Borrelia burgdorferi membranes are the primary targets of reactive oxygen species

Spirochetes living in an oxygen-rich environment or when challenged by host immune cells are exposed to reactive oxygen species (ROS). These species can harm/destroy cysteinyl residues, iron-sulphur clusters, DNA and polyunsaturated lipids, leading to inhibition of growth or cell death. Because Borrelia burgdorferi contains no intracellular iron, DNA is most likely not a major target for ROS via Fenton reaction. In support of this, growth of B. burgdorferi in the presence of 5 mM H2O2 had no effect on the DNA mutation rate (spontaneous coumermycin A1 resistance), and cells treated with 10 mM t-butyl hydroperoxide or 10 mM H2O2 show no increase in DNA damage. Unlike most bacteria, B. burgdorferi incorporates ROS-susceptible polyunsaturated fatty acids from the environment into their membranes. Analysis of lipoxidase-treated B. burgdorferi cells by Electron Microscopy showed significant irregularities indicative of membrane damage. Fatty acid analysis of cells treated with lipoxidase indicated that host-derived linoleic acid had been dramatically reduced (50-fold) in these cells, with a corresponding increase in the levels of malondialdehyde by-product (fourfold). These data suggest that B. burgdorferi membrane lipids are targets for attack by ROS encountered in the various stages of the infective cycle

Magnetic Reversal on Vicinal Surfaces

We present a theoretical study of in-plane magnetization reversal for vicinal ultrathin films using a one-dimensional micromagnetic model with nearest-neighbor exchange, four-fold anisotropy at all sites, and two-fold anisotropy at step edges. A detailed "phase diagram" is presented that catalogs the possible shapes of hysteresis loops and reversal mechanisms as a function of step anisotropy strength and vicinal terrace length. The steps generically nucleate magnetization reversal and pin the motion of domain walls. No sharp transition separates the cases of reversal by coherent rotation and reversal by depinning of a ninety degree domain wall from the steps. Comparison to experiment is made when appropriate.Comment: 12 pages, 8 figure

Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs

Substance abuse and addiction are the most costly of all the neuropsychiatric disorders. In the last decades, much progress has been achieved in understanding the effects of the drugs of abuse in the brain. However, efficient treatments that prevent relapse have not been developed. Drug addiction is now considered a brain disease, because the abuse of drugs affects several brain functions. Neurological impairments observed in drug addicts may reflect drug-induced neuronal dysfunction and neurotoxicity. The drugs of abuse directly or indirectly affect neurotransmitter systems, particularly dopaminergic and glutamatergic neurons. This review explores the literature reporting cellular and molecular alterations reflecting the cytotoxicity induced by amphetamines, cocaine and opiates in neuronal systems. The neurotoxic effects of drugs of abuse are often associated with oxidative stress, mitochondrial dysfunction, apoptosis and inhibition of neurogenesis, among other mechanisms. Understanding the mechanisms that underlie brain dysfunction observed in drug-addicted individuals may contribute to improve the treatment of drug addiction, which may have social and economic consequences.http://www.sciencedirect.com/science/article/B6SYS-4S50K2J-1/1/7d11c902193bfa3f1f57030572f7034

A positive deviance approach to understanding key features to improving diabetes care in the medical home

Contains fulltext : 118403.pdf (publisher's version ) (Open Access)PURPOSE The medical home has gained national attention as a model to reorganize primary care to improve health outcomes. Pennsylvania has undertaken one of the largest state-based, multipayer medical home pilot projects. We used a positive deviance approach to identify and compare factors driving the care models of practices showing the greatest and least improvement in diabetes care in a sample of 25 primary care practices in southeast Pennsylvania. METHODS We ranked practices into improvement quintiles on the basis of the average absolute percentage point improvement from baseline to 18 months in 3 registry-based measures of performance related to diabetes care: glycated hemoglobin concentration, blood pressure, and low-density lipoprotein cholesterol level. We then conducted surveys and key informant interviews with leaders and staff in the 5 most and least improved practices, and compared their responses. RESULTS The most improved/higher-performing practices tended to have greater structural capabilities (eg, electronic health records) than the least improved/lower-performing practices at baseline. Interviews revealed striking differences between the groups in terms of leadership styles and shared vision; sense, use, and development of teams; processes for monitoring progress and obtaining feedback; and presence of technologic and financial distractions. CONCLUSIONS Positive deviance analysis suggests that primary care practices' baseline structural capabilities and abilities to buffer the stresses of change may be key facilitators of performance improvement in medical home transformations. Attention to the practices' structural capabilities and factors shaping successful change, especially early in the process, will be necessary to improve the likelihood of successful medical home transformation and better care