Voyages astraux et hors du corps. Héautoscopie, extase et hallucinations expérientielles d'origine épileptique [Astral and out-of-body voyages. Heautoscopy, ecstasis and experimental hallucinations of epileptic origin]

We report a 38 year-old patient who had temporoparietal epilepsy and unusual ictal "out of body" experiences that remained undiagnosed for more than ten years, until her admission for a motor seizure of the left hemibody. Out of body episodes were experienced as intense and ecstatic astral journeys. EEG showed a bilateral extension of epileptiform abnormalities to the parietal regions, predominantly on the right side. We discuss the various forms of heautoscopy and their putative mechanisms. We suggest that a disturbance in representing space in independent extrapersonal and personal coordinates might be as crucial as the elusive hypothesis of a body schema disorder. Combined involvement of the parietal neocortex and temporolimbic structures might allow those experiences to gain a subjective vividness which appears to be indissociable from normal conscious experiences.

The role of population origin and microenvironment in seedling emergence and early survival in Mediterranean maritime pine (Pinus pinaster Aiton).

Understanding tree recruitment is needed to forecast future forest distribution. Many studies have reported the relevant ecological factors that affect recruitment success in trees, but the potential for genetic-based differences in recruitment has often been neglected. In this study, we established a semi-natural reciprocal sowing experiment to test for local adaptation and microenvironment effects (evaluated here by canopy cover) in the emergence and early survival of maritime pine (Pinus pinaster Aiton), an emblematic Mediterranean forest tree. A novel application of molecular markers was also developed to test for family selection and, thus, for potential genetic change over generations. Overall, we did not find evidence to support local adaptation at the recruitment stage in our semi-natural experiment. Moreover, only weak family selection (if any) was found, suggesting that in stressful environments with low survival, stochastic processes and among-year climate variability may drive recruitment. Nevertheless, our study revealed that, at early stages of recruitment, microenvironments may favor the population with the best adapted life strategy, irrespectively of its (local or non-local) origin. We also found that emergence time is a key factor for seedling survival in stressful Mediterranean environments. Our study highlights the complexity of the factors influencing the early stages of establishment of maritime pine and provides insights into possible management actions aimed at environmental change impact mitigation. In particular, we found that the high stochasticity of the recruitment process in stressful environments and the differences in population-specific adaptive strategies may difficult assisted migration schemes.

The Amish Mennonites: A sketch of Their Origin, and of Their Settlement in Iowa, with Their Creed in an Appendix,1894.

Traces the origin and growth of the Mennonite movement from its first summation into a creed in Holland and its story as it has been recorded in American, and in later years in Iowa.

Effects of common origin and common rearing environment on variance in ectoparasite load and phenotype of nestling Alpine swifts

Knowledge of the quantitative genetics of resistance to parasitism is key to appraise host evolutionary responses to parasite selection. Here, we studied effects of common origin (i.e. genetic and pre-hatching parental effects) and common rearing environment (i.e. post-hatching parental effects and other environment effects) on variance in ectoparasite load in nestling Alpine swifts (Apus melba). This colonial bird is intensely parasitized by blood sucking louse-flies that impair nestling development and survival. By cross-fostering half of the hatchlings between pairs of nests, we show strong significant effect of common rearing environment on variance (90.7% in 2002 and 90.9% in 2003) in the number of louse-flies per nestling and no significant effect of common origin on variance in the number of louse-flies per nestling. In contrast, significant effects of common origin were found for all the nestling morphological traits (i.e. body mass, wing length, tail length, fork length and sternum length) under investigation. Hence, our study suggests that genetic and pre-hatching parental effects play little role in the distribution of parasites among nestling Alpine swifts, and thus that nestlings have only limited scope for evolutionary responses against parasites. Our results highlight the need to take into consideration environmental factors, including the evolution of post-hatching parental effects such as nest sanitation, in our understanding of host-parasite relationships.

Auditory verbal hallucinations of epileptic origin.

Complex auditory hallucinations are often characterized by hearing voices and are then called auditory verbal hallucinations (AVHs). While AVHs have been extensively investigated in psychiatric patients suffering from schizophrenia, reports from neurological patients are rare and, in most cases, incomplete. Here, we characterize AVHs in 9 patients suffering from pharmacoresistant epilepsy by analyzing the phenomenology of AVHs and patients' neuropsychological and lesion profiles. From a cohort of 352 consecutively examined patients with epilepsy, 9 patients suffering AVHs were identified and studied by means of a semistructured interview, neuropsychological tests, and multimodal imaging, relying on a combination of functional and structural neuroimaging data and surface and intracranial EEG. We found that AVHs in patients with epilepsy were associated with prevalent language deficits and damage to posterior language areas and basal language areas in the left temporal cortex. Auditory verbal hallucinations, most of the times, consisted in hearing a single voice of the same gender and language as the patient and had specific spatial features, being, most of the times, perceived in the external space, contralateral to the lesion. We argue that the consistent location of AVHs in the contralesional external space, the prominence of associated language deficits, and the prevalence of lesions to the posterior temporal language areas characterize AVHs of neurological origin, distinguishing them from those of psychiatric origin.

Macular and retinal dysfunction of unknown origin in adults with normal fundi: evidence for an autoimmune pathophysiology.

Here we report the discovery of and phenotypic characterization of a retinal disorder of unknown origin in adults using clinical, electrophysiological and psychophysical techniques, and to seek the presence of circulating retinal autoantibodies in the sera of these patients. Sixteen patients were identified with progressive bilateral visual loss over a period of months. Ten of the patients were male, and the average age was 55.3 years (range from 43 to 76 years). Known causes such as carcinoma-associated retinopathy, acute zonal occult outer retinopathy and hereditary cone dystrophy appeared unlikely. Investigations included electrophysiology, fundus autofluorescence imaging and psychophysical tests. The sera of these patients were analyzed with indirect immunocytochemistry and Western immunoblot analysis on murine (BALB/c) retinal tissue for the presence of retinal autoantibodies. Bilateral visual loss and photophobia progressed over a period of months to years (average 28.7 months, range 3-67) and subsequently stabilized. No abnormality was observed by biomicroscopy, angiography or autofluorescence imaging. Electrophysiology indicated predominant cone-system dysfunction, either macular or generalized, and post-phototransduction involvement in 9 patients (56%). Photopic and scotopic visual fields and dark adaptation kinetics showed both cone and rod system involvement in all cases. Heterogeneous immunohistochemical staining patterns were seen with the sera of these patients as compared with controls. A majority of the affected patients (9/15) stained with an antinuclear pattern. The retinal autoantibodies from the sera of most patients reacted with the retinal proteins of molecular weight between 34 and 40 kDa. The aetiology of this distinctive retinal disorder therefore appears to be mediated through an autoimmune mechanism.

Identification of human IKK-2 inhibitors of natural origin (Part II): in Silico prediction of IKK-2 inhibitors in natural extracts with known anti-inflammatory activity.

Human inhibitor NF-κB kinase 2 (hIKK-2) is the primary component responsible for activating NF-κB in response to various inflammatory stimuli. Thus, synthetic ATP-competitive inhibitors for hIKK-2 have been developed as anti-inflammatory compounds. We recently reported a virtual screening protocol (doi:10.1371/journal.pone.0016903) that is able to identify hIKK-2 inhibitors that are not structurally related to any known molecule that inhibits hIKK-2 and that have never been reported to have anti-inflammatory activity. In this study, a stricter version of this protocol was applied to an in-house database of 29,779 natural products annotated with their natural source. The search identified 274 molecules (isolated from 453 different natural extracts) predicted to inhibit hIKK-2. An exhaustive bibliographic search revealed that anti-inflammatory activity has been previously described for: (a) 36 out of these 453 extracts; and (b) 17 out of 30 virtual screening hits present in these 36 extracts. Only one of the remaining 13 hit molecules in these extracts shows chemical similarity with known synthetic hIKK-2 inhibitors. Therefore, it is plausible that a significant portion of the remaining 12 hit molecules are lead-hopping candidates for the development of new hIKK-2 inhibitors.

Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study.

BACKGROUND: Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. METHODS AND RESULTS: The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged > or =55 years, having suffered an ischemic stroke (< or =3 months) or a transient ischemic attack (< or =8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2-4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. CONCLUSIONS: The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event.

A mixed ecologic-cohort comparison of physical activity & weight among young adults from five populations of African origin.

BACKGROUND: Examination of patterns and intensity of physical activity (PA) across cultures where obesity prevalence varies widely provides insight into one aspect of the ongoing epidemiologic transition. The primary hypothesis being addressed is whether low levels of PA are associated with excess weight and adiposity. METHODS: We recruited young adults from five countries (500 per country, 2500 total, ages 25-45 years), spanning the range of obesity prevalence. Men and women were recruited from a suburb of Chicago, Illinois, USA; urban Jamaica; rural Ghana; peri-urban South Africa; and the Seychelles. PA was measured using accelerometry and expressed as minutes per day of moderate-to-vigorous activity or sedentary behavior. RESULTS: Obesity (BMI ≥ 30) prevalence ranged from 1.4% (Ghanaian men) to 63.8% (US women). South African men were the most active, followed by Ghanaian men. Relatively small differences were observed across sites among women; however, women in Ghana accumulated the most activity. Within site-gender sub-groups, the correlation of activity with BMI and other measures of adiposity was inconsistent; the combined correlation across sites was -0.17 for men and -0.11 for women. In the ecological analysis time spent in moderate-to-vigorous activity was inversely associated with BMI (r = -0.71). CONCLUSION: These analyses suggest that persons with greater adiposity tend to engage in less PA, although the associations are weak and the direction of causality cannot be inferred because measurements are cross-sectional. Longitudinal data will be required to elucidate direction of association.

The long non-coding RNA NEAT1 is increased in IUGR placentas, leading to potential new hypotheses of IUGR origin/development.

INTRODUCTION: Intrauterine Growth Restriction (IUGR) is a multifactorial disease defined by an inability of the fetus to reach its growth potential. IUGR not only increases the risk of neonatal mortality/morbidity, but also the risk of metabolic syndrome during adulthood. Certain placental proteins have been shown to be implicated in IUGR development, such as proteins from the GH/IGF axis and angiogenesis/apoptosis processes. METHODS: Twelve patients with term IUGR pregnancy (birth weight < 10th percentile) and 12 CTRLs were included. mRNA was extracted from the fetal part of the placenta and submitted to a subtraction method (Clontech PCR-Select cDNA Subtraction). RESULTS: One candidate gene identified was the long non-coding RNA NEAT1 (nuclear paraspeckle assembly transcript 1). NEAT1 is the core component of a subnuclear structure called paraspeckle. This structure is responsible for the retention of hyperedited mRNAs in the nucleus. Overall, NEAT1 mRNA expression was 4.14 (±1.16)-fold increased in IUGR vs. CTRL placentas (P = 0.009). NEAT1 was exclusively localized in the nuclei of the villous trophoblasts and was expressed in more nuclei and with greater intensity in IUGR placentas than in CTRLs. PSPC1, one of the three main proteins of the paraspeckle, co-localized with NEAT1 in the villous trophoblasts. The expression of NEAT1_2 mRNA, the long isoform of NEAT1, was only modestly increased in IUGR vs. CTRL placentas. DISCUSSION/CONCLUSION: The increase in NEAT1 and its co-localization with PSPC1 suggests an increase in paraspeckles in IUGR villous trophoblasts. This could lead to an increased retention of important mRNAs in villous trophoblasts nuclei. Given that the villous trophoblasts are crucial for the barrier function of the placenta, this could in part explain placental dysfunction in idiopathic IUGR fetuses.

Fever of unknown origin in a Swiss-born child: don't miss tuberculosis!

Tuberculosis incidence is low in Switzer land. We report here on a Swiss-born toddler. Tuberculosis manifested with a fever of unknown origin, mimicking an inflammatory or autoimmune disorder triggering a high dose of corticosteroid treatment. The disease went unrecognized for several weeks until development of a miliary tuberculosis with advanced central nervous system involvement. This case highlights the difficulties encountered in diagnosing tuberculosis and in identifying the origin of this case. It reminds us that this disease must never be forgotten when facing a child with persistent fever who must be screened for, before starting immunosuppressive therapy.

Fatigue prolongée ou chronique d'origine indéterminée [Prolonged or chronic fatigue of unknown origin].

Although prolonged or chronic fatigue is a very common complaint in primary care medicine, a biomedical obvious cause is often not found. In such a case, for women between 18 and 50 years with a ferritin level of less than 50 µg/l in the absence of anaemia, an iron supplementation may be associated with an improvement in fatigue. Appropriate treatment is also important for depression, anxiety or insomnia. In other cases, the approach is essentially non-pharmacological in the form of lifestyle advice, empathy and cognitive behavioural therapy as well as progressive and adapted physical exercises. Bien que la fatigue prolongée ou chronique soit une plainte très fréquente en médecine de premier recours, une cause biomédicale évidente n'est souvent pas retrouvée. Dans une telle situation, pour les femmes entre 18 et 50 ans avec un taux de ferritine inférieur à 50 µg/l en l'absence d'anémie, un traitement de fer peut être associé à une amélioration de la fatigue. Un traitement adapté est également important en cas de dépression, d'anxiété ou d'insomnie. Dans les autres situations, la prise en charge est essentiellement non pharmacologique sous forme de conseils d'hygiène de vie, d'empathie, de thérapie cognitivo-comportementale ainsi que d'exercices physiques progressifs et adaptés.

Assessment of the discrimination of animal fat by FT_Raman spectroscopy

In recent years, there has been an increased attention towards the composition of feeding fats. In the aftermath of the BSE crisis all animal by-products utilised in animal nutrition have been subjected to close scrutiny. Regulation requires that the material belongs to the category of animal by-products fit for human consumption. This implies the use of reliable techniques in order to insure the safety of products. The feasibility of using rapid and non-destructive methods, to control the composition of feedstuffs on animal fats has been studied. Fourier Transform Raman spectroscopy has been chosen for its advantage to give detailed structural information. Data were treated using chemometric methods as PCA and PLS-DA which have permitted to separate well the different classes of animal fats. The same methodology was applied on fats from various types of feedstock and production technology processes. PLS-DA model for the discrimination of animal fats from the other categories presents a sensitivity and a specificity of 0.958 and 0.914, respectively. These results encourage the use of FT-Raman spectroscopy to discriminate animal fats.