Chronic kidney disease impairs prognosis in electrical storm

Journal of Interventional Cardiac Electrophysiology - The study sought to assess the prognostic impact of chronic kidney disease (CKD) in patients with electrical storm (ES). ES represents a...     

Alzheimer's disease beta-amyloid peptides are released in association with exosomes

Although the exact etiology of Alzheimer's disease (AD) is a topic of debate, the consensus is that the accumulation of beta-amyloid (Abeta) peptides in the senile plaques is one of the hallmarks of the progression of the disease. The Abeta peptide is formed by the amyloidogenic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases. The endocytic system has been implicated in the cleavages leading to the formation of Abeta. However, the identity of the intracellular compartment where the amyloidogenic secretases cleave and the mechanism by which the intracellularly generated Abeta is released into the extracellular milieu are not clear. Here, we show that beta-cleavage occurs in early endosomes followed by routing of Abeta to multivesicular bodies (MVBs) in HeLa and N2a cells. Subsequently, a minute fraction of Abeta peptides can be secreted from the cells in association with exosomes, intraluminal vesicles of MVBs that are released into the extracellular space as a result of fusion of MVBs with the plasma membrane. Exosomal proteins were found to accumulate in the plaques of AD patient brains, suggesting a role in the pathogenesis of AD.     

Body surface potential mapping investigating the ventricular activation patterns in the cardiac resynchronization of patients with left bundle-branch block and heart failure

Body surface potential mapping assessed mean cardiac electrical activation times displayed by isochronal maps in the right ventricle (RV; right ventricle mean activation time [mRV]), anterior septal area (anterior septal area mean activation time [mAS]), and left ventricle (left ventricle mean activation time [mLV]) of 28 patients (mean, 61.07 years; congestive heart failure class III-IV; ejection fraction, < or =40%; left bundle-branch block [LBBB] QRS, 180.17 milliseconds), before and after biventricular pacemaker implantation, comparing them, using reference values from a control group of healthy individuals with normal hearts (GNL), in (1) baseline native LBBB, where mRV and mAS values were similar (40.99 vs 43.62 milliseconds), with mLV delayed (80.99 milliseconds, P < .01) and dyssynchronous with RV/anterior septal area; (2) single-site RV pacing, where mRV was greater than in GNL (86.82 milliseconds, P < .001), with greater mAS/mLV difference (63.41 vs 102.7 milliseconds; P < .001); and (3) biventricular pacing (BIV-PM), where mLV and mRV were similar (71.99 vs 71.58 milliseconds), mRV was greater than in GNL and native LBBB (71.58 vs 35.1 and 40.99 milliseconds; P < .001), and mAS approached values in GNL and native LBBB (51.28 vs 50.14 and 43.62 milliseconds). Body surface potential mapping showed that similar RV/left ventricle activation times during biventricular pacing, nearing mAS, indicate synchronized ventricular activation pattern in patients with congestive heart failure/LBBB.     

Songbirds tune their vocal tract to the fundamental frequency of their song

In human speech, the sound generated by the larynx is modified by articulatory movements of the upper vocal tract, which acts as a variable resonant filter concentrating energy near particular frequencies, or formants, essential in speech recognition. Despite its potential importance in vocal communication, little is known about the presence of tunable vocal tract filters in other vertebrates. The tonal quality of much birdsong, in which upper harmonics have relatively little energy, depends on filtering of the vocal source, but the nature of this filter is controversial. Current hypotheses treat the songbird vocal tract as a rigid tube with a resonance that is modulated by the end-correction of a variable beak opening. Through x-ray cinematography of singing birds, we show that birdsong is accompanied by cyclical movements of the hyoid skeleton and changes in the diameter of the cranial end of the esophagus that maintain an inverse relationship between the volume of the oropharyngeal cavity and esophagus and the song's fundamental frequency. A computational acoustic model indicates that this song-related motor pattern tunes the major resonance of the oropharyngeal-esophageal cavity to actively track the song's fundamental frequency.     

Requirement of the human T-cell leukemia virus (HTLV-1) tax-stimulated HIAP-1 gene for the survival of transformed lymphocytes

Human T cell leukemia virus type 1 (HTLV-1), the cause of adult T cell leukemia (ATL), induces clonal expansion of infected T-cells in nonleukemic individuals and immortalizes T cells in vitro. The resistance against apoptotic stimuli of these cells hints at a viral survival function in addition to a proliferation-stimulating activity. Here we describe the up-regulation of the antiapoptotic HIAP-1/CIAP-2 gene as a consistent phenotype of HTLV-1-transformed and ATL-derived cultures and its stimulation by the viral oncoprotein Tax. Cotransfections revealed a 60-fold increase of HIAP-1 promoter activity mediated by Tax mainly via nuclear factor-kappaB (NF-kappaB) activation. To address the relevance of virally increased HIAP-1 levels for the survival of HTLV-1-transformed cells, its expression was RNA interference (RNAi) suppressed using a lentiviral transduction system. This resulted in a dramatic reduction of cell growth, a strong induction of apoptosis rates, and increased caspases 3/7 activity, which is known to be suppressed by HIAP-1. Thus, the Tax-mediated HIAP-1 overexpression is required to suppress endogenous apoptosis and, therefore, is essential for the survival of HTLV-1-transformed lymphocytes. Moreover, this points to HIAP-1 as an important target of the HTLV-1-mediated NF-kappaB activation.     

Effect of Aspiration Thrombectomy on Microvascular Obstruction in NSTEMI Patients : The TATORT-NSTEMI Trial

Background

Aspiration thrombectomy in ST-segment elevation myocardial infarction is recommended by current guidelines based on several randomized trials. There are no trials assessing thrombectomy in non–ST-segment elevation myocardial infarction (NSTEMI) patients.

Objectives

The TATORT-NSTEMI (Thrombus Aspiration in Thrombus Containing Culprit Lesions in Non–ST-Elevation Myocardial Infarction) trial sought to assess the effect of aspiration thrombectomy on microvascular injury in patients with NSTEMI compared with standard percutaneous coronary intervention (PCI).

Methods

This prospective, controlled, multicenter study randomized 440 patients to adjunctive thrombectomy (n = 221) compared with conventional PCI (n = 219) in NSTEMI patients with thrombus-containing lesions. The primary endpoint of the extent of microvascular obstruction (MO) in the percentage of left ventricular mass (%LV) was assessed by cardiac magnetic resonance imaging within 4 days. Secondary endpoints included infarct size, myocardial salvage index, and angiographic parameters including myocardial blush grade and Thrombolysis In Myocardial Infarction flow grade. The combined clinical endpoint consisted of death, reinfarction, target vessel revascularization, and new congestive heart failure within 6 months.

Results

The primary endpoint of MO was not different between the thrombectomy and the standard PCI group with 2.0%LV (interquartile range [IQR]: 0.8 to 4.1) versus 1.4%LV (IQR: 0.7 to 2.6) (p = 0.17). Similarly, no significant differences were observed for infarct size (8.6%LV; IQR: 4.0 to 14.7 vs. 7.4%LV; IQR: 4.1 to 13.1; p = 0.46), myocardial salvage index (63.3; IQR: 35.4 to 87.2 vs. 65.6; IQR: 46.9 to 82.6; p = 0.45), or angiographic parameters such as blush grade (p = 0.63) and Thrombolysis In Myocardial Infarction flow grade (p = 0.66). Clinical follow-up at 6 months revealed no differences in the combined clinical endpoints (p = 0.22).

Conclusions

Aspiration thrombectomy in conjunction with PCI in NSTEMI with a thrombus-containing lesion does not lead to a reduction in MO. (Thrombus Aspiration in Thrombus Containing Culprit Lesions in Non-ST-Elevation Myocardial Infarction [TATORT-NSTEMI]; NCT01612312).     

Treatment Optimization of Aortocoronary Dissection as a Complication After Heart Catheterization Using Coronary Computerized Tomographic Angiography

We present the case of a 71-year-old patient with a chronic total occlusion of the right coronary artery (RCA) resulting in a retrograde aortic dissection as a complication of coronary intervention. Acute therapy consisted of coronary stent implantation into the proximal RCA to cover the dissection's entry. One day after, computed tomography-guided angiography revealed a progression of the intramural aortic hematoma with a residual dissection at the RCA ostium. Recurrent coronary angiography was performed to implant another stent covering the entry. Imaging at follow-up demonstrated complete coverage of the Dunning dissection and regression of the intramural aortic hematoma.     

From the Cover: Species interactions and the structure of complex communication networks

A universal challenge faced by animal species is the need to communicate effectively against a backdrop of heterospecific signals. It is often assumed that this need results in signal divergence to minimize interference among community members, yet previous support for this idea is mixed, and few studies have tested the opposing hypothesis that interactions among competing species promote widespread convergence in signaling regimes. Using a null model approach to analyze acoustic signaling in 307 species of Amazonian birds, we show that closely related lineages signal together in time and space and that acoustic signals given in temporal or spatial proximity are more similar in design than expected by chance. These results challenge the view that multispecies choruses are structured by temporal, spatial, or acoustic partitioning and instead suggest that social communication between competing species can fundamentally organize signaling assemblages, leading to the opposite pattern of clustering in signals and signaling behavior.One of the core principles of animal communication is that signals should be detectable and convey an accurate message against a noisy background (1–3). This background can involve direct overlap of sounds, as in the case of masking by simultaneous signals (4, 5), or simply the co-occurrence of different species using confusingly similar signals at the same location (6–8). As most animals communicate within assemblages of related species, the problem of signal interference is widespread and may have far-reaching implications for the evolution of signals and signaling behavior. This concept—variously termed the “noisy neighbors” hypothesis (9) or “cocktail party problem” (10)—has attracted much attention over recent years. However, the extent to which it provides a general explanation for patterns of signaling in animal communities remains contentious (6, 8).The traditional view is that the signaling strategies of animals are shaped by limiting similarity among competitors, much as competition for ecological resources is thought to promote partitioning of niche space (11–13). Partitioning of signal space may occur if species compete for position near overcrowded transmission optima, and, concurrently, if overlap in signal design impairs the detection or discrimination of signals mediating mate choice and resource competition (14). Under these conditions, mechanisms of selection against misdirected aggression (e.g., character displacement) or the production of unfit hybrids (e.g., reinforcement) are predicted to drive phenotypic divergence (9), whereas similar mechanisms may lead to related species signaling at different times or in different locations (13). These pathways theoretically lead to structural, temporal, and spatial partitioning of signals and signalers in animal assemblages, but tests of these patterns have produced mixed results (6, 11, 15).A contrasting possibility is that selection for signal divergence is weak and that co-occurring species instead show the opposite pattern of signal clustering (16). One potential driver of this pattern is that shared habitats can exert convergent selection on signals (17). Another is that signals often have dual function in mate attraction and resource defense (18), potentially mediating competition among closely related species for ecological resources (19). Thus, multispecies choruses may operate to some degree as extended communication networks, not only within species (20) but between species. The effect of such a network would be to increase the likelihood of interspecific communication involving closely related species with similar signals. A pattern of signal clustering caused by communication among similar congeners may be further exaggerated when competitive interactions among species promote signal similarity (16). This process may occur when individuals with convergent agonistic signals have higher fitness because they are better at defending resources against both conspecific and heterospecific competitors, driving convergent evolution (21, 22). Taken together, these alternative views suggest that the most pervasive effect of species interactions on animal communication systems may not be partitioning, as generally proposed, but synchrony and stereotypy among competing species.Progress in resolving these opposing viewpoints has been limited because most studies of signaling assemblages have compiled lists of species co-occurring at particular localities and then compared multiple assemblages across regional scales (6, 15). This approach may be misleading because of spatial biases in phylogenetic relationships and habitat. On the one hand, sympatric species tend to be significantly older than allopatric species, at least within radiations (23, 24), and thus the signals of co-occurring lineages may be more divergent than expected by chance simply because they have had more time to diverge, exaggerating the evidence for partitioning. Conversely, species co-occurring at local scales may be less divergent because they are segregated by habitat across a study site and therefore are unlikely to signal together. Although some studies (7, 11) partially overcome these issues by sampling assemblages from single points in space, none has considered the effects of habitat and the potential role of competitive interactions among related species (16). Moreover, previous studies have generally assessed partitioning in relatively small assemblages (<30 species), reducing both the likelihood of competition over transmission optima and the power of statistical tests.Here, we sample >90 signaling assemblages (Fig. S1) containing a combined total of >300 species (Dataset S1) to assess the role of species interactions in structuring and organizing the dawn chorus of Amazonian rainforest birds. Each assemblage comprised species producing acoustic signals, identified from standardized 120-min sound recordings taken at points distributed across a single study locality. We also restricted analyses to 10-min time blocks and assumed that assemblages of species signaling in these blocks were forced to discriminate among each other (i.e., they were each other’s background noise) and also that they had an increased likelihood of signaling simultaneously (i.e., directly masking each other’s signals). We use the term cosignaling to describe pairs of species signaling during the same 10- or 120-min time block and thus not necessarily signaling simultaneously. We coded all assemblages for habitat and time of day, calculated the acoustic similarity of cosignaling species using spectrographic analyses of voice recordings, and estimated the evolutionary relatedness of cosignaling species using a hierarchical taxonomic framework.Our null hypothesis states that species interactions have no effect on chorus structure and thus that species with similar signals are randomly distributed in space and time (Fig. 1A). The distance between signals in observed choruses should not differ significantly from that expected by chance, accounting for habitat and evolutionary relationships. We envisage two scenarios that may falsify the null. The partitioning hypothesis predicts that signal design is evenly spaced across communities, with a larger distance between co-occurring signals than predicted by chance (Fig. 1B). The network hypothesis predicts that competing species interact using phylogenetically conserved signals and thus that signals are clustered in distribution, with a smaller distance between co-occurring signals than predicted by chance (Fig. 1C). The partitioning and network hypotheses involve different forms of species interaction with opposing effects on chorus structure. Although we do not measure species interactions directly, we follow standard approaches in assuming that such interactions predict patterns in the trait structure of assemblages (25).Open in a separate windowFig. 1.Predictions of three hypotheses proposed to structure multispecies choruses, illustrated using hypothetical seven-species choruses with signal design plotted in multivariate signaling space. The null hypothesis that species interactions have no effect predicts that signal structure is random (A), generating an intermediate mean nearest-neighbor distance d. The partitioning hypothesis predicts an evenly spaced signal structure (B) reflected in larger values for d. The network hypothesis predicts that related species will signal together, causing signals to be clustered around optima (C), and generating small values for d. We test these predictions by assessing whether d, viewed across a sample of communities, is higher or lower than expected by chance. We calculated d in two ways: d₁ (Upper) is the mean nearest neighbor distance [nnd] across all community members; and d₂ (Lower) is the mean nnd across the three pairs of species with most similar signals.Our aims were to (i) quantify acoustic properties of signals transmitted in the dawn chorus; (ii) estimate the degree of signal similarity among cosignaling species; and (iii) compare the observed distribution of signal properties with that expected by chance. We also consider spatial explanations for chorus structure, including the reduced cosignaling of species with similar signals through spatial partitioning. This form of segregation may occur because ecological competition is elevated in tropical bird communities (26), causing parapatric (27) or “checkerboard” distributions (28) among closely related species, thus potentially leading to apparent signal partitioning by competitive exclusion. The network hypothesis predicts the opposite pattern as closely related species should synchronize their signaling activity using shared territorial signals. We test these predictions by comparing 120-min (spatially segregated) and 10-min (nonsegregated) choruses and using taxonomic relatedness to estimate the degree of cosignaling between close relatives.The Amazonian dawn chorus provides one of the world’s most diverse multispecies signaling assemblages and an ideal system for exploring the effects of competition on signaling strategies for three reasons. First, visibility is hampered by dense vegetation, and thus long-distance signaling is forced into one modality (acoustic communication). Second, background noise levels are extremely high as a result of other organisms, including insects, amphibians, and primates, suggesting that selection for partitioning of acoustic signals should be maximized (12). Finally, many tropical species are permanently resident and apparently interspecifically territorial, using acoustic signals to mediate competitive interactions with heterospecifics (18, 26, 29). In combination, these factors imply that large numbers of species compete both for ecological resources and a narrow window of optimal signaling space (7, 30), providing a context in which to test the relative importance of acoustic partitioning and interspecific communication networks.     

Factors associated with engaging socially marginalized HIV-positive persons in primary care

This paper examines factors associated with engaging socially marginalized HIV-positive persons in primary care using interview and chart review data from 984 clients presenting for services at 10 agencies participating in a multisite demonstration project. The sample was predominantly minority, and many reported drug and mental health problems as well as housing instability. At baseline, roughly half of the participants were engaged in HIV primary care; the other participants were either not at all engaged in HIV primary care or somewhat engaged in care. Those who were somewhat engaged in care were very similar to those who were not at all engaged in care, and significantly different than those who were fully engaged in care across a number of demographic, health status/utilization, and barriers to care items and fared equally poorly with regard to engagement in care at 12-month follow-up. In 12-month longitudinal analyses, 58% of those not engaged at baseline ( n = 517) became more fully engaged in care. In the final multivariate model that controlled for disease stage, decreases in drug use, structural barriers, and unmet needs were associated with engagement in care. Interventions that focus on decreasing structural barriers and unmet support services needs, addressing negative health beliefs and attending to drug use are promising public health strategies to engage marginalized HIV-positive persons in HIV primary care.