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Neglected: Some Say the U.S. is Ignoring the Commemoration of the Slave Trade\u27s End
Impact of particle size, oxidation state and capping agent of different cerium dioxide nanoparticles on the phosphate-induced transformations at different pH and concentration
The potential hazard posed by nanomaterials can be significantly influenced by transformations which these materials undergo during their lifecycle, from manufacturing through to disposal. The transformations may depend on the nanomaterialsā own physicochemical properties as well as the environment they are exposed to. This study focuses on the mechanisms of transformation of cerium oxide nanoparticles (CeO NPs) in laboratory experiments which simulate potential scenarios in which the NPs are exposed to phosphate-bearing media. We have experimented with the transformation of four different kinds of CeO NPs, in order to investigate the effects of nanoparticle size, capping agent (three were uncapped and one was PVP capped) and oxidation state (two consisted mostly of Ce and two were a mix of Ce/Ce). They were exposed to a reaction solution containing KHPO, citric acid and ascorbic acid at pH values of 2.3, 5.5 and 12.3, and concentrations of 1mM and 5mM. The transformations were followed by UV-vis, zeta potential and XRD measurements, which were taken after 7 and 21 days, and by transmission electron microscopy after 21 days. X-ray photoelectron spectroscopy was measured at 5mM concentration after 21 days for some samples. Results show that for pH 5 and 5mM phosphate concentration, CePO NPs were formed. Nanoparticles that were mostly Ce did not dissolve at 1mM reagent concentration, and did not produce CePO NPs. When PVP was present as a capping agent it proved to be an extra reducing agent, and CePO was found under all conditions used. This is the first paper where the transformation of CeO NPs in the presence of phosphate has been studied for particles with different size, shapes and capping agents, in a range of different conditions and using many different characterisation methods
Trends in Antibiotic Use and Nosocomial Pathogens in Hospitalized Veterans With Pneumonia at 128 Medical Centers, 2006-2010
This national Department of Veterans Affairs study of hospitalizations for pneumonia found a dramatic increase in broad-spectrum antibiotic use from 2006 to 2010, without an increase in nosocomial pathogens or improvement in the match between coverage and pathoge
Coronary-artery bypass surgery in patients with ischemic cardiomyopathy
BACKGROUND
The survival benefit of a strategy of coronary-artery bypass grafting (CABG) added to
guideline-directed medical therapy, as compared with medical therapy alone, in patients
with coronary artery disease, heart failure, and severe left ventricular systolic
dysfunction remains unclear.
METHODS
From July 2002 to May 2007, a total of 1212 patients with an ejection fraction of 35%
or less and coronary artery disease amenable to CABG were randomly assigned to
undergo CABG plus medical therapy (CABG group, 610 patients) or medical therapy
alone (medical-therapy group, 602 patients). The primary outcome was death from any
cause. Major secondary outcomes included death from cardiovascular causes and death
from any cause or hospitalization for cardiovascular causes. The median duration of
follow-up, including the current extended-follow-up study, was 9.8 years.
RESULTS
A primary outcome event occurred in 359 patients (58.9%) in the CABG group and in
398 patients (66.1%) in the medical-therapy group (hazard ratio with CABG vs. medical
therapy, 0.84; 95% confidence interval [CI], 0.73 to 0.97; P=0.02 by log-rank test). A
total of 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the
medical-therapy group died from cardiovascular causes (hazard ratio, 0.79; 95% CI,
0.66 to 0.93; P=0.006 by log-rank test). Death from any cause or hospitalization for
cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and in 524
patients (87.0%) in the medical-therapy group (hazard ratio, 0.72; 95% CI, 0.64 to 0.82;
P<0.001 by log-rank test).
CONCLUSIONS
In a cohort of patients with ischemic cardiomyopathy, the rates of death from any
cause, death from cardiovascular causes, and death from any cause or hospitalization
for cardiovascular causes were significantly lower over 10 years among patients who
underwent CABG in addition to receiving medical therapy than among those who received
medical therapy alone. (Funded by the National Institutes of Health; STICH [and
STICHES] ClinicalTrials.gov number, NCT00023595.
Huntington's disease pathogenesis: two sequential components
Historically, Huntingtonās disease (HD; OMIM #143100) has played an important role in the enormous advances in human genetics seen over the past four decades. This familial neurodegenerative disorder involves variable onset followed by consistent worsening of characteristic abnormal movements along with cognitive decline and psychiatric disturbances. HD was the first autosomal disease for which the genetic defect was assigned to a position on the human chromosomes using only genetic linkage analysis with common DNA polymorphisms. This discovery set off a multitude of similar studies in other diseases, while the HD gene, later renamed HTT, and its vicinity in chromosome 4p16.3 then acted as a proving ground for development of technologies to clone and sequence genes based upon their genomic location, with the growing momentum of such advances fueling the Human Genome Project. The identification of the HD gene has not yet led to an effective treatment, but continued human genetic analysis of genotype-phenotype relationships in large HD subject populations, first at the HTT locus and subsequently genome-wide, has provided insights into pathogenesis that divide the course of the disease into two sequential, mechanistically distinct components
A modifier of Huntington's disease onset at the MLH1 locus
Huntingtonās disease (HD) is a dominantly inherited neurodegenerative disease caused by an expanded CAG repeat in HTT.
Many clinical characteristics of HD such as age at motor onset are determined largely by the size of HTT CAG repeat.
However, emerging evidence strongly supports a role for other genetic factors in modifying the disease pathogenesis driven
by mutant huntingtin. A recent genome-wide association analysis to discover genetic modifiers of HD onset age provided
initial evidence for modifier loci on chromosomes 8 and 15 and suggestive evidence for a locus on chromosome 3. Here, genotyping
of candidate single nucleotide polymorphisms in a cohort of 3,314 additional HD subjects yields independent confirmation
of the former two loci and moves the third to genome-wide significance at MLH1, a locus whose mouse orthologue
modifies CAG length-dependent phenotypes in a Htt-knock-in mouse model of HD. Both quantitative and dichotomous association
analyses implicate a functional variant on 32% of chromosomes with the beneficial modifier effect that delays HD
motor onset by 0.7 years/allele. Genomic DNA capture and sequencing of a modifier haplotype localize the functional variation
to a 78 kb region spanning the 3āend of MLH1 and the 5āend of the neighboring LRRFIP2, and marked by an isoleucinevaline
missense variant in MLH1. Analysis of expression Quantitative Trait Loci (eQTLs) provides modest support for altered
regulation of MLH1 and LRRFIP2, raising the possibility that the modifier affects regulation of both genes. Finally, polygenic
modification score and heritability analyses suggest the existence of additional genetic modifiers, supporting expanded, comprehensive
genetic analysis of larger HD datasets
Structure based inhibitor design targeting glycogen phosphorylase b. Virtual screening, synthesis, biochemical and biological assessment of novel N-acyl-Ī²-d-glucopyranosylamines
Glycogen phosphorylase (GP) is a validated target for the development of new type 2 diabetes treatments. Exploiting the Zinc docking database, we report the in silico screening of 1888 Ī²- D-glucopyranose-NH-CO-R putative GP inhibitors differing only in their R groups. CombiGlide and GOLD docking programs with different scoring functions were employed with the best performing methods combined in a āconsensus scoringā approach to ranking of ligand binding affinities for the active site. Six selected candidates from the screening were then synthesized and their inhibitory potency was assessed both in vitro and ex vivo. Their inhibition constantsā values, in vitro, ranged from 5 to 377 ĀµM while two of them were effective at causing inactivation of GP in rat hepatocytes at low ĀµM concentrations. The crystal structures of GP in complex with the inhibitors were defined and provided the structural basis for their inhibitory potency and data for further structure based design of more potent inhibitors
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