[The impact of hypoxia on the ion channels in cystic fibrosis bronchial epithelial cells]. / Impact de l'hypoxie sur les canaux ioniques dans des cellules épithéliales bronchiques mucoviscidosiques.

Cystic fibrosis is a disease caused by a mutation on the CFTR gene coding for a chloride channel. The dominant mutation F508del eliminates the CFTR protein at the surface of epithelial cells, causing an accumulation of viscous mucus in the airways. In advanced stages of the disease, respiratory failure is associated with cellular hypoxia. Our project aims not only to describe the impact of hypoxia on ion channels and to highlight the underlying signaling pathways involved, but also to test the effectiveness of current CF treatments under the above-mentioned conditions.

[Epidemiology, etiology and psychosocial impact of urogenital fistulas in a cohort of 170 consecutive patients managed in three treatment centers in Burkina Faso from 2010 to 2012]. / Aspects épidémiologiques, étiologiques et impact psychosocial des fistules urogénitales dans une cohorte de 170 patientes consécutives, prises en charge dans trois centres du Burkina Faso de 2010 à 2012.

OBJECTIVE: To describe the socio-demographical aspects, etiologies and psychosocial consequences of urogenital fistula patients (UGF) in Burkina Faso (BF). PATIENTS AND METHODS: Descriptive study of a cohort of consecutive patients during a period of 18 months (December 1st 2010 to August 31st 2012) in three centers of treatment in BF. Each patient has had a standardized complete medical observation focused on sociodemographics, clinical finding, past medical history and etiologies of UGF. Some patients had an interview with a psychologist. RESULTS: One hundred and seventy patients with mean age 35 years (minimum: 16, maximum: 70) were enrolled during the study period. The majority of patients were housewives (90.5%, n=152) and illiterates (92.9%, n=158). Among the patients, 62.4% (n=106) lived in rural zones. Obstetrical fistula was the most common cause of UGF (87.6%, n=149) in our study and prolonged labor occurred in 93.3% (n=139) of cases with 17.5% (n=26) who delivered at home. The majority of our cases were vesico-vaginal fistula (70.6%, n=120). Fifty-five patients (32.4%) were divorced after the fistula. The sensation of humiliation and sadness were noted at all the patients who had a psychological evaluation and 87.5% (n=14) of them have had suicidal ideas. CONCLUSION: The UGF are frequent in Burkina Faso and obstetrical etiology is dominant. The physical and psychosocial repercussions are important for the women victims of this pathology. LEVEL OF EVIDENCE: 4.

Spatial pattern of BOLD fMRI activation reveals cross-modal information in auditory cortex.

Recent findings suggest that neural representations in early auditory cortex reflect not only the physical properties of a stimulus, but also high-level, top-down, and even cross-modal information. However, the nature of cross-modal information in auditory cortex remains poorly understood. Here, we used pattern analyses of fMRI data to ask whether early auditory cortex contains information about the visual environment. Our data show that 1) early auditory cortex contained information about a visual stimulus when there was no bottom-up auditory signal, and that 2) no influence of visual stimulation was observed in auditory cortex when visual stimuli did not provide a context relevant to audition. Our findings attest to the capacity of auditory cortex to reflect high-level, top-down, and cross-modal information and indicate that the spatial patterns of activation in auditory cortex reflect contextual/implied auditory information but not visual information per se.

Pre-stimulus pattern of activity in the fusiform face area predicts face percepts during binocular rivalry.

Visual input is ambiguous, yet conscious experience is unambiguous. In binocular rivalry the two eyes receive conflicting images, but only one of them is consciously perceived at a time. Here we search for the neural sites of the competitive interactions underlying this phenomenon by testing whether neural pattern activity occurring before stimulus presentation can predict the initial dominant percept in binocular rivalry and, if so, where in the brain such predictive activity is found. Subjects were scanned while viewing an image of a face in one eye and an image of a house in the other eye with anaglyph glasses. The rivalrous stimulus was presented briefly for each trial, and the subject indicated which of the two images he or she preferentially perceived. Our results show that BOLD fMRI multivariate pattern activity in the fusiform face area (FFA) before the stimulus is presented predicts which of the two images will be dominant, suggesting that higher extrastriate areas, such as the FFA, are not only correlated with, but may also be involved in determining the initial dominant percept in binocular rivalry. Furthermore, by examining pattern activity before and after trial onset, we found that pre-trial activity in the FFA for the rivalrous face trials is no more similar to the post-trial activity for the non-rivalrous face trials than to that for the non-rivalrous house trials, indicating a dissociation between neural pattern information, which predicts a given state of awareness, and mean responses, which reflect the state of awareness ultimately achieved.

A state observer for the Virgo inverted pendulum.

We report an application of Kalman filtering to the inverted pendulum (IP) of the Virgo gravitational wave interferometer. Using subspace method system identification techniques, we calculated a linear mechanical model of Virgo IP from experimental transfer functions. We then developed a Kalman filter, based on the obtained state space representation, that estimates from open loop time domain data, the state variables of the system. This allows the observation (and eventually control) of every resonance mode of the IP mechanical structure independently.

In-vacuum Faraday isolation remote tuning.

In-vacuum Faraday isolators (FIs) are used in gravitational wave interferometers to prevent the disturbance caused by light reflected back to the input port from the interferometer itself. The efficiency of the optical isolation is becoming more critical with the increase of laser input power. An in-vacuum FI, used in a gravitational wave experiment (Virgo), has a 20 mm clear aperture and is illuminated by an almost 20 W incoming beam, having a diameter of about 5 mm. When going in vacuum at 10(-6) mbar, a degradation of the isolation exceeding 10 dB was observed. A remotely controlled system using a motorized lambda=2 waveplate inserted between the first polarizer and the Faraday rotator has proven its capability to restore the optical isolation to a value close to the one set up in air.

[Primary localized bladder amyloidosis]. / L'amylose vésicaoe primitive localisée.

Amyloidosis constitutes a group of storage diseases concerning various proteins, classified as a function of the type of protein. Localized pseudo tumoral amyloidosis of the urinary tract is a rare affection with bladder like the most frequent localisation. In spite of contribution of computerized tomography scans and MRI, the diagnosis is always based on histological examination of cystoscopy samples. Investigations are required to eliminate a generalized amyloidosis or a malignant lymphoproliferation. Treatment should be as conservative as possible on the outside of a massive and recurrent haematuria to be able to involve vital prognosis.

Comparison of phenotypic and genotypic markers for characterization of an outbreak of Salmonella serotype Havana in captive raptors.

AIMS: To establish a typing method for tracing the epidemic relationship of 16 strains of Salmonella serotype Havana isolated from captive raptors showing no symptomatology and residing in a wildlife hospital in Spain. METHODS AND RESULTS: Antimicrobial susceptibility testing, ribotyping, pulsed field gel electrophoresis (PFGE) and amplified fragment length polymorphism (AFLP) methodology were applied. Ten unrelated strains of serotype Havana were included as a control group to provide a basis of for the efficiency of the different markers used. All outbreak-related strains were resistant to nalidixic acid and streptomycin and showed the same ripotype, pulsotype and AFLP pattern. CONCLUSIONS: This is the first time that AFLP analysis has been tested with serotype Havana isolates and it has demonstrated to be the most useful epidemiological tool for discriminating between unrelated and outbreak-related strains of this serotype. The results obtained suggest that all the Salmonella serotype Havana isolates represented a common outbreak strain whose origin of contamination could not be established although it is thought that it was the poultry meat used for raptors'diet. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study suggests the importance of microbiological analysis of these products in order to prevent contamination and dissemination of Salmonellae in this kind of Hospital.

Prevalence of epilepsy in northeast Madrid.

During a period of 42 months, we studied the prevalence of epilepsy in a specific health district, composing by four towns with 98,405 inhabitants older than 10 years. This has been accomplished by a two-phase cross-sectional study. The prevalence rate observed was 4.12/1000 inhabitants for all types of epilepsy. No significant differences were found between the sexes. Sixty-three per cent of affected individuals had partial seizures, with a confirmed cause in 45%. Fifty-five patients with single unprovoked seizures, were also identified but not included in the prevalence rate.

Towards a cellular and molecular understanding of neurulation.

Neurulation occurs during the early embryogenesis of chordates, and it results in the formation of the neural tube, a dorsal hollow nerve cord that constitutes the rudiment of the entire adult central nervous system. The goal of studies on neurulation is to understand its tissue, cellular and molecular basis, as well as how neurulation is perturbed during the formation of neural tube defects. The tissue basis of neurulation consists of a series of coordinated morphogenetic movements within the primitive streak (e.g., regression of Hensen's node) and nascent primary germ layers formed during gastrulation. Signaling occurs between Hensen's node and the nascent ectoderm, initiating neurulation by inducing the neural plate (i.e., actually, by suppressing development of the epidermal ectoderm). Tissue movements subsequently result in shaping and bending of the neural plate and closure of the neural groove. The cellular basis of the tissue movements of neurulation consists of changes in the behavior of the constituent cells; namely, changes in cell number, position, shape, size and adhesion. Neurulation, like any morphogenetic event, occurs within the milieu of generic biophysical determinants of form present in all living tissues. Such forces govern and to some degree control morphogenesis in a tissue-autonomous manner. The molecular basis of neurulation remains largely unknown, but we suggest that neurulation genes have evolved to work in concert with such determinants, so that appropriate changes occur in the behaviors of the correct populations of cells at the correct time, maximizing the efficiency of neurulation and leading to heritable species- and axial-differences in this process. In this article, we review the tissue and cellular basis of neurulation and provide strategies to determine its molecular basis. We expect that such strategies will lead to the identification in the near future of critical neurulation genes, genes that when mutated perturb neurulation in a highly specific and predictable fashion and cause neurulation defects, thereby contributing to the formation of neural tube defects.

Classification scheme for genes expressed during formation and progression of the avian primitive streak.

We have systematically examined the expression patterns of thirteen genes by in situ hybridization during the formation and progression of the avian primitive streak. Based on common patterns of expression, we classify these genes into three distinct groups. Group 1 genes, subdivided into group 1A (Wnt8c, Slug, Vg1, and Nodal) and group 1B (Fgf8, Brachyury, and Cripto), were expressed first in the epiblast and then, throughout most of the length of the primitive streak. Group 2 genes, namely, cNot1, Sonic hedgehog (Shh), Hnf3 beta and Chordin, were confined to the rostral end of the primitive streak, and then, to Hensen's node. In contrast, Group 3 genes, comprising Goosecoid (GSC) and Crescent, were expressed in the hypoblast. This classification scheme provides a rational basis for categorizing genes expressed during avian gastrulation, and such systematization is likely to provide insight into the relationships among different genes and their potential roles in key events of gastrulation.

Subtractive hybridization identifies chick-cripto, a novel EGF-CFC ortholog expressed during gastrulation, neurulation and early cardiogenesis.

EGF-CFC genes encode a novel class of extracellular, membrane-associated proteins that notably play an important role during vertebrate gastrulation. Whereas the two cysteine-rich domains that characterize these proteins, namely the extracellular EGF-like and the CFC domain, are known to be encoded by two evolutionarily conserved exons, it is generally assumed, based on weak primary sequence identity, that the remaining parts of the protein differ among vertebrates, suggesting that known members of the EGF-CFC family do not represent true orthologs. Here, by characterizing the full cDNA and genomic sequences of a new EGF-CFC gene in chick, and by comparing them with their counterparts in human (CRIPTO), mouse (cripto and cryptic), Xenopus (FRL-1) and zebrafish (one-eyed pinhead), we show that all EGF-CFC genes share an identical genomic organization over the entire coding region. Not only are the central two exons (coding for the EGF-like and CFC motifs) conserved, but also conserved are the total number of exons, their size, their intron phase and their correlation with discrete protein modules, in particular those modules that allow the EGF-CFC motif to become membrane-associated. Therefore, despite apparent divergence between their 5' and 3'-terminal exons, all known CRIPTO-related genes are structurally orthologous. We named this novel ortholog in bird, chick-cripto. We report the mRNA distribution of chick-cripto, which begins in the epiblast of the gastrula, with a pattern similar to EGF-CFC genes of other vertebrates.

Direct vascular actions of methyclothiazide and indapamide in aorta of spontaneously hypertensive rats.

In vitro experiments were designed to assess the inhibitory effect of the thiazide diuretics methyclothiazide (MCTZ), the hydrochlorothiazide (HCTZ), and the thiazide-related diuretic indapamide (IND) on contractile responses to norepinephrine (NE) and arginine vasopressin (AVP) of aortic rings from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Changes in the tension of aortic ring preparations were measured isometrically. MCTZ (10(-4) M) induced endothelium-dependent inhibition of the vasoconstrictor responses to NE and AVP only in aortas from SHR, and the maximal vasoconstrictive effect of NE and AVP was decreased by 59 +/- 11% and 32.3 +/- 13%, respectively. Indapamide (10(-4) M) also induced endothelium-dependent inhibition of the contractile response to AVP in aortic rings from SHR, and the maximal vasoconstrictive effect of AVP was decreased by 33 +/- 5%. In contrast, HCTZ did not inhibit the contractile response to either NE or AVP, even at the highest concentration. This study provides evidence that methyclothiazide and indapamide inhibit the contractile response induced by norepinephrine and/or arginine vasopressin on SHR aortic preparations via an endothelium-dependent mechanism.

[Effect of methyclothiazide on the entry of calcium into vascular smooth muscle cells]. / Effets du méthyclothiazide sur l'entrée de calcium dans la cellule musculaire lisse vasculaire.

The possible involvement of calcium and potassium channels in mediating the vascular actions of methyclothiazide (MCTZ), a thiazide diuretic, was investigated in isolated aortic rings from 12 week-old hypertensive rats. MCTZ (10(-4) M) inhibits the contractile response induced by addition of Ca2+ to a depolarizing solution, the maximal contracture is reduced by 87.16 +/- 6.4%. Furthermore this inhibitory effect was unaffected by charybdotoxine a selective blocker of calcium-activated K+ channels (Kca). This suggesting that MCTZ inhibits voltage-gated Ca2+ channels and blunts the Ca2+ entry into vascular smooth muscle cells. This inhibition was partially attenuated by either mechanical removal of the endothelium or N omega-nitro-L-arginine (NOLA) treatment, suggesting that MCTZ effects are also mediated by an endothelium-dependent mechanism involving endothelium-dependent relaxing factor (EDRF)/nitric oxide (NO) release. Taken together, these observations could point to a role of voltage-gated Ca2+ channels and endothelial release of EDRF/NO in the antihypertensive action of MCTZ.

Ectodermal markers delineate the neural fold interface during avian neurulation.

The formation and morphogenesis of the neural folds are important processes underlying neurulation. We showed previously that these processes comprise four key events in avian embryos: epithelial ridging, kinking, delamination, and apposition. Collectively, these events establish the paired, bilaminar neural folds, which fuse in the dorsal midline during late neurulation to close the neural groove and to establish the neural tube. Here, we use an antisense riboprobe for a new gene called Plato, as well as an antibody for a previously cloned transcription factor, AP-2, as markers to identify critical subpopulations of ectodermal cells during the formation and morphogenesis of the avian neural folds. Plato antisense riboprobe marks the cranial neural ectoderm and premigratory cranial neural crest cells, whereas AP-2 antibody marks the epidermal ectoderm and the early migratory neural crest. We show that subpopulations of ectodermal cells at the forebrain and midbrain levels undergo considerable rearrangement within the neural fold transition zone, which redistributes incipient neural crest cells from the neural ectodermal side of the forming neural fold interface to the epidermal ectodermal side. Additionally, we show that Plato and AP-2 provide useful markers for delineating the incipient neural fold interface.

Evidence that translation of smooth muscle alpha-actin mRNA is delayed in the chick promyocardium until fusion of the bilateral heart-forming regions.

Heart development in the chick embryo proceeds from bilateral mesodermal primordia established during gastrulation. These primordia migrate to the midline and fuse into a single heart trough. During their migration as a cohesive sheet, the cells of the paired heart fields become epithelial and undergo cardiac differentiation, exhibiting organized myofibrils and rhythmic contractions near the time of their fusion. Between the stages of cardiomyoblast commitment and overt differentiation of cardiomyocytes, a significant time interval exists. Using a new riboprobe (usmaar) for whole-mount in situ hybridization in chick embryos, we report the earliest phases of smooth muscle alpha-actin (smaa) mRNA distribution during the precontractile developmental window. We show that ingressed heart-forming regions express smaa by the head-process stage (Hamburger and Hamilton stage 5). In addition, we used usmaar to study the formation and early morphogenesis of the heart. Consistent with fate mapping studies (Garcia-Martinez and Schoenwolf [1993] Dev. Biol. 159:706-719; Schoenwolf and Garcia-Martinez [1995] Cell Mol. Biol. Res. 41:233-240; Garcia-Martinez et al., in preparation), our results with this probe, combined with detailed histological and SEM analyses of the so-called cardiac crescent, demonstrate unequivocally that the heart arises from separated and paired heart rudiments, rather than from a single crescent-shaped rudiment (that is, prior to fusion of the paired heart rudiments to establish the straight-heart tube, the rostral midline of the cardiac crescent lacks mesodermal cells and consequently fails to label with usmaar). Smaa is also expressed in the splanchnic and somatic mesoderm, marking the earliest step in coelom formation. Consequently, we also used usmaar to describe formation of the pericardium. Finally, we provide evidence of a post-transcriptional level of control of smaa gene expression in the heart fields. Our results suggest that the expression of smaa may mark a primitive mesodermal state from which definitive cell types can be derived through inductive events.

[Upward and downward gaze palsy with a unilateral mesencephalic hemorrhage]. / Parálisis combinada de la mirada vertical tras hemorragia unilateral del mesencéfalo.

INTRODUCTION: Acute vascular lesions limited to the midbrain can yield varied disturbances of eye movements. They are more often infarcts than hemorrhages. CLINICAL CASE: We present the case of a 49 year old, non-hypertensive man who presented with sudden onset of bilateral up and down gaze palsy. CT defined a unilateral hemorrhage in the right mesencephalic tegmentum. CONCLUSION: Cases of upward and downward gaze palsy in association with unilateral upper midbrain hemorrhage are very uncommon. We present a new case.

Characterizing and reporting pelvic floor defects: the revised New York classification system.

The authors have devised a conceptual model and reporting system for characterizing, grading and staging pelvic floor defects. The system is user friendly and simple to learn and apply. It is based on commonly known anatomic landmarks and can be performed without memorizing or referring to a separate characterization and reporting plan. Completing the accompanying forms is self-explanatory and provides the information needed for proper comprehension and recording of anatomic defects. The model and reporting format have been used at our institutions for 5 years by medical students, residents, fellows and attendings. It has several advantages over the Pelvic Organ Prolapse Quantitation (POPQ) system: (1) it uses known anatomic landmarks rather than alphabetic labels; (2) it grades lateral wall defects which the POPQ system omits; (3) it recognizes and reports isolated defects or tears which present as bulges in the vaginal walls without downward linear descent (prolapse); (4) it uses a one-page reporting form and a one-page checklist and vaginal profile; (5) it can be done easily in both the supine and the standing positions; (6) it requires simple instruments and a disposable measuring tape available in most office settings; (7) it includes urethral hypermobility in its reporting scheme; (8) it includes cervical length, perineal descent and other measurements in its reporting scheme; and (9) it is similar enough to the POPQ system that easy conversion to, and integration with, the POPQ reporting form and vaginal profile is possible. Prospective trials testing the validity of this system and comparing it with the POPQ system for validity, reliability, reproducibility, test-retest analysis, and interobserver and intraobserver variance are warranted.

Parálisis combinada de la mirada vertical tras hemorragia unilateral del mesencéfalo / Upward and downward gaze palsy with a unilateral mesencephalic hemorrhage

Introducción. Las lesiones del mesencéfalo pueden dar lugar a trastornos diversos de la motilidad ocular entre los que destacan las supranucleares de la mirada vertical. Las causas vasculares son poco frecuentes y más a menudo se trata de infartos que de hemorragias. Caso clínico. Presentamos el caso de un varón de 49 años normotenso que presentó de modo brusco parálisis combinada de la mirada vertical superior e inferior. Una TC de cráneo demostró un hematoma localizado en el tegmento mesencefálico derecho. Conclusión. Presentamos un nuevo caso de parálisis combinada de la mirada vertical relacionado con un hematoma mesencefálico unilateral, una patología de presentación muy infrecuente (AU)

[Fibrinogen: a cardiovascular risk factor]. / Fibrinogène: facteur de risque cardiovasculaire.

AN INDEPENDENT RISK FACTOR: Pathophysiological and epidemiological data show that fibrinogen is an independent risk factor for atherosclerosis with a synergistic effect on classical risk factors. CORONARY ARTERIES: Serum fibrinogen level is an independent predictor of the presence and severity of atheromatous lesions of the coronary arteries. It is also predictive of coronary events such as sudden death, myocardial infarction or angina pectoris. OTHER VESSELS: Fibrinogen is also a marker of cerebrovascular events or transient ischemia and a factor predictive of recurrent cerebrovascular events. Serum fibrinogen level is correlated with the progression of carotid lesions. Finally, fibrinogen is an independent predictive factor of the severity of atherosclerosis of the thoracic aorta, lower limb arteriopathy, and more generally silent atherosclerotic plaques. PERSPECTIVES: A large-scale prospective study is needed to determine whether drug-induced reduction in serum fibrinogen can reduce the rate of cardiovascular events.