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

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

Acute coronary occlusion secondary to radiofrequency catheter ablation of a left lateral accessory pathway

A case of asymptomatic acute coronary occlusion secondary to radiofrequency catheter ablation of a left lateral accessory pathway is reported. Due to post-procedural ST modifications of the surface ECG, a coronary angiography was performed which disclosed total occlusion of the first marginal branch of the left circumflex coronary artery. A cute myocardial infarction was confirmed by moderate cardiac enzyme release, abnormal myocardial perfusion scan and mild lateral hypokinesia at echocardiographv. This rare but potentially harmful complication of interventional electrophysiology should be kept in mind and coronary angiography performed immediately when coronary occlusion related to radiofrequency application is suspecte

Effects of exposure to hypoxia on the signal-averaged electrocardiogram in healthy subjects

The effects of hypoxia on the signal-averaged ECG (SAECG) were investigated in 26 healthy active subjects with no suggestion of cardiac disease. The SAECG was recorded in each resting subject in normoxic and hypoxic normobaric conditions (inspired O2 fraction 20.7 vs 10.0%) which lowered resting arterial O2 saturation from 98.6 +0.6% to 77.7 ± 8%. Recordings from four subjects (three men) met the definition of abnormal late potentials at baseline; in all these subjects but one, who exhibited an improved but still abnormal QRS duration, these parameters returned to normal in hypoxic conditions. The duration of the filtered QRS was significantly reduced (from 107.6 ±13.2 to 101.6 ± 11.3 ms, P<001), the duration of the low amplitude signals in the terminal portion of the QRS <40 μ V (LAS) significantly decreased (from 26.5 ± 9.5 to 22.7 ± 7.9 ms, P<005) and the root mean square voltage in the last 40 ms (Term-RMS) increased non-significantly (from 55.8±40.2 to 69.1±38.3 μV, P=0.058). Hypoxia determined a higher (P<0.05) heart rate increase in subjects with abnormal records than in normal subjects. These data could be related to a sympathic discharge. They suggest that: (1) variation in heart rate could affect the SAECG; (2) exposure to hypoxia improves SAECG parameters in healthy subjects, possibly related to sympathetic discharge; (3) abnormal records collected during sinus bradycardia could represent a type of false-positive expression of late potentials in young active adult

Intra-hisian 2:1 atrioventricular block secondary to Lyme disease

We describe a case of Lyme carditis with intra-hisian 2:1 atrioventricular (AV) block documented by electrophysiological study. To our knowledge, only two cases of AV block at the level of the His bundle has been described in the literature. Sinus rhythm was restored after 4 days of i.v. ceftriaxon

Phylogeny of the "orchid-like" bladderworts (gen. Utricularia sect. Orchidioides and Iperua : Lentibulariaceae) with remarks on the stolon-tuber system

Background and Aims The "orchid-like" bladderworts (Utricularia) comprise 15 species separated into two sections: Orchidioides and Iperua. These robust and mostly epiphytic species were originally grouped within the section Orchidioides by the first taxonomical systems. These species were later split into two sections when sect. Iperua was proposed. Due to the lack of strong evidence based on a robust phylogenetic perspective, this study presents a phylogenetic proposal based on four different DNA sequences (plastid and nuclear) and morphology to test the monophyly of the two sections. Methods In comparison with all previous phylogenetic studies, the largest number of species across the sections was covered: 11 species from sections Orchidioides and Iperua with 14 species as an external group. Maximum likelihood and Bayesian inferences were applied to DNA sequences of rps16, trnL-F, matK, the internal transcribed spacer (ITS) and three morphological characters: (1) the crest of the corolla; (2) the primary organs in the embryo; and (3) tubers. Additionally, a histochemical analysis of the stolons and tubers is presented from an evolutionary perspective. Key Results The analyses showed the paraphyly of sect. Iperua, since Utricularia humboldtii is more related to the clade of sect. Orchidioides. Utricularia cornigera is grouped in the sect. Iperua clade based on chloroplast DNA sequences, but it is nested to sect. Orchidioides according to ITS dataset. Morphological characters do not support the breaking up of the 'orchid-like' species into two sections, either. Moreover, the stolon-tuber systems of both sections serve exclusively for water storage, according to histological analyses. Conclusions This study provides strong evidence, based on DNA sequences from two genomic compartments (plastid and nucleus) and morphology to group the Utricularia sect. Orchidioides into the sect. Iperua. The tubers are important adaptations for water storage and have been derived from stolons at least twice in the phylogenetic history of 'orchid-like' bladderworts

International Veterinary Epilepsy Task Force recommendations for systematic sampling and processing of brains from epileptic dogs and cats

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals. The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures. Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements. The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations

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

Female germ unit in Genlisea and Utricularia, with remarks about the evolution of the extra-ovular female gametophyte in members of Lentibulariaceae

Lentibulariaceae is the largest family among carnivorous plants which displays not only an unusual morphology and anatomy but also the special evolution of its embryological characteristics. It has previously been reported by authors that Utricularia species lack a filiform apparatus in the synergids. The main purposes of this study were to determine whether a filiform apparatus occurs in the synergids of Utricularia and its sister genus Genlisea, and to compare the female germ unit in these genera. The present studies clearly show that synergids in both genera possess a filiform apparatus; however, it seems that Utricularia quelchii synergids have a simpler structure compared to Genlisea aurea and other typical angiosperms. The synergids are located at the terminal position in the embryo sacs of Pinguicula, Genlisea and were probably also located in that position in common Utricularia ancestor. This ancestral characteristic still occurs in some species from the Bivalvaria subgenus. An embryo sac, which grows out beyond the limit of the integument and has contact with nutritive tissue, appeared independently in different Utricularia lineages and as a consequence of this, the egg apparatus changes position from apical to lateral

Systems-Scale Analysis Reveals Pathways Involved in Cellular Response to Methamphetamine

Background: Methamphetamine (METH), an abused illicit drug, disrupts many cellular processes, including energy metabolism, spermatogenesis, and maintenance of oxidative status. However, many components of the molecular underpinnings of METH toxicity have yet to be established. Network analyses of integrated proteomic, transcriptomic and metabolomic data are particularly well suited for identifying cellular responses to toxins, such as METH, which might otherwise be obscured by the numerous and dynamic changes that are induced. Methodology/Results: We used network analyses of proteomic and transcriptomic data to evaluate pathways in Drosophila melanogaster that are affected by acute METH toxicity. METH exposure caused changes in the expression of genes involved with energy metabolism, suggesting a Warburg-like effect (aerobic glycolysis), which is normally associated with cancerous cells. Therefore, we tested the hypothesis that carbohydrate metabolism plays an important role in METH toxicity. In agreement with our hypothesis, we observed that increased dietary sugars partially alleviated the toxic effects of METH. Our systems analysis also showed that METH impacted genes and proteins known to be associated with muscular homeostasis/ contraction, maintenance of oxidative status, oxidative phosphorylation, spermatogenesis, iron and calcium homeostasis. Our results also provide numerous candidate genes for the METH-induced dysfunction of spermatogenesis, which have not been previously characterized at the molecular level. Conclusion: Our results support our overall hypothesis that METH causes a toxic syndrome that is characterized by the altered carbohydrate metabolism, dysregulation of calcium and iron homeostasis, increased oxidative stress, and disruption of mitochondrial functions