Peritoneal Dialysis Fluid Concentrations of Linezolid in the Treatment of Vancomycin‐Resistant Enterococcus faecium Peritonitis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90108/1/phco.23.12.1322.32702.pd

Linezolid Clearance During Continuous Venovenous Hemodiafiltration: A Case Report

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90207/1/phco.23.8.1071.32874.pd

Formation of filopodia-like bundles in vitro from a dendritic network

We report the development and characterization of an in vitro system for the formation of filopodia-like bundles. Beads coated with actin-related protein 2/3 (Arp2/3)–activating proteins can induce two distinct types of actin organization in cytoplasmic extracts: (1) comet tails or clouds displaying a dendritic array of actin filaments and (2) stars with filament bundles radiating from the bead. Actin filaments in these bundles, like those in filopodia, are long, unbranched, aligned, uniformly polar, and grow at the barbed end. Like filopodia, star bundles are enriched in fascin and lack Arp2/3 complex and capping protein. Transition from dendritic to bundled organization was induced by depletion of capping protein, and add-back of this protein restored the dendritic mode. Depletion experiments demonstrated that star formation is dependent on Arp2/3 complex. This poses the paradox of how Arp2/3 complex can be involved in the formation of both branched (lamellipodia-like) and unbranched (filopodia-like) actin structures. Using purified proteins, we showed that a small number of components are sufficient for the assembly of filopodia-like bundles: Wiskott-Aldrich syndrome protein (WASP)–coated beads, actin, Arp2/3 complex, and fascin. We propose a model for filopodial formation in which actin filaments of a preexisting dendritic network are elongated by inhibition of capping and subsequently cross-linked into bundles by fascin

Lateralization of Simulated Sources and Echoes Differing in Frequency Based on Interaural Temporal Differences

This study examined listeners’ ability to process interaural temporal differences (ITDs) in one of two sequential sounds when the two differed in spectral content. A correlational analysis assessed weights given to ITDs of simulated source and echo pulses for echo delays of 8–128ms for conditions in which responses were based on the source or echo, a 3000-Hz Gaussian (target) pulse. The other (distractor) pulse was spectrally centered at 1500, 2000, 3000, 4000, or 5000 Hz. Also measured were proportion correct and proportion of responses predicted from the weights. Regardless of whether the echo or source pulse served as the target, target weight, and proportion correct increased with increasing distractor frequency, consistent with low-frequency dominance [Divenyi, J. Acoust. Soc. Am. 91, 1078–1084 (1992)]. Effects of distractor frequency were observed at echo delays out to 128 ms when the source served as the target, but only out to 64 ms when the echo served as the target. At echo delays beyond 8 ms, recency effects were exhibited with higher proportions correct obtained for judgments based on the echo pulse than the source pulse

Hybridization between wild and cultivated potato species in the Peruvian Andes and biosafety implications for deployment of GM potatoes

The nature and extent of past and current hybridization between cultivated potato and wild relatives in nature is of interest to crop evolutionists, taxonomists, breeders and recently to molecular biologists because of the possibilities of inverse gene flow in the deployment of genetically-modified (GM) crops. This research proves that natural hybridization occurs in areas of potato diversity in the Andes, the possibilities for survival of these new hybrids, and shows a possible way forward in case of GM potatoes should prove advantageous in such areas

Characterization of candidate genes in inflammatory bowel disease-associated risk loci

GWAS have linked SNPs to risk of inflammatory bowel disease (IBD), but a systematic characterization of disease-associated genes has been lacking. Prior studies utilized microarrays that did not capture many genes encoded within risk loci or defined expression quantitative trait loci (eQTLs) using peripheral blood, which is not the target tissue in IBD. To address these gaps, we sought to characterize the expression of IBD-associated risk genes in disease-relevant tissues and in the setting of active IBD. Terminal ileal (TI) and colonic mucosal tissues were obtained from patients with Crohn\u27s disease or ulcerative colitis and from healthy controls. We developed a NanoString code set to profile 678 genes within IBD risk loci. A subset of patients and controls were genotyped for IBD-associated risk SNPs. Analyses included differential expression and variance analysis, weighted gene coexpression network analysis, and eQTL analysis. We identified 116 genes that discriminate between healthy TI and colon samples and uncovered patterns in variance of gene expression that highlight heterogeneity of disease. We identified 107 coexpressed gene pairs for which transcriptional regulation is either conserved or reversed in an inflammation-independent or -dependent manner. We demonstrate that on average approximately 60% of disease-associated genes are differentially expressed in inflamed tissue. Last, we identified eQTLs with either genotype-only effects on expression or an interaction effect between genotype and inflammation. Our data reinforce tissue specificity of expression in disease-associated candidate genes, highlight genes and gene pairs that are regulated in disease-relevant tissue and inflammation, and provide a foundation to advance the understanding of IBD pathogenesis

Relevance of biotic pathways to the long-term regulation of nuclear waste disposal. Topical report on reference eastern humid low-level sites

The purpose of the work reported here was to develop an order-of-magnitude estimate for the potential dose to man resulting from biotic transport mechanisms at a humid reference low-level waste site in the eastern US. A description of the reference site is presented that includes the waste inventories, site characteristics and biological communites. Parameter values for biotic transport processes are based on data reported in current literature. Transport and exposure scenarios are developed for assessing biotic transport during 500 years following site closure. Calculations of radionuclide decay and waste container decomposition are made to estimate the quantities available for biotic transport. Doses to man are calculated for the biological transport of radionucludes at the reference site after loss of institutional control. These dose estimates are compared to dose estimates we calculated for the intruder-agricultural scenarios reported in the DEIS for 10 CFR 61 (NRC). Dose to man estimates as a result of cumulative biotic transport are calculated to be of the same order-of-magnitude as the dose resulting from the more commonly evaluated human intrusion scenario. The reported lack of potential importance of biotic transport at low-level waste sites in earlier assessment studies is not confirmed by findings presented in this report. Through biotic transport, radionuclides can be moved to locations where they can enter exposure pathways to man

Evaluation of high-dose rifampin in patients with new, smear-positive tuberculosis (HIRIF): study protocol for a randomized controlled trial.

BACKGROUND: Evidence has existed for decades that higher doses of rifampin may be more effective, but potentially more toxic, than standard doses used in tuberculosis treatment. Whether increased doses of rifampin could safely shorten treatment remains an open question. METHODS/DESIGN: The HIRIF study is a phase II randomized trial comparing rifampin doses of 20 and 15 mg/kg/day to the standard 10 mg/kg/day for the first 2 months of tuberculosis treatment. All participants receive standard doses of companion drugs and a standard continuation-phase treatment (4 months, 2 drugs). They are followed for 6 months post treatment. Study participants are adults with newly diagnosed, previously untreated, smear positive (≥2+) pulmonary tuberculosis. The primary outcome is rifampin area under the plasma concentration-time curve (AUC0-24) after at least 14 days of study treatment/minimum inhibitory concentration. 180 randomized participants affords 90 % statistical power to detect a difference of at least 14 mcg/mL*hr between the 20 mg/kg group and the 10 mg/kg group, assuming a loss to follow-up of up to 17 %. DISCUSSION: Extant evidence suggests the potential for increased doses of rifampin to shorten tuberculosis treatment duration. Early studies that explored this potential using intermittent, higher dosing were derailed by toxicity. Given the continued large, global burden of tuberculosis with nearly 10 million new cases annually, shortened regimens with existing drugs would offer an important advantage to patients and health systems. TRIAL REGISTRATION: This trial was registered with clinicaltrials.gov (registration number: NCT01408914 ) on 2 August 2011