Concealed anterograde accessory pathway conduction during the induction of orthodromic reciprocating tachycardia

AbstractThe purpose of this study was to determine whether concealed anterograde accessory pathway conduction occurs during the induction of orthodromic tachycardia by an artrial extrastimulus (S2). Sixteen patients with an overt (n = 9) or concealed (n = 7) accessory pathway had inducible orthodromic tachycardia by S2during an atrial drive (S1) cycle length of 500 to 650 ms. A ventricular extrastimulus (S3) was introduced coincident with the His depolarization resulting from S2during the longest S1S2interval that reproducibly induced orthodromic tachycardia. The S1S3interval was decreased in 10 ms steps until S3reached ventricular refractoriness. Retrograde accessory pathway conduction of S3in the presence and absence of S2was compared at the same S1S3intervals.In the absence of S2there was retrograde accessory pathway conduction after S3in each patient. In the presence of S2, in patients with overt pre-excitation, retrograde accessory pathway conduction after S3was absent in one patient, prolonged in four patients and present only after long S1S3intervals in three patients. Only one patient had unchanged retrograde conduction regardless of the presence or absence of S2. In patients with a concealed accessory pathway, retrograde accessory pathway conduction after S3was absent in five patients and was prolonged in two. Thus, concealed anterograde accessory pathway conduction was present in 15 of 16 patients at the time of orthodromic tachycardia induction.In conclusion, concealed anterograde accessory pathway conduction occurs in a majority of patients with an overt or a concealed accessory pathway during induction of orthodromic tachycardia by an atrial extrastimulus. In some patients, the initiation of orthodromic tachycardia may depend on a critical interaction between the degree of concealed anterograde accessory pathway conduction and atrioventricular conduction delay after S2

Changes in Carbon Oxidation State of Metagenomes Along Geochemical Redox Gradients

There is widespread interest in how geochemistry affects the genomic makeup of microbial communities, but the possible impacts of oxidation-reduction (redox) conditions on the chemical composition of biomacromolecules remain largely unexplored. Here we document systematic changes in the carbon oxidation state, a metric derived from the chemical formulas of biomacromolecular sequences, using published metagenomic and metatranscriptomic datasets from 18 studies representing different marine and terrestrial environments. We find that the carbon oxidation states of DNA, as well as proteins inferred from coding sequences, follow geochemical redox gradients associated with mixing and cooling of hot spring fluids in Yellowstone National Park (USA) and submarine hydrothermal fluids. Thermodynamic calculations provide independent predictions for the environmental shaping of the gene and protein composition of microbial communities in these systems. On the other hand, the carbon oxidation state of DNA is negatively correlated with oxygen concentration in marine oxygen minimum zones. In this case, a thermodynamic model is not viable, but the low carbon oxidation state of DNA near the ocean surface reflects a low GC content, which can be attributed to genome reduction in organisms adapted to low-nutrient conditions. We also present evidence for a depth-dependent increase of oxidation state at the species level, which might be associated with alteration of DNA through horizontal gene transfer and/or selective degradation of relatively reduced (AT-rich) extracellular DNA by heterotrophic bacteria. Sediments exhibit even more complex behavior, where carbon oxidation state minimizes near the sulfate-methane transition zone and rises again at depth; markedly higher oxidation states are also associated with older freshwater-dominated sediments in the Baltic Sea that are enriched in iron oxides and have low organic carbon. This geobiochemical study of carbon oxidation state reveals a new aspect of environmental information in metagenomic sequences, and provides a reference frame for future studies that may use ancient DNA sequences as a paleoredox indicator

Class Is Not Dead! It Has Been Buried Alive

By means of a reanalysis of the most relevant data source—the International Social Mobility and Politics File—this article criticizes the newly grown consensus in political sociology that class voting has declined since World War II. An increase in crosscutting cultural voting, rooted in educational differences rather than a decline in class voting, proves responsible for the decline of traditional class-party alignments. Moreover, income differences have not become less but more consequential for voting behavior during this period. It is concluded that the new consensus has been built on quicksand. Class is not dead—it has been buried alive under the increasing weight of cultural voting, systematically misinterpreted as a decline in class voting because of the widespread application of the so-called Alford index

Combined N-of-1 trials to investigate mexiletine in non-dystrophic myotonia using a Bayesian approach; study rationale and protocol

Background: To obtain evidence for the clinical and cost-effectiveness of treatments for patients with rare diseases is a challenge. Non-dystrophic myotonia (NDM) is a group of inherited, rare muscle diseases characterized by muscle stiffness. The reimbursement of mexiletine, the expert opinion drug for NDM, has been discontinued in some countries due to a lack of independent randomized controlled trials (RCTs). It remains unclear however, which concessions can be accepted towards the level 1 evidence needed for coverage decisions, in rare diseases. Considering the large number of rare diseases with a lack of treatment evidence, more experience with innovative trial designs is needed. Both NDM and mexiletine are well suited for an N-of-1 trial design. A Bayesian approach allows for the combination of N-of-1 trials, which enables the assessment of outcomes on the patient and group level simultaneously. Methods/Design: We will combine 30 individual, double-blind, randomized, placebo-controlled N-of-1 trials of mexiletine (600 mg daily) vs. placebo in genetically confirmed NDM patients using hierarchical Bayesian modeling. Our results will be compared and combined with the main results of an international cross-over RCT (mexiletine vs. placebo in NDM) published in 2012 that will be used as an informative prior. Similar criteria of eligibility, treatment regimen, end-points and measurement instruments are employed as used in the international cross-over RCT. Discussion: The treatment of patients with NDM with mexiletine offers a unique opportunity to compare outcomes and efficiency of novel N-of-1 trial-based designs and conventional approaches in producing evidence of clinical and cost-effectiveness of treatments for patients with rare diseases

In-hospital costs associated with new percutaneous coronary devices

To determine the relative economic impact of alternative methods of coronary revascularization, in-hospital patient accounts were reviewed in 149 patients undergoing elective coronary angioplasty (n = 50), coronary atherectomy (n = 72) or intracoronary stent placement (n = 27) over an 18-month period. Clinical and angiographic features were similar in the 3 groups, except that prior restenosis was seen more often in patients undergoing intracoronary stent placement. Procedural success, obtained in >90% of patients, was independent of the treatment strategy. Total in-hospital stay was significantly longer in patients undergoing intracoronary stent placement than in patients undergoing coronary angioplasty and directional atherectomy (4.9 +/- 2.4 days vs 1.5 +/- 1.3 and 2.2 +/- 3.9 days, respectively; p < 0.0001). Furthermore, the total in-hospital charges were significantly higher in patients undergoing intracoronary stent placement ($12,574 +/-$4,564 vs $6,220 +/-$5,716; p < 0.001) and directional atherectomy ($8,329 +/-$8,588 vs $6,220 +/-$5,716; p < 0.01) than in patients undergoing coronary angioplasty, reflecting overall differences in room costs, laboratory fees and pharmacy fees. The longer in-hospital stay in the intracoronary stent group was primarily attributed to the time required for anticoagulation with coumadin. It is concluded that a 102 and 34% increase in early hospital charges resulted with stenting or directional atherectomy, respectively, compared with coronary angioplasty. These increased in-hospital charges were chiefly due to the prolonged hospitalization time, device cost, laboratory fees and, in patients with intracoronary stents, the prolonged time needed to achieve systemic anticoagulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29116/1/0000155.pd

A metastable equilibrium model for the relative abundances of microbial phyla in a hot spring

Many studies link the compositions of microbial communities to their environments, but the energetics of organism-specific biomass synthesis as a function of geochemical variables has rarely been assessed. We describe a thermodynamic model that integrates geochemical and metagenomic data for biofilms sampled at five sites along a thermal and chemical gradient in the outflow channel of the hot spring known as ‘‘Bison Pool’’ in Yellowstone National Park. The relative abundances of major phyla in individual communities sampled along the outflow channel are modeled by computing metastable equilibrium among model proteins with amino acid compositions derived from metagenomic sequences. Geochemical conditions are represented by temperature and activities of basis species, including pH and oxidation-reduction potential quantified as the activity of dissolved hydrogen. By adjusting the activity of hydrogen, the model can be tuned to closely approximate the relative abundances of the phyla observed in the community profiles generated from BLAST assignments. The findings reveal an inverse relationship between the energy demand to form the proteins at equal thermodynamic activities and the abundance of phyla in the community.Although the metabolisms used by many members of these communities are driven by chemical disequilibria, the results support the possibility that higher-level patterns of chemotrophic microbial ecosystems are shaped by metastable equilibrium states that depend on both the composition of biomass and the environmental conditions

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

A Naturally Occurring Bovine Tauopathy Is Geographically Widespread in the UK

Many human neurodegenerative diseases are associated with hyperphosphorylation and widespread intra-neuronal and glial associated aggregation of the microtubule associated protein tau. In contrast, animal tauopathies are not reported with only senescent animals showing inconspicuous tau labelling of fine processes albeit significant tau aggregation may occur in some experimental animal disease. Since 1986, an idiopathic neurological condition of adult cattle has been recognised in the UK as a sub-set of cattle slaughtered as suspect bovine spongiform encephalopathy cases. This disorder is characterised by brainstem neuronal chromatolysis and degeneration with variable hippocampal sclerosis and spongiform change. Selected cases of idiopathic brainstem neuronal chromatolysis (IBNC) were identified from archive material and characterised using antibodies specific to several tau hyperphosphorylation sites or different isoforms of the tau microtubule binding region. Labelling was also carried out for alpha synuclein, ubiquitin, TDP43, Aβ 1-42, Aβ 1-40. Widespread tau labelling was identified in all IBNC brains examined and with each of seven tau antibodies recognising different hyperphosphorylated sites. Labelling with each antibody was associated with dendrites, neuronal perikarya and glia. Thus IBNC is a sporadic, progressive neurological disease predominantly affecting aged cattle that occurs throughout the UK and is associated with hyperphosphorylation of tau, a rare example of a naturally-occurring tauopathy in a non-primate species. Secondary accumulation of alpha synuclein and ubiquitin was also present. The neuropathology does not precisely correspond with any human tauopathy. The cause of IBNC remains undetermined but environmental factors and exposure to agrochemicals needs to be considered in future aetiological investigations

Calculation of the relative metastabilities of proteins in subcellular compartments of Saccharomyces cerevisiae

[abridged] Background: The distribution of chemical species in an open system at metastable equilibrium can be expressed as a function of environmental variables which can include temperature, oxidation-reduction potential and others. Calculations of metastable equilibrium for various model systems were used to characterize chemical transformations among proteins and groups of proteins found in different compartments of yeast cells. Results: With increasing oxygen fugacity, the relative metastability fields of model proteins for major subcellular compartments go as mitochondrion, endoplasmic reticulum, cytoplasm, nucleus. In a metastable equilibrium setting at relatively high oxygen fugacity, proteins making up actin are predominant, but those constituting the microtubule occur with a low chemical activity. A reaction sequence involving the microtubule and spindle pole proteins was predicted by combining the known intercompartmental interactions with a hypothetical program of oxygen fugacity changes in the local environment. In further calculations, the most-abundant proteins within compartments generally occur in relative abundances that only weakly correspond to a metastable equilibrium distribution. However, physiological populations of proteins that form complexes often show an overall positive or negative correlation with the relative abundances of proteins in metastable assemblages. Conclusions: This study explored the outlines of a thermodynamic description of chemical transformations among interacting proteins in yeast cells. The results suggest that these methods can be used to measure the degree of departure of a natural biochemical process or population from a local minimum in Gibbs energy.Comment: 32 pages, 7 figures; supporting information is available at http://www.chnosz.net/yeas