Risk of acquired drug resistance during short-course directly observed treatment of tuberculosis in an area with high levels of drug resistance.

BACKGROUND: Data on the performance of standardized short-course directly observed treatment (DOTS) of tuberculosis (TB) in areas with high levels of drug resistance and on the potential impact of DOTS on amplification of resistance are limited. Therefore, we analyzed treatment results from a cross-sectional sample of patients with TB enrolled in a DOTS program in an area with high levels of drug resistance in Uzbekistan and Turkmenistan in Central Asia. METHODS: Sputum samples for testing for susceptibility to 5 first-line drugs and for molecular typing were obtained from patients starting treatment in 8 districts. Patients with sputum smear results positive for TB at the end of the intensive phase of treatment and/or at 2 months into the continuation phase were tested again. RESULTS. Among 382 patients with diagnoses of TB, 62 did not respond well to treatment and were found to be infected with an identical Mycobacterium tuberculosis strain when tested again; 19 of these patients had strains that developed new or additional drug resistance. Amplification occurred in only 1.2% of patients with initially susceptible or monoresistant TB strains, but it occurred in 17% of those with polyresistant strains (but not multidrug-resistant strains, defined as strains with resistance to at least isoniazid and rifampicin) and in 7% of those with multidrug-resistant strains at diagnosis. Overall, 3.5% of the patients not initially infected with multidrug-resistant TB strains developed such strains during treatment. Amplification of resistance, however, was found only in polyresistant Beijing genotype strains. CONCLUSIONS: High levels of amplification of drug resistance demonstrated under well-established DOTS program conditions reinforce the need for implementation of DOTS-Plus for multidrug-resistant TB in areas with high levels of drug resistance. The strong association of Beijing genotype and amplification in situations of preexisting resistance is striking and may underlie the strong association between this genotype and drug resistance

Rabies screen reveals GPe control of cocaine-triggered plasticity.

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the increase in GPe labelling. Inhibition of GPe activity revealed that it contributes to two forms of cocaine-triggered behavioural plasticity, at least in part by disinhibiting dopamine neurons in the ventral tegmental area. These results suggest that rabies-based unbiased screening of changes in input populations can identify previously unappreciated circuit elements that critically support behavioural adaptations

In-situ local phase-transitioned MoSe2 in La0.5Sr0.5CoO3-?? heterostructure and stable overall water electrolysis over 1000 hours

Developing efficient bifunctional catalysts for overall water splitting that are earth-abundant, cost-effective, and durable is of considerable importance from the practical perspective to mitigate the issues associated with precious metal-based catalysts. Herein, we introduce a heterostructure comprising perovskite oxides (La0.5Sr0.5CoO3?????) and molybdenum diselenide (MoSe2) as an electrochemical catalyst for overall water electrolysis. Interestingly, formation of the heterostructure of La0.5Sr0.5CoO3????? and MoSe2 induces a local phase transition in MoSe2, 2???H to 1???T phase, and more electrophilic La0.5Sr0.5CoO3????? with partial oxidation of the Co cation owing to electron transfer from Co to Mo. Together with these synergistic effects, the electrochemical activities are significantly improved for both hydrogen and oxygen evolution reactions. In the overall water splitting operation, the heterostructure showed excellent stability at the high current density of 100???mA???cm???2 over 1,000???h, which is exceptionally better than the stability of the state-of-the-art platinum and iridium oxide couple

Influence of surface atomic structure demonstrated on oxygen incorporation mechanism at a model perovskite oxide

Perovskite oxide surfaces catalyze oxygen exchange reactions that are crucial for fuel cells, electrolyzers, and thermochemical fuel synthesis. Here, by bridging the gap between surface analysis with atomic resolution and oxygen exchange kinetics measurements, we demonstrate how the exact surface atomic structure can determine the reactivity for oxygen exchange reactions on a model perovskite oxide. Two precisely controlled surface reconstructions with (4 × 1) and (2 × 5) symmetry on 0.5 wt.% Nb-doped SrTiO3(110) were subjected to isotopically labeled oxygen exchange at 450 °C. The oxygen incorporation rate is three times higher on the (4 × 1) surface phase compared to the (2 × 5). Common models of surface reactivity based on the availability of oxygen vacancies or on the ease of electron transfer cannot account for this difference. We propose a structure-driven oxygen exchange mechanism, relying on the flexibility of the surface coordination polyhedra that transform upon dissociation of oxygen molecules.Austrian Science Fund (SFB “ Functional Oxide Surfaces and Interfaces ” - FOXSI, Project F 45)European Research Council Advanced Grant (“OxideSurfaces” (Project ERC-2011-ADG_20110209))National Science Foundation (U.S.). Division of Materials Research (CAREER Award Grant No. 1055583

A biophysical model of endocannabinoid-mediated short term depression in hippocampal inhibition

Memories are believed to be represented in the synaptic pathways of vastly interconnected networks of neurons. The plasticity of synapses, that is, their strengthening and weakening depending on neuronal activity, is believed to be the basis of learning and establishing memories. An increasing number of studies indicate that endocannabinoids have a widespread action on brain function through modulation of synap–tic transmission and plasticity. Recent experimental studies have characterised the role of endocannabinoids in mediating both short- and long-term synaptic plasticity in various brain regions including the hippocampus, a brain region strongly associated with cognitive functions, such as learning and memory. Here, we present a biophysically plausible model of cannabinoid retrograde signalling at the synaptic level and investigate how this signalling mediates depolarisation induced suppression of inhibition (DSI), a prominent form of shortterm synaptic depression in inhibitory transmission in hippocampus. The model successfully captures many of the key characteristics of DSI in the hippocampus, as observed experimentally, with a minimal yet sufficient mathematical description of the major signalling molecules and cascades involved. More specifically, this model serves as a framework to test hypotheses on the factors determining the variability of DSI and investigate under which conditions it can be evoked. The model reveals the frequency and duration bands in which the post-synaptic cell can be sufficiently stimulated to elicit DSI. Moreover, the model provides key insights on how the state of the inhibitory cell modulates DSI according to its firing rate and relative timing to the post-synaptic activation. Thus, it provides concrete suggestions to further investigate experimentally how DSI modulates and is modulated by neuronal activity in the brain. Importantly, this model serves as a stepping stone for future deciphering of the role of endocannabinoids in synaptic transmission as a feedback mechanism both at synaptic and network level

On the relativistic KMS condition for the P(\phi)_2 model

The relativistic KMS condition introduced by Bros and Buchholz provides a link between quantum statistical mechanics and quantum field theory. We show that for the $P(\phi)_2$ model at positive temperature, the two point function for fields satisfies the relativistic KMS condition

Mammary tuberculosis – importance of recognition and differentiation from that of a breast malignancy: report of three cases and review of the literature

<p>Abstract</p> <p>Background</p> <p>While tuberculosis of the breast is an extremely uncommon entity seen in western populations, it accounts for up to 3% of all treatable breast lesions in developing countries.</p> <p>Case presentations</p> <p>We reviewed three female cases of mammary tuberculosis that were diagnosed and treated in Turkey during the same calendar year. All three patients presented with a painful breast mass. In all cases, fine needle aspiration was nondiagnostic for mammary tuberculosis. However, the diagnosis of mammary tuberculosis was confirmed by histopathologic evaluation at the time of open surgical biopsy. All three patients were treated with antituberculous therapy for six months. At the end of the treatment period, each patient appeared to be clinically and radiologically without evidence of residual disease.</p> <p>Conclusion</p> <p>The diagnosis of mammary tuberculosis rests on the appropriate clinical suspicion and the histopathologic findings of the breast lesion. Its recognition and differentiation from that of a breast malignancy is absolutely necessary. Antituberculous chemotherapy, initiated immediately upon diagnosis, forms the mainstay of treatment for mammary tuberculosis.</p

Mycobacterial infections in a large Virginia hospital, 2001-2009

<p>Abstract</p> <p>Background</p> <p>In areas where both tuberculosis (TB) and nontuberculous mycobacteria (NTM) are prevalent, descriptive studies of the clinical features of individual mycobacteria are needed to inform clinical triage.</p> <p>Methods</p> <p>We queried the University of Virginia Clinical Data Repository for all mycobacterial infections from 2001-2009.</p> <p>Results</p> <p>Of 494 mycobacterial infections in 467 patients there were 22 species. Patients with pulmonary Tb were more likely to be reported as immigrants (p < 0.001) and less likely to have a predisposing risk factor for NTM (pre-existing lung disease or host predisposition; p = 0.002). Review of chest CT scans revealed that TB infection was more likely to exhibit cavities and pleural effusion than NTM infection (p < 0.05). Among NTM infections <it>M. kansasii</it>, <it>M. xenopi</it>, and <it>M. fortuitum </it>were more likely than MAC to have cavities. There were at least 83 patients that met criteria for NTM lung disease and these were caused by 9 species. <it>M. abscessus </it>infection was associated with cystic fibrosis and <it>M. xenopi </it>infection was associated with male gender.</p> <p>Conclusions</p> <p>In our center mycobacterial infections were common and of diverse species. Immigrant status, cavities, and effusion were associated with TB vs. NTM.</p