Significance of ventricular late potentials in non-ischaemic dilated cardiomyopathy

To assess the incidence and clinical significance of ventricular late potentials in non-ischaemic dilated cardiomyopathy, 51 consecutive (44 male, seven female, mean age 53± 11 years) patients with dilated cardiomyopathy were studied. Twenty-eight patients (55%) were in New York Heart Association functional class III or IV, 34 out of 51 (76%) had a left ventricular ejection fraction of less than 40%, 10 out of 51 (20%) had a history of sustained ventricular tachycardia ( VT), 24 out of 37 (65%) had runs of non-sustained ventricular tachycardia during Holier monitoring and 15 out of 51 (29%) had a left bundle branch block. A signal-averaged electrocardiogram (gain 106 x, bipolar chest leads, filters 100-300 Hz) was performed in all the patients; late potentials were considered present if the total filtered QRS duration was longer than 118 ms and the interval between the end of QRS and the voltage 40 μV was more than 40 ms in the absence of left bundle branch block (total filtered QRS duration > 140 ms and interval between the end of QRS and the voltage 40 μV>50ms in the presence of left bundle branch block). Ventricular late potentials were detected in 22 out of 51 patients (43%). Late potentials were present in 80% (eight out of 10) of patients with sustained ventricular tachycardia but in only 34% (14 of 41) without sustained ventricular tachycardia (P < 0.01). This difference remained statistically significant even when patients with a left bundle branch block were excluded from the analysis (4 out of 6 vs 4 out of 30, P<0.01). To identify patients with dilated cardiomyopathy and sustained ventricular tachycardia, signal-averaging had a sensitivity of 80%, a specificity of 66%, a positive predictive value of 36% and a negative predictive value of 93%. It is concluded that, in non-ischaemic dilated cardiomyopathy, the signal-averaged electrocardiogram allows the identification of patients with sustained ventricular tachycardia, even in the presence of a left bundle branch bloc

Predicting Impaired Extinction of Traumatic Memory and Elevated Startle

Emotionally traumatic experiences can lead to debilitating anxiety disorders, such as phobias and Post-Traumatic Stress Disorder (PTSD). Exposure to such experiences, however, is not sufficient to induce pathology, as only up to one quarter of people exposed to such events develop PTSD. These statistics, combined with findings that smaller hippocampal size prior to the trauma is associated with higher risk of developing PTSD, suggest that there are pre-disposing factors for such pathology. Because prospective studies in humans are limited and costly, investigating such pre-dispositions, and thus advancing understanding of the genesis of such pathologies, requires the use of animal models where predispositions are identified before the emotional trauma. Most existing animal models are retrospective: they classify subjects as those with or without a PTSD-like phenotype long after experiencing a traumatic event. Attempts to create prospective animal models have been largely unsuccessful.Here we report that individual predispositions to a PTSD-like phenotype, consisting of impaired rate and magnitude of extinction of an emotionally traumatic event coupled with long-lasting elevation of acoustic startle responses, can be revealed following exposure to a mild stressor, but before experiencing emotional trauma. We compare, in rats, the utility of several classification criteria and report that a combination of criteria based on acoustic startle responses and behavior in an anxiogenic environment is a reliable predictor of a PTSD-like phenotype.There are individual predispositions to developing impaired extinction and elevated acoustic startle that can be identified after exposure to a mildly stressful event, which by itself does not induce such a behavioral phenotype. The model presented here is a valuable tool for studying the etiology and pathophysiology of anxiety disorders and provides a platform for testing behavioral and pharmacological interventions that can reduce the probability of developing pathologic behaviors associated with such disorders

Ensemble Kalman filter assimilation of temperature and altimeter data with bias correction and application to seasonal prediction

To compensate for a poorly known geoid, satellite altimeter data is usually analyzed in terms of anomalies from the time mean record. When such anomalies are assimilated into an ocean model, the bias between the climatologies of the model and data is problematic. An ensemble Kalman filter (EnKF) is modified to account for the presence of a forecast-model bias and applied to the assimilation of TOPEX/Poseidon (T/P) altimeter data. The online bias correction (OBC) algorithm uses the same ensemble of model state vectors to estimate biased-error and unbiased-error covariance matrices. Covariance localization is used but the bias covariances have different localization scales from the unbiased-error covariances, thereby accounting for the fact that the bias in a global ocean model could have much larger spatial scales than the random error.The method is applied to a 27-layer version of the Poseidon global ocean general circulation model with about 30-million state variables. Experiments in which T/P altimeter anomalies are assimilated show that the OBC reduces the RMS observation minus forecast difference for sea-surface height (SSH) over a similar EnKF run in which OBC is not used. Independent in situ temperature observations show that the temperature field is also improved. When the T/P data and in situ temperature data are assimilated in the same run and the configuration of the ensemble at the end of the run is used to initialize the ocean component of the GMAO coupled forecast model, seasonal SSH hindcasts made with the coupled model are generally better than those initialized with optimal interpolation of temperature observations without altimeter data. The analysis of the corresponding sea-surface temperature hindcasts is not as conclusive

Adenosine has two faces: Regionally dichotomous adenosine tone in a model of epilepsy with comorbid sleep disorders

Objective: Adenosine participates in maintaining the excitatory/inhibitory balance in neuronal circuits. Studies indicate that adenosine levels in the cortex and hippocampus increase and exert sleep pressure in sleep-deprived and control animals, whereas in epilepsy reduced adenosine tone promotes hyperexcitability. To date, the role of adenosine in pathological conditions that result in both seizures and sleep disorders is unknown. Here, we determined adenosine tone in sleep and seizure regulating brain regions of Kv1.1 knockout (KO) mice, a model of temporal epilepsy with comorbid sleep disorders. Methods: 1) Reverse phase-high performance liquid chromatography (RP-HPLC) was performed on brain tissue to determine levels of adenosine and adenine nucleotides. 2) Multi-electrode array extracellular electrophysiology was used to determine adenosine tone in the hippocampal CA1 region and the lateral hypothalamus (LH). Results: RP-HPLC indicated a non-significant decrease in adenosine (~50%, p = 0.23) in whole brain homogenates of KO mice. Regional examination of relative levels of adenine nucleotides indicated decreased ATP and increased AMP in the cortex and hippocampus and increased adenosine in cortical tissue. Using electrophysiological and pharmacological techniques, estimated adenosine levels were ~35% lower in the KO hippocampal CA1 region, and 1–2 fold higher in the KO LH. Moreover, the increased adenosine in KO LH contributed to lower spontaneous firing rates of putative wake-promoting orexin/hypocretin neurons. Interpretation: This is the first study to demonstrate a direct correlation of regionally distinct dichotomous adenosine levels in a single model with both epilepsy and comorbid sleep disorders. The weaker inhibitory tone in the dorsal hippocampus is consistent with lower seizure threshold, whereas increased adenosine in the LH is consistent with chronic partial sleep deprivation. This work furthers our understanding of how adenosine may contribute to pathological conditions that underlie sleep disorders within the epileptic brain

Coordinated regulation of transcription by CcpA and the \u3ci\u3eStaphylococcus aureus\u3c/i\u3e twocomponent system HptRS

The success of Staphylococcus aureus as a pathogen is due in part to its ability to adapt to changing environmental conditions using signal transduction pathways, such as metaboliteresponsive regulators and two-component systems. S. aureus has a two-component system encoded by the gene pair sav0224 (hptS) and sav0223 (hptR) that regulate the hexose phosphate transport (uhpT) system in response to extracellular glucose-6-phosphate. Glycolytic intermediates such as glucose-6-phosphate are important carbon sources that also modulate the activity of the global metabolite-responsive transcriptional regulator CcpA. Because uhpT has a putative CcpA binding site in its promoter and it is regulated by HptR, it was hypothesized the regulons of CcpA and HptR might intersect. To determine if the regulatory domains of CcpA and HptRS overlap, ccpA was deleted in strains SA564 and SA564- ΔhptRS and growth, metabolic, proteomic, and transcriptional differences were assessed. As expected, CcpA represses hptS and hptR in a glucose dependent manner; however, upon CcpA derepression, the HptRS system functions as a transcriptional activator of metabolic genes within the CcpA regulon. Importantly, inactivation of ccpA and hptRS altered sensitivity to fosfomycin and ampicillin in the absence of exogenous glucose-6-phosphate, indicating that both CcpA and HptRS modulate antibiotic susceptibility

Behavioral and Endocrine Consequences of Simultaneous Exposure to Two Different Stressors in Rats: Interaction or Independence?

Although behavioral and endocrine consequences of acute exposure to stressors have been extensively studied, little is known about how simultaneous exposure to two different stressors interacts to induce short- and long-term effects. In the present experiment we studied this interaction in adult male rats exposed to cat fur odor (impregnated cloth) or immobilization on boards either separately or simultaneously. We reasoned that exposure to the odor of a potential predator while immobilized, may potentiate its negative consequences as compared to exposure to only one of the stressors. Exposure to cat odor elicited the expected reduction of activity and avoidance of the area where the impregnated cloth was located. The endocrine response (plasma levels of ACTH and corticosterone, as a measure of the hypothalamic-pituitary-adrenal axis, HPA) was markedly greater after immobilization than after cat fur odor and no additive effects were found by simultaneous exposure to both stressors. Cat odor, but not immobilization, increased anxiety-like behavior as evaluated in the elevated plus-maze 7 days after the stressors, with no evidence of enhanced HPA activation. In addition, cat odor exposure resulted in long-lasting (8 days later) fear conditioning to the box containing a clean cloth, which was reflected by hypoactivity, avoidance of the cloth area and enhanced HPA activation. All these effects were similarly observed in rats exposed simultaneously to cat odor and immobilization. In rats only exposed to immobilization, only some weak behavioral signs of fear conditioning were found, but HPA activation in response to the context paired to immobilization was enhanced to the same extent as in cat odor-exposed animals, supporting a certain degree of endocrine conditioning. The present results did not reveal important behavioral interactions between the two stressors when animals experienced both simultaneously, whereas some interactions were found regarding HPA activation. Theoretical implications are discussed

Spontaneous Firings of Carnivorous Aquatic Utricularia Traps: Temporal Patterns and Mechanical Oscillations

Aquatic species of Utricularia are carnivorous plants living in environments poor in nutrients. Their trapping mechanism has fascinated generations of scientists and is still debated today. It was reported recently that Utricularia traps can fire spontaneously. We show here that these spontaneous firings follow an unexpected diversity of temporal patterns, from “metronomic” traps which fire at fixed time intervals to “random” patterns, displaying more scattered firing times. Some “bursting” traps even combine both aspects, with groups of fast regular firings separated by a variable amount of time. We propose a physical model to understand these very particular behaviors, showing that a trap of Utricularia accomplishes mechanical oscillations, based on continuous pumping and sudden opening of the trap door (buckling). We isolate the key parameters governing these oscillations and discuss the effect of their fluctuations

Language and ethnobiological skills decline precipitously in Papua New Guinea, the world's most linguistically diverse nation

Papua New Guinea is home to >10% of the world’s languages and rich and varied biocultural knowledge, but the future of this diversity remains unclear. We measured language skills of 6,190 students speaking 392 languages (5.5% of the global total) and modeled their future trends using individual-level variables characterizing family language use, socioeconomic conditions, students’ skills, and language traits. This approach showed that only 58% of the students, compared to 91% of their parents, were fluent in indigenous languages, while the trends in key drivers of language skills (language use at home, proportion of mixed-language families, urbanization, students’ traditional skills) predicted accelerating decline of fluency to an estimated 26% in the next generation of students. Ethnobiological knowledge declined in close parallel with language skills. Varied medicinal plant uses known to the students speaking indigenous languages are replaced by a few, mostly nonnative species for the students speaking English or Tok Pisin, the national lingua franca. Most (88%) students want to teach indigenous language to their children. While crucial for keeping languages alive, this intention faces powerful external pressures as key factors (education, cash economy, road networks, and urbanization) associated with language attrition are valued in contemporary society