Time courses and quantitative analysis of atrial fibrillation episode number and duration after circular plus linear left atrial lesions: trigger elimination or substrate modification: early or delayed cure?

OBJECTIVES We sought to analyze the time course of atrial fibrillation (AF) episodes before and after circular plus linear left atrial ablation and the percentage of patients with complete freedom from AF after ablation by using serial seven-day electrocardiograms (ECGs). BACKGROUND The curative treatment of AF targets the pathophysiological corner stones of AF (i.e., the initiating triggers and/or the perpetuation of AF). The pathophysiological complexity of both may not result in an "all-or-nothing" response but may modify number and duration of AF episodes. METHODS In patients with highly symptomatic AF, circular plus linear ablation lesions were placed around the left and right pulmonary veins, between the two circles, and from the left circle to the mitral annulus using the electroanatomic mapping system. Repetitive continuous 7-day ECGs administered before and after catheter ablation were used for rhythm follow-up. RESULTS In 100 patients with paroxysmal (n = 80) and persistent (n = 20) AF, relative duration of time spent in AF significantly decreased over time (35 +/- 37% before ablation, 26 +/- 41% directly after ablation, and 10 +/- 22% after 12 months). Freedom from AF stepwise increased in patients with paroxysmal AF and after 12 months measured at 88% or 74% depending on whether 24-h ECG or 7-day ECG was used. Complete pulmonary vein isolation was demonstrated in <20% of the circular lesions. CONCLUSIONS The results obtained in patients with AF treated with circular plus linear left atrial lesions strongly indicate that substrate modification is the main underlying pathophysiologic mechanism and that it results in a delayed cure instead of an immediate cure.

IL-33 is a mediator rather than a trigger of the acute allergic response in humans

BACKGROUND IL-33 enhances FcεRI-induced mediator release in human basophils without inducing degranulation itself. In contrast, studies in mice suggested that in the presence of high IgE levels, IL-33 triggers degranulation and anaphylaxis of similar severity as specific allergen. Consistent with this view, sera of atopic patients contain elevated levels of IL-33 after anaphylaxis. In this study, we determined whether IL-33 is potentially anaphylactogenic in humans with high IgE levels by regulating exocytosis independent of FcεRI cross-linking. Furthermore, we investigated whether IL-33 is released upon allergen provocation in vivo. METHODS In subjects with high serum IgE levels, we measured IL-33-induced histamine/LTC4 in vitro, CD63 translocation ex vivo, and responsiveness of mast cells in vivo by skin prick test (SPT). In asthma patients, release of IL-33 and its correlation with early (tryptase)- and late-phase markers (IL-13 levels, eosinophil numbers) of the allergic response were assessed in bronchoalveolar lavage fluids (BALFs) after allergen challenge. RESULTS IL-33 itself does not trigger basophil degranulation in vitro and ex vivo, even in subjects with high serum IgE levels, and negative SPTs demonstrate that skin mast cells do not degranulate in response to IL-33. However, in response to allergen challenge, IL-33 is rapidly released into BALFs at levels that do not correlate with other immediate- and late-phase parameters. CONCLUSION IL-33 is unlikely an independent trigger of anaphylaxis even in subjects with high IgE levels. However, the rapid release of IL-33 upon allergen provocation in vivo supports its role as a mediator of immediate allergic responses.

Possible earthquake trigger for 6th century mass wasting deposit at Lake Ohrid (Macedonia/Albania)

Abstract. Lake Ohrid shared by the Republics of Albania and Macedonia is formed by a tectonically active graben within the south Balkans and suggested to be the oldest lake in Europe. Several studies have shown that the lake provides a valuable record of climatic and environmental changes and a distal tephrostratigraphic record of volcanic eruptions from Italy. Fault structures identified in seismic data demonstrate that sediments have also the potential to record tectonic activity in the region. Here, we provide an example of linking seismic and sedimentological information with tectonic activity and historical documents. Historical documents indicate that a major earthquake destroyed the city of Lychnidus (today: city of Ohrid) in the early 6th century AD. Multichannel seismic profiles, parametric sediment echosounder profiles, and a 10.08m long sediment record from the western part of the lake indicate a 2m thick mass wasting deposit, which is tentatively correlated with this earthquake. The mass wasting deposit is chronologically well constrained, as it directly overlays the AD472/AD 512 tephra. Moreover, radiocarbon dates and cross correlation with other sediment sequences with similar geochemical characteristics of the Holocene indicate that the mass wasting event took place prior to the onset of the Medieval Warm Period, and is attributed it to one of the known earthquakes in the region in the early 6th century AD.

Does World Natural Heritage status trigger sustainable regional development efforts?

Today, there are over 200 World Natural Heritage (WNH) sites. Although the original aim of the World Heritage (WH) Convention was to spark off concerted international efforts to preserve sites of outstanding and universal value, today a multitude of expectations rests on WNH sites in terms of conservation, tourism, management and regional development. This paper identifies the effects of WNH status on sustainable regional development and the driving factors behind these effects. The results are based on a global survey of WNH sites and qualitative interviews with key WNH personnel. The paper shows that WNH status can be an important trigger for sustainable regional development, but its effectiveness depends on a number of intricately interwoven ‘soft’ success factors. Clearer policies and management guidelines, as envisaged by UNESCO, are crucial to achieving a balance between conservation and development.

More conflict does not trigger more adjustment of cognitive control for subsequent events: A study of the bivalency effect

Encountering a conflict triggers an adjustment of cognitive control. This adjustment of cognitive control can even affect subsequent performance. The purpose of the present study was to determine whether more conflict triggers more adjustment of cognitive control for subsequent performance. To this end, we focussed on the bivalency effect, that is, the adjustment of cognitive control following the conflict induced by bivalent stimuli (i.e., stimuli with relevant features for two tasks). In two experiments, we tested whether the amount of conflict triggered by bivalent stimuli affected the bivalency effect. Bivalent stimuli were either compatible (i.e., affording one response) or incompatible (i.e., affording two different responses). Thus, compatible bivalent stimuli involved a task conflict, whereas incompatible bivalent stimuli involved a task and a response conflict. The results showed that the bivalency effect was not affected by this manipulation. This indicates that more conflict does not trigger more adjustment of cognitive control for subsequent performance. Therefore, only the occurrence of conflict--not its amount--is determinant for cognitive control.

More conflict does not trigger more adjustment of cognitive control for subsequent performance: A study of the bivalency effect

Encountering a conflict triggers an adjustment of cognitive control. This adjustment of cognitive control can even affect subsequent performance. The purpose of the present study was to determine whether more conflict triggers more adjustment of cognitive control for subsequent performance. To this end, we focussed on the bivalency effect, that is, the adjustment of cognitive control following the conflict induced by bivalent stimuli (i.e., stimuli with relevant features for two tasks). In two experiments, we tested whether the amount of conflict triggered by bivalent stimuli affected the bivalency effect. Bivalent stimuli were either compatible (i.e., affording one response) or incompatible (i.e., affording two different responses). Thus, compatible bivalent stimuli involved a task conflict, whereas incompatible bivalent stimuli involved a task and a response conflict. The results showed that the bivalency effect was not affected by this manipulation. This indicates that more conflict does not trigger more adjustment of cognitive control for subsequent performance. Therefore, only the occurrence of conflict – not its amount – is determinant for cognitive control

Factors that trigger emergency physicians to contact a poison centre: findings from a Swiss study.

OBJECTIVE Poison centres offer rapid and comprehensive support for emergency physicians managing poisoned patients. This study investigates institutional, case-specific and poisoning-specific factors which influence the decision of emergency physicians to contact a poison centre. METHODS Retrospective, consecutive review of all poisoning-related admissions to the emergency departments (EDs) of a primary care hospital and a university hospital-based tertiary referral centre during 2007. Corresponding poison centre consultations were extracted from the poison centre database. Data were matched and analysed by logistic regression and generalised linear mixed models. RESULTS 545 poisonings were treated in the participating EDs (350 (64.2%) in the tertiary care centre, 195 (35.8%) in the primary care hospital). The poison centre was consulted in 62 (11.4%) cases (38 (61.3%) by the tertiary care centre and 24 (38.7%) by the primary care hospital). Factors significantly associated with poison centre consultation included gender (female vs male) (OR 2.99; 95% CI 1.69 to 5.29; p<0.001), number of ingested substances (>1 vs 1) (OR 2.84; 95% CI 1.65 to 4.9; p<0.001) and situation (accidental vs intentional) (OR 2.76; 95% CI 1.05 to 7.25; p=0.039). In contrast, age, medical history and hospital size did not influence poison centre consultation. Poison centre consultation was significantly higher during the week, and significantly less during night shifts. The poison centre was consulted significantly more when patients were admitted to intensive care units (OR 5.81; 95% CI 3.25 to 10.37; p<0.001). Asymptomatic and severe versus mild cases were associated with more frequent consultation (OR 4.48; 95% CI 1.78 to 11.26; p=0.001 and OR 2.76; 95% CI 1.42 to 5.38; p=0.003). CONCLUSIONS We found low rates of poison centre consultation by emergency physicians. It appears that intensive care unit admission and other factors reflecting either complexity or uncertainty of the clinical situation are the strongest predictors for poison centre consultation. Hospital size did not influence referral behaviour.

The Salmonella pathogenicity island (SPI)-2 and SPI-1 type III secretion systems allow Salmonella serovar typhimurium to trigger colitis via MyD88-dependent and MyD88-independent mechanisms.

Salmonella typhimurium can colonize the gut, invade intestinal tissues, and cause enterocolitis. In vitro studies suggest different mechanisms leading to mucosal inflammation, including 1) direct modulation of proinflammatory signaling by bacterial type III effector proteins and 2) disruption or penetration of the intestinal epithelium so that penetrating bacteria or bacterial products can trigger innate immunity (i.e., TLR signaling). We studied these mechanisms in vivo using streptomycin-pretreated wild-type and knockout mice including MyD88(-/-) animals lacking an adaptor molecule required for signaling via most TLRs. The Salmonella SPI-1 and the SPI-2 type III secretion systems (TTSS) contributed to inflammation. Mutants that retain only a functional SPI-1 (M556; sseD::aphT) or a SPI-2 TTSS (SB161; DeltainvG) caused attenuated colitis, which reflected distinct aspects of the colitis caused by wild-type S. typhimurium: M556 caused diffuse cecal inflammation that did not require MyD88 signaling. In contrast, SB161 induced focal mucosal inflammation requiring MyD88. M556 but not SB161 was found in intestinal epithelial cells. In the lamina propria, M556 and SB161 appeared to reside in different leukocyte cell populations as indicated by differential CD11c staining. Only the SPI-2-dependent inflammatory pathway required aroA-dependent intracellular growth. Thus, S. typhimurium can use two independent mechanisms to elicit colitis in vivo: SPI-1-dependent and MyD88-independent signaling to epithelial cells and SPI-2-dependent intracellular proliferation in the lamina propria triggering MyD88-dependent innate immune responses.

Reciprocity as a trigger of social cooperation in contemporary immigration societies?

While the system stabilizing function of reciprocity is widely acknowledged, much less attention has been paid to the argument that reciprocity might initiate social cooperation in the first place. This paper tests Gouldner’s early assumption that reciprocity may act as a ‘starting mechanism’ of social cooperation in consolidating societies. The empirical test scenario builds on unequal civic engagement between immigrants and nationals, as this engagement gap can be read as a lack of social cooperation in consolidating immigration societies. Empirical analyses using survey data on reciprocal norms and based on Bayesian hierarchical modelling lend support for Gouldner’s thesis, underlining thereby the relevance of reciprocity in today’s increasingly diverse societies: individual norms of altruistic reciprocity elevate immigrants’ propensity to volunteer, reducing thereby the engagement gap between immigrants and natives in the area of informal volunteering. In other words, compliance with altruistic reciprocity may trigger cooperation in social strata, where it is less likely to occur. The positive moderation of the informal engagement gap through altruistic reciprocity turns out to be most pronounced for immigrants who are least likely to engage in informal volunteering, meaning low, but also high educated immigrants.

The granulocyte orphan receptor CEACAM4 is able to trigger phagocytosis of bacteria.

Human granulocytes express several glycoproteins of the CEACAM family. One family member, CEACAM3, operates as a single-chain phagocytic receptor, initiating the detection, internalization, and destruction of a limited set of gram-negative bacteria. In contrast, the function of CEACAM4, a closely related protein, is completely unknown. This is mainly a result of a lack of a specific ligand for CEACAM4. By generating chimeric proteins containing the extracellular bacteria-binding domain of CEACAM3 and the transmembrane and cytoplasmic part of CEACAM4 (CEACAM3/4) we demonstrate that this chimeric receptor can trigger efficient phagocytosis of attached particles. Uptake of CEACAM3/4-bound bacteria requires the intact ITAM of CEACAM4, and this motif is phosphorylated by Src family PTKs upon receptor clustering. Furthermore, SH2 domains derived from Src PTKs, PI3K, and the adapter molecule Nck are recruited and associate directly with the phosphorylated CEACAM4 ITAM. Deletion of this sequence motif or inhibition of Src PTKs blocks CEACAM4-mediated uptake. Together, our results suggest that this orphan receptor of the CEACAM family has phagocytic function and prompt efforts to identify CEACAM4 ligands.

Circulating tumor cells as trigger to hematogenous spreads and potential biomarkers to predict the prognosis in ovarian cancer.

Despite several improvements in the surgical field and in the systemic treatment, ovarian cancer (OC) is still characterized by high recurrence rates and consequently poor survival. In OC, there is still a great lack of knowledge with regard to cancer behavior and mechanisms of recurrence, progression, and drug resistance. The OC metastatization process mostly occurs via intracoelomatic spread. Recent evidences show that tumor cells generate a favorable microenvironment consisting in T regulatory cells, T infiltrating lymphocytes, and cytokines which are able to establish an "immuno-tolerance mileau" in which a tumor cell can become a resistant clone. When the disease responds to treatment, immunoediting processes and cancer progression have been stopped. A similar inhibition of the immunosuppressive microenvironment has been observed after optimal cytoreductive surgery as well. In this scenario, the early identification of circulating tumor cells could represent a precocious signal of loss of the immune balance that precedes cancer immunoediting and relapse. Supporting this hypothesis, circulating tumor cells have been demonstrated to be a prognostic factor in several solid tumors such as colorectal, pancreatic, gastric, breast, and genitourinary cancer. In OC, the role of circulating tumor cells is still to be defined. However, as opposed to healthy women, circulating tumor cells have been demonstrated in peripheral blood of OC patients, opening a new research field in OC diagnosis, treatment monitoring, and follow-up.

Depolarization-dependent synaptic potentiation and hyperexcitability induced by a Ca2+-independent trigger

Despite vast research efforts since Cajal's seminal thoughts on the adaptation of the nervous system, researchers have only recently begun to understand the diversity of forms of neuronal plasticity and its mechanisms. All known forms of activity-dependent neuronal plasticity utilize alterations in [Ca 2+]i as a signal of changes in the membrane voltage. Ca 2+ sensors trigger modifications in excitability or synaptic strength that last from seconds to weeks and presumably years. Intriguingly, Kunjilwar et al., (unpublished observations) discovered in peripheral sensory axons of Aplysia that the induction of depolarization-dependent long-term axonal hyperexcitability does not require Ca2+ transients. Here we show that induction of depolarization-dependent intermediate-term and long-term synaptic potentiation in Aplysia occurs in conditions that prevent Ca2+ entry through voltage-gated channels and elevation of [Ca2+]i. We found that the intermediate-term synaptic potentiation induced under conditions expected to prevent Ca 2+ transients is associated with increased excitability of sensory neuron axons near presynaptic terminals, suggesting that the synaptic potentiation involves a presynaptic locus. The Ca2+-independent intermediate- and long-term synaptic potentiation appeared similar to previously reported Ca2+-dependent modifications in Aplysia. ^