Sivelestat relieves respiratory distress refractory to dexamethasone in all-trans retinoic acid syndrome: a report of two cases

Kawasaki K, Akaike H, Miyauchi A, Ouchi K. Sivelestat relieves respiratory distress refractory to dexamethasone in all-trans retinoic acid syndrome: a report of two cases. Treatment with all-trans retinoic acid (ATRA) improves the prognosis of patients with acute promyelocytic leukemia (APL), but ATRA syndrome may occur as a possible fatal side effect, especially in cases refractory to medication or involving pulmonary hemorrhage. We describe two patients with APL who suffered from intracranial hemorrhage. The first patient was a 16-yr-old girl who was treated with ATRA and then developed respiratory distress refractory to treatment with dexamethasone combined with anthracycline-cytarabine cytoreduction therapy. Treatment with Sivelestat, a small molecule inhibitor of neutrophil elastase, achieved rapid improvement in oxygenation and chest radiograph findings, and the patient has been in complete remission for 24 months. The second patient was a 10-yr-old boy in whom pulmonary hemorrhage developed following administration of ATRA, dexamethasone and cytoreduction therapy. Aspiration and administration of Sivelestat improved oxygenation and he remained stable. Hematological improvement was also achieved, but the patient died of brain dysfunction because of cerebral edema accompanied by intracranial bleeding. The two cases suggest that Sivelestat may be effective as an additional agent in the treatment of refractory ATRA syndrome, and, therefore, prospective randomized studies of treatment protocols are warranted

Chiral U(1) flavor models and flavored Higgs doublets: the top FB asymmetry and the Wjj

We present U(1) flavor models for leptophobic Z' with flavor dependent couplings to the right-handed up-type quarks in the Standard Model, which can accommodate the recent data on the top forward-backward (FB) asymmetry and the dijet resonance associated with a W boson reported by CDF Collaboration. Such flavor-dependent leptophobic charge assignments generally require extra chiral fermions for anomaly cancellation. Also the chiral nature of U(1)' flavor symmetry calls for new U(1)'-charged Higgs doublets in order for the SM fermions to have realistic renormalizable Yukawa couplings. The stringent constraints from the top FB asymmetry at the Tevatron and the same sign top pair production at the LHC can be evaded due to contributions of the extra Higgs doublets. We also show that the extension could realize cold dark matter candidates.Comment: 40 pages, 10 figures, added 1 figure and extended discussion, accepted for publication in JHE

2015 Update on Acute Adverse Reactions to Gadolinium based Contrast Agents in Cardiovascular MR. Large Multi-National and Multi-Ethnical Population Experience With 37788 Patients From the EuroCMR Registry

Objectives: Specifically we aim to demonstrate that the results of our earlier safety data hold true in this much larger multi-national and multi-ethnical population. Background: We sought to re-evaluate the frequency, manifestations, and severity of acute adverse reactions associated with administration of several gadolinium- based contrast agents during routine CMR on a European level. Methods: Multi-centre, multi-national, and multi-ethnical registry with consecutive enrolment of patients in 57 European centres. Results: During the current observation 37788 doses of Gadolinium based contrast agent were administered to 37788 patients. The mean dose was 24.7 ml (range 5–80 ml), which is equivalent to 0.123 mmol/kg (range 0.01 - 0.3 mmol/kg). Forty-five acute adverse reactions due to contrast administration occurred (0.12 %). Most reactions were classified as mild (43 of 45) according to the American College of Radiology definition. The most frequent complaints following contrast administration were rashes and hives (15 of 45), followed by nausea (10 of 45) and flushes (10 of 45). The event rate ranged from 0.05 % (linear non-ionic agent gadodiamide) to 0.42 % (linear ionic agent gadobenate dimeglumine). Interestingly, we also found different event rates between the three main indications for CMR ranging from 0.05 % (risk stratification in suspected CAD) to 0.22 % (viability in known CAD). Conclusions: The current data indicate that the results of the earlier safety data hold true in this much larger multi-national and multi-ethnical population. Thus, the “off-label” use of Gadolinium based contrast in cardiovascular MR should be regarded as safe concerning the frequency, manifestation and severity of acute events

Bee products prevent VEGF-induced angiogenesis in human umbilical vein endothelial cells

<p>Abstract</p> <p>Background</p> <p>Vascular endothelial growth factor (VEGF) is a key regulator of pathogenic angiogenesis in diseases such as cancer and diabetic retinopathy. Bee products [royal jelly (RJ), bee pollen, and Chinese red propolis] from the honeybee, <it>Apis mellifera</it>, have been used as traditional health foods for centuries. The aim of this study was to investigate the anti-angiogenic effects of bee products using human umbilical vein endothelial cells (HUVECs).</p> <p>Methods</p> <p>In an <it>in vitro </it>tube formation assay, HUVECs and fibroblast cells were incubated for 14 days with VEGF and various concentrations of bee products [RJ, ethanol extract of bee pollen, ethanol extract of Chinese red propolis and its constituent, caffeic acid phenethyl ester (CAPE)]. To clarify the mechanism of <it>in vitro </it>angiogenesis, HUVEC proliferation and migration were induced by VEGF with or without various concentrations of RJ, bee pollen, Chinese red propolis, and CAPE.</p> <p>Results</p> <p>RJ, bee pollen, Chinese red propolis, and CAPE significantly suppressed VEGF-induced <it>in vitro </it>tube formation in the descending order: CAPE > Chinese red propolis >> bee pollen > RJ. RJ and Chinese red propolis suppressed both VEGF-induced HUVEC proliferation and migration. In contrast, bee pollen and CAPE suppressed only the proliferation.</p> <p>Conclusion</p> <p>Among the bee products, Chinese red propolis and CAPE in particular showed strong suppressive effects against VEGF-induced angiogenesis. These findings indicate that Chinese red propolis and CAPE may have potential as preventive and therapeutic agents against angiogenesis-related human diseases.</p

Beautiful Mirrors at the LHC

We explore the "Beautiful Mirrors" model, which aims to explain the measured value of $A^b_{FB}$, discrepant at the $2.9\sigma$ level. This scenario introduces vector-like quarks which mix with the bottom, subtly affecting its coupling to the $Z$. The spectrum of the new particles consists of two bottom-like quarks and a charge -4/3 quark, all of which have electroweak interactions with the third generation. We explore the phenomenology and discovery reach for these new particles at the LHC, exploring single mirror quark production modes whose rates are proportional to the same mixing parameters which resolve the $A_{FB}^b$ anomaly. We find that for mirror quark masses $\lesssim 500 GeV, a 14 TeV LHC with 300 {\rm fb}^{-1}$ is required to reasonably establish the scenario and extract the relevant mixing parameters.Comment: version to be published in JHE

On Unbounded Composition Operators in L2L^2-Spaces

Fundamental properties of unbounded composition operators in $L^2$-spaces are studied. Characterizations of normal and quasinormal composition operators are provided. Formally normal composition operators are shown to be normal. Composition operators generating Stieltjes moment sequences are completely characterized. The unbounded counterparts of the celebrated Lambert's characterizations of subnormality of bounded composition operators are shown to be false. Various illustrative examples are supplied

Circuit Quantum Electrodynamics with a Spin Qubit

Circuit quantum electrodynamics allows spatially separated superconducting qubits to interact via a "quantum bus", enabling two-qubit entanglement and the implementation of simple quantum algorithms. We combine the circuit quantum electrodynamics architecture with spin qubits by coupling an InAs nanowire double quantum dot to a superconducting cavity. We drive single spin rotations using electric dipole spin resonance and demonstrate that photons trapped in the cavity are sensitive to single spin dynamics. The hybrid quantum system allows measurements of the spin lifetime and the observation of coherent spin rotations. Our results demonstrate that a spin-cavity coupling strength of 1 MHz is feasible.Comment: Related papers at http://pettagroup.princeton.edu

Green Production of Anionic Surfactant Obtained from Pea Protein

A pea protein isolate was hydrolyzed by a double enzyme treatment method in order to obtain short peptide sequences used as raw materials to produce lipopeptides-based surfactants. Pea protein hydrolysates were prepared using the combination of Alcalase and Flavourzyme. The influence of the process variables was studied to optimize the proteolytic degradation to high degrees of hydrolysis. The average peptide chain lengths were obtained at 3–5 amino acid units after a hydrolysis of 30 min with the mixture of enzymes. Then, N-acylation in water, in presence of acid chloride (C12 and C16), carried out with a conversion rate of amine functions of 90%, allowed to obtain anionic surfactant mixtures (lipopeptides and sodium fatty acids). These two steps were performed in water, in continuous and did not generate any waste. This process was therefore in line with green chemistry principles. The surface activities (CMC, foaming and emulsifying properties) of these mixtures were also studied. These formulations obtained from natural renewable resources and the reactions done under environmental respect, could replace petrochemical based surfactants for some applications

Spatial heterogeneity and peptide availability determine CTL killing efficiency in vivo

The rate at which a cytotoxic T lymphocyte (CTL) can survey for infected cells is a key ingredient of models of vertebrate immune responses to intracellular pathogens. Estimates have been obtained using in vivo cytotoxicity assays in which peptide-pulsed splenocytes are killed by CTL in the spleens of immunised mice. However the spleen is a heterogeneous environment and splenocytes comprise multiple cell types. Are some cell types intrinsically more susceptible to lysis than others? Quantitatively, what impacts are made by the spatial distribution of targets and effectors, and the level of peptide-MHC on the target cell surface? To address these questions we revisited the splenocyte killing assay, using CTL specific for an epitope of influenza virus. We found that at the cell population level T cell targets were killed more rapidly than B cells. Using modeling, quantitative imaging and in vitro killing assays we conclude that this difference in vivo likely reflects different migratory patterns of targets within the spleen and a heterogeneous distribution of CTL, with no detectable difference in the intrinsic susceptibilities of the two populations to lysis. Modeling of the stages involved in the detection and killing of peptide-pulsed targets in vitro revealed that peptide dose influenced the ability of CTL to form conjugates with targets but had no detectable effect on the probability that conjugation resulted in lysis, and that T cell targets took longer to lyse than B cells. We also infer that incomplete killing in vivo of cells pulsed with low doses of peptide may be due to a combination of heterogeneity in peptide uptake and the dissociation, but not internalisation, of peptide-MHC complexes. Our analyses demonstrate how population-averaged parameters in models of immune responses can be dissected to account for both spatial and cellular heterogeneity

Accuracy of magnetic resonance studies in the detection of chondral and labral lesions in femoroacetabular impingement : systematic review and meta-analysis

Background: Several types of Magnetic resonance imaging (MRI) are commonly used in imaging of femoroacetabular impingement (FAI), however till now there are no clear protocols and recommendations for each type. The aim of this meta-analysis is to detect the accuracy of conventional magnetic resonance imaging (cMRI), direct magnetic resonance arthrography (dMRA) and indirect magnetic resonance arthrography (iMRA) in the diagnosis of chondral and labral lesions in femoroacetabular impingement (FAI). Methods: A literature search was finalized on the 17th of May 2016 to collect all studies identifying the accuracy of cMRI, dMRA and iMRA in diagnosing chondral and labral lesions associated with FAI using surgical results (arthroscopic or open) as a reference test. Pooled sensitivity and specificity with 95% confidence intervals using a random-effects meta-analysis for MRI, dMRA and iMRA were calculated also area under receiver operating characteristic (ROC) curve (AUC) was retrieved whenever possible where AUC is equivocal to diagnostic accuracy. Results: The search yielded 192 publications which were reviewed according inclusion and exclusion criteria then 21 studies fulfilled the eligibility criteria for the qualitative analysis with a total number of 828 cases, lastly 12 studies were included in the quantitative meta-analysis. Meta-analysis showed that as regard labral lesions the pooled sensitivity, specificity and AUC for cMRI were 0.864, 0.833 and 0.88 and for dMRA were 0.91, 0.58 and 0.92. While in chondral lesions the pooled sensitivity, specificity and AUC for cMRI were 0.76, 0.72 and 0.75 and for dMRA were 0.75, 0.79 and 0.83, while for iMRA were sensitivity of 0.722 and specificity of 0.917. Conclusions: The present meta-analysis showed that the diagnostic test accuracy was superior for dMRA when compared with cMRI for detection of labral and chondral lesions. The diagnostic test accuracy was superior for labral lesions when compared with chondral lesions in both cMRI and dMRA. Promising results are obtained concerning iMRA but further studies still needed to fully assess its diagnostic accuracy