to clinical treatment trials

Low temperature properties of the fermionic mixtures with mass imbalance in optical lattice

We study the attractive Hubbard model with mass imbalance to clarify low temperature properties of the fermionic mixtures in the optical lattice. By combining dynamical mean-field theory with the continuous-time quantum Monte Carlo simulation, we discuss the competition between the superfluid and density wave states at half filling. By calculating the energy and the order parameter for each state, we clarify that the coexisting (supersolid) state, where the density wave and superfluid states are degenerate, is realized in the system. We then determine the phase diagram at finite temperatures.Comment: 5 pages, 4 figures, accepted for publication in J. Phys. Soc. Jp

Placebo-controlled study in neuromyelitis optica : ethical and design considerations

BACKGROUND: To date, no treatment for neuromyelitis optica (NMO) has been granted regulatory approval, and no controlled clinical studies have been reported. OBJECTIVE: To design a placebo-controlled study in NMO that appropriately balances patient safety and clinical-scientific integrity. METHODS: We assessed the "standard of care" for NMO to establish the ethical framework for a placebo-controlled trial. We implemented measures that balance the need for scientific robustness while mitigating the risks associated with a placebo-controlled study. The medical or scientific community, patient organizations, and regulatory authorities were engaged early in discussions on this placebo-controlled study, and their input contributed to the final study design. RESULTS: The N-MOmentum study (NCT02200770) is a clinical trial that randomizes NMO patients to receive MEDI-551, a monoclonal antibody that depletes CD19+ B-cells, or placebo. The study design has received regulatory, ethical, clinical, and patient approval in over 100 clinical sites in more than 20 countries worldwide. CONCLUSION: The approach we took in the design of the N-MOmentum trial might serve as a roadmap for other rare severe diseases when there is no proven therapy and no established clinical development path

Variational Monte Carlo Study of Spin-Gapped Normal State and BCS-BEC Crossover in Two-Dimensional Attractive Hubbard Model

We study properties of normal, superconducting (SC) and CDW states for an attractive Hubbard model on the square lattice, using a variational Monte Carlo method. In trial wave functions, we introduce an interspinon binding factor, indispensable to induce a spin-gap transition in the normal state, in addition to the onsite attractive and intersite repulsive factors. It is found that, in the normal state, as the interaction strength $|U|/t$ increases, a first-order spin-gap transition arises at $|U_{\rm c}|\sim W$ ($W$: band width) from a Fermi liquid to a spin-gapped state, which is conductive through hopping of doublons. In the SC state, we confirm by analysis of various quantities that the mechanism of superconductivity undergoes a smooth crossover at around |U_{\ma{co}}|\sim |U_{\rm c}| from a BCS type to a Bose-Einstein condensation (BEC) type, as $|U|/t$ increases. For |U|<|U_{\ma{co}}|, quantities such as the condensation energy, a SC correlation function and the condensate fraction of onsite pairs exhibit behavior of $\sim \exp(-t/|U|)$, as expected from the BCS theory. For |U|>|U_{\ma{co}}|, quantities such as the energy gain in the SC transition and superfluid stiffness, which is related to the cost of phase coherence, behave as $\sim t^2/|U|\propto T_{\rm c}$, as expected in a bosonic scheme. In this regime, the SC transition is induced by a gain in kinetic energy, in contrast with the BCS theory. We refer to the relevance to the pseudogap in cuprate superconductors.Comment: 14 pages, 22 figures, submitted to Journal of the Physical Society of Japa

Bioatividade da semente de abacate (Persea americana Mill) sobre Atta sexdens Forel, 1908 (Hymenoptera: Formicidae).

As formigas-cortadeiras são consideradas importantes pragas de plantações florestais,agricultura e pecuária. No Brasil, o método de controle mais utilizado é por meio de iscasformicidas à base de sulfluramida, ingrediente ativo associado a diversos danos ambientais. Assim,a busca por métodos sustentáveis para o controle de formigas-cortadeiras, como o uso de extratosbotânicos, tem aumentado. O objetivo do trabalho foi avaliar o potencial do óleo da semente deabacate no controle de Atta sexdens Forel, 1908 (Hymenoptera: Formicidae). Os frutos de abacate(variedade Ouro Verde) foram pesados, lavados, e as sementes separadas da porção comestível(mesocarpo). As sementes foram raladas, secas em estufa de ar circulante e as amostrasarmazenadas em geladeira. O óleo da semente de abacate foi extraído com o uso do solventehexano pelo método de Soxhlet. Para avaliar a toxicidade do óleo sobre as operárias de A. sexdensfoi realizado um teste tópico com diferentes volumes (tratamentos): V1 - 0,25; V2 - 0,5; V3 - 0,75;V4 - 1,0 e V5 - 2,0 μL, além do controle (0,5 μL de água destilada). O óleo foi aplicado commicropipeta no pronoto das operárias forrageiras (n = 30; total = 180), que foram individualizadasem recipientes plásticos de 30 mL e mantidas em BOD a 24 ± 2°C. A mortalidade de operárias foiavaliada a cada 24 horas durante oito dias. Os dados foram submetidos ao teste não paramétrico deFriedman, e as médias comparadas pelo teste de SNK (p ≤ 0,05). Foi observada diferençasignificativa entre o controle e o tratamento V1, bem como entre V1 e os demais tratamentos (V2 aV5). No oitavo dia, com exceção do controle, todos os tratamentos apresentaram mortalidadeacumulada de 100%. O óleo da semente de abacate, quando aplicado em via tópica, demonstroucontrole potencial sobre operárias de A. sexdens. Com base nesse resultado preliminar, serárealizada a caracterização química do óleo para a identificação dos compostos químicos compropriedades inseticidas

Hierarchically Porous Gd3+-Doped CeO2 Nanostructures for the Remarkable Enhancement of Optical and Magnetic Properties

Rare earth ion-doped CeO2 has attracted more and more attention because of its special electrical, optical, magnetic, or catalytic properties. In this paper, a facile electrochemical deposition route was reported for the direct growth of the porous Gd-doped CeO2. The formation process of Gd-doped CeO2 composites was investigated. The obtained deposits were characterized by SEM, EDS, XRD, and XPS. The porous Gd3+- doped CeO2 (10 at% Gd) displays a typical type I adsorption isotherm and yields a large specific surface area of 135 m2/g. As Gd3+ ions were doped into CeO2 lattice, the absorption spectrum of Gd3+-doped CeO2 nanocrystals exhibited a red shift compared with porous CeO2 nanocrystals and bulk CeO2, and the luminescence of Gd3+-doped CeO2 deposits was remarkably enhanced due to the presence of more oxygen vacancies. In addition, the strong magnetic properties of Gd-doped CeO2 (10 at% Gd) were observed, which may be caused by Gd3+ ions or more oxygen defects in deposits. In addition, the catalytic activity of porous Gd-doped CeO2 toward CO oxidation was studied

Chronic VEGF Blockade Worsens Glomerular Injury in the Remnant Kidney Model

VEGF inhibition can promote renal vascular and parenchymal injury, causing proteinuria, hypertension and thrombotic microangiopathy. The mechanisms underlying these side effects are unclear. We investigated the renal effects of the administration, during 45 days, of sunitinib (Su), a VEGF receptor inhibitor, to rats with 5/6 renal ablation (Nx). Adult male Munich-Wistar rats were distributed among groups S+V, sham-operated rats receiving vehicle only; S+Su, S rats given Su, 4 mg/kg/day; Nx+V, Nx rats receiving V; and Nx+Su, Nx rats receiving Su. Su caused no change in Group S. Seven and 45 days after renal ablation, renal cortical interstitium was expanded, in association with rarefaction of peritubular capillaries. Su did not worsen hypertension, proteinuria or interstitial expansion, nor did it affect capillary rarefaction, suggesting little angiogenic activity in this model. Nx animals exhibited glomerulosclerosis (GS), which was aggravated by Su. This effect could not be explained by podocyte damage, nor could it be ascribed to tuft hypertrophy or hyperplasia. GS may have derived from organization of capillary microthrombi, frequently observed in Group Nx+Su. Treatment with Su did not reduce the fractional glomerular endothelial area, suggesting functional rather than structural cell injury. Chronic VEGF inhibition has little effect on normal rats, but can affect glomerular endothelium when renal damage is already present