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Thermally activated Peierls dimerization in ferromagnetic spin chains.
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We demonstrate that a Peierls dimerization can occur in ferromagnetic spin chains activated by thermal fluctuations. The dimer order parameter and entanglement measures are studied as functions of the modulation of the magnetic exchange interaction and temperature, using a spin-wave theory and the density-matrix renormalization group. We discuss the case where a periodic modulation is caused by spin-phonon coupling and the case where electronic states effectively induce such a modulation. The importance of the latter for a number of transition metal oxides is highlighted.
| 18,999,635
|
High-energy collision of two black holes.
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We study the head-on collision of two highly boosted equal mass, nonrotating black holes. We determine the waveforms, radiated energies, and mode excitation in the center of mass frame for a variety of boosts. For the first time we are able to compare analytic calculations, black-hole perturbation theory, and strong field, nonlinear numerical calculations for this problem. Extrapolation of our results, which include velocities of up to 0.94c, indicate that in the ultrarelativistic regime about 14+/-3% of the energy is converted into gravitational waves. This gives rise to a luminosity of order 10_(-2)c_(5)/G, the largest known so far in a black-hole merger.
| 18,999,655
|
Next-to-next-to-leading order corrections to three-jet observables in electron-positron annihilation.
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I report on a numerical program, which can be used to calculate any infrared safe three-jet observable in electron-positron annihilation to next-to-next-to-leading order in the strong coupling constant alpha(s). The results are compared to a recent calculation by another group. Numerical differences in three color factors are discussed and explained.
| 18,999,659
|
Onset of pi(0) suppression studied in Cu+Cu collisions at sqrt S NN=22.4, 62.4, and 200 GeV.
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Neutral pion transverse momentum (p(T)) spectra at midrapidity (|y| less than or approximately 0.35) were measured in Cu+Cu collisions at sqrt[s(NN)]=22.4, 62.4, and 200 GeV. Relative to pi_(0) yields in p+p collisions scaled by the number of inelastic nucleon-nucleon collisions (N(coll) the pi_(0) yields for p(T) more than or approximately 2 GeV/c in central Cu+Cu collisions are suppressed at 62.4 and 200 GeV whereas an enhancement is observed at 22.4 GeV. A comparison with a jet-quenching model suggests that final state parton energy loss dominates in central Cu+Cu collisions at 62.4 and 200 GeV, while the enhancement at 22.4 GeV is consistent with nuclear modifications in the initial state alone.
| 18,999,660
|
Resistive-wall-mode active rotation in the RFX-mod device.
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The fundamental question of how the flow velocity of the background plasma can influence the motion of magnetohydrodynamics instabilities and, in the ultimate analysis, their stability is addressed. The growth of resistive-wall-mode instabilities in toroidal confinement devices well represents one example of such a problem. In this Letter, we illustrate a new strategy that allowed, for the first time in a reversed field pinch experiment, a fully controlled rotation of a nonresonant instability by means of a set of active coils and how the new findings compare with numerical modeling.
| 18,999,679
|
Time-dependent density-functional theory and strongly correlated systems: insight from numerical studies.
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We illustrate the scope of time-dependent density-functional theory for strongly correlated (lattice) models out of equilibrium. Using the exact many-body time evolution, we reverse engineer the exact exchange correlation (xc) potential v_(xc) for small Hubbard chains exposed to time-dependent fields. We introduce an adiabatic local density approximation to v_(xc) for the 1D Hubbard model and compare it to exact results, to gain insight about approximate xc potentials. Finally, we provide some remarks on the v-representability for the 1D Hubbard model.
| 18,999,689
|
Zener polaron ordering variants induced by A-site ordering in half-doped manganites.
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We have studied the magnetism of the half-doped charge ordered manganite YBaMn2O6. A formation of ferromagnetic plaquettes of four Mn atoms in the charge ordered phase below T_{CO} approximately 480 K is inferred from high temperature magnetic susceptibility data and the magnetic structure, as determined by neutron powder diffraction at T=1.5 K. The results indicate that new fourfold Mn paramagnetic units form between T_{N}<T<T_{CO}, and that they order in a noncollinear mode below T_{N}=190 K. The magnetism of YBaMn2O6 is consistent with what is expected from the Zener polarons ordering picture of the charge ordering phenomenon in manganites [A. Daoud-Aladine, Phys. Rev. Lett. 89, 097205 (2002)10.1103/PhysRevLett.89.097205].
| 18,999,692
|
Spin wave dispersion on the nanometer scale.
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Hot electrons injected into antiferromagnetic Mn layers from the tip of a low temperature scanning tunneling microscope have been used to determine the energies, lifetimes, and momenta of antiferromagnetic spin waves on the nanometer scale. The spin waves show a linear dispersion with a velocity of 160+/-10 meV A and lifetimes that scale linearly with energy in agreement with neutron scattering and theory. It is shown that the method is sensitive enough to detect the influence of surface anisotropies on the spin wave dispersion.
| 18,999,706
|
Inference from matrix products: a heuristic spin-glass algorithm.
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We present an algorithm for finding ground states of two-dimensional spin-glass systems based on ideas from matrix product states in quantum information theory. The algorithm works directly at zero temperature and defines an approximation to the energy whose accuracy depends on a parameter k. We test the algorithm against exact methods on random field and random bond Ising models, and we find that accurate results require a k which scales roughly polynomially with the system size. The algorithm also performs well when tested on small systems with arbitrary interactions, where no fast, exact algorithms exist. The time required is significantly less than Monte Carlo schemes.
| 18,999,711
|
Causality-based criteria for a negative refractive index must be used with care.
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Using the principle of causality as expressed in the Kramers-Kronig relations, we derive a generalized criterion for a negative refractive index that admits imperfect transparency at an observation frequency omega. It also allows us to relate the global properties of the loss (i.e., its frequency response) to its local behavior at omega. However, causality-based criteria rely on the group velocity, not the Poynting vector. Since the two are not equivalent, we provide some simple examples to compare the two criteria.
| 18,999,712
|
Excitations of one-dimensional Bose-Einstein condensates in a random potential.
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We examine bosons hopping on a one-dimensional lattice in the presence of a random potential at zero temperature. Bogoliubov excitations of the Bose-Einstein condensate formed under such conditions are localized, with the localization length diverging at low frequency as l(omega) approximately 1/omega(alpha). We show that the well-known result alpha=2 applies only for sufficiently weak random potential. As the random potential is increased beyond a certain strength, alpha starts decreasing. At a critical strength of the potential, when the system of bosons is at the transition from a superfluid to an insulator, alpha=1. This result is relevant for understanding the behavior of the atomic Bose-Einstein condensates in the presence of random potential, and of the disordered Josephson junction arrays.
| 18,999,729
|
Evolution of entanglement between distinguishable light states.
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We investigate the evolution of quantum correlations over the lifetime of a multiphoton state. Measurements reveal time-dependent oscillations of the entanglement fidelity for photon pairs created by a single semiconductor quantum dot. The oscillations are attributed to the phase acquired in the intermediate, nondegenerate, exciton-photon state and are consistent with simulations. We conclude that emission of photon pairs by a typical quantum dot with finite polarization splitting is in fact entangled in a time-evolving state, and not classically correlated as previously regarded.
| 18,999,730
|
Variable-range projection model for turbulence-driven collisions.
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We discuss the relative speeds DeltaV of inertial particles suspended in a highly turbulent gas when the Stokes number, a dimensionless measure of their inertia, is large. We identify a mechanism giving rise to the distribution P(DeltaV) approximately exp(-C|DeltaV|(4/3)) (for some constant C). Our conclusions are supported by numerical simulations, and by the analytical solution of a model equation of motion. The results determine the rate of collisions between suspended particles. They are relevant to the hypothesized mechanism for formation of planets by aggregation of dust particles in circumstellar nebula.
| 18,999,752
|
Unconventional quasiparticle lifetime in graphene.
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We address the question of how large can the lifetime of electronic states be at low energies in graphene, below the scale of the optical phonon modes. For this purpose, we study the many-body effects at the K point of the spectrum, which induce a strong coupling between electron-hole pairs and out-of-plane phonons. We show the existence of a soft branch of hybrid states below the electron-hole continuum when graphene is close to the charge neutrality point, leading to an inverse lifetime proportional to the cube of the quasiparticle energy. This implies that a crossover should be observed in transport properties, from such a slow decay rate to the lower bound given at very low energies by the decay into acoustic phonons.
| 18,999,770
|
Generalized Elliott-Yafet theory of electron spin relaxation in metals: origin of the anomalous electron spin lifetime in MgB2.
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The temperature dependence of the electron-spin relaxation time in MgB2 is anomalous as it does not follow the resistivity above 150 K; it has a maximum around 400 K and decreases for higher temperatures. This violates the well established Elliot-Yafet theory of spin relaxation in metals. The anomaly occurs when the quasiparticle scattering rate (in energy units) is comparable to the energy difference between the conduction and a neighboring bands. The anomalous behavior is related to the unique band structure of MgB2 and the large electron-phonon coupling. The saturating spin relaxation is the spin transport analogue of the Ioffe-Regel criterion of electron transport.
| 18,999,776
|
K-doping dependence of the Fermi surface of the iron-arsenic Ba1-xKxFe2As2 superconductor using angle-resolved photoemission spectroscopy.
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We use angle-resolved photoemission spectroscopy to investigate the electronic properties of the newly discovered iron-arsenic superconductor Ba_(1-x)K_(x)Fe_(2)As_(2) and nonsuperconducting BaFe_(2)As_(2). Our study indicates that the Fermi surface of the undoped, parent compound BaFe_(2)As_(2) consists of hole pocket(s) at Gamma (0,0) and larger electron pocket(s) at X (1,0), in general agreement with full-potential linearized plane wave calculations. Upon doping with potassium, the hole pocket expands and the electron pocket becomes smaller with its bottom approaching the chemical potential. Such an evolution of the Fermi surface is consistent with hole doping within a rigid-band shift model. Our results also indicate that the full-potential linearized plane wave calculation is a reasonable approach for modeling the electronic properties of both undoped and K-doped iron arsenites.
| 18,999,778
|
Role of reversibility in viral capsid growth: a paradigm for self-assembly.
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Self-assembly at submicroscopic scales is an important but little understood phenomenon. A prominent example is virus capsid growth, whose underlying behavior can be modeled using simple particles that assemble into polyhedral shells. Molecular dynamics simulation of shell formation in the presence of an atomistic solvent provides new insight into the self-assembly mechanism, notably that growth proceeds via a cascade of strongly reversible steps and, despite the large variety of possible intermediates, only a small fraction of highly bonded forms appear on the pathway.
| 18,999,841
|
Spin states of holes in Ge/Si nanowire quantum dots.
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We investigate tunable hole quantum dots defined by surface gating Ge/Si core-shell nanowire heterostructures. In single level Coulomb-blockade transport measurements at low temperatures spin doublets are found, which become sequentially filled by holes. Magnetotransport measurements allow us to extract a g factor g approximately 2 close to the value of a free spin-1/2 particle in the case of the smallest dot. In less confined quantum dots smaller g factor values are observed. This indicates a lifting of the expected strong spin-orbit interaction effects in the valence band for holes confined in small enough quantum dots. By comparing the excitation spectrum with the addition spectrum we tentatively identify a hole exchange interaction strength chi approximately 130 microeV.
| 18,999,847
|
Frustration, area law, and interference in quantum spin models.
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We study frustrated quantum systems from a quantum information perspective. Within this approach, we find that highly frustrated systems do not follow any general "area law" of block entanglement, while weakly frustrated ones have area laws similar to those of nonfrustrated systems away from criticality. To calculate the block entanglement in systems with degenerate ground states, typical in frustrated systems, we define a "cooling" procedure of the ground state manifold and propose a frustration degree and a method to quantify constructive and destructive interference effects of entanglement.
| 18,999,858
|
Continuous paranematic-to-nematic ordering transitions of liquid crystals in tubular silica nanochannels.
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The optical birefringence of rodlike nematogens (7CB, 8CB), imbibed in parallel silica channels with 10 nm diameter and 300 microm length, is measured and compared to the thermotropic bulk behavior. The orientational order of the confined liquid crystals, quantified by the uniaxial nematic ordering parameter, evolves continuously between paranematic and nematic states, in contrast to the discontinuous isotropic-to-nematic bulk phase transitions. A Landau-de Gennes model reveals that the strength of the orientational ordering fields, imposed by the silica walls, is beyond a critical threshold, that separates discontinuous from continuous paranematic-to-nematic behavior. Quenched disorder effects, attributable to wall irregularities, leave the transition temperatures affected only marginally, despite the strong ordering fields in the channels.
| 18,999,865
|
Presence of serum carbonic anhydrase autoantibodies in patients relapsed after autologous stem cell transplantation indicates an improved prognosis.
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Here we report patients with Hodgkin's disease and multiple myeloma, who relapsed/progressed after high dose therapy and autologous stem cell transplantation. In patients who developed aplastic anemia type syndrome, spontaneous tumor regression was observed and concomitantly high titers of serum autoantibodies were found. In order to identify the antibody specificity, two-dimensional electrophoresis, blotting and immunoreactions were used to analyze the peripheral blood stem cell extract with autoantibodies containing serum. The unique protein spot visualized exclusively by serum of patients with aplastic anemia type syndrome was identified as carbonic anhydrase I (CA I, accession No. P00915 and Q7M316) by means of mass spectrometry. The specificity of autoantibodies was confirmed by reaction with commercial CAs I, II, IX and XII. Immunoreaction in Western blots with these CA isoforms differed in sera obtained from patients with various types of the disease. Sera of Hodgkin's disease patients reacted with CA I, II and XII; sera of multiple myeloma patients reacted with the CA I, II, XII and IX. Patients developing and/or possessing CA autoantibodies had a significant survival benefit over those who did not develop CA anhydrase autoantibodies. Possible relevance of the presence of CA autoantibodies and clinical outcome is discussed.
| 18,999,876
|
Prognosis in hormon receptor negative breast cancer patients according to ERBB2 status.
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Breast carcinomas represent a heterogenous group of tumors and recent studies have demonstrated several subtypes of breast cancer by gene expression profiles. This study aimed to compare hormon receptor negative (ER-/PR-/ERBB2+) and triple negative (ER-/PR-/ERBB2-) patients in terms of prognosis and to show that molecularly defined subtypes can be distinguished by conventional laboratory methods. Patients treated between 2001-2007 for hormon receptor negative breast cancer were retrospectively studied. In addition to the conventional prognostic factors, effect of ERBB2 status of the patients on disease-free and overall survival was evaluated. Hormon receptor and ERBB2 status were determined by immunuhistochemistry and fluorescence in-situ hybridization. 141 patients were eligible for the study. Number of patients with ERBB2 positive and triple negative tumors was 70 and 71, respectively, and two groups were comparable in terms of study parameters. Tumor size, grade, axillary status, patient groups, and adjuvant chemotherapy and radiotherapy showed significant impact on disease-free survival and overall survival was significantly dependent on axillary status, type of surgery, and patient groups in univariate analysis. In multivariate analysis, patient groups, tumor grade, and axillary status were independent prognostic factors for disease-free survival whereas patient groups, extent of surgery, and axillary status were independent prognostic factors for overall survival. This study has indicated that ERBB2 negative patients had worse survival among hormon receptor negative breast cancer patients and showed that molecularly defined subtypes of breast cancer can be differentiated by immunuhistochemistry in terms of prognosis.
| 18,999,885
|
Evaluation of two gene-silencing constructs for resistance to tomato yellow leaf curl viruses in Nicotiana benthamiana plants.
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Infiltration of Agrobacterium tumefaciens into intact plant leaves of N. benthamiana was used to test the efficiency of two virus-based silencing constructs conferring resistance to the closely related begomoviruses. The constructs contained the most conserved sequences of the coat protein (CP) gene and replication-associated protein (Rep) gene of Tomato yellow leaf curl Sardinia virus (Sicily strain) (TYLCSV-[Sic]). Both constructs formed a hairpin structure that enhanced the post-transcriptional gene-silencing mechanism. When agro-infiltrated plants were challenged separately with infectious viruses TYLCSV-[Sic] and Tomato yellow leaf curl virus (TYLCV), the plants showed resistance to TYLCSV-[Sic], but not to the related TYLCV.
| 18,999,888
|
Information and consent in internet paternity testing: focus on minors' protection in Italy.
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Paternity testing in Italy is usually performed by private laboratories and universities having direct contacts with the applicants. Recently, the number of paternity tests offered through laboratory websites has increased in Italy and Europe. The execution of genetic tests, including paternity testing based on DNA analysis, represents a complex act, which contains three main steps. Paternity analyses carried out by laboratories via Internet are performed on samples collected by the applicants and then mailed back to the laboratories without any patient-physician relationship. Information is given to the subjects through the laboratory's website or mailed with the test order form. The execution of "household" DNA analysis without technical precautions may provide an incorrect response with severe consequences on the individual who has undergone testing, on the family involved, and on society in general. The problems connected with this kind of analysis are not technical, but ethical and deontological. In this work, we will discuss the problems related to information and consent by way of outlining the relevant Italian laws and codes of medical ethics. The Italian Privacy's Guarantor is assessing the ethical and legal implications, but regulations are not yet in place. We believe that adequate information related to this practice cannot be given via Internet, and, consequently, the validity of the consent expressed during this kind of procedure can be uncertain. Further, we will analyze issues regarding the importance of minors' protection when a paternity test is performed via Internet. In our opinion, the complexity of the situations and expectations linked to paternity investigations require a special sensitivity in dealing with each case, based on a patient-physician relationship in the decision-making process especially referring to the defense of the minors' well-being.
| 18,999,916
|
Prenatal diagnosis: update on invasive versus noninvasive fetal diagnostic testing from maternal blood.
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The modern obstetrics care includes noninvasive prenatal diagnosis testing such as first trimester screening performed between 11 and 14 weeks' gestation and second trimester screening performed between 15 and 20 weeks. In these screening tests, biochemical markers are measured in the maternal blood with or without ultrasound for fetal nuchal translucency with reported accuracy of up to 90%. Invasive procedures, including amniocentesis or chorionic villi sampling, are used to achieve over 99% accuracy. During these procedures direct fetal material is examined and, therefore, these tests are highly accurate with the caveat of a small risk for pregnancy loss. Much research now focuses on other noninvasive highly accurate and risk-free tests that will identify fetal material in the maternal blood. Fetal cells and fetal DNA/RNA provide fetal information but are hard to find in an overwhelming background of maternal cells and in the absence of specific fetal cell markers. The most experience has been accumulated with fetal rhesus and fetal sex determination from maternal blood, with an accuracy of up to 100% by using gene sequences that are absent from maternal blood. Although not clinically applicable yet, fetal cells, fetal DNA/RNA and fetal proteomics in combination with cutting edge technology are described to prenatally diagnose aneuploidies and single-gene disorders.
| 18,999,924
|
High expression of circadian gene mPer2 diminishes radiosensitivity of tumor cells.
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The aim of this study was to study mPeriod2 gene expression influencing the radiosensitivity of mouse tumor cells exposed to 60Co-gamma-rays. Lewis lung carcinoma (LLC) and EMT6 cells were induced by phorbol myristate acetate or transfected with pcDNA3.1-mPer2 and irradiated with 60Co-gamma-rays, then analyzed with several methods, such as flow cytometry, single-cell gel electrophoresis assay (SCGE), reverse-transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry, cell-clone-forming analysis, and so forth. In SCGE analysis, the mPer2 high-expression groups exposed to gamma-rays presented lighter DNA damage, compared with controls (p < 0.05). Clone-forming efficiency and cell-survival curve showed that cells transfected with pcDNA3.1-mPer2 formed more clones than control groups and had augmented mean lethal dose (D(0)), near field dose (Dq), decreasing extrapolation number (N), and a higher survival and clone-forming rate. RT-PCR analysis revealed a decreased expression of bax and p53, an increased expression of c-myc, bcl-2, and Rad51, and increased proportionality of bcl-2/bax, whereas p21 didn't change obviously in irradiated mPer2-transfected LLC cells. This research suggests that the circadian system is involved in the protection and restoration of tumor cells against environmental detriments, such as 60Co-gamma-ray radiographic inspection. The gene, mPer2, might be considered as an inhibitor in tumor radiotherapy.
| 18,999,929
|
Cetuximab: preclinical evaluation of a monoclonal antibody targeting EGFR for radioimmunodiagnostic and radioimmunotherapeutic applications.
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The monoclonal antibody, cetuximab, binds to epidermal growth-factor receptor and thus provides an opportunity to create both imaging and therapies that target this receptor. The potential of cetuximab as a radioimmunoconjugate, using the acyclic bifunctional chelator, CHX-A"-DTPA, was investigated. The pharmacokinetic behavior in the blood was determined in mice with and without tumors. Tumor targeting and scintigraphic imaging were evaluated in mice bearing xenografts of LS-174T (colorectal), SHAW (pancreatic), SKOV3 (ovarian), DU145 (prostate), and HT-29 (colorectal). Excellent tumor targeting was observed in each of the models with peak tumor uptakes of 59.8 +/- 18.1, 22.5 +/- 4.7, 33.3 +/- 5.7, 18.2 +/- 7.8, and 41.7 +/- 10.8 injected dose per gram (%ID/g) at 48-72 hours, respectively. In contrast, the highest tumor %ID/g obtained in mice bearing melanoma (A375) xenografts was 6.3 +/- 1.1 at 72 hours. The biodistribution of (111)In-cetuximab was also evaluated in nontumor-bearing mice. The highest %ID/g was observed in the liver (9.3 +/- 1.3 at 24 hours) and the salivary glands (8.1 +/- 2.8 at 72 hours). Scintigraphy showed excellent tumor targeting at 24 hours. Blood pool was evident, as expected, but cleared over time. At 168 hours, the tumor was clearly discernible with negligible background.
| 18,999,934
|
A virtual reality environment for patient data visualization and endoscopic surgical planning.
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Visualizing patient data in a three-dimensional (3D) representation can be an effective surgical planning tool.As medical imaging technologies improve with faster and higher resolution scans, the use of virtual reality for interacting with medical images adds another level of realism to a 3D representation. The software framework presented in this paper is designed to load and display any DICOM/PACS-compatible 3D image data for visualization and interaction in an immersive virtual environment. In "examiner" mode, the surgeon can interact with a 3D virtual model of the patient by using an intuitive set of controls designed to allow slicing, coloring,and windowing of the image to show different tissue densities and enhance important structures. In the simulated"endoscopic camera" mode, the surgeon can see through the point of view of a virtual endoscopic camera to navigate inside the patient. These tools allow the surgeon to perform virtual endoscopy on any suitable structure.The software is highly scalable, as it can be used on a single desktop computer to a cluster of computers in an immersive multiprojection virtual environment. By wearing a pair of stereo glasses, a surgeon becomes immersed within the model itself, thus providing a sense of realism, as if the surgeon is "inside" the patient.
| 18,999,974
|
Surgical performance with head-mounted displays in laparoscopic surgery.
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The difficulties of laparoscopic surgery include two-dimensional image projection and loss of alignment between the surgeon's hands and visual field. Head-mounted displays (HMDs) allow freedom from gazing at a stationary overhead monitor, thus improving ergonomics. Modern HMDs offer greatly improved image quality and reduced bulk and weight. We compared two types of HMDs with conventional overhead image display. Twelve preclinical medical students (i.e., laparoscopic novices) completed the standardized bead-passing task in a Fundamentals of Laparoscopic Surgery box trainer, using a wall-mounted monitor(WALL), a solid-state high-resolution dual full-visual graphic array (VGA) HMD (HIGH-HMD), or a lightweight commercial 1/4 VGA HMD (LOW-HMD). Participants performed each task by using the three image displays. The order in which they performed each test was randomly assigned to minimize the carryover effect.Students were then asked to grade comfort and image quality on a scale from 1 (worst) to 5 (best). Statistical comparison of the time per bead was performed with the Kruskal-Wallis test, and P < 0.05 was considered significant. Average time per bead (total beads = 12/participant/test) was 14.2 seconds for WALL, 13.2 seconds for LOW-HMD, and 12.5 seconds for HIGH-HMD (P 0.05). The comfort ratings were 3.67 +/- 0.82, 3.50 +/- 1.38,and 3.83 +/- 0.75, respectively, and image quality was rated as 3.00 +/- 0.63, 2.83 +/- 1.47 and 4.67 +/- 0.52, respectively. The high-resolution HMD offered significantly better image quality and allowed faster task performance than a lower resolution model of HMD, and both performed better than the overhead display. The high-resolution HMD was not significantly more comfortable than the low-resolution model, given its added weight. HMDs alone may only be of incremental benefit in improving performance in laparoscopic surgery.However, their greatest promise is in their combination with other advances in imaging and image manipulation technology, as they open the door to individualized image display.
| 18,999,982
|
Sixty years of nuclear moments.
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In keeping with the tradition of prefatory articles for the Annual Review of Physical Chemistry, this is an autobiographical essay describing my scientific career. I begin with my background and education at Dartmouth and Caltech and follow with my half-century of research and teaching at MIT. I emphasize subjects that I found especially interesting or important, including average Hamiltonians and the beginnings of high-resolution nuclear magnetic resonance (NMR) in solids, broadband spin decoupling in liquids, NMR at milli-Kelvin temperatures, and the exploration of basic physical principles by computer. Throughout I recall with affection my mentors, colleagues, and students.
| 18,999,988
|
The anticancer agent chaetocin is a competitive substrate and inhibitor of thioredoxin reductase.
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We recently reported that the antineoplastic thiodioxopiperazine natural product chaetocin potently induces cellular oxidative stress, thus selectively killing cancer cells. In pursuit of underlying molecular mechanisms, we now report that chaetocin is a competitive and selective substrate for the oxidative stress mitigation enzyme thioredoxin reductase-1 (TrxR1) with lower K(m) than the TrxR1 native substrate thioredoxin (Trx; chaetocin K(m) = 4.6 +/- 0.6 microM, Trx K(m) = 104.7 +/- 26 microM), thereby attenuating reduction of the critical downstream ROS remediation substrate Trx at achieved intracellular concentrations. Consistent with a role for TrxR1 targeting in the anticancer effects of chaetocin, overexpression of the TrxR1 downstream effector Trx in HeLa cells conferred resistance to chaetocin-induced, but not to doxorubicin-induced, cytotoxicity. As the TrxR/Trx pathway is of central importance in limiting cellular reactive oxygen species (ROS)--and as chaetocin exerts its selective anticancer effects via ROS imposition--the inhibition of TrxR1 by chaetocin has potential to explain its selective anticancer effects. These observations have important implications not just with regard to the mechanism of action and clinical development of chaetocin and related thiodioxopiperazines, but also with regard to the utility of molecular targets within the thioredoxin reductase/thioredoxin pathway in the development of novel candidate antineoplastic agents.
| 18,999,987
|
Ultrafast dynamics in reverse micelles.
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Recent advances in ultrafast laser technology have spurred investigations of microheterogeneous solutions. In particular, researchers have explored details of reverse micelles (RMs), which present isolated droplets of polar solvent sequestered from a continuous nonpolar phase by a surfactant layer. This review explores recent studies utilizing a variety of ultrafast laser techniques to uncover details about structure and dynamics in various RMs. Using ultrafast vibrational spectroscopy, researchers have probed hydrogen-bond dynamics and vibrational energy relaxation in RMs. These studies have developed our understanding of reverse micellar structure, identifying varying water environments in the RMs. In a plethora of experiments employing probe molecules, researchers have explored the confined environment presented by RMs and their impact on a range of chemical reactions. These studies have shown that confinement, rather than the specific interactions with surfactants, is an important factor determining the impact of the reverse micellar environment on the chemistry.
| 18,999,990
|
Principles and progress in ultrafast multidimensional nuclear magnetic resonance.
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Multidimensional acquisitions play a central role in the progress and applications of nuclear magnetic resonance (NMR) spectroscopy. Such experiments have been collected traditionally as an array of one-dimensional scans, with suitably incremented delay parameters that encode along independent temporal domains the nD spectral distribution being sought. During the past few years, an ultrafast approach to nD NMR has been introduced that is capable of delivering any type of multidimensional spectrum in a single transient. This method operates by departing from the canonical nD NMR scheme and by replacing its temporal encoding with a series of spatial manipulations derived from magnetic resonance imaging. The present survey introduces the main principles of this subsecond approach to spectroscopy, focusing on the applications that have hitherto been demonstrated for single-scan two-dimensional NMR in different areas of chemistry.
| 18,999,994
|
Current research in preterm birth.
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Preterm birth is one of the leading causes of infant mortality and the leading cause of infant morbidity in the United States. It accounts for >70% of neonatal deaths and almost half of long-term neurological disabilities. The Centers for Disease Control and Prevention (CDC) is collaborating with state health departments, universities, communities, and healthcare providers to understand why preterm births occur and how to address preterm birth risk factors. These collaborations include identification of genetic and other biological markers for the early detection of women at high risk of preterm birth; improving understanding of the relationships among psychosocial stress, immune and inflammatory responses, and preterm risk; and designing community strategies to improve the health of pregnant women. By conducting public health research activities that explore the genetic, biological, clinical, behavioral, social, and community determinants of preterm birth, CDC will continue to elucidate the complex interactions of these factors and how they influence preterm birth.
| 19,000,029
|
Polish medical students' perceptions of the nursing profession: a cross-sectional study.
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This study explored perceptions of the nursing profession held by medical students in Poland. Specifically, this study aimed to: (i) elicit medical students' opinions about the nursing profession; (ii) identify what skills and abilities they perceive as important for nurses and (iii) ascertain what nursing functions are considered a major component of the nurse's job. A cross-sectional study, based on the social construct of role theory, was conducted in medical universities from 2005 to 2006 in three cities situated in different regions of Poland: Białystok, Bydgoszcz and Kraków. A total of 900 medical students, 300 students in each region, in medical school years 1, 3 and 6 completed the Professional Nursing Image Survey. The most favourable nurse characteristics were: 'professional reliability', 'demonstration of good technical skills' and the personal characteristics of friendliness and courteousness. Medication administration, recording vital signs and administering intravenous therapy were most frequently identified as a major part of the nurses' role. In conclusion, the opinions of Polish medical students suggest that nursing therapeutic activities trump independent nursing practice activities.
| 19,000,084
|
Exercising impressive impressions: the exercise stereotype in male targets.
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The main purpose of this study was to investigate the exercise stereotype and the non-exerciser stereotype on male targets, and the moderating effects of impression motivation in 184 female and 73 male Swedish undergraduate students. The participants read a description of one of the following male targets: a typical exerciser, an active living target, an excessive exerciser, a non-exerciser, or a control target, and then rated these targets on 12 personality (e.g. lazy-hard worker, dependent-independent) and eight physical (e.g. scrawny-muscular, sick-healthy) dimensions. They also completed the Impression Motivation scale of the Self-Presentation in Exercise Questionnaire, measuring motivation to self-present as an exerciser. MANCOVAs demonstrated a significant main effect for both personality and physical attributes (P<0.05). Overall, the typical exerciser, the active living target, and the excessive targets received more positive ratings than, in particular the non-exerciser target but also the control target. The non-exerciser target was rated less favorably compared with the control target. The impression motivation of the participants moderated the exercise status/rating relationship for the physical but not the personality attributes. The results of the study are discussed in the context of gender and cultural aspects of the exercise stereotype phenomenon.
| 19,000,098
|
Mouth rinse but not ingestion of a carbohydrate solution improves 1-h cycle time trial performance.
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The aim of the present study was to further explore the influence of ingestion and mouth rinse with a carbohydrate-electrolyte solution (CES) on the performance during a approximately 1 h high-intensity time trial on trained subjects. Subjects rinsed around the mouth or ingested a 6% isotonic CES or placebo (14 mL/kg body weight) before and throughout a time trial in which they had to accomplish a set amount of work (975+/-85 kJ) as quickly as possible. In the mouth rinse conditions, time to complete the test was shorter (P=0.02) with CES (61.7+/-5.1 min) than with placebo (64.1+/-6.5 min), whereas in the ingestion conditions, there was no difference between placebo (62.5+/-6.9 min) and CES (63.2+/-6.9 min). Although power output and lactate concentration during exercise were significantly higher when subjects rinsed their mouth with CES compared with placebo, the rating of perceived exertion values did not differ. Blood glucose concentration increased after ingestion of but not after mouth rinse with CES. The interesting finding of the present study is that rinsing the mouth with but not ingestion of CES resulted in improved performance.
| 19,000,099
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Do anthropometric and fitness characteristics vary according to birth date distribution in elite youth academy soccer players?
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We examined whether maturity, anthropometric profiles and fitness measures vary according to birth date distribution in elite, under-14 youth academy soccer players. The selection year was divided into four quarters, with 160 male players grouped according to individual birth date. Players had their skeletal age determined and were assessed using a battery of standard anthropometric and physical performance tests. Players born across all quarters of the year were investigated for differences in the various performance characteristics using multi- and univariate analyses. An uneven birth distribution was observed, with players born early in the selection year highly represented (P<0.01). A significant difference in height was observed across quarters (P<0.01) with higher values reported in the earlier-born players. No significant differences were observed across any of the fitness measures, although the trend was for players born in the first quarter to out-perform peers born in the later quarters. These findings suggest that the relative age of the performer may not always be linked to a significant advantage in physical components. The selection criteria for entry into the academy may explain the present results.
| 19,000,100
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Identification of a new HLA DRB1 allele (HLA-DRB1*1167) in a potential hematopoietic stem cell donor from Iraqi Kurdistan.
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High-resolution polymerase chain reaction sequence-specific primer typing and sequence-based typing of the human leukocyte antigen (HLA) gene DRB1 in a potential hematopoietic stem cell donor of Kurdish ethnicity revealed a new allelic variant of HLA-DRB1*11. The sequence was named DRB1*1167, and comparison with previously described DRB1 alleles demonstrated a mixed pattern shared with some DRB1*08 alleles.
| 19,000,134
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Structural aspects of B*4617 molecule, a novel HLA-B*46 allele identified by sequence-based typing.
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New allele B*4617 showed one nucleotide difference with B*460101 at codon 167 (TGG-->TCG).
| 19,000,137
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Genetic association between functional haplotype of collagen type III alpha 1 and chronic hepatitis B and cirrhosis in Koreans.
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Collagen type III alpha 1 (COL3A1) is one of the extracelluar matrix (ECM) proteins. The expression of COL3A1 is closely related to chronic liver diseases. In this study, we investigated whether single nucleotide polymorphisms (SNPs) of COL3A1 confer genetic susceptibility to patients with hepatitis B virus-infected liver diseases including chronic hepatitis B (CH), liver cirrhosis (CIR), and hepatocellular carcinoma (HCC). A total of 399 Korean (KOR) people, 111 patients with CH, 95 patients with CIR, 86 patients with HCC, and 107 spontaneously recovery, were genotyped for 16 SNPs of the COL3A1 gene. The 'A' allele of rs3106796 was highly associated with the CH [odds ratio (OR) = 1.62, P = 0.01], CIR (OR = 1.67, P = 0.01), and HCC (OR = 1.59, P = 0.03). There were six polymorphic SNPs that could be divided into two linkage disequilibrium (LD) blocks. The haplotype pattern of the KOR control seems to be similar to the patterns displayed in the Japanese, Chinese, and Caucasian populations sampled in the International HapMap project. Haplotype 3 (A-G-A) of the LD block 2 was significantly associated with CH (OR = 2.23, P = 0.02), CIR (OR = 2.24, P = 0.03), and HCC (OR = 2.27, P = 0.03). Moreover, diplotype analysis showed that they had increased relative risk for CH and CIR in the two diplotypes, dt3 (A-G-A/G-G-A; OR = 4.05, P = 0.01) and dt6 (A-A-A/A-G-A; OR = 7.42, P = 0.01 and OR = 5.84, P = 0.05) against dt1 (G-G-A/G-G-A), the most common diplotype in both KOR groups. In vitro reporter gene assays showed that the constructs containing the 'G' allele of rs3106796 appear to exert lower transcriptional activity of COL3A1 than the 'A' allele, depending on the promoter types.
| 19,000,145
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Unusual presentation of Ramsay Hunt syndrome in renal transplant patients: case report and literature review.
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Ramsay Hunt syndrome (RHS) is a rare manifestation of varicella zoster virus (VZV) infection that accounts for around 12% of all cases of facial paralysis. Although it is more common in immunosuppressed individuals, it has not been yet reported in kidney transplant recipients. We describe the case of a 41-year-old man with a history of renal transplant for whom the diagnosis and treatment of RHS were delayed owing to an unusual presentation. We also review the literature on VZV infection in renal transplant patients.
| 19,000,154
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VH1/BRL2 receptor-like kinase interacts with vascular-specific adaptor proteins VIT and VIK to influence leaf venation.
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VH1/BRL2 is a receptor-like kinase of the BRI1 family with a role in vascular development. In developing Arabidopsis leaves it is expressed first in ground cells and then becomes restricted to provascular and procambial cells as venation forms. We isolated proteins interacting with the activated (phosphorylated) cytoplasmic domain of VH1/BRL2, and found that most belong to three processes: proteasome activity, vesicle traffic and intracellular signal transduction. Two adaptor proteins are included that we named VIT [VH1-interacting tetratricopeptide repeat (TPR)-containing protein] and VIK (VH1-interacting kinase), which are co-expressed in the same cells as VH1/BRL2 at two distinct time points in vein differentiation. Mutation of either adaptor or of VH1 results in vein pattern defects and in alterations in response to auxin and brassinosteroids. We propose that these two adaptors facilitate the diversification and amplification of a ligand signal perceived by VH1/BRL2 in multiple downstream pathways affecting venation.
| 19,000,166
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Arabidopsis mitogen-activated protein kinase MPK12 interacts with the MAPK phosphatase IBR5 and regulates auxin signaling.
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Mitogen-activated protein kinase (MAPK) phosphatases are important negative regulators in the MAPK signaling pathways responsible for many essential processes in plants, including development, stress management and hormonal responses. A mutation in INDOLE-3-BUTYRIC ACID-RESPONSE5 (IBR5), which is predicted to encode a dual-specificity MAPK phosphatase, was previously reported to confer reduced sensitivity to auxin and ABA in Arabidopsis roots. To further characterize IBR5, and to understand how it might help integrate MAPK cascades with hormone signaling, we searched for IBR5-interacting MAPKs. Yeast two-hybrid assays, in vitro binding assays and in vivo protein co-immunoprecipitation studies demonstrated that MPK12 and IBR5 are physically coupled. The C-terminus of MPK12 appears to be essential for its interaction with IBR5, and in vitro dephosphorylation and immunocomplex kinase assays indicated that activated MPK12 is efficiently dephosphorylated and inactivated by IBR5. MPK12 and IBR5 mRNAs are both widely expressed across Arabidopsis tissues, and at the subcellular level each protein is predominantly localized in the nucleus. In transgenic plants with reduced expression of the MPK12 gene, root growth is hypersensitive to exogenous auxins, but shows normal ABA sensitivity. MPK12 suppression in an ibr5 background partially complements the ibr5 auxin-insensitivity phenotype. Our results demonstrate that IBR5 is a bona fide MAPK phosphatase, and suggest that MPK12 is both a physiological substrate of IBR5 and a novel negative regulator of auxin signaling in Arabidopsis.
| 19,000,167
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Efficacy of topical PUVA soaks for palmoplantar dermatoses: an audit.
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With a lack of evidence base for individual topical PUVA protocols, treatment is presently based on the consensus of current practice. This audit was designed to investigate the effectiveness of topical PUVA for palmoplantar dermatoses. Phototherapy notes were reviewed on all patients who received hand and/or foot PUVA 2002-2007 in the Northern Health and Social Care Trust (NHSCT), Northern Ireland. Thirty patients met the inclusion criteria for the study. The mean number of treatments, maximum single UVA dose, and cumulative dose, were 18.4, 4.2 J/cm2, and 48.3 J/cm2, respectively. A positive response to treatment occurred in 51.3% of patients, which fell short of the 70% standard set. In a multivariate logistic regression analysis, number of treatments (P=0.04) and maximum single UVA dose (P=0.03) were the only variables associated with positive treatment outcome. The response was not influenced significantly by skin type, concurrent topical treatments, or cumulative UVA dose. Limitations to the study: Small patient numbers may have prevented the statistical significance of individual variables. UV dose increments should be clearly defined to avoid excess caution at the expense of an adequate patient response, and a minimum of 20 treatments administered to all patients, if tolerated.
| 19,000,183
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Evidence-based outcomes in pain research and clinical practice.
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The growing emphasis on evidence-based medicine dictates that reliable, evidence-based outcomes be utilized in documenting response to treatment, as well as determining the treatment efficacy and cost-effectiveness of different treatment modalities. The biopsychosocial model conceptualizes pain as a complex multifactorial interaction of biological, psychological, and social components that play a role in the development, exacerbation, and perpetuation of pain. As a result, outcomes relevant to pain management are necessarily complex and multifactorial in nature. Two broad categories of evidence-based outcomes relevant to pain management are discussed: patient-reported outcomes and objective outcomes. Patient-reported outcomes are discussed within the context of pain measures, health-related quality of life, and psychological constructs. Objective outcomes are discussed within the context of healthcare utilization and occupational status. The discussion within each section highlights the unique constructs measured by each category of outcome measure and highlights their consistency with current evidence-based guidelines and knowledge from pain research.
| 19,000,173
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RcDhn5, a cold acclimation-responsive dehydrin from Rhododendron catawbiense rescues enzyme activity from dehydration effects in vitro and enhances freezing tolerance in RcDhn5-overexpressing Arabidopsis plants.
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Dehydrins (DHNs) are typically induced in response to abiotic stresses that impose cellular dehydration. As extracellular freezing results in cellular dehydration, accumulation of DHNs and development of desiccation tolerance are believed to be key components of the cold acclimation (CA) process. The present study shows that RcDhn5, one of the DHNs from Rhododendron catawbiense leaf tissues, encodes an acidic, SK(2) type DHN and is upregulated during seasonal CA and downregulated during spring deacclimation (DA). Data from in vitro partial water loss assays indicate that purified RcDhn5 protects enzyme activity against a dehydration treatment and that this protection is comparable with acidic SK(n) DHNs from other species. To investigate the contribution of RcDhn5 to freezing tolerance (FT), Arabidopsis plants overexpressing RcDhn5 under the control of 35S promoter were generated. Transgenic plants exhibited improved 'constitutive' FT compared with the control plants. Furthermore, a small but significant improvement in FT of RcDhn5-overexpressing plants was observed after 12 h of CA; however, this gained acclimation capacity was not sustained after a 6-day CA. Transcript profiles of cold-regulated native Arabidopsis DHNs (COR47, ERD10 and ERD14) during a CA time-course suggests that the apparent lack of improvement in cold-acclimated FT of RcDhn5-overexpressing plants over that of wild-type controls after a 6-day CA might have been because of the dilution of the effect of RcDhn5 overproduction by a strong CA-induced expression of native Arabidopsis DHNs. This study provides evidence that RcDhn5 contributes to freezing stress tolerance and that this could be, in part, because of its dehydration stress-protective ability.
| 19,000,195
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The devil you know: neuroticism predicts neural response to uncertainty.
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Individuals differ in the extent to which they respond negatively to uncertainty. Although some individuals feel little discomfort when facing the unknown, those high in neuroticism find it aversive. We examined neurophysiological responses to uncertainty using an event-related potential framework. Participants completed a time-estimation task while their neural activity was recorded via electroencephalography. The feedback-related negativity (FRN), an evoked potential that peaks approximately 250 ms after the receipt of feedback information, was examined under conditions of positive, negative, and uncertain feedback. The magnitude of these responses was then analyzed in relation to individual differences in neuroticism. As expected, a larger FRN was observed after negative feedback than after positive feedback for all participants. For individuals who scored highly on trait neuroticism, however, uncertain feedback produced a larger neural response than did negative feedback. These results are discussed in terms of affective responses to uncertainty among neurotic individuals.
| 19,000,202
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Black + white = black: hypodescent in reflexive categorization of racially ambiguous faces.
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Historically, the principle of hypodescent specified that individuals with one Black and one White parent should be considered Black. Two experiments examined whether categorizations of racially ambiguous targets reflect this principle. Participants studied ambiguous target faces accompanied by profiles that either did or did not identify the targets as having multiracial backgrounds (biological, cultural, or both biological and cultural). Participants then completed a speeded dual-categorization task requiring Black/not Black and White/not White judgments (Experiments 1 and 2) and deliberate categorization tasks requiring participants to describe the races (Experiment 2) of target faces. When a target was known to have mixed-race ancestry, participants were more likely to rapidly categorize the target as Black (and not White); however, the same cues also increased deliberate categorizations of the targets as "multiracial." These findings suggest that hypodescent still characterizes the automatic racial categorizations of many perceivers, although more complex racial identities may be acknowledged upon more thoughtful reflection.
| 19,000,204
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Which thoughts count? Algorithms for evaluating satisfaction in relationships.
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Individuals differ in both their motivation to obtain incentives in their relationships (approach goals) and their motivation to dampen the threats in their relationships (avoidance goals). When evaluating relationship satisfaction, individuals with strong approach goals should weigh positive features in their relationships more heavily than do individuals low in approach goals, and individuals with strong avoidance social goals should weigh negative features more than do individuals with weaker avoidance social goals. In a study testing this idea, participants were randomly signaled several times a day to report their positive (passion) and negative (insecurity) thoughts about their current romantic partner. At the end of the day, they reported their overall relationship satisfaction. The results confirmed the hypotheses: Algorithms used to assess relationship satisfaction differ as a function of goal strength. We discuss the results not in terms of biases in subjective evaluation, but rather in terms of variations in the very definition of satisfaction.
| 19,000,214
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Effect of weaning to oestrus interval and equine chorionic gonadotropin on vaginal electrical impedance during peri-oestrus in sows.
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The influence of weaning to oestrus interval, its interaction with parity and equine chorionic gonadotropin (eCG) on changes of vaginal impedance in sows after weaning was examined. The impedance measurements were carried out by a four-terminal method. Sows were monitored for oestrus via exposure to a sexually mature boar. The interval from weaning to oestrus was longer in primiparous than multiparous sows (p<0.01). A significant negative correlation was found between the interval from weaning to oestrus and parity. Repeated measures analysis showed that the interval from weaning to oestrus and parity and their interactions had a significant effect on the vaginal impedance in peri-oestrus. The vaginal impedance during pro-oestrus gradually decreased in all groups of sows with the weaning to oestrus interval from 4 to 8 days (p<0.05). In the subsequent period, the vaginal impedance increased and was significantly lower from 1 to 3 days after oestrus onset in sows with the weaning to oestrus interval 7-8 days than 4-6 days. Similarly, the vaginal impedance during pro-oestrus gradually decreased in all groups of sows with parity 1-5 (p<0.01). In the next period, the vaginal impedance increased and was significantly lower from 2-3 days after oestrus onset in sows of parity 1 than parity 2-5. Repeated measures analysis showed that eCG treatment had a significant effect on the vaginal impedance in peri-oestrus. Sows treated with eCG displayed the decrease and increase of vaginal impedance due to oestrus onset earlier than untreated sows. The results indicate that the weaning to oestrus interval, its interaction with parity and eCG markedly affect the vaginal impedance in sows during peri-oestrus.
| 19,000,219
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Physical activity and healthy eating in the after-school environment.
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No research to date has extensively described moderate and vigorous physical activity (MVPA) and healthful eating (HE) opportunities in the after-school environment. The current study described the quality of the after-school environment for its impact on children's MVPA and HE. An alliance of 7 elementary schools and Boys and Girls Clubs who worked with the Cooperative Extension Service in Lawrence, KS, was selected to participate in a larger intervention study. After-school settings were observed for information regarding session type, session context, leader behavior, physical activity, and snack quality using validated instruments such as the System for Observing Fitness Instruction Time. Data presented are baseline measures for all sites. Participating children (n = 144) were primarily non-Hispanic white (60%) and in fourth grade (69%). After-school sites offered 4 different sessions per day (active recreation, academic time, nonactive recreation, and enrichment activities). Children were provided with a daily snack. On 36% of the days observed, this snack included fruit, fruit juice, or vegetables. There was significantly more time spent in MVPA during free play sessions (69%) compared to organized adult-led sessions (51%). There was also significantly more discouragement of physical activity during organized adult-led sessions (29%) as compared to the free play sessions (6%). The quality of after-school programs can be improved by providing fruits and vegetables as snacks; offering more free play activities; training the after-school staff in simple, structured games for use in a variety of indoor and outdoor settings; and training after-school staff to promote and model MVPA and HE in and out of the after-school setting.
| 19,000,239
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Remission of diabetes mellitus in cats with diabetic ketoacidosis.
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Diabetic ketoacidosis (DKA) has long been considered a key clinical feature of type-1 diabetes mellitus (DM) in humans although. An increasing number of cases of ketoacidosis have been reported in people with type-2 DM. Cats initially diagnosed with DKA can achieve remission from diabetes. Cats with DKA and diabetic remission are more likely to have been administered glucocorticoids before diagnosis. Twelve cats with DKA and 7 cats with uncomplicated DM. Retrospective case review. Medical records of cats presenting with DKA or DM were evaluated. Diabetic remission was defined as being clinically unremarkable for at least 1 month after insulin withdrawal. The cats were assigned to 1 of 3 groups: (1) cats with DKA and diabetic remission; (2) cats with DKA without diabetic remission; and (3) cats with DM and diabetic remission. Seven cats with DKA had remission from diabetes. These cats had significantly higher concentrations of leukocytes and segmented neutrophils, and significantly lower concentrations of eosinophils in blood and had pancreatic disease more often than did cats with uncomplicated DM and diabetic remission. With regard to pretreatment, 3/7 cats in group 1, 1/5 cats in group 2, and 1/7 cats in group 3 had been treated with glucocorticoids. Remission of DM in cats presenting with DKA is possible. Cats with DKA and remission have more components of a stress leucogram, pancreatic disease, and seemed to be treated more often with glucocorticoids than cats with uncomplicated DM and diabetic remission.
| 19,000,245
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Phase I dose escalation of single-agent vinblastine in dogs.
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Vinblastine (VBL) is commonly used in dogs at a dosage of 2.0 mg/m2. The minimal toxicity observed at this dosage indicates that higher dosages might be well tolerated. The maximum tolerated dosage (MTD) for a single VBL treatment is higher than the previously published dosage of 2.0 mg/m2. Twenty-three dogs with lymphoma or cutaneous mast cell tumors. Dogs received 1 single-agent VBL treatment IV. The starting dosage was 3.0 mg/m2, and dosages were increased in increments of 0.5 mg/m2 in cohorts of 3 dogs. Hematologic toxicity was assessed with weekly CBCs. Gastrointestinal toxicity was assessed from medical histories from owners. Once the MTD was determined, additional dogs were treated with VBL at that dosage. Dogs whose cancers responded to VBL continued to receive treatments q2-3 weeks. VBL dosages ranged from 3.0 to 4.0 mg/m2. Neutropenia was the dose-limiting toxicity, with the nadir identified 7 days after treatment and resolving by 14 days after treatment. The MTD was 3.5 mg/m2. Sixteen dogs were treated at this dosage, and 3 experienced severe toxicity characterized by asymptomatic grade 4 neutropenia, febrile grade 4 neutropenia, and death. Gastrointestinal toxicity was mild and self-limiting. Preliminary evidence of antitumor activity was identified in 2 of 12 dogs with lymphoma treated at the MTD. In dogs, single-agent VBL is well tolerated at a dosage of 3.5 mg/m2 IV. At this dosage, the minimum safe treatment interval is q2 weeks, and adjunct treatment with prophylactic antibiotics should be considered.
| 19,000,250
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Disposition and safety of zonisamide after intravenous and oral single dose and oral multiple dosing in normal hound dogs.
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The purpose of this study was to determine an oral dosing regimen of zonisamide in healthy dogs such that therapeutic concentrations would be safely reached and maintained at steady-state. Adult hound dogs (n = 8) received a single IV (6.9) and an oral (PO) dose (10.3 mg/kg) using a randomized cross-over design. Zonisamide was then administered at 10.3 mg/kg PO every 12 h for 8 weeks. Zonisamide was quantitated in blood compartments or urine by HPLC and data were subjected to noncompartmental pharmacokinetic analysis. Comparisons were made among blood compartments (one-way anova; P </= 0.05). Differences among blood compartments occurred in all derived pharmacokinetic paramenters for each route of administration after single and multiple dosing. After single PO dosing, plasma C(max) was 14.4 +/- 2.3 mcg/mL and elimination half-life was 17.2 +/- 3.6 h. After IV dosing, volume of distribution was 1.1 +/- 0.25 L/kg, clearance was 58 +/- 11 mL/h/kg and elimination t(1/2) was 12.9 +/- 3.6 h. Oral bioavailability was 68 +/- 12%; fraction of unbound drug approximated 60%. At steady-state (4 days), differences occurred for for all parameters except C(max) and C(min.) Plasma C(max) at steady-state was 56 +/- 12 mcg/mL, with 10% fluctuation between C(max) and C(min.) Plasma t(1/2) (h) was 23.52 +/- 5.76 h. Clinical laboratory tests remained normal, with the exception of total T4, which was below normal limits at study end. In conclusion, 10 mg/kg twice daily results in peak plasma zonisamide which exceeds the recommended human therapeutic range (10 to 40 microg/mL) and is associated with suppression of thyroid hormone synthesis. A reasonable b.i.d starting dose for canine epileptics would be 3 mg/kg. Zonisamide monitored in either serum or plasma should be implemented at approximately 7 days.
| 19,000,278
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Milk feeding and dietary patterns predict weight and fat gains in infancy.
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Current guidelines recommend that infants are exclusively breast fed for the first 6 months of life, with particular solid foods being gradually introduced from 6 months. Our objective was to compare the growth of infants whose feeding most closely followed current guidelines with the growth of infants with other feeding practices. Participants were 1740 infants in a prospective cohort study in Southampton, UK. At 6 and 12 months, infants' milk feeding was recorded, diets assessed using food frequency questionnaires (FFQ), and anthropometry performed. Principal components analysis was used to identify patterns of foods in the diet using the food intakes assessed by the FFQs. Two patterns ('infant guidelines' and 'adult foods') explained most variance in infant diet at 6 and 12 months of age. The main outcomes were conditional growth in weight, length and skinfold thickness from 0-6 and 6-12 months. Infants who were breast fed from 0-6 months gained weight, length and adiposity more slowly than formula-fed infants, independent of age at introduction of solids and maternal factors: compared with infants who were breast fed from 0-6 months, formula-fed infants gained 0.21 standard deviation scores (SDS) in weight [95% confidence interval (CI) 0.00, 0.42]. Infants whose dietary pattern was most similar to current feeding guidelines, with high frequencies of fresh fruit and vegetables, home-prepared foods and breast milk, gained weight and skinfold thickness more rapidly from 6 to 12 months than other infants, independent of milk feeding, age at introduction of solids and maternal factors. Compared with infants in the lowest quarter, infants in the highest 'infant guidelines' score quarter gained 0.24 SDS [95% CI 0.06, 0.43] in weight and 0.26 SDS [95% CI 0.07, 0.45] in skinfold thickness. Conversely, infants whose diets had the highest frequencies of breads and processed foods gained weight less rapidly from 6 to 12 months than other infants. The extent to which the patterns of diet and growth we have described will influence the current or later health of infants is unknown. We are following up the infants in this study to assess the impact of these patterns beyond the first year of life. These associations should also be examined in other settings and populations.
| 19,000,296
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Assays with lower detection limits: implications for epidemiological investigations.
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Epidemiological investigations of health effects related to chronic low-level exposures or other circumstances often face the difficult task of dealing with levels of biomarkers that are hard to detect and/or quantify. In these cases instrumentation may not adequately measure biomarker levels. Reasons include a failure of instruments to detect levels below a certain value or, alternatively, interference by error or 'noise'. Current laboratory practice determines a 'limit of detection (LOD)', or some other detection threshold, as a function of the distribution of instrument 'noise'. Although measurements are produced above and below this threshold in many circumstances, rather than numerical data, all points observed below this threshold may be reported as 'not detected'. The focus of this process of determination of the LOD is instrument noise and avoiding false positives. Moreover, uncertainty is assumed to apply only to the lowest values, which are treated differently from above-threshold values, thereby potentially creating a false dichotomy. In this paper we discuss the application of thresholds to measurement of biomarkers and illustrate how conventional approaches, though appropriate for certain settings, may fail epidemiological investigations. Rather than automated procedures that subject observed data to a standard threshold, the authors advocate investigators to seek information on the measurement process and request all observed data from laboratories (including the data below the threshold) to determine appropriate treatment of those data.
| 19,000,298
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Mental health of refugees following state-sponsored repatriation from Germany.
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In recent years, Voluntary Assisted Return Programmes (VARPs) have received increasing funding as a potential way of reducing the number of refugees in EU member states. A number of factors may affect the mental well-being of returnees. These include adjustment to the home country following return, difficult living conditions, and long-term effects resulting from the severe traumatic stress that had originally driven the affected out of their homes. Little is known about the extent to which these and other factors may promote or inhibit the willingness of refugees to return to their country of origin. The present pilot study investigated refugees who returned to their country of origin after having lived in exile in Germany for some 13 years. Forty-seven VARP participants were interviewed concerning their present living conditions, their views of their native country, and their attitudes towards a potential return prior to actually returning. 33 participants were interviewed nine months after returning to their country of origin. Mental health and well-being were assessed using the questionnaires Posttraumatic Stress Diagnostic Scale (PDS) and EUROHIS and the structured Mini International Neuropsychiatric Interview (M.I.N.I.).Our objectives were to examine the mental health status of refugees returning to their home country following an extended period of exile. We also aimed to assess the circumstances under which people decided to return, the current living conditions in their home country, and retrospective returnee evaluations of their decision to accept assisted return. Prior to returning to their home country, participants showed a prevalence rate of 53% for psychiatric disorders. After returning, this rate increased to a sizeable 88%. Substantial correlations were found between the living situation in Germany, the disposition to return, and mental health. For two thirds of the participants, the decision to return was not voluntary. Psychological strain among study participants was of a considerable magnitude. As a result of traumatic stress experienced during war and refuge, victims were vulnerable and not well equipped to cope with either post-migration stressors in exile or with a return to their country of origin. It is noteworthy that the majority returned under pressure from immigration authorities. Living conditions after return (such as housing, work, and health care) were poor and unstable. Participants also had great difficulty readapting to the cultural environment after having lived abroad for an average of 13 years. Current VARPs do not take these factors into account and are therefore not able to assist in a humanitarian reintegration of voluntary returnees.
| 19,000,300
|
Timing of supplementation of selenium and isoflavones determines prostate cancer risk factor reduction in rats.
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High dietary intake of selenium or isoflavones reduces risk factors for prostate cancer. We tested whether combined supplementation of these two dietary components would reduce prostate cancer risk factors in rats more than supplementation of each component individually. Male Noble rat pups were exposed from conception to diets containing an adequate (0.33-0.45 mg/kg diet) or high (3.33-3.45 mg/kg) concentration of selenium as Se-methylselenocysteine and a low (10 mg/kg) or high (600 mg/kg) level of isoflavones in a 2 x 2 factorial design. Pups consumed their respective diets until sacrifice at 35, 100, or 200 days. Male Noble rat breeders, whose exposure to the diets began after puberty, were sacrificed at 336 days. Rats were weighed biweekly. Blood was collected at the time of sacrifice and body fat and prostates were dissected and weighed. Serum levels of leptin, IGF-1, and testosterone were determined using ELISA kits. Serum levels of isoflavones were assayed by GC/MS. Liver activity of selenium-dependent glutathione peroxidase 1 was measured as an indicator of selenium status. Serum isoflavone concentrations were nearly 100-fold higher at 35 days of age (1187.1 vs. 14.4 ng/mL, mean +/- SD) in pups fed the high vs. low isoflavone diets, and remained so at 100 and 200 days, and in breeders. There were no dietary differences in liver glutathione peroxidase activity in pups or breeders. High isoflavone intake significantly (p = 0.001-0.047) reduced body weight in rat pups from 35 days onward, but not in breeders. Body fat and leptin were likewise significantly reduced by high isoflavones in pups while effects in breeders were less pronounced but still significant. High intake of Se and isoflavones each decreased serum IGF-1 in pups at 100 and 200 days, but not in breeders. No consistent dietary effects were observed on serum testosterone or relative weights of prostates. In pups, the combination of high isoflavones and high selenium produced the lowest weight gain, the lowest serum leptin, and the lowest serum IGF-1 concentrations of all four diets. Combined intake of high selenium and high isoflavones may achieve greater chemopreventive effects than either compound individually. The timing of supplementation may determine the significance of its effects.
| 19,000,315
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Large vestibular aqueduct syndrome and endolymphatic hydrops: two presentations of a common primary inner-ear dysfunction?
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To present the theory that large vestibular aqueduct syndrome (i.e. the recognised existence of an enlarged vestibular aqueduct with progressive sensorineural hearing loss) and endolymphatic hydrops are due to a common primary dysfunction of inner-ear fluid homeostasis. Case report and review of the world literature concerning large vestibular aqueduct syndrome and endolymphatic hydrops. We report a family in which one sibling suffered from large vestibular aqueduct syndrome while the other had classic Ménière's disease. This suggests that large vestibular aqueduct syndrome and endolymphatic hydrops, in some cases, may be due to a common primary dysfunction of inner-ear fluid homeostasis. To our knowledge, this is the first report in the world literature to postulate that variation in the relative compliance of inner-ear membranes could be the factor that determines the manifestation of the disorder as either endolymphatic hydrops or large vestibular aqueduct syndrome.
| 19,000,343
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Effects of intestinal constituents and lipids on intestinal formation and pharmacokinetics of desethylamiodarone formed from amiodarone.
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To model the impact of intestinal components associated with a high fat meal on metabolism of amiodarone, rat everted intestinal sacs were evaluated for their ability to metabolize the drug to its active metabolite (desethylamiodarone) under a variety of conditions. The preparations were obtained from fasted rats or rats pretreated with 1% cholesterol in peanut oil. After isolation of the tissues, the intestinal segments were immersed in oxygenated Krebs Henseleit buffer containing varying concentrations of bile salts, cholesterol, lecithin and lipase with or without soybean oil emulsion as a source of triglycerides. Amiodarone uptake was similar between the five 10-cm segments isolated distally from the stomach. Desethylamiodarone was measurable in all segments. Based on the metabolite-to-drug concentration ratio within the tissues, there was little difference in metabolic efficiency between segments for any of the treatments. Between treatments, however, it appeared that the lowest level of metabolism was noted in rats pretreated with 1% cholesterol in peanut oil. This reduction in metabolic efficiency was not observed in gut sacs from the fasted rats to which soybean oil emulsion was directly added to the incubation media. Despite the apparent reduction in intestinal metabolism, there was no apparent change in the ratio of metabolite-to-drug area under the plasma concentration versus time ratios of fasted rats and those given 1% cholesterol in peanut oil, suggesting that the intestinal presystemic formation of desethylamiodarone is not substantial.
| 19,000,367
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Modulating effect of polyethylene glycol on the intestinal transport and absorption of prednisolone, methylprednisolone and quinidine in rats by in-vitro and in-situ absorption studies.
|
The effects of polyethylene glycol 20000 (PEG 20000) on the intestinal absorption of prednisolone, methylprednisolone and quinidine, three P-glycoprotein (P-gp) substrates, across the isolated rat intestinal membranes were examined by an in-vitro diffusion chamber system. The serosal-to-mucosal (secretory) transport of these P-gp substrates was greater than their mucosal-to-serosal (absorptive) transport, indicating that their net movement across the intestinal membranes was preferentially in the secretory direction. The polarized secretory transport of these drugs was remarkably diminished and their efflux ratios decreased in the presence of PEG 20000. In addition, PEG 20000 did not affect the transport of Lucifer yellow, a non-P-gp substrate. The intestinal membrane toxicity of PEG 20000 was evaluated by measuring the release of alkaline phosphatase (ALP) and protein from the intestinal membranes. The release of ALP and protein was enhanced in the presence of 20 mM sodium deoxycholate (NaDC), a positive control, while these biological parameters did not change in the presence of 0.1-5% (w/v) PEG 20000. These findings indicated that the intestinal membrane damage caused by PEG 20000 was not a main reason for the enhanced absorptive transport of these P-gp substrates in the presence of PEG 20000. Furthermore, the transepithelial electrical resistance (TEER) of rat jejunal membranes in the presence or absence of PEG 20000 was measured by a diffusion chamber method. PEG 20000 (0.1-5.0 % w/v) did not change the TEER values of the rat jejunal membranes, indicating that the increase in the absorptive transport of these P-gp substrates might not be due to the increased transport of these P-gp substrates via a paracellular pathway caused by PEG 20000. Finally, the effect of PEG 20000 on the intestinal absorption of quinidine was examined by an in-situ closed-loop method. The intestinal absorption of quinidine was significantly enhanced in the presence of 0.1-1.0% (w/v) PEG 20000. These findings suggest that PEG 20000 might be a useful excipient to improve the intestinal absorption of quinidine, which is mainly secreted by a P-gp-mediated efflux system in the intestine.
| 19,000,368
|
The effect of high glucose on SERT, the human plasmalemmal serotonin transporter.
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The aim of this work was to investigate the effect of short- and long-term high-glucose exposure on the plasmalemmal serotonin transporter (SERT)-mediated uptake of [(3)H]-serotonin (5-HT) by Caco-2 cells. Short-term exposure of Caco-2 cells to high apical glucose levels (30 mM for 2 h or 40 mM for 1 h) decreased the uptake of [(3)H]-5-HT by 20-30%. On the other hand, long-term (21-24 weeks) exposure of the cells to high (25 mM) glucose caused a 30% increase in the uptake of [(3)H]5-HT. Under these conditions, the affinity of the transporter for 5-HT and noradrenaline was not significantly changed, and the inhibitory potencies of fluoxetine and desipramine were also unchanged. In conclusion, high-glucose levels modulate SERT activity. A short-term exposure of the cells to a high concentration of glucose decreases the activity of the transporter, whereas a longer exposure of the cells to a high concentration of glucose increases the activity of SERT, without interfering with its affinity.
| 19,000,377
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Protein malnutrition and aging affects entraining and intensity of locomotor activity and body temperature circadian rhythms in rats.
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Independently, chronic protein malnutrition and aging have been shown to affect locomotor activity (LA) and body temperature (BT) rhythms in mammals. The objective of the present study was to ascertain the combined effects of these two factors by examining period, entrainment and other circadian parameters between LA and BT rhythms. Chronic protein malnourished (PM) and well-nourished (WN) male Sprague-Dawley rats (550-590 days of age) were implanted with activity temperature intraperitoneal radio transmitters (Mini Mitter) and exposed to different lighting protocols during at least 10 days - light-dark cycles (LD 12:12), constant darkness (DD), skeleton photoperiod (SP) and again LD. Results indicate that parametric entrainment, achieved by means of complete photoperiod, is not negatively affected in malnourished rats; however, it is affected under non-parametric entrainment like SP. A different free running period between the LA and BT circadian rhythms was detected for well-nourished and malnourished aged rats.
| 19,000,379
|
Cost-effectiveness of magnetic resonance imaging of the knee for patients presenting in primary care.
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Musculoskeletal problems generate high costs. Of these disorders, patients with knee problems are commonly seen by GPs. Magnetic resonance imaging (MRI) of the knee is an accurate diagnostic test, but there is uncertainty as to whether GP access to MRI for these patients is a cost-effective policy. To investigate the cost-effectiveness of GP referral to early MRI and a provisional orthopaedic appointment, compared with referral to an orthopaedic specialist without prior MRI for patients with continuing knee problems. Cost-effectiveness analysis alongside a pragmatic randomised trial. Five-hundred and thirty-three patients consulting their GP about a knee problem were recruited from 163 general practices at 11 sites across the UK. Two-year costs were estimated from the NHS perspective. Health outcomes were expressed in terms of quality-adjusted life years (QALYs), based on patient responses to the EQ-5D questionnaire administered at baseline, and at 6, 12, and 24 months' follow-up. Early MRI is associated with a higher NHS cost, by £294 ($581; €435) per patient (95% confidence interval [CI] = £31 to £573), and a larger number of QALYs, by 0.050 (95% CI = −0.025 to 0.118). Mean differences in cost and QALYs generated an incremental cost per QALY gained of £5840 ($11 538; €8642). At a cost per QALY threshold of £20 000, there is a 0.81 probability that early MRI is a cost-effective use of NHS resources [corrected]. GP access to MRI for patients presenting in primary care with a continuing knee problem represents a cost-effective use of health service resources.
| 19,000,394
|
[Application of multicolor fluorescence in situ hybridization to early diagnosis of esophageal squamous cell carcinoma].
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Detection of chromosome aberrations has been applied to diagnose some tumors. However, there are no chromosomal markers for the diagnosis of esophageal carcinoma so far. This study was to analyze aberrations of some chromosomes in esophageal squamous cell carcinoma (ESCC) and its premalignant lesions, thus to explore the application of multicolor fluorescence in situ hybridization (M-FISH) for the early diagnosis and risk prediction of precursor lesions of ESCC. Aberration statuses of chromosomes 3, 8, 10, 12, 17 and 20 were investigated in 124 esophageal tissue samples from 113 patients using M-FISH with chromosome-specific centromere DNA probes. The relationship between chromosome gains and clinicopathologic parameters was analyzed. Copy number gains on chromosomes 3, 8, 10, 12, 17 and 20 in ESCC were 80.9% (93/115), 81.0% (94/116), 70.5% (79/112), 75.9% (85/112), 68.7% (79/115) and 82.8% (48/58), respectively. No statistical relations were found between chromosome aberrations and clinicopathologic parameters (P>0.05). Polysomy rates of the six chromosomes in precursor lesions were 62.5% (5/8), 75.0% (6/8), 62.5% (5/8), 87.5% (7/8), 87.5% (7/8) and 100% (3/3); while those in early-stage ESCC were 80.0% (12/15), 93.8% (15/16), 71.4% (10/14), 64.3% (9/14), 75.0% (12/16) and 63.6% (7/11). Positive aneuploidy rates of chromosomes 3,8,10,12,17 and 20 are highly detected in both ESCC and its precursor lesions. M-FISH is helpful in the early diagnosis of ESCC, thus it may be used as a method to predict the risk to ESCC.
| 19,000,442
|
[Correlation of cell cycle alteration to SOCS-1 gene demethylation induced by arsenic trioxide in myeloma cell lines].
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Recent studies suggest strong therapeutic potentials of arsenic trioxide (As2O3) for multiple myeloma(MM), which may be due to As2O3-induced demethylation of tumor suppressor genes. This study was to explore the correlation of cell cycle alteration to SOCS-1 gene demethylation after As2O3 induction in MM cell lines in vitro. MM cell lines U266 and RPMI8226 were used. Cell proliferation and cell cycle of MM cells after the treatment of As2O3 were assessed by MTT assay and flow cytometry, respectively. Methylation status was detected by methylation specific PCR (MSP-PCR), and gene expression of SOCS-1 was measured by real-time PCR in MM cells before and after As2O3 treatment. As2O3 significantly inhibited the growth of U266 and RPMI8226 cells in a dose-dependent manner. The cell cycle of U266 and RPMI8226 were arrested at G0/G1 phase. Compared with the wild type, the percentage of cells was increased at G0-G1 phase, but decreased at S phase after the treatment of As2O3 for 72 h (P < 0.05). The mRNA expression of SOCS-1 gene was significantly increased with hemi-methylation (As2O3, 0.5 micromol/L,72 h) or complete demethylation (As2O3, 1.0 micromol/L or As2O3, 2.0 micromol/L,72 h) of the SOCS-1 gene in comparison with the wide type (P<0.05). As2O3 could induce cell cycle alteration of MM, which might be related to demethylation and reexpression of SOCS-1 gene in MM cell lines. The study might provide a new approach to elucidate the mechanism of the antitumor effect of As2O3 in MM.
| 19,000,444
|
[Expression of TNF-like weak inducer of apoptosis (TWEAK) and its relationship to microvessel density in breast cancer].
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The expression of TNF-like weak inducer of apoptosis (TWEAK) in breast cancer remains disputable. This study was to investigate the expression of TWEAK in breast cancer tissues and breast cancer cell lines with different invasive abilities, and the relationship of TWEAK with microvessel density (MVD). Immunohistochemical S-P method was adopted to detect the expression of TWEAK in 70 specimens of breast cancer and 30 specimens of adjacent normal breast tissues. The protein expression of TWEAK was determined by Western blot in a poorly invasive breast cancer cell line MCF-7 and a highly invasive breast cell line MDA-MB-231. Secretion of TWEAK was measured by ELISA assay in MCF-7 and MDA-MB-231 cells. The expression of TWEAK was higher in breast cancer (60%) than in adjacent normal breast tissues( 6.67%) (P<0.05), and is higher in infiltrating ductal carcinoma of the breast (76.67 %) than in breast ductal carcinoma in situ (42.85%) (P=0.003). MVD was higher in infiltrating ductal carcinoma of the breast than in breast ductal carcinoma in situ (P<0.05). The expression of TWEAK was significantly correlated with MVD in infiltrating ductal carcinoma of the breast(r=0.611), but not with breast ductal carcinoma in situ (r=0.015). The expression of TWEAK and secretion of soluble TWEAK were higher in MDA-MB-231 cells than in MCF-7 cells (t=4.259, P=0.007; t=3.6504, P=0.006 ). TWEAK expression is related to the metastatic ability of breast cancer.
| 19,000,449
|
[Efficacy of GDP regimen (gemcitabine, dexamethasone, and cisplatin) on relapsed or refractory aggressive non-Hodgkin's Lymphoma: a report of 24 cases].
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The prognosis of relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) after front-line therapy remains poor. The development of more effective and less toxic salvage regimens remains a major challenge. Gemcitabine is effective in treating lymphoma and, when combined with cisplatin, is effective for some solid tumors. This study was to evaluate the efficacy of GDP regimen (gemcitabine, dexamethasone, and cisplatin) on relapsed or refractory aggressive NHL, and observe the adverse events. Patients with relapsed or refractory aggressive NHL, measurable disease, and had received previously at least one chemotherapy regimen were enrolled and treated with GDP regimen (gemcitabine 1000 mg/m2 on Days 1 and 8, dexamethasone 20-40 mg on Days 1-3, and cisplatin 25 mg/m2 on Days 1-3) every 3 weeks. The efficacy and adverse events were evaluated according to the WHO criteria. Twenty-four patients had received a total of 76 chemotherapy cycles, and were assessable for efficacy and adverse events. Five (20.8%) patients had complete response, 9 had partial response, 8 had stable disease, and 2 had progressive disease. The overall response rate (RR) was 58.3% for assessable patients; it was 57.1% for B-cell NHL patients and 60.0% for T-cell NHL patients (P=0.889). The median follow-up was 1.2 years. The 1-year overall survival rate was 41.7%; it was 42.9% in B-cell NHL patients and 40.0% in T-cell NHL patients (P=0.986). The occurrence rate was 37.5% for grade III/IV leucopenia, 25.0% for thrombocytopenia, and 16.7% for anemia in all patients. Non-hematologic toxicities were mild. There was no treatment-related death. Two patients proceeded to stem cell transplantation after salvage chemotherapy and obtained sufficient stem cells. GDP regimen is an effective and relatively nontoxic salvage chemotherapy regimen for relapsed or refractory aggressive NHL.
| 19,000,458
|
[Epidemiology of drug poisoning in the Ramón y Cajal University Hospital during a year].
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In recent years, there has been an increase of drugs poisoning cases seen in the Emergency Department. This study has aimed to evaluate the characteristics of these cases in the Ramón and Cajal Hospital in Madrid. A descriptive analysis about the drug poisonings diagnosed in 2004 was performed, using a retrospective search in the database of the electronic clinical records. The studied variables were gender, age, intention, drugs, admission into the hospital and relapse. There were 566 drug poisoning (47%) with a cumulative incidence of 0.1%, in which women (62.3%) were found to predominate, and the average patient age was 42.46+/-19.97 years (range 14-100 years). In 64.31% of the cases (566), only one kind of drug was used, benzodiazepine being the most common. This appeared at least once in 62% of the cases. Furthermore, 83% were cases of voluntary poisoning. Of the involuntary poisonings, digoxin was the most common drug with a frequency of 58.4%. A total of 28.6% of the cases were admitted into hospital, while the total number of patients who suffered a relapse in this period was 10%. Voluntary drug intoxications are caused mostly by psychoactive drugs, likely due to a high prevalence of underlying psychiatric disease in these patients. However, unintentional intoxications are mainly found in patients under chronic treatment with drugs such as digoxin and antiepileptics. More studies should be carried out to analyze which kind of preventive actions could reduce or avoid the high number of relapses.
| 19,000,470
|
[New CCR5 inhibitor antiretroviral drugs and integrase inhibitors].
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Two new antiretroviral drugs belonging to a new drug family have recently been marketed in Spain. These are maraviroc (CCR5 correceptor inhibitor) and raltegravir (integrase inhibitor). These have the advantage of not presenting crossed resistance with other previously administered antiretroviral drugs, converting them into the cornerstone of the rescue treatment in the patient infected by a multiresistant viral strain. The scientific evidence available on these two drugs is reviewed in this work and its indications in the HIV infected patient are discussed.
| 19,000,475
|
[Effect of the location of previous atherosclerotic disease on prognosis in diabetic patients. The Barbanza Diabetes Study].
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To assess the effect of different forms of atherosclerotic disease on prognosis in diabetic patients. This multicenter prospective cohort study involved 1423 consecutive patients with diabetes mellitus who were recruited by 31 primary care physicians. The patients' characteristics were recorded and they were followed up for 45 +/- 10 months. The mean age of the patients (50% male) was 66 years, 64% had hypertension, 70% had dyslipidemia, and 26% had had a previous cardiovascular event. By the end of follow-up, 81 (6.2%) had died, 40 (3%) of whom due to cardiovascular causes, and 393 (30%) had been hospitalized, 179 (14%) of whom for cardiovascular disease. Multivariate analysis identified the following factors as independent predictors of mortality: age (hazard ratio [HR]=1.08; 95% confidence interval [CI],1.05-1.11), previous cardiovascular disease (HR=2.15; 95% CI, 1.12-4.14) and diuretic treatment (HR=3.40; 95% CI, 1.76-6.56), while the prescription of an angiotensin-converting enzyme inhibitor or an angiotensin-receptor antagonist had a protective effect (HR=0.48; 95% CI, 0.25-0.93). Compared with diabetics without a previous cardiovascular event, the risk of a cardiovascular event during follow-up was greater in those with a history of either ischemic heart disease (HR=2.48; 95% CI, 1.51-4.07), cerebrovascular disease (HR=2.51; 95% CI, 1.28-4.92), or peripheral vascular disease (HR=1.46; 95% CI, 0.81-2.60). The increase in the risk of a cardiovascular event was similar in diabetics with ischemic heart disease and those with cerebrovascular disease. In both cases, the risk was more than double that in patients without a history of cardiovascular disease.
| 19,000,492
|
[Desquamative interstitial pneumonia and respiratory bronchiolitis-associated interstitial lung disease: data from the Spanish patient registry].
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Among the idiopathic interstitial lung diseases, respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) and desquamative interstitial pneumonia (DIP) make up a subgroup of rare diseases that are clearly smoking related. Few large case series have been published. We describe 19 cases registered in Spain: 12 patients with DIP and 7 with RB-ILD. Clinical and radiologic features are described along with clinical course, treatments applied, and outcomes. With the exception of 2 patients with DIP, all were smokers or ex-smokers. Cough and dyspnea were the most common symptoms at onset in both diseases. The most frequent radiologic findings were ground-glass opacity in DIP and pulmonary nodules in BR-ILD. Most patients were treated with corticosteroids. Outcomes were good in general; only 1 patient, with DIP, died.
| 19,000,514
|
[Spirometric evaluation of respiratory involvement in asymptomatic multinodular goiter with an intrathoracic component].
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Respiratory tract obstruction is underestimated in asymptomatic intrathoracic goiter. Our aim was to evaluate the involvement of the upper airway of asymptomatic patients with intrathoracic multinodular goiter, assessing the effect on respiratory function by means of spirometry. We selected 21 patients with asymptomatic intrathoracic goiter on whom a thyroidectomy had been performed. Spirometry was done in supine decubitus and in standing position before and 3 months after surgery. The preoperative study in decubitus showed mild obstruction in 4 cases (20%). In 2 of these cases this condition was also present in standing position (10%). Spirometry became normal after surgery in the 4 patients with obstruction. To conclude, spirometry in asymptomatic intrathoracic goiter shows mild obstruction of respiratory function in 10% to 20% of cases, depending on position. Surgery was associated with normalization of the abnormal parameters and an improvement in the remaining parameters. These data support the need to schedule surgery as soon as possible.
| 19,000,515
|
Additional renoprotective effects of azelnidipine combined with angiotensin receptor blockers in patients with diabetic nephropathy.
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Azelnidipine has been reported to have antioxidant effects and attenuates tubulointerstitial ischemia. The aim of the present study was to determine whether azelnidipine exerts additional renoprotective effects to angiotensin II receptor blockers (ARBs) in hypertensive patients with diabetic nephropathy and microalbuminuria. 45 hypertensive patients with diabetes mellitus and microalbuminuria who were already being treated with ARBs were enrolled in this study. Azelnidipine was added to the drug treatment of 30 patients (8 mg/day, n = 15, or 16 mg/day, n = 15) whilst the remaining 15 control patients were not treated with azelnidipine. In all patients, urinary 8-hydroxydeoxyguanosine (8-OHdG) levels and urinary liver-type fatty acid-binding protein (L-FABP) levels were significantly correlated (r = 0.587, p = 0.0006). However, urinary albumin excretion (UAE) was not correlated with the levels of urinary 8-OHdG (r = 0.1975, p = 0.2956) or urinary L-FABP (r = 0.2057, p = 0.2759). Azelnidipine significantly reduced UAE, urinary 8-OHdG and urinary L-FABP after 6 (p < 0.05) and 12 months (p < 0.05). Although blood pressure was comparable between the azelnidipine doses of 8 and 16 mg/day, the UAE (p < 0.05 after 12 months), urinary 8-OHdG (p < 0.05 after 6 and 12 months) and urinary L-FABP (p < 0.05 after 6 and 12 months) levels were more significantly reduced in patients receiving the higher dose of 16 mg/day. These data may suggest that the addition of azelnidipine treatment to therapy with ARBs has dose-dependent antioxidant and renoprotective effects beyond blood pressure-lowering effects in hypertensive diabetic nephropathy patients.
| 19,000,538
|
Multicenter prospective randomized, double-blind comparative study between lanthanum carbonate and calcium carbonate as phosphate binders in Japanese hemodialysis patients with hyperphosphatemia.
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The efficacy of lanthanum carbonate as a phosphate binder for the treatment of hyperphosphatemia has been reported, but not from a double-blind, comparator-controlled comparative study. The safety and efficacy of lanthanum carbonate and calcium carbonate on serum phosphate and calcium levels in Japanese hemodialysis patients were assessed by a randomized, double-blind, comparator-controlled, parallel group, multicenter study. This study is the first study using a randomized, double-blind method to compare lanthanum carbonate and calcium carbonate as phosphate binders. In the double-blind phase, the changes in the serum phosphate level were similar in the lanthanum carbonate and calcium carbonate groups. The differences in the corrected serum calcium level or the calcium x phosphate products between the 2 groups were not statistically significant. However, the mean change in the corrected serum calcium level from baseline to the last outpatient visit was significantly lower in the lanthanum carbonate group than in the calcium carbonate group. The incidence of hypercalcemia in the lanthanum carbonate group was also significantly lower than in the calcium carbonate group. Both compounds show similar efficacy on the serum phosphate level in patients undergoing hemodialysis when the dose is managed in a dose-variable and double-blind manner. However, lanthanum carbonate is superior in terms of lowering the incidence of hypercalcemia.
| 19,000,540
|
Subjective sleep efficiency of hemodialysis patients.
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Sleep disturbances have a major influence on quality of life. A commonly used measure of sleep disturbances is sleep efficiency. The purpose of this study was to investigate the prevalence of decreased subjective sleep efficiency in hemodialysis patients. An additional goal was to identify clinical, dialysis or laboratory parameters that are independently associated with decreased sleep efficiency. Adult stable hemodialysis patients (n = 112) filled out a sleep questionnaire during a three day investigation period. In addition, healthy control subjects (n = 44) filled out the same questionnaire. From this questionnaire sleep efficiency (ratio of total sleep time to time spent in bed) was derived as a measure for sleep disturbances in this population. Laboratory, demographic and dialysis data were collected during the investigation period. For statistical analysis linear regression models were used. Median subjective sleep efficiency in hemodialysis patients was 80%, which was significantly less compared to the median subjective sleep efficiency of control subjects of 88% (p pound 0.05). Approximately 40% of the patients used sleep medication. However, less than 20% of them indicated improved sleep behavior when using these drugs. Elevated levels of phosphate and urea correlated independently with impaired sleep efficiency. Hemoglobin levels between 10 and 12 g/dl were associated with better sleep efficiency. In conclusion, decreased sleep efficiency was frequently reported in hemodialysis patients and can be associated with biochemical parameters. Hemoglobin, phosphate and urea levels can affect subjective sleep efficiency.
| 19,000,541
|
Zotepine-induced spontaneous ejaculation.
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A man with schizophrenia received regular haloperidol ester therapy, but his psychotic symptoms were not mitigated. A combination of zotepine and haloperidol was then used to relieve the psychotic symptoms. However, the patient developed spontaneous ejaculations, which occurred many times a day while undergoing haloperidol and zotepine therapy. These events were not preceded by sexual stimulation and were not associated with a pleasurable sensation. The discomfort disappeared after discontinuing zotepine. Zotepine-induced spontaneous ejaculation was, therefore, diagnosed. There are few reports of drug-related spontaneous ejaculation. Clinicians need to recognize the possibility of zotepine-related spontaneous ejaculation because sexual side effects have an impact on medical adherence.
| 19,000,555
|
Large outbreaks of Salmonella Typhimurium infection in Denmark in 2008.
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An outbreak of Salmonella Typhimurium phage type U292 has been ongoing in Denmark since 1 April, with 1,054 cases registered until 23 October 2008. Extensive investigations including hypothesis-generating interviews, matched case-control studies, cohort studies in embedded outbreaks, shopping list analyses, analyses of food samples from patient's homes, trace-back analyses and extensive microbiological analysis of products have not provided clear indications of a specific source of infection but the main hypothesis is that the vehicle of the outbreak are different pork products. In addition to the large U292 outbreak, at least four other S. Typhimurium outbreaks (caused by phage types U288, DT120, DT3 and DT135) have been investigated in Denmark in 2008.
| 19,000,563
|
Anti-cockroach and anti-mouse IgE are associated with early wheeze and atopy in an inner-city birth cohort.
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The relationships between cockroach and mouse allergen exposure, anti-cockroach and anti-mouse IgE, and wheeze, rhinitis, and atopic dermatitis in children as young as age 3 years are of public health importance but have not been thoroughly evaluated. We hypothesized that inner-city children might have anti-cockroach and anti-mouse IgE by age 3 years, and their presence would be associated with respiratory and atopic symptoms. Children were followed prospectively from birth through age 3 years (n = 404). Residential levels of cockroach and mouse allergens, sera levels of anti-cockroach and anti-mouse IgE, and parental report of wheeze, rhinitis, and atopic dermatitis were measured. The odds of early wheeze were significantly higher among children who had IgE to cockroach (odds ratio [OR], 3.3; 95% CI, 1.8-6.2), mouse (OR, 4.6; 95% CI, 2.3-9.0), or both (OR, 9.7; 95% CI, 3.4-27.3). The odds of rhinitis or atopic dermatitis were also higher among children with IgE to cockroach, mouse, or both. Higher IgE class to cockroach and mouse was associated with wheeze and atopic dermatitis (tests for trend, P < .002). Children age 2 to 3 years who have anti-cockroach and anti-mouse IgE are at increased risk of wheeze and atopy. Moreover, a dose-response relationship was found between higher IgE class and increased prevalence of wheeze, rhinitis, or atopic dermatitis. These findings indicate the importance of reducing exposure to cockroach and mouse allergens for susceptible children.
| 19,000,580
|
Complications of arteriovenous hemodialysis access: recognition and management.
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English language citations reporting complications of arteriovenous access for hemodialysis are critically reviewed and discussed. Venous hypertension, arterial steal syndrome, and high-output cardiac failure occur as a result of hemodynamic alterations potentiated by access flow. Uremic and diabetic neuropathies are common but may obfuscate recognition of potentially correctable problems such as compression or ischemic neuropathy. Mechanical complications include pseudoaneurysm, which may develop from a puncture hematoma, degeneration of the wall, or infection. Dysfunctional hemostasis, hemorrhage, noninfectious fluid collections, and access-related infections are, in part, manifestations of the adverse effects of uremia on the function of circulating hematologic elements. Impaired erythropoiesis is successfully managed with hormonal stimulation; perhaps, similar therapies can be devised to reverse platelet and leukocyte dysfunction and reduce bleeding and infectious complications.
| 19,000,594
|
Chemical characteristics and volatile profile of genetically modified peanut cultivars.
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Genetic engineering has been used to modify peanut cultivars for improving agronomic performance and pest resistance. Food products developed through genetic engineering have to be assessed for their safety before approval for human consumption. Preservation of desirable chemical, flavor and aroma attributes of the peanut cultivars during the genetic modifications is critical for acceptance of genetically modified peanuts (GMP) by the food industry. Hence, the main objective of this study is to examine chemical characteristics and volatile profile of GMP. The genetically modified peanut cultivars, 188, 540 and 654 were obtained from the USDA-ARS in Stillwater, Oklahoma. The peanut variety Okrun was examined as a control. The volatile analysis was performed using a gas chromatograph/mass spectrometer (GC/MS) equipped with an olfactory detector. The peanut samples were also analyzed for their moisture, ash, protein, sugar and oil compositions. Experimental results showed that the variations in nutritional composition of peanut lines examined in this study were within the values reported for existing cultivars. There were minor differences in volatile profile among the samples. The implication of this study is significant, since it shows that peanut cultivars with greater pest and fungal resistance were successfully developed without major changes in their chemical characteristics.
| 19,000,610
|
Utilization of fermented barley extract obtained from a by-product of barley shochu for nisin production.
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Fermented barley extract (FBE) obtained from a barley shochu by-product (shochu kasu) and its ethanol fractions were evaluated as a medium and supplement, respectively, for nisin A production by Lactococcus lactis subsp. lactis ATCC 11454. A Brix 2.5 FBE medium supplemented with glucose provided a high level of nisin A production with a nisin yield comparable to that from a nutritionally rich laboratory medium (basal medium). By adding the ethanol-insoluble (EI) fraction of FBE to the basal medium, nisin A production was enhanced concomitant with an increase in bacterial cell growth, while the ethanol-soluble (ES) fraction had a negative effect on nisin A production. These findings indicate that FBE obtained from shochu kasu can be utilized as a preferable medium for nisin A production and could be converted into a value-added food product having preservative functions. The procedure developed in this study would promote recycling of shochu kasu.
| 19,000,617
|
Amyotrophic lateral sclerosis linked to a novel SOD1 mutation with muscle mitochondrial dysfunction.
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative motor neuron disorder. Mutations in Cu,Zn superoxide dismutase (SOD1) cause approximately 20% of familial ALS. One of the possible mechanisms whereby they induce disease is mitochondrial dysfunction in motor neurons. Here we describe a patient with ALS and muscle mitochondrial oxidative defect associated with a novel SOD1 mutation. Direct sequencing of SOD1 gene revealed a heterozygous mutation in codon 22 substituting a highly conserved amino acid, from glutamine to arginine (Q22R). Muscle biopsy showed a neurogenic pattern associated with cytochrome c oxidase (COX) deficiency in several muscle fibers. Western blot analysis demonstrated a reduction in SOD1 content in the cytoplasmic and mitochondrial fractions. These results suggest that a minute quantity of mutant SOD1 protein contributes to a mitochondrial toxicity also in muscle tissue.
| 19,000,626
|
Development of CoMFA and CoMSIA models of cytotoxicity data of anti-HIV-1-phenylamino-1H-imidazole derivatives.
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3D-QSAR models of 1-Phenylamino-1H-imidazole derivatives with cytotoxic potential have been developed using CoMFA and CoMSIA. Models were built keeping both 10% and 25% of molecules in test set. The Database and Field-Fit alignments were used for CoMFA model development. The best QSAR model was obtained from CoMFA analysis using Database alignment and employing 25% molecules in the test set (r(pred)(2) of 0.91 and r(m)(2) of 0.652). Database alignment with different fields such as Steric (S), Electrostatic (E), Acceptor (A), Donor (D) and Hydrophobic (H) was employed for CoMSIA model development. The best CoMSIA model was obtained by using the SHE fields and employing 25% molecules in the test set (r(pred)(2) of 0.789 and r(m)(2) of 0.410).
| 19,000,644
|
Nelfinavir induces TRAIL receptor upregulation in ovarian cancer cells.
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HIV protease inhibitors are currently being discussed to be useful as new and alternative anti-cancer agents, especially as second line treatments for chemo-resistant human cancer types. Among three clinically applied HIV protease inhibitors tested, we found a high efficacy of nelfinavir on ovarian cancer cells, accompanied by apoptosis (annexin binding) and necrosis (propidium iodide permeability). In vitro, at concentrations used to induce cell death in ovarian cancer cells, nelfinavir had no effect on the cellular viability of fibroblasts or peripheral blood mononuclear leukocytes. Nelfinavir sensitized ovarian cancer cells to treatment with an apoptosis-inducing TRAIL receptor antibody due to upregulation of the TRAIL receptor DR5 as shown by RT-PCR and FACScan analysis. We conclude that nelfinavir, an already approved drug, is a highly efficient agent against ovarian cancer cells and could sensitize ovarian cancer cells to TRAIL treatment, either therapeutically applied or endogenously produced by cells of the immune system.
| 19,000,651
|
Tissue slices for the evaluation of metabolism-based toxicity with the example of diclofenac.
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Drug-induced organ injury is a multifaceted process, involving numerous cell types and mediators, and remains a significant safety issue in pharmaceutical development and clinical therapy. Organotypic in vitro models, including precision-cut tissue slices, possess the multi-cellular, structural and functional features of in vivo tissue to facilitate the elucidation of mechanisms of drug-induced organ injury and to characterize species susceptibilities. This study reviews diclofenac-induced hepatotoxicity and presents data comparing the metabolism, specific binding of diclofenac products to cellular proteins and the effects on liver function in rat, monkey and human liver slices. Concentration- and time-dependent increases in specific protein binding demonstrate the progressive nature of the toxicity. Altered liver function correlated with the species differences in the extent of diclofenac metabolism (rat>monkey or human). Liver injury was not detectable within 24h, unlike specific protein binding, yet it developed by 48 h and lower concentrations of diclofenac exhibited effects by 72 h, demonstrating that continued metabolism and the accumulation of specific protein binding could lead to altered cell function. The decline of liver slice ATP levels at concentrations not affecting GSH levels implicates mitochondrial dysfunction as a primary indicator of hepatotoxicity, of which oxidative stress may be a contributing cause. Diclofenac affected monkey liver slices function at similar concentrations as rat liver slices, while human liver slices exhibited less extensive specific protein binding and required higher diclofenac concentrations to alter cell function.
| 19,000,659
|
Chromogranin A and C-terminal endothelin-1 precursor fragment add independent prognostic information to amino-terminal proBNP in patients with acute destabilized heart failure.
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The aim of this study was to evaluate the prognostic value of chromogranin A (CgA) and C-terminal endothelin-1 precursor fragment (CT-proET-1) in patients with acute destabilized heart failure. 137 consecutive patients with acute destabilized heart failure attending the emergency department of a tertiary care hospital were prospectively enrolled. Plasma concentrations of CgA, CT-proET-1, and amino-terminal proBNP (NT-proBNP) were measured at baseline. The endpoint was defined as all-cause mortality; the study participants were followed up for 365 days. Decedents (n=41) had higher median plasma concentrations of CgA (9.7 vs. 6.0 nmol/L; p=0.002), CT-proET-1 (120 vs. 72 pmol/L; p=0.006), and NT-proBNP (5112 vs. 2610 ng/L; p<0.001) at baseline than survivors (n=96). Applying Cox proportional-hazards regression analyses, increased CgA (>6.6 nmol/L), CT-proET-1 (>79 pmol/L), and NT-proBNP (>3275 ng/L) revealed significant risk ratios of 1.96 (95% CI, 1.04-3.70) for CgA, 2.56 (95% CI, 1.33-4.95) for CT-proET-1, and 2.05 (95% CI, 1.09-3.87) for NT-proBNP. When the cohort was stratified according to median CgA and NT-proBNP concentrations, and to median CT-proET-1 and NT-proBNP concentrations, respectively, Cox proportional-hazards regression analyses showed the highest risk for death in patients with both increased CgA and NT-proBNP (risk ratio, 3.65; 95% CI, 1.44-9.28), and increased CT-proET-1 and NT-proBNP (risk ratio, 4.03; 95% CI, 1.61-8.88). Our study demonstrates that increased CgA and CT-proET-1 plasma concentrations at the initial presentation of patients with acute destabilized heart failure in the emergency department add independent prognostic information in addition to NT-proBNP measurement.
| 19,000,665
|
Progesterone receptor in the forebrain of female gray short-tailed opossums: effects of exposure to male stimuli.
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Progesterone receptor immunoreactivity (PRir) in brain areas involved in reproductive behavior in eutherian species was examined for the first time in a female marsupial, the gray short-tailed opossum (Monodelphis domestica, hereinafter, opossum). PRir in nuclei of neurons, measured as area covered by stained nuclei, was seen in the arcuate nucleus (Arc); anteroventral periventricular nucleus (AVPv); bed nucleus of the stria terminalis (BST); medial preoptic area (MPOA), and ventromedial hypothalamus (VMH), but not in control areas adjacent to the hypothalamus or cortex. Female opossums are induced into cytological, urogenital sinus (UGS), estrus by male pheromones and into behavioral estrus, i.e., receptivity, by pairing with a male, and both estradiol (E) and progesterone (P) are involved in induction of receptivity in intact and ovariectomized females. PRir in the AVPv, MPOA, and VMH was very low in females that had never been exposed to males or their scent marks, i.e., naïve anestrous (NVA) females, and either previous or current exposure to males or their scent marks was associated with elevated PRir. PRir was significantly higher in the AVPv and MPOA of anestrous females with previous but no current exposure to males and their scent marks, i.e., experienced anestrous (EXPA) females, than in NVA females, but PRir was significantly lower in the MPOA and VMH of EXPA females than in females that were behaviorally receptive and had recently copulated, i.e., behavioral receptive estrous (BRE) females. PRir was higher in the VMH of both UGS estrous (UGSE) and BRE females compared to that in EXPA animals, but PRir did not differ between UGSE and BRE females in any of the 3 brain areas examined, including the MPOA These results provide evidence that pheromonal induction of estrus and sexual receptivity in opossums is associated with elevation of PRir in the VMH and MPOA and that prior exposure to males or their pheromones, even in the absence of current male stimuli, is associated with persistent elevation of PRir in the AVPv and MPOA.
| 19,000,689
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A multiplexed immunoassay for detection of antibodies against avian influenza virus.
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Avian influenza (AI) is a highly contagious disease in poultry and outbreaks can have dramatic economic and health implications. For effective disease surveillance, rapid and sensitive assays are needed to detect antibodies against AI virus (AIV) proteins. In this study, we report the development of a multiplexed fluorescence microsphere immunoassay (FMIA) for detection of antibodies against AIV proteins in poultry. Recombinant nucleoprotein (NP), matrix protein (M1), and non-structural protein 1 (NS1) were expressed using a baculovirus expression system, purified and covalently coupled to fluorescent xMAP microspheres. Using these reagents, a triplex bead assay was developed for the Luminex platform. The assay displayed minimal cross reactivity when screened against a panel of reference sera raised against common avian viruses. For detection of anti-NP antibodies, the sensitivity and specificity of the assay were comparable to a commercially available ELISA. The assay was also employed to investigate the early kinetics of antibody response in chickens infected with AIV. Our results suggest that NP should be the protein of choice when detecting AI infections in commercial chickens, as the immune response was higher and persisted longer than that of M1 and NS1 proteins. This report provides a framework from which a more robust assay could be developed to profile exposure to many AIV subtypes in a single test.
| 19,000,692
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Nicotine metabolic rate predicts successful smoking cessation with transdermal nicotine: a validation study.
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Transdermal nicotine is widely used for smoking cessation, but only approximately 20% of smokers quit successfully with this medication. Interindividual variability in nicotine metabolism rate may influence treatment response. This study sought to validate, and extend in a larger sample, our previous finding that the ratio of plasma nicotine metabolites 3'-hydroxycotinine (3-HC)/cotinine, a measure of nicotine metabolism rate, predicts response to nicotine patch. A sample of 568 smokers was enrolled in a study that provided counseling and 8-weeks of 21 mg nicotine patch. Pretreatment 3-HC/cotinine ratio was examined as a predictor of 7-day point prevalence abstinence, verified with breath carbon monoxide (CO), 8 weeks after the quit date. Controlling for sex, race, age, and nicotine dependence, smokers in the upper 3 quartiles of 3-HC/cotinine ratio (faster metabolizers) were approximately 50% less likely to be abstinent vs. smokers in the first quartile (slow metabolizers; 28% vs. 42%; OR=.54 [95% CI:.36-.82], p=.003). Among abstainers, plasma nicotine levels (assessed 1 week after treatment began) decreased linearly across the 3-HC/cotinine ratio (beta=-3.38, t[355]=-3.09, p<.05). These data support the value of the 3-HC/cotinine ratio as a biomarker to predict success with transdermal nicotine for smoking cessation.
| 19,000,709
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No interaction of body mass index and smoking on diabetes mellitus risk in elderly women.
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We sought to assess the interaction of smoking and body mass index (BMI) on diabetes risk. We analyzed data from a community-based prospective cohort of 41,836 women from Iowa who completed a baseline survey in 1986 and five subsequent surveys through 2004. The final analysis included 36,839 participants. At baseline (1986), there were 66% never smokers, 20% former smokers, and 14% current smokers. Subjects represented 40% normal weight, 38% overweight, and 22% obese individuals. Compared to normal weight women, the hazard ratio (HR) for diabetes was increased in overweight (HR 1.96; 95% CI 1.75-2.19) and obese subjects (HR 3.58; 95% CI 3.19-4.02). The hazard ratio for diabetes increased in a dose-dependent manner with smoking intensity. Compared to never smokers, former smokers had a higher risk for diabetes (HR 1.22; 95% CI 1.11-1.34). Among current smokers, the hazard ratio for diabetes was 1.21 (95% CI 0.95-1.53) for 1-19 pack-year smokers, 1.33 (95% CI 1.12-1.57) for 20-39 pack-year smokers, and 1.45 (95% CI 1.23-1.71) for > or =40 pack-year smokers. Similar trends were observed when the results were stratified by BMI. A test of interaction between BMI and smoking on diabetes risk was not statistically significant. Our findings suggest that smoking increases diabetes risk through a BMI-independent mechanism.
| 19,000,710
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Characterization of compounds on nicotinic acetylcholine receptor alpha7 channels using higher throughput electrophysiology.
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Alpha7 nicotinic acetylcholine receptor channels are important ligand-gated ion channels that are fast desensitizing, cation selective and have been implicated in the pathophysiology of schizophrenia and Alzheimer's disease. We report here high quality alpha7 parallel patch clamp recordings using the QPatch automated patch clamp system. The QPatch patch clamps up to 48 cells in parallel with the same high fidelity as conventional patch clamp. EC(50) and IC(50) values were comparable to values obtained with conventional patch clamp. The EC(50) value for acetylcholine (ACh) on the QPatch with area under the curve (AUC) analysis was 26microM compared to a value of 29microM determined from conventional patch clamp experiments. Sequential additions of ACh can be made with minimal decay of the peak amplitude. The competitive alpha7 antagonist methyllycaconitine (MLA) blocked currents with an IC(50) value of 0.25nM which is similar to published IC(50) values for MLA. Finally, two different classes of positive allosteric modulators represented by PNU-120596 and NS-1738 elicited characteristic responses, thus allowing accurate characterization of modulation and measurements of potency. These results demonstrate that alpha7 nicotinic acetylcholine receptor channels can be studied reliably in a higher throughput, parallel manner with the QPatch automated patch clamp system.
| 19,000,713
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Ephedra sinica inhibits complement activation and improves the motor functions after spinal cord injury in rats.
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The activation of complement system has been known as an important and significant reaction against the secondary injury after spinal cord injury (SCI). In the present study, we investigated the effect of Ephedra sinica to the inflammation or complement system of injured spinal cord and the influence to the functional recovery after spinal cord injury in rats. We prepared the complement-inhibiting component from E. sinica. Contusive spinal cord injury was induced to Sprague-Dawley rats. We administrated the product from E. sinica to E. sinica group, while distilled water was administered to the control group by gavage after SCI. Complement hemolytic activity (CH50), expression of C3 and C9, myeloperoxidase activity, and motor function were evaluated in E. sinica group and control group. The CH50, complement depositions, and myeloperoxidase activity in the E. sinica group were significantly reduced as compared to the control group. The motor function of E. sinica group was significantly improved from the 7th day as compared with the control group. The results demonstrated that E. sinica might reduce inflammation and improve motor function in rats after spinal cord injury by inhibiting complement activation. The present study has shown that complement system is playing an important role in spinal cord injury, and the possibility of a new therapy strategy, inhibiting or controlling the complement activation and inflammation, for spinal cord injury.
| 19,000,748
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Antibodies for the treatment of bacterial infections: current experience and future prospects.
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Antibodies can be used for the prevention and treatment of bacterial infections in animal models of disease. Current antibody technology allows the generation of high affinity human/humanized antibodies that can be optimized for antibacterial activity and in vivo biodistribution and pharmacokinetics. Such antibodies have exquisite selectivity for their bacterial target antigen and promise efficacy and safety. Why are there no monoclonal antibody products approved for the treatment or prevention of bacterial infections? Can antibodies succeed where antibiotics are failing? Some antibody therapies are currently being evaluated in clinical trials but several have failed despite positive data in animal disease models. This review will discuss the pros and cons of antibody therapeutics targeted at bacterial infections.
| 19,000,762
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A review of the current use of rituximab in autoimmune diseases.
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Rituximab is a human/murine chimeric monoclonal antibody primarily used for treating non-Hodgkin's B-cell lymphoma. Recently it has also been used in the treatment of several autoimmune diseases. A literature review was conducted to determine the efficacy of rituximab in the treatment of some of these autoimmune diseases. Multiple mechanisms proposed for the rituximab mediated B cell depletion are also discussed. The efficacy of rituximab is well-established and it is FDA approved for treatment of Rheumatoid arthritis. In this review, data on the use of rituximab is presented from 92 studies involving 1197 patients with the following diseases: systemic lupus erythematosus, idiopathic thrombocytopenic purpura, anti-neutrophil cytoplasmic antibody associated vasculitis, Grave's disease, autoimmune hemolytic anemia, pemphigus vulgaris, hemophilia A, cold agglutinin disease, Sjogren's syndrome, graft vs. host disease, thrombotic thrombocytopenic purpura, cryoglobulinemia, IgM mediated neuropathy, multiple sclerosis, neuromyelitis optica, idiopathic membranous nephropathy, dermatomyositis, and opsoclonus myoclonus. The efficacy varies among different autoimmune diseases. The cumulative data would suggest that in the vast majority of studies in this review, RTX has a beneficial role in their treatment. While rituximab is very effective in the depletion of B cells, current research suggests it may also influence other cells of the immune system by re-establishing immune homeostasis and tolerance. The safety profile of RTX reveals that most reactions are infusion related. In patients with autoimmune diseases the incidence of serious and severe side effects is low. Systemic infection still remains a major concern and may result in death.
| 19,000,786
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Evolutionary biology: microsporidia sex--a missing link to fungi.
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The evolutionary origins of the microsporidia, a group of intracellular eukaryotic pathogens, have been unclear. Genome analysis of a sex locus and other gene clusters has now revealed conserved synteny with zygomycete fungi, indicating that microsporidia are true fungi descended from a zygomycete ancestor.
| 19,000,798
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Evolutionary biology: patchy food may maintain a foraging polymorphism.
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Two naturally-occurring alleles in the nematode Caenorhabditis elegans that differ by a single amino acid and cause striking differences in foraging behavior are probably maintained by selection in patchy environments.
| 19,000,800
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Social evolution: this microbe will self-destruct.
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Phenotypic noise and social evolution in microbes have recently attracted huge interdisciplinary interest. A new study highlights the interaction between these phenomena and its implications for self-destructive cooperation.
| 19,000,802
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Structure of the kinesin13-microtubule ring complex.
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To investigate the mechanism of kinesin13-induced microtubule depolymerization, we have calculated a three-dimensional (3D) map of the kinesin13-microtubule ring complex, using cryo-electron microscopy (cryo-EM) and image analysis. An atomic model of the complex was produced by docking the crystal structures of tubulin and a kinesin13 motor domain (MD) into the 3D map. The model reveals a snapshot of the depolymerization mechanism by providing a 3D view of the complex formed between the kinesin13 MD and a curved tubulin protofilament (pf). It suggests that contacts mediated by kinesin13 class-specific residues in the putative microtubule-binding site stabilize intra-dimer tubulin curvature. In addition, a tubulin-binding site on the kinesin13 MD was identified. Mutations at this class-conserved site selectively disrupt the formation of microtubule-associated ring complexes.
| 19,000,825
|
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