Nancecraven5349

Appropriate use of magnetic resonance imaging (MRI) in elderly breast cancer (BC) patients remains unclear; we sought to identify the indications and implications of MRI use in our elderly BC population. Women 70 years of age or older at first BC diagnosis with an MRI performed at our institution either perioperatively or in follow-up were included from a prospectively maintained database from 2000 to 2010. Univariate logistic regression was used to test associations with disease identified by MRI only (additional ipsilateral, contralateral, or new cancer) following perioperative MRI. 305 BCs were imaged in 286 patients. 133 were imaged with MRI in the perioperative setting alone, 88 had only follow-up MRIs after BC treatment, and 65 had both. Indications for perioperative MRI include extent of disease evaluation (181; 91%); occult primary (10; 5%); high-risk screening (5; 3%); and abnormal physical exam with negative conventional imaging (2; 1%). Disease identified by MRI only for occult primary cases was 4/10 (40%; 95% confidence interval 12.2-73.8%) and 14/181 (7.7%; 95% confidence interval 4.3-12.6%) for perioperative MRIs performed for extent of disease evaluation. Analysis of imaging and tumor characteristics failed to find significant predictors of disease identified by MRI only. A total of 369 post-treatment follow-up MRIs were performed in 148 patients with a median of 2 MRIs per patient (range 1-8), with seven cases of disease identified by MRI only (1.9%; 95% confidence interval 0.8-3.9%). MRI had the greatest benefit in women presenting with an occult primary cancer and minimal additional benefit in elderly patients with BC undergoing MRI imaging for extent of disease evaluation or in post-treatment surveillance.Recently, academic chemists have renewed their interest in the development of 1,1'-binaphthalene-2,2'-diol (BINOL)-derived chiral ligands. read more Six years ago, a working hypothesis, that the chirality matching of hybrid chirality on a ligand could probably lead to high levels of stereoselective induction, prompted us to use the axial chirality of BINOL derivatives to generate new stereogenic centers within the same molecule with high stereoselectivity, obtaining as a result sterically favorable ligands for applications in asymmetric catalysis. This Personal Account describes our laboratory's efforts toward the development of a novel class of BINOL-derived atropisomers bearing both axial and sp(3) central chirality, the so-called Ar-BINMOLs, for asymmetric synthesis. Furthermore, on the basis of the successful application of Ar-BINMOLs and their derivatives in asymmetric catalysis, the search for highly efficient and enantioselective processes also compelled us to give special attention to the BINOL-derived multifunctional ligands with multiple stereogenic centers for use in catalytic asymmetric reactions.The luminescence properties of two compounds, [C(NH2)3][Eu(EDTA)(H2O)3] (I) and [C(NH2)3]2[Yb0.97Eu0.03(EDTA)(H2O)2]ClO4·6H2O (II), were determined. The weighted sum of luminescence spectra of I and II was used to reproduce the spectra of the Eu-EDTA system in aqueous solution in the temperature range 276-363 K. By implementing this method it was possible to determine the thermodynamic functions (ΔH = 18113 ± 506 J mole(-1) and ΔS = 62.5 ± 4.9 J mole(-1) K(-1)) of the reaction [Eu(EDTA)(H2O)3](-)⇆ [Eu(EDTA)(H2O)2](-) + H2O, which is difficult using other methods.The neurobiological underpinnings of anxiety are of paramount importance to the development of effective therapeutic treatments. To date, there is considerable pharmacological evidence suggesting that the suppression of hippocampal theta frequency is a robust and predictive assay of anxiolytic drug action. Recently, this idea has been challenged using histamine (2-(4-imidazolyl)ethanamine), an endogenous neurotransmitter involved in a number of brain and behavioral functions. Here, we systematically evaluate the effects of dorsal and ventral hippocampal histamine infusions on evoked theta frequency and behavioral anxiety. Given the complex pharmacological profile of histamine and its receptors in the hippocampus, we reasoned that local intra-hippocampal infusions would be a powerful test of the theta suppression model. While dorsal hippocampal infusions of histamine produced neither significant changes in anxious-like behavior in the elevated plus maze nor changes of evoked theta, ventral infusions of histamine produced potent behavioral anxiolysis which corresponded to an increase, and not a decrease, in evoked theta frequency. As a positive neurophysiological control, we demonstrated that diazepam, a proven anxiolytic drug, decreased the frequency of hippocampal theta following both dorsal and ventral hippocampal infusions. Our results further challenge the hippocampal theta frequency suppression model as a measure of anxiolytic drug action. This article is part of the Special Issue entitled 'Histamine Receptors'.CEP-32215 is a new, potent, selective, and orally bioavailable inverse agonist of the histamine H3 receptor (H3R) with drug-like properties. High affinity in human (hH3R Ki = 2.0 ± 0.2 nM) and rat (rH3R Ki = 3.6 ± 0.7 nM) H3R radioligand binding assays was demonstrated. Potent functional antagonism (Kb = 0.3 ± 0.1 nM) and inverse agonism (EC50 = 0.6 ± 0.2 nM) were demonstrated in [(35)S]guanosine 5(')-O-(γ-thio)-triphosphate binding assays. Oral bioavailability and dose-related exposure was consistent among rat, dog, and monkey. After oral dosing, occupancy of H3R by CEP-32215 was estimated by the inhibition of ex vivo binding in rat cortical slices (ED50 = 0.1 mg/kg p.o.). Functional antagonism in brain was demonstrated by the inhibition of R-α-methylhistamine-induced drinking in the rat dipsogenia model (ED50 = 0.92 mg/kg). CEP-32215 significantly increased wake duration in the rat EEG model at 3-30 mg/kg p.o. Increased motor activity, sleep rebound or undesirable events (such as spike wave or seizure activity) was not observed following doses up to 100 mg/kg p.o., indicating an acceptable therapeutic index. CEP-32215 may have potential utility in the treatment of a variety of sleep disorders. This article is part of the Special Issue entitled 'Histamine Receptors'.Aberrant immunity contributes to the pathogenesis of acute-on-chronic hepatitis B liver failure (ACHBLF), and A20 is a newly identified negative regulatory molecule of the immune response. However, no data have been reported for the role of A20 in ACHBLF. This study aimed to investigate A20 mRNA expression in ACHBLF and to determine the potential of A20 as a biomarker for the prognosis of ACHBLF. Quantitative real-time polymerase chain reaction (qPCR) was used to measure the mRNA expression of A20 in peripheral blood mononuclear cells (PBMCs) from 137 ACHBLF patients, 105 chronic hepatitis B (CHB) and 35 healthy controls (HCs). A secondary cohort with 37 ACHBLF patients was set up as validation data set. The plasma levels of interleukin (IL)-1β, IL-6 and IL-10 were determined using enzyme-linked immunosorbent assay (ELISA). Receiver-operating characteristic (ROC) curves were used to determine the predictive value of A20 for the prognosis of ACHBLF patients. A20 mRNA expression in ACHBLF was significantly higher compared with CHB and HCs. In ACHBLF patients, A20 mRNA was closely associated with total bilirubin, albumin, international normalized ratio, prothrombin time activity and model for end-stage liver disease. Furthermore, A20 mRNA was significantly correlated with IL-6 and IL-10. An optimal cut-off value of 12.32 for A20 mRNA had significant power in discriminating survival or death in ACHBLF patients. In conclusion, our results suggest that the up-regulation of the A20 gene might contribute to the severity of ACHBLF and A20 mRNA level might be a potential predictor for the prognosis of ACHBLF.

Pure red blood cell aplasia (PRCA) is a complication of ABO major-incompatible stem cell transplantation, likely due to the persistence of memory B lymphocytes of recipient origin, which produce hemagglutinins against ABO antigens on donor RBCs. At present no standard of care is established for this complication.

We report a case of PRCA after allogeneic bone marrow transplantation, successfully treated with plasma exchange (PEX) after failing erythropoietin administration.

The patient fully recovered from RBC aplasia.

This case suggests a role for PEX in the treatment of PRCA after allogeneic stem cell transplantation.

This case suggests a role for PEX in the treatment of PRCA after allogeneic stem cell transplantation.While recent advances have been gained on genome evolution in angiosperm lineages, virtually nothing is known about karyotype evolution in the other group of seed plants, the gymnosperms. Here we used high density gene-based linkage mapping to compare the karyotype structure of two families of conifers (the most abundant group of gymnosperms) separated around 290 million years ago Pinaceae and Cupressaceae. We propose for the first time a model based on the fusion of 20 ancestral chromosomal blocks that may have shaped the modern karyotpes of Pinaceae (with n=12) and Cupressaceae (with n=11). The considerable difference in modern genome organization between these two lineages contrasts strongly with the remarkable level of synteny already reported within the Pinaceae. It also suggests a convergent evolutionary mechanism of chromosomal block shuffling that has shaped the genomes of the spermatophytes.

Pain-related anxiety and depression are well known to be comorbid with chronic pain and adversely affect patient quality of life. Recent studies have shown that anxiety-like behaviors also develop with acute surgical pain, but the effects of general anesthetics on acute pain-related anxiety are unknown.

The present study aimed to compare the effects of different general anesthetics on anxiety-like behaviors that follow formalin-induced acute pain in a rat model.

Formalin-induced acute inflammatory pain was established by intraplantar injection of 1% formalin without anesthesia or with anesthesia using the clinical anesthetics sevoflurane, propofol, or pentobarbital sodium. Anxiety-like behaviors were studied using the open-field test and elevated plus maze. Phosphorylated extracellular signal-regulated kinase (p-ERK) 1/2 expression in the anterior cingulate cortex (ACC) and spinal cord was examined using immunohistochemistry.

Anxiety-like behaviors were observed at 24 and 72 h post-formalin injection. Concomitantly, p-ERK 1/2 expression was upregulated in the ACC at 1 and 24 h post-formalin injection. While all three general anesthetics effectively blocked nociceptive responses and activation of ERK in the rat ACC following formalin injection during anesthesia, only sevoflurane inhibited ERK activation in the spinal cord and ACC at 24 h post-injection.

This study suggests that sevoflurane, but not intravenous anesthetics, inhibits pain-related anxiety, along with ERK activation in the ACC, probably through inhibition of spinal nociceptive transmission. Intraoperative application of inhaled anesthetics may be a better choice to reduce postoperative anxiety.

This study suggests that sevoflurane, but not intravenous anesthetics, inhibits pain-related anxiety, along with ERK activation in the ACC, probably through inhibition of spinal nociceptive transmission. Intraoperative application of inhaled anesthetics may be a better choice to reduce postoperative anxiety.