Beta-blockers and mechanical dyssynchrony in heart failure assessed by radionuclide ventriculography.

BACKGROUND: Radionuclide ventriculography (RNVG) can be used to quantify mechanical dyssynchrony and may be a valuable adjunct in the assessment of heart failure with reduced ejection fraction (HFrEF). The study aims to investigate the effect of beta-blockers on mechanical dyssynchrony using novel RNVG phase parameters. METHODS: A retrospective study was carried out in a group of 98 patients with HFrEF. LVEF and dyssynchrony were assessed pre and post beta-blockade. Dyssynchrony was assessed using synchrony, entropy, phase standard deviation, approximate entropy, and sample entropy from planar RNVG phase images. Subgroups split by ischemic etiology were also investigated. RESULTS: An improvement in dyssynchrony and LVEF was measured six months post beta-blockade for both ischemic and non-ischemic groups. CONCLUSIONS: A significant improvement in dyssynchrony and LVEF was measured post beta-blockade using novel measures of dyssynchrony.

Radionuclide ventriculography phase analysis for risk stratification of patients undergoing cardiotoxic cancer therapy.

BACKGROUND: Accurate diagnostic tools to identify patients at risk of cancer therapy-related cardiac dysfunction (CTRCD) are critical. For patients undergoing cardiotoxic cancer therapy, ejection fraction assessment using radionuclide ventriculography (RNVG) is commonly used for serial assessment of left ventricular (LV) function. METHODS: In this retrospective study, approximate entropy (ApEn), synchrony, entropy, and standard deviation from the phase histogram (phase SD) were investigated as potential early markers of LV dysfunction to predict CTRCD. These phase parameters were calculated from the baseline RNVG phase image for 177 breast cancer patients before commencing cardiotoxic therapy. RESULTS: Of the 177 patients, 11 had a decline in left ventricular ejection fraction (LVEF) of over 10% to an LVEF below 50% after treatment had commenced. This patient group had a significantly higher ApEn at baseline to those who maintained a normal LVEF throughout treatment. Of the parameters investigated, ApEn was superior for predicting the risk of CTRCD. Combining ApEn with the baseline LVEF further improved the discrimination between the groups. CONCLUSIONS: The results suggest that RNVG phase analysis using approximate entropy may aid in the detection of sub-clinical LV contraction abnormalities, not detectable by baseline LVEF measurement, predicting a subsequent decline in LVEF.

First experimental evidence for a bis-ethene chromium(I) complex forming from an activated ethene oligomerization catalyst.

A bis-ethene chromium(I) species, which is the postulated key intermediate in the widely accepted metallacyclic mechanism for ethene oligomerization, is experimentally observed. This catalytic transformation is an important commercial route to linear α-olefins (primarily, 1-hexene and 1-octene), which act as comonomers for the production of polyethene. Here, electron paramagnetic resonance studies of a catalytic system based on [Cr(CO)4(PNP)][Al(OC(CF3)3)4] [PNP = Ph2PN(iPr)PPh2] activated with Et6Al2 provide the first unequivocal evidence for a chromium(I) bis-ethene complex. The concentration of this species is enhanced under ethene and isotope labeling studies that confirm its composition as containing [Cr(C2H4)2(CO)2(PNP)]+ These observations open a new route to mechanistic studies of selective ethene oligomerization.

Study of η and η' Photoproduction at MAMI.

The reactions γp→ηp and γp→η^{'}p are measured from their thresholds up to the center-of-mass energy W=1.96 GeV with the tagged-photon facilities at the Mainz Microtron, MAMI. Differential cross sections are obtained with unprecedented statistical accuracy, providing fine energy binning and full production-angle coverage. A strong cusp is observed in the total cross section for η photoproduction at the energies in the vicinity of the η^{'} threshold, W=1896 MeV (E_{γ}=1447 MeV). Within the framework of a revised ηMAID isobar model, the cusp, in connection with a steep rise of the η^{'} total cross section from its threshold, can only be explained by a strong coupling of the poorly known N(1895)1/2^{-} state to both ηp and η^{'}p. Including the new high-accuracy results in the ηMAID fit to available η and η^{'} photoproduction data allows the determination of the N(1895)1/2^{-} properties.

Molecular fingerprinting of principal neurons in the rodent hippocampus: A neuroinformatics approach.

Neurons are often classified by their morphological and molecular properties. The online knowledge base Hippocampome.org primarily defines neuron types from the rodent hippocampal formation based on their main neurotransmitter (glutamate or GABA) and the spatial distributions of their axons and dendrites. For each neuron type, this open-access resource reports any and all published information regarding the presence or absence of known molecular markers, including calcium-binding proteins, neuropeptides, receptors, channels, transcription factors, and other molecules of biomedical relevance. The resulting chemical profile is relatively sparse: even for the best studied neuron types, the expression or lack thereof of fewer than 70 molecules has been firmly established to date. The mouse genome-wide in situ hybridization mapping of the Allen Brain Atlas provides a wealth of data that, when appropriately analyzed, can substantially augment the molecular marker knowledge in Hippocampome.org. Here we focus on the principal cell layers of dentate gyrus (DG), CA3, CA2, and CA1, which together contain approximately 90% of hippocampal neurons. These four anatomical parcels are densely packed with somata of mostly excitatory projection neurons. Thus, gene expression data for those layers can be justifiably linked to the respective principal neuron types: granule cells in DG and pyramidal cells in CA3, CA2, and CA1. In order to enable consistent interpretation across genes and regions, we screened the whole-genome dataset against known molecular markers of those neuron types. The resulting threshold values allow over 6000 very-high confidence (>99.5%) expressed/not-expressed assignments, expanding the biochemical information content of Hippocampome.org more than five-fold. Many of these newly identified molecular markers are potential pharmacological targets for major neurological and psychiatric conditions. Furthermore, our approach yields reasonable expression/non-expression estimates for every single gene in each of these four neuron types with >90% average confidence, providing a considerably complete genetic characterization of hippocampal principal neurons.

Name-calling in the hippocampus (and beyond): coming to terms with neuron types and properties.

Widely spread naming inconsistencies in neuroscience pose a vexing obstacle to effective communication within and across areas of expertise. This problem is particularly acute when identifying neuron types and their properties. Hippocampome.org is a web-accessible neuroinformatics resource that organizes existing data about essential properties of all known neuron types in the rodent hippocampal formation. Hippocampome.org links evidence supporting the assignment of a property to a type with direct pointers to quotes and figures. Mining this knowledge from peer-reviewed reports reveals the troubling extent of terminological ambiguity and undefined terms. Examples span simple cases of using multiple synonyms and acronyms for the same molecular biomarkers (or other property) to more complex cases of neuronal naming. New publications often use different terms without mapping them to previous terms. As a result, neurons of the same type are assigned disparate names, while neurons of different types are bestowed the same name. Furthermore, non-unique properties are frequently used as names, and several neuron types are not named at all. In order to alleviate this nomenclature confusion regarding hippocampal neuron types and properties, we introduce a new functionality of Hippocampome.org: a fully searchable, curated catalog of human and machine-readable definitions, each linked to the corresponding neuron and property terms. Furthermore, we extend our robust approach to providing each neuron type with an informative name and unique identifier by mapping all encountered synonyms and homonyms.

Polarization Transfer in Wide-Angle Compton Scattering and Single-Pion Photoproduction from the Proton.

Wide-angle exclusive Compton scattering and single-pion photoproduction from the proton have been investigated via measurement of the polarization transfer from a circularly polarized photon beam to the recoil proton. The wide-angle Compton scattering polarization transfer was analyzed at an incident photon energy of 3.7 GeV at a proton scattering angle of θ_{cm}^{p}=70°. The longitudinal transfer K_{LL}, measured to be 0.645±0.059±0.048, where the first error is statistical and the second is systematic, has the same sign as predicted for the reaction mechanism in which the photon interacts with a single quark carrying the spin of the proton. However, the observed value is ~3 times larger than predicted by the generalized-parton-distribution-based calculations, which indicates a significant unknown contribution to the scattering amplitude.

Compton scattering for spectroscopic detection of ultra-fast, high flux, broad energy range X-rays.

Compton side-scattering has been used to simultaneously downshift the energy of keV to MeV energy range photons while attenuating their flux to enable single-shot, spectrally resolved, measurements of high flux X-ray sources to be undertaken. To demonstrate the technique a 1 mm thick pixelated cadmium telluride detector has been used to measure spectra of Compton side-scattered radiation from a Cobalt-60 laboratory source and a high flux, high peak brilliance X-ray source of betatron radiation from a laser-plasma wakefield accelerator.

Prospects for future advancements in islet cell transplantation.

Islet cell transplantation holds great promise for treating patients with type 1 diabetes mellitus (T1DM), and for preventing unstable metabolic state commonly refereed to as brittle diabetes in patients that undergo pancreatic resection given that it is a relatively noninvasive procedure and an attractive alternative to pancreas transplantation for restoring endogenous insulin secretion. The success of recent clinical trials for allogeneic islet transplantation as well as the increasing centers that perform auto-transplantation is showing that the beta cell replacement therapy for the treatment of patients with diabetes or total pancreatectomy has been firmly established. It needs only to be improved and made more widely available to the millions of desperate patients who search for alternatives to a life of insulin injections, hypoglycemia and the risks of end-organ damage. Steady progress has been achieved in recent years in different areas in the pancreatic islet transplantation process including islet cell processing, preservation, and immune therapies that justify optimism. To implement this therapeutic approach to larger cohorts of patients that would benefit from the restoration of beta cell function requires multiple interventions and the standardization of the different stages of islet transplant process. This article will review the possible areas of intervention and the ongoing research toward this important goal.

Intense gamma-ray source in the giant-dipole-resonance range driven by 10-TW laser pulses.

A gamma-ray source with an intense component around the giant dipole resonance for photonuclear absorption has been obtained via bremsstrahlung of electron bunches driven by a 10-TW tabletop laser. 3D particle-in-cell simulation proves the achievement of a nonlinear regime leading to efficient acceleration of several sequential electron bunches per each laser pulse. The rate of the gamma-ray yield in the giant dipole resonance region (8

Compton-scattering cross section on the proton at high momentum transfer.

Cross-section values for Compton scattering on the proton were measured at 25 kinematic settings over the range s=5-11 and -t=2-7 GeV2 with a statistical accuracy of a few percent. The scaling power for the s dependence of the cross section at fixed center-of-mass angle was found to be 8.0+/-0.2, strongly inconsistent with the prediction of perturbative QCD. The observed cross-section values are in fair agreement with the calculations using the handbag mechanism, in which the external photons couple to a single quark.

[Diabetes and heart transplantation]. / Diabetes und Herztransplantation.

Diabetes is frequently encountered in patients presenting with end-stage heart failure to be listed for transplantation. While diabetes used to be a contra-indication for heart transplantation, careful preoperative evaluation and individualized postoperative medication lead to long-term outcome after heart transplantation equal to non-diabetic patients. About 1/3 of transplanted patients develop a post-transplant diabetes. Several risk factors have been identified leading to this condition. Mostly, post-transplant diabetes is of temporary nature. Several studies have shown no impact of diabetes on the incidence of rejection, malignancies, and transplant vasculopathy. However, glucose intolerance must be taken into consideration when planing immunosuppressive therapy since different medications have distinct impact on glucose metabolism after transplant. A multidisciplinary team allows for closely monitoring and treating patients with diabetes after heart transplant.

Properties of the endosomal-lysosomal system in the human central nervous system: disturbances mark most neurons in populations at risk to degenerate in Alzheimer's disease.

Specific antibodies and cytochemical markers combined with several imaging and morphometric techniques were used to characterize the endosomal-lysosomal system in mature neurons of the normal human central nervous system and to quantitate changes in its function in Alzheimer's disease. Compartments containing cathespin D (Cat D) and other acid hydrolases included a major subpopulation of mature lysosomes lacking mannose-6-phosphate receptors (MPR) and smaller populations of late endosomes (MPR-positive) and lipofuscin granules (MPR-negative). Antibodies to the pro-isoform of Cat D decorated perinuclear vacuolar compartments corresponding to late endosomes. Neurons and glia contained lysosomes with differing complements of acid hydrolases, implying different processing capabilities. Endosome/lysosome number per unit volume of cytoplasm was relatively well conserved within populations of normal neurons. By contrast, in morphometric analyses of Alzheimer's disease brains, 80-93% of pyramidal cells in the prefrontal cortex (laminae III or V) and hippocampus (CA2, CA3) displayed two- to eightfold higher numbers of hydrolase-positive vacuolar compartments than did corresponding cell populations in age-matched normal brains. Only 5-10% of cerebellar Purkinje cells, a less vulnerable population, showed the same statistically significant elevations. Most affected in these brain regions and in subcortical areas seemed otherwise normal by conventional histological staining and ultrastructural inspection. That both lysosomal and pro-Cat D- and MPR-positive endosomal compartments increased in number demonstrates that the endosomal-lysosomal system is activated markedly in vulnerable neuronal populations of Alzheimer's disease brains and implies that endocytosis or autophagy or both are accelerated persistently at an early stage of cellular compromise, greatly surpassing the degree of activity associated with normal aging. Early activation of the endosomal-lysosomal system represents a biological event potentially linking major etiological factors in Alzheimer's disease, including defective membrane proteins, apolipoprotein E function, and altered amyloid precursor protein processing.

ANN compression of morphologically similar ECG complexes.

A compression algorithm for electrocardiogram signals is presented, based on an auto-associative neural network. Issues of weight and activation coding are considered, and compression performances of various network sizes are compared. A unique feature is the performance improvement achieved using DC level removal. A comparison with existing techniques is provided.

Lysosomal abnormalities in degenerating neurons link neuronal compromise to senile plaque development in Alzheimer disease.

Antibodies to the lysosomal hydrolases, cathepsins B and D and beta-hexosaminidase A, revealed alterations of the endosomal-lysosomal system in neurons of the Alzheimer disease brain, which preceded evident degenerative changes and became marked as atrophy, neurofibrillary pathology, or chromatolysis developed. At the earliest stages of cell atrophy, hydrolase-positive lysosomes accumulated at the basal pole and then massively throughout the perikarya and proximal and proximal dendrites of affected pyramidal neurons in Alzheimer prefrontal cortex and hippocampus, far exceeding the changes of normal aging. Secondary lysosomes as well as tertiary residual bodies (lysosomes/lipofuscin) increased implying stimulated, autophagocytosis and lysosomal system activation. Less affected brain regions, such as the thalamus, displayed similar though less extensive alterations. Certain thalamic neurons exhibited a distinctive lysosome-related abnormality characterized by the presence of cell surface blebs of varying size and number filled with intense hydrolase immunoreactivity. At more advanced stages of degeneration in still intact neurons, hydrolase-positive lipofuscin, particularly in the form of abnormally large aggregates, nearly filled the cytoplasm. Similar lipofuscin aggregates were observed in abundance in the extracellular space following cell lysis and were usually associated with deposits of the beta-amyloid protein. Degenerating neurons and their processes were the major source of these aggregates within senile plaques which contained high concentrations of acid hydrolases. We have shown in previous studies that these lysosomal hydrolases in plaques are enzymatically-active. The persistence of lysosomal structures in the brain parenchyma after neurons have degenerated is a striking and potentially diagnostic feature of Alzheimer disease which has not been observed, to our knowledge, in other degenerative diseases. The lysosomal response in degenerating Alzheimer neurons represents a probable link between an early activation of the lysosomal system in at-risk, normal-appearing neurons and the end-stage contribution of lysosomes to senile plaque formation and emphasizes a slowly progressive disturbance of the lysosomal system throughout the development of Alzheimer disease.

Underutilization of pneumococcal vaccine in nursing home in Washington State: report of a serotype-specific outbreak and a survey.

PURPOSE: To describe an outbreak of pneumococcal disease in a Washington state nursing home and to report a survey of pneumococcal vaccine utilization in Washington nursing homes. PATIENTS AND METHODS: Outbreak. Data were collected from nursing home residents' records. Nasopharyngeal cultures were obtained from residents and staff. Survey. Fifty-four randomly selected Washington nursing homes were surveyed about pneumococcal vaccine utilization and policies. RESULTS: Outbreak. Three confirmed and 4 possible cases of pneumococcal disease occurred over 9 days among 94 residents; 5 patients (71%) died. Cases were identified among 6 of 42 residents on 1 wing, compared with 1 of 52 on the other 2 wings (relative risk 7.4, 95% confidence interval 1.0, 398.5). Streptococcus pneumoniae serotype 9V was cultured from the blood of 3 confirmed case-patients and the nasopharynx of 2 of 73 residents. Only 7% of residents had received pneumococcal vaccine, including one case-patient who had received 14-valent vaccine without serotype 9V. Survey. Only 22% of residents were reported to have received pneumococcal vaccine; vaccination status was unknown for 66%. Physician discretion determined pneumococcal vaccination in 49 (91%) nursing homes; 9 (17%) had a written policy. Two major barriers to pneumococcal vaccination were cited: low priority among physicians (43%) and difficulty in determining residents' vaccine history (37%). CONCLUSIONS: A pneumococcal disease outbreak among undervaccinated nursing home residents probably resulted from person-to-person transmission. Pneumococcal vaccine appears to be underutilized in Washington state nursing homes.

The lysosomal system in neurons. Involvement at multiple stages of Alzheimer's disease pathogenesis.

Disturbed lysosomal function may be implicated at several stages of Alzheimer's pathogenesis. Lysosomes and acid hydrolases accumulate in the majority of neocortical pyramidal neurons before typical degenerative changes can be detected, indicating that altered lysosome function is among the earliest markers of metabolic dysfunction in Alzheimer's disease. These early alterations could reflect accelerated membrane and protein turnover, defective lysosome or hydrolase function, abnormal lysosomal trafficking or any combination of these possibilities. Because APP is partly metabolized in lysosomes, early disturbances in lysosomal function could promote the production of abnormal and/or neurotoxic APP fragments within intact cells. Lysosomal abnormalities progressively worsen as neurons begin to degenerate. Based on existing literature on cell death, increased perturbation and instability of the lysosomal system may be expected to contribute to the atrophy and eventual lysis of the neuron. Finally, the release of hydrolase-filled lysosomes and lipofuscin aggregates from dying neurons accounts for the abundant deposition of enzymatically active acid hydrolases of all classes in the extracellular space--a phenomenon that may be unique to Alzheimer's disease. Acting on APP present in surrounding dystrophic neurites, cellular debris and astrocyte processes, dysregulated hydrolases may cleave APP in atypical sequential patterns, thereby generating self-aggregating protease-resistant APP fragments that can be only processed to beta-amyloid. Genetic mutations or posttranslational factors of APP should further enhance the generation of amyloidogenic fragments by a dysregulated lysosomal system. Given that very little, if any, beta-amyloid is detected intracellularly, yet extracellular beta-amyloid is very abundant, our data suggest that the final steps of APP processing and the generation of most beta-amyloid in the brain parenchyma occur extracellularly and may involve one or more lysosomal proteases.

Detection of Chlamydia pneumoniae by polymerase chain reaction.

While criteria for serodiagnosis of Chlamydia pneumoniae infection are well established, isolation of the organism is often difficult. To increase detection of this organism, C. pneumoniae-specific sequences were identified to permit amplification of C. pneumoniae by polymerase chain reaction (PCR). A cloned C. pneumoniae 474-bp PstI fragment was shown by dot blot and Southern hybridization to differentiate C. pneumoniae from the other Chlamydia spp., react with all C. pneumoniae isolates tested, and not recognize DNA from normal throat flora or common respiratory tract agents. This cloned fragment was sequenced and primers for use in PCR were chosen on the bases of GenBank analysis, G + C ratio, and absence of secondary structure. All C. pneumoniae isolates tested were amplified by the HL-1-HR-1 primer pair or the HM-1-HR-1 primer pair, producing the expected 437- and 229-bp amplification products, respectively. None of the Chlamydia trachomatis serovars (B/TW-5/OT, C/TW-3/OT, D/UW-3/Cx, E/UW-5/Cx, F/UW-6/Cx, H/UW-4/Cx, I/UW-12/Ur, and L2/434/Bu), Chlamydia psittaci strains (Mn, 6BC, GPIC, FP, and OA), HeLa cells, or other organisms tested were amplified. Reaction conditions including MgCl2, oligonucleotides, and primer concentrations and temperature were optimized before application to clinical samples. Clinical specimens from patients from whom C. pneumoniae was isolated were also positive by PCR, while samples from patients with known C. trachomatis or C. psittaci infection were not amplified by PCR.

Effect of delay in processing on lysis-centrifugation blood culture results from marrow transplant patients.

The effect of delay in processing on results of lysis-centrifugation (LC; Isolator) blood cultures was assessed in 4,577 paired blood specimens. Blood specimens were obtained at all hours from 384 febrile marrow transplant patients with indwelling venous catheters and were processed by the LC technique and by a conventional two-bottle method. Most patients (84%) were receiving broad-spectrum antibiotics at the time of blood culture. Specimens were delivered to the laboratory, where Isolator tubes were held at 35 degrees C and processed in batches between 0700 and 1730 h daily. This procedure resulted in a delay beyond the manufacturer-suggested processing time of less than 8 h for 1,853 (42%) of the LC cultures. There was no overall difference in the recovery of organisms present in LC cultures processed after being held for 8 to 24 h compared with the conventional two-bottle method. LC methodology had shorter time to detection than the conventional method for detection of Candida spp. and Pseudomonas spp. (P less than 0.05). However, time to detection for Streptococcus spp. and members of the family Enterobacteriaceae, responsible for 16.3% of total isolates, was prolonged significantly by delay in processing when compared with the conventional two-bottle method (P less than 0.01). Results of this study support the recommendation of the manufacturer for processing of Isolator tubes within 8 h or less. Although one can safely delay processing beyond 8 h in terms of total recovery of organisms, such delays were associated with longer time to detection for certain important potentially pathogenic organisms which accounted for a sizeable proportion of blood culture isolates from marrow transplant patients.