Comparison of influenza hospitalization outcomes among adults, older adults, and octogenarians: a US national population-based study.

OBJECTIVES: This study sought to more fully elucidate the age-related trends in influenza mortality with a secondary goal of uncovering implications for treatment and prevention. METHODS: In this retrospective cohort analysis of data from the Nationwide Readmission Database, patients with influenza as a primary or secondary discharge diagnosis were separated into three age groups: 55 638 adults aged 20-64 years, 36 862 adults aged 65-79 years and 41 806 octogenarians aged ≥80 years. Propensity score (PS) weighting was performed to isolate age from other baseline differences. Crude and PS-weighted hazard ratios (HR) were calculated from the in-hospital all-cause 30-day mortality rate. Admission threshold bias was minimized by comparison of influenza with bacterial pneumonia mortality. RESULTS: Adults aged 20-64 years experienced higher in-hospital 30-day mortality compared with older adults aged 65-79 years (HR 0.66; 95% CI 0.55-0.79). Octogenarians had the highest mortality rate, but this was statistically insignificant compared with the adult cohort (HR 1.09; 95% CI 0.94-1.27). This trend was not explained by admission threshold bias: the 30-day mortality rate due to in-hospital bacterial pneumonia increased consistently with age (older adult HR 1.45; 95% CI 1.32-1.59; octogenarian HR 1.99; 95% CI 1.82-2.18). CONCLUSIONS: Adults aged 20-64 years and octogenarians were more likely to experience all-cause 30-day mortality during influenza hospitalization compared with older adults aged 65-79 years. These data emphasize the importance of prevention and suggest the need for more tailored treatment interventions based on risk stratification that includes age.

Efficiency of Transluminal Angioplasty of Hepatic Venous Outflow Obstruction in Pediatric Liver Transplantation.

BACKGROUND: Our aim in this study was to evaluate long-term efficiency of hepatic venous balloon angioplasty (BA) and stent placement (SP) for hepatic venous outflow obstruction (HVOO) in pediatric liver transplantation (LT). METHODS: From January 1999 to September 2016, 262 pediatric patients underwent LT at our hospital. Ten were diagnosed with HVOO, which included 8 living donor grafts and 2 split liver grafts. BA and SP were used in management of these 10 patients with HVOO. After intervention, Doppler ultrasound (DUS) was the major follow-up modality for comparing efficiency of BA and SP. RESULTS: The incidence of HVOO was 3.8% (10 of 262) in our pediatric LTs. Of the 10 HVOO cases, 5 had SP, 3 had BA once, 1 had BA twice, and 1 had BA twice along with SP. The patent hepatic vein was maintained after a mean follow-up of 7.4 (range, 0.04-17) years. Recurrent rate of HVOO after BA was 42%. Neither recurrent HVOO nor stent migration occurred after SP and throughout long-term follow-up. CONCLUSION: Hepatic venous SP was found to be more effective and safe than BA for treatment of HVOO in pediatric LT for long-term follow-up.

Electronic structure and characteristics of Fe 3d valence states of Fe(1.01)Se superconductors under pressure probed by x-ray absorption spectroscopy and resonant x-ray emission spectroscopy.

The electronic structure and characteristics of Fe 3d valence states of iron-chalcogenide Fe(1.01)Se superconductors under pressure were probed with x-ray absorption spectroscopy and resonant x-ray emission spectroscopy (RXES). The intensity of the pre-edge peak at ~7112.7 eV of the Fe K-edge x-ray absorption spectrum of Fe(1.01)Se decreases for pressure from 0.5 GPa increased to 6.9 GPa. The satellite line Kß' was reduced in intensity upon applying pressure and became absent for pressure 52 GPa. Fe(1.01)Se shows a small net magnetic moment of Fe(2+), likely arising from strong Fe-Fe spin fluctuations. The 1s3p-RXES spectra of Fe(1.01)Se at pressures 0.5, 6.9, and 52 GPa recorded at the Fe K-edge reveal that unoccupied Fe 3d states exhibit a delocalized character, stemming from hybridization of Fe 3d and 4p orbitals arising from a local distortion around the Fe atom in a tetrahedral site. Application of pressure causes suppression of this on-site Fe 3d-Fe 4p hybridization, and thereby decreases the intensity of the pre-edge feature in the Fe K-edge absorption spectrum of Fe(1.01)Se. Compression enhances spin fluctuations at Fe sites in Fe(1.01)Se and increases the corresponding T(c), through a competition between nearest-neighbor ferromagnetic and next-nearest-neighbor antiferromagnetic superexchange interactions. This result aids our understanding of the physics underlying iron-based superconductors.

Core-level positive-ion and negative-ion fragmentation of gaseous and condensed HCCl3 using synchrotron radiation.

We investigated the dissociation dynamics of positive-ion and negative-ion fragments of gaseous and condensed HCCl(3) following photoexcitation of Cl 2p electrons to various resonances. Based on ab initio calculations at levels HF/cc-pVTZ and QCISD/6-311G∗, the first doublet structures in Cl L-edge x-ray absorption spectrum of HCCl(3) are assigned to transitions from the Cl (2P(3/2),(1/2)) initial states to the 10a(1)(∗) orbitals. The Cl 2p → 10a(1)(∗) excitation of HCCl(3) induces a significant enhancement of the Cl(+) desorption yield in the condensed phase and a small increase in the HCCl(+) yield in the gaseous phase. Based on the resonant photoemission of condensed HCCl(3), excitations of Cl 2p electrons to valence orbitals decay predominantly via spectator Auger transitions. The kinetic energy distributions of Cl(+) ion via the Cl 2p → 10a(1)(∗) excitation are shifted to higher energy ∼0.2 eV and ∼0.1 eV relative to those via the Cl 2p → 10e(∗) excitation and Cl 2p → shape resonance excitation, respectively. The enhancement of the yields of ionic fragments at specific core-excited resonance states is assisted by a strongly repulsive surface that is directly related to the spectator electrons localized in the antibonding orbitals. The Cl(-) anion is significantly reinforced in the vicinity of Cl 2p ionization threshold of gaseous HCCl(3), mediated by photoelectron recapture through post-collision interaction.

Pressure-dependent electronic structures in multiferroic DyMnO(3): A combined lifetime-broadening-suppressed x-ray absorption spectroscopy and ab initio electronic structure study.

Variations in the electronic structure and structural distortion in multiferroic DyMnO(3) were probed by synchrotron x-ray diffraction, lifetime-broadening-suppressed x-ray absorption spectroscopy (XAS), and ab initio electronic structure calculations. The refined x-ray diffraction data enabled an observation of a diminished local Jahn-Teller distortion of Mn sites within MnO(6) octahedra in DyMnO(3) on applying the hydrostatic pressure. The intensity of the white line in Mn K-edge x-ray absorption spectra of DyMnO(3) progressively increased with the increasing pressure. With the increasing hydrostatic pressure, the absorption threshold of an Mn K-edge spectra of DyMnO(3) shifted toward a greater energy, whereas the pre-edge line slightly shifted to a smaller energy. We provide the spectral evidence for the pressure-induced bandwidth broadening for manganites. The intensity enhancement of the white line in Mn K-edge spectra is attributed to a diminished Jahn-Teller distortion of MnO(6) octahedra in compressed DyMnO(3). A comparison of the pressure-dependent XAS spectra with the ab initio electronic structure calculations and full calculations of multiple scattering using the code FDMNES shows the satisfactory agreement between experimental and calculated Mn K-edge spectra.

Dissociation dynamics of positive-ion and negative-ion fragments of gaseous and condensed Si(CH(3))(2)Cl(2) via Si 2p, Cl 2p, and Cl 1s core-level excitations.

The state-selective positive-ion and negative-ion dissociation pathways of gaseous and condensed Si(CH(3))(2)Cl(2) following Cl 2p, Cl 1s, and Si 2p core-level excitations have been characterized. The excitations to a specific antibonding state (15a(1) (*) state) of gaseous Si(CH(3))(2)Cl(2) at the Cl 2p, Cl 1s, and Si 2p edges produce significant enhancement of fragment ions. This ion enhancement at specific core-excited states correlates closely with the ion kinetic energy distribution. The results deduced from ion kinetic energy distribution are consistent with results of quantum-chemical calculations on Si(CH(3))(2)Cl(2) using the ADF package. The Cl(-) desorption yields for Si(CH(3))(2)Cl(2)Si(100) at approximately 90 K are notably enhanced at the 15a(1) (*) resonance at both Cl 2p and Si 2p edges. The resonant enhancement of Cl(-) yield occurs through the formation of highly excited states of the adsorbed molecules. These results provide insight into the state-selective ionic fragmentation of molecules via core-level excitation.

Facilitation of conditioned fear extinction by d-cycloserine is mediated by mitogen-activated protein kinase and phosphatidylinositol 3-kinase cascades and requires de novo protein synthesis in basolateral nucleus of amygdala.

Recent results showed that either systemic or intra-amygdala administration of d-cycloserine, a partial agonist at the glycine modulatory site on the glutamate N-methyl-d-aspartate receptor facilitates the extinction of conditioned fear. Here we evaluated the role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase in the basolateral nucleus of amygdala on the effect of d-cycloserine. The facilitation effect of d-cycloserine on fear extinction and mitogen-activated protein kinase activation was completely blocked by intra-amygdala administration of mitogen-activated protein kinase inhibitor PD98059 (500 ng/side, bilaterally) or U0-126 (20 microM/side, bilaterally). Furthermore, phosphatidylinositol 3-kinase inhibitor (wortmannin, 5.0 microg/side, bilaterally) infused into the basolateral nucleus of amygdala significantly reduced both facilitation effect of d-cycloserine and phosphatidylinositol 3-kinase activation. Intra-amygdala administration of a transcription inhibitor (actinomycin D, 10 microg dissolved in 1.6 microl vehicle; 0.8 microl per side) and a translation inhibitor (anisomycin, 125 microg dissolved in 1.6 microl vehicle; 0.8 microl per side) completely blocked the facilitation effect of d-cycloserine. Control experiments indicated the blockage by actinomycin D or anisomycin were not due to lasting damage to the basolateral nucleus of amygdala or state dependency. In addition, none of the active drugs used here altered the expression of conditioned fear. These results suggested that phosphatidylinositol 3-kinase and mitogen-activated protein kinase-dependent signaling cascades and new protein synthesis within the basolateral nucleus of amygdala played important roles in the d-cycloserine facilitation of the extinction of conditioned fear.

State selective enhanced production of excited fragments and ionic fragments of gaseous Si(CH3)2Cl2 and solid-state analogs following core-level excitation.

State-selective fragmentation dynamics for excited fragments and ionic fragments of gaseous and condensed Si(CH3)2Cl2 following Cl 2p and Si 2p core-level excitations have been characterized. The Cl 2p-->15a1* excitation of Si(CH3)2Cl2 induces significant enhancement of the Cl+ desorption yield in the condensed phase and the Si(CH3)+2 and SiCH+3 yields in the gaseous phase. The core-to-Rydberg excitations at both Si 2p and Cl 2p edges lead to enhanced production of the excited fragments. These complementary results provide deeper insight into the origin of state-selective fragmentation of molecules via core-level excitation.

Genetic testing in spinocerebellar ataxia in Taiwan: expansions of trinucleotide repeats in SCA8 and SCA17 are associated with typical Parkinson's disease.

DNA tests in normal subjects and patients with ataxia and Parkinson's disease (PD) were carried out to assess the frequency of spinocerebellar ataxia (SCA) and to document the distribution of SCA mutations underlying ethnic Chinese in Taiwan. MJD/SCA3 (46%) was the most common autosomal dominant SCA in the Taiwanese cohort, followed by SCA6 (18%) and SCA1 (3%). No expansions of SCA types 2, 10, 12, or dentatorubropallidoluysian atrophy (DRPLA) were detected. The clinical phenotypes of these affected SCA patients were very heterogeneous. All of them showed clinical symptoms of cerebellar ataxia, with or without other associated features. The frequencies of large normal alleles are closely associated with the prevalence of SCA1, SCA2, MJD/SCA3, SCA6, and DRPLA among Taiwanese, Japanese, and Caucasians. Interestingly, abnormal expansions of SCA8 and SCA17 genes were detected in patients with PD. The clinical presentation for these patients is typical of idiopathic PD with the following characteristics: late onset of disease, resting tremor in the limbs, rigidity, bradykinesia, and a good response to levodopa. This study appears to be the first report describing the PD phenotype in association with an expanded allele in the TATA-binding protein gene and suggests that SCA8 may also be a cause of typical PD.

A role for the PI-3 kinase signaling pathway in fear conditioning and synaptic plasticity in the amygdala.

Western blot analysis of neuronal tissues taken from fear-conditioned rats showed a selective activation of phosphatidylinositol 3-kinase (PI-3 kinase) in the amygdala. PI-3 kinase was also activated in response to long-term potentiation (LTP)-inducing tetanic stimulation. PI-3 kinase inhibitors blocked tetanus-induced LTP as well as PI-3 kinase activation. In parallel, these inhibitors interfered with long-term fear memory while leaving short-term memory intact. Tetanus and forskolin-induced activation of mitogen-activated protein kinase (MAPK) was blocked by PI-3 kinase inhibitors, which also inhibited cAMP response element binding protein (CREB) phosphorylation. These results provide novel evidence of a requirement of PI-3 kinase activation in the amygdala for synaptic plasticity and memory consolidation, and this activation may occur at a point upstream of MAPK activation.

Mitogen-activated protein kinase cascade in the basolateral nucleus of amygdala is involved in extinction of fear-potentiated startle.

Previous results indicate that intra-amygdala infusions of NMDA receptor antagonists block the extinction of conditioned fear. Mitogen-activated protein kinase (MAPK) can be activated by NMDA receptor stimulation and is involved in excitatory fear conditioning. Here, we evaluate the role of MAPK within the basolateral amygdala in the extinction of conditioned fear. Rats received 10 light-shock pairings. After 24 hr, fear was assessed by eliciting the acoustic startle reflex in the presence of the conditioned stimulus (CS) (CS-noise trials) and also in its absence (noise-alone trials). Rats subsequently received an intra-amygdala or intrahippocampal infusion of either 20% DMSO or the MAPK inhibitor PD98059 (500 ng/side) followed 10 min later by 30 presentations of the light CS without shock (extinction training). After 24 hr, they were again tested for fear-potentiated startle. PD98059 infusions into the basolateral amygdala but not the hippocampus significantly reduced extinction, which was otherwise evident in DMSO-infused rats. Control experiments indicated that the effect of intra-amygdala PD98059 could not be attributed to lasting damage to the amygdala or to state dependency. These results suggest that a MAPK-dependent signaling cascade within or very near the basolateral amygdala plays an important role in the extinction of conditioned fear.

State-specific enhancement of Cl+ and Cl- desorption for SiCl4 adsorbed on a Si(100) surface following Cl 2 p and Si 2 p core-level excitations.

State-specific desorption for SiCl4 adsorbed on a Si(100) surface at approximately 90 K with variable coverage following the Cl 2p and Si 2p core-level excitations has been investigated using synchrotron radiation. The Cl+ yields show a significant enhancement following the Cl 2p-->8a*1 excitation. The Cl- yields are notably enhanced at the 8a*1 resonance at both Cl 2p and Si 2p edges. The enhancement of the Cl- yield occurs through the formation of highly excited states of the adsorbed molecules. These results provide some new dissociation processes from adsorbates on surfaces via core-level excitation.

Protective effects of anti-C5a peptide antibodies in experimental sepsis.

We evaluated antibodies to different peptide regions of rat C5a in the sepsis model of cecal ligation and puncture (CLP) for their protective effects in rats. Rabbit polyclonal antibodies were developed to the following peptide regions of rat C5a: amino-terminal region (A), residues 1-16; middle region (M), residues 17-36; and the carboxyl-terminal region (C), residues 58-77. With rat neutrophils, the chemotactic activity of rat C5a was significantly inhibited by antibodies with the following rank order: anti-C > anti-M >> anti-A. In vivo, antibodies to the M and C (but not A) regions of C5a were protective in experimental sepsis, as determined by survival over a 10-day period, in a dose-dependent manner. The relative protective efficacies of anti-C5a preparations (in descending order of efficacy) were anti-C > anti-M >> anti-A. In CLP rats, a delay in infusion of antibodies, which were injected at 6 or 12 h after CLP, still resulted in significant improvement in survival rates. These in vivo and in vitro data suggest that there are optimal targets on C5a for blockade during sepsis and that delayed infusion of anti-C5a antibody until after onset of clinical evidence of sepsis still provides protective effects.

Role of C5a in multiorgan failure during sepsis.

In humans with sepsis, the onset of multiorgan failure (MOF), especially involving liver, lungs, and kidneys, is a well known complication that is associated with a high mortality rate. Our previous studies with the cecal ligation/puncture (CLP) model of sepsis in rats have revealed a C5a-induced defect in the respiratory burst of neutrophils. In the current CLP studies, MOF occurred during the first 48 h with development of liver dysfunction and pulmonary dysfunction (falling arterial partial pressure of O(2), rising partial pressure of CO(2)). In this model an early respiratory alkalosis developed, followed by a metabolic acidosis with increased levels of blood lactate. During these events, blood neutrophils lost their chemotactic responsiveness both to C5a and to the bacterial chemotaxin, fMLP. Neutrophil dysfunction was associated with virtually complete loss in binding of C5a, but binding of fMLP remained normal. If CLP animals were treated with anti-C5a, indicators of MOF and lactate acidosis were greatly attenuated. Under the same conditions, C5a binding to blood neutrophils remained intact; in tandem, in vitro chemotactic responses to C5a and fMLP were retained. These data suggest that, in the CLP model of sepsis, treatment with anti-C5a prevents development of MOF and the accompanying onset of blood neutrophil dysfunction. This may explain the protective effects of anti-C5a in the CLP model of sepsis.

Quantitative measurement on three-dimensional computed tomography: an experimental validation using phantom objects.

BACKGROUND: The use of 3-dimensional computed tomography (CT) imaging has been applied to the craniofacial region as well as to many other parts of the human body. Quantitative measurements have frequently been performed on the 3-dimensional images. However, critical validation of the measurement has been insufficient in the literature. This study was designed to evaluate the errors of the 3-dimensional measurements. METHODS: Four phantom objects, a cube, a sphere, a cylinder, and a life-size adult skull model, were scanned using standard CT acquisition protocol. The data were transferred, reformatted, and displayed on an IBM-compatible personal computer running AnalyzePC 2.5 software. Linear, area, and volume measurements were obtained using one of the two methods. The first was physical measurement of the phantom objects using a caliper for linear measurement and mathematical calculations for area and volume measurements. The second was done by computer measurement on 3-dimensional images using the AnalyzePC 2.5 program. Each measurement was performed twice. The differences were compared between the repeated measurements and between the two methods. RESULTS: The images were displayed according to standard 3-dimensional CT protocol. The differences between the measurements were insignificant and ranged from 0.00 to 2.57%. CONCLUSION: This study validated the accuracy of the quantitative measurements on 3-dimensional CT images.

Involvement of mitogen-activated protein kinase in hippocampal long-term potentiation.

Mitogen-activated protein kinase (MAPK) cascade classically is thought to be involved in cellular transformation, including proliferation and differentiation. Recent behavioral studies suggest that MAPK may also have a role in learning and memory. Long-term potentiation (LTP), a candidate mechanism for learning and memory, has at least two distinct temporal phases: an early phase (E-LTP) which lasts for 1-2 h and a late phase (L-LTP) which can persist >/=3 h. Here, we report that PD 098059, a selective inhibitor of MAPK cascade, attenuates L-LTP induced by bath application of forskolin without affecting basal synaptic transmission. This effect was mimicked by direct injection of animals with MAPK antisense oligonucleotide into the hippocampal CA1 region. MAPK activity measured by using a synthetic peptide corresponding to the sequence surrounding the major site of phosphorylation of the myelin-basic protein by MAPK was enhanced by forskolin. The same antisense treatment also completely inhibited the increased MAPK activity. These results demonstrate an involvement of MAPK in the induction of L-LTP in the hippocampal CA1 neurons.

Masking of forskolin-induced long-term potentiation by adenosine accumulation in area CA1 of the rat hippocampus.

At hippocampal Schaffer collateral-CA1 synapses, activation of beta-adrenergic receptors and adenylyl cyclase increases transmitter release. However, this effect is transient, which is in contrast to that seen at mossy fiber-CA3 synapses, where activation of cyclic-AMP-dependent protein kinase results in long-lasting facilitation of transmitter release, a phenomenon known as a presynaptic form of long-term potentiation. The present study was aimed at investigating whether forskolin, an adenylyl cyclase activator, could produce long-term effects at the Schaffer collateral-CA1 synapses using extracellular recording techniques. As has been reported previously, forskolin persistently increased the amplitude of evoked population spikes without having a long-term effect on the field excitatory postsynaptic potentials. However, under the conditions where adenosine A1 receptors are inhibited, cyclic-AMP metabolism is disrupted or the transport of cyclic-AMP is blocked, forskolin induces long-term potentiation. Forskolin-induced potentiation is associated with a decrease in paired-pulse facilitation and is blocked by the cyclic-AMP-dependent protein kinase inhibitor Rp-adenosine-3',5'-cyclic monophosphorothioate. Activation of N-methyl-D-aspartate receptors is not required for forskolin-induced long-term potentiation, because pretreatment of slices with the N-methyl-D-aspartate receptor antagonist D-2-amino-5-phosphonovalerate did not prevent forskolin-induced potentiation. These results suggest that blockade of adenosine A1 receptors unmasks forskolin-induced long-term potentiation, and activation of cyclic-AMP-dependent protein kinase induces a form of long-term potentiation which is different from that induced by tetanic stimulation.

Promotion of forskolin-induced long-term potentiation of synaptic transmission by caffeine in area CA1 of the rat hippocampus.

Caffeine which is present in soft drinks has been shown to increase alertness and allays drowsiness and fatigue. The aim of this study is to investigate whether caffeine could produce a long-term effect on the synaptic transmission using extracellular recording technique in the hippocampal slices. Bath application of caffeine (100 microM) reversibly increased the slope of field excitatory postsynaptic potential (fEPSP). Forskolin (25 microM) by its own did not affect the fEPSP significantly. However, in the presence of caffeine, forskolin induced a long-term potentiation (LTP) of fEPSP. Enprofylline which has been shown to exhibit some actions like caffeine but with a low adenosine antagonistic potency did not affect the normal synaptic transmission or the effect of forskolin at a lower concentration (10 microM). However, when the concentrations were increased to 20 and 50 microM, enprofylline significantly enhanced the fEPSP slope and promoted forskolin-induced LTP. The parallel increase of fEPSP and promotion of LTP observed with enprofylline suggests that adenosine A1 antagonism is the primary mechanism behind caffeine's effect. This hypothesis was further strengthened by the finding that promotion of forskolin-induced LTP was mimicked by the non-xanthine adenosine antagonist 9-chloro-2-(furyl)[1,2,4]triazolo [1,5-c]quinazolin-5-amine (CGS 15943). The promotion of forskolin-induced LTP provides a cellular basis behind caffeine's increase in capacity for sustained intellectual performance.

Determination of methylamphetamine and related compounds in human urine by high performance liquid chromatography/electrospray/mass spectrometry.

A study of liquid chromatography/electrospray/mass spectrometry (LC/ES/MS) for the determination of methylamphetamine and related compounds (amphetamine, ephedrine, phenylpropanolamine) in human urine was undertaken. We assessed the effect of collision induced dissociation (CID) spectra generated by varying exit voltage of capillary and skimmer. The responses of ES/MS in different mobile phase and the effects of mobile phase modifier were examined. An isocratic LC method using methanol/water (80/20) and acetic acid (0.001%) as a modifier to separate these compounds was developed. Microporous ultrafiltration technique was employed to pre-treat urine sample prior to LC/ES/MS analysis. Good recoveries for methylamphetamine and amphetamine were determined as well as linearity, detection limit and precision associated with this method were determined. Drug spiked urine samples and urine samples of methylamphetamine addicts were successfully measured by this newly developed method.