Temporal mechanisms of myogenic specification in human induced pluripotent stem cells.

Understanding the mechanisms of myogenesis in human induced pluripotent stem cells (hiPSCs) is a prerequisite to achieving patient-specific therapy for diseases of skeletal muscle. hiPSCs of different origin show distinctive kinetics and ability to differentiate into myocytes. To address the unique cellular and temporal context of hiPSC differentiation, we perform a longitudinal comparison of the transcriptomic profiles of three hiPSC lines that display differential myogenic specification, one robust and two blunted. We detail temporal differences in mechanisms that lead to robust myogenic specification. We show gene expression signatures of putative cell subpopulations and extracellular matrix components that may support myogenesis. Furthermore, we show that targeted knockdown of ZIC3 at the outset of differentiation leads to improved myogenic specification in blunted hiPSC lines. Our study suggests that ß-catenin transcriptional cofactors mediate cross-talk between multiple cellular processes and exogenous cues to facilitate specification of hiPSCs to mesoderm lineage, leading to robust myogenesis.

[Ankle brachial pressure index (ABPI): color-Doppler versus ultrasound Doppler correlation study in 98 patients after analysis of interobserver reproducibility]. / Étude de corrélation de mesure des index de pression systolique à la cheville (IPSc) par Doppler couleur versus Doppler continu sur une population de 98 patients après analyse de la reproductibilité interobservateur.

OBJECTIVE: Ankle Brachial Pressure Index (ABPI) by Doppler ultrasound is the gold standard non invasive method for screening of peripheral arterial disease (PAD). This reference method is little used in routine practice, particularly by vascular disease specialists since the most recent ultrasound devices no longer have continuous wave probes. The purpose of our survey was to assess interobserver reproducibility of color-Doppler measurements made in a first population, then second, to assess the correlation between ABPI measurements made with color-Doppler and with ultrasound Doppler in a second population. METHODS: One hundred twenty patients meeting screening criteria for AOMI defined by the French Health Authorities (HAS, 2006) participated in the study between October 2010 and April 2011 in the Echo Doppler and Vascular Medicine unit of the Brest University teaching hospital: 22 patients for interobserver reproducibility and 98 for color-Doppler - continuous Doppler correlation study. Two independent operators measured the ABPI index in each of the 98 patients using color-Doppler and continuous Doppler in random order, producing 353 measurements. Reliability and reproducibility were assessed using the intraclass correlation coefficient of correlation (ICC) determined with Spearman and the Bland-Altman methods. RESULTS: The ABPI was less than 0.90 in 62% of patients. The color-Doppler reproducibility study showed a mean difference of 0.02 [95% CI: -0.02 to 0.17] using the Bland Altman method with ICC equal to 0.89 (P<0.001). For the intermethod correlation study, the mean difference was 0.03 [95% CI: -0.17 to 0.23], with ICC equal to 0.84 (P<0.001). CONCLUSION: Color-Doppler could be an alternative to Doppler ultrasound for PAD screening or follow-up, depending on the results of further evaluations in larger populations.

Treating hot flushes in menopausal women with homeopathic treatment--results of an observational study.

OBJECTIVE: There is great controversy concerning treatment for menopausal symptoms. We evaluated homeopathic treatments for hot flushes and their effect on quality of life in menopausal women. METHODS: Open, multi-national prospective, pragmatic and non-comparative observational study of homeopathic treatments prescribed and their effectiveness, observing their impact on quality of life. RESULTS: Ninety-nine physicians in 8 countries took part in this study and included 438 patients with an average age of 55. Homeopathic medicines were prescribed to all patients; 98% of the prescription lines were for homeopathic medicines. Lachesis mutus, Belladonna, Sepia officinalis, Sulphur and Sanguinaria canadensis were the most prescribed. A non-homeopathic treatment and/or food supplement prescribed for 5% of the patients. This observational study revealed a significant reduction (p<0.001) in the frequency of hot flushes by day and night and a significant reduction in the daily discomfort they caused (mean fall of 3.6 and 3.8 points respectively, on a 10cm visual analogue scale; p<0.001). Ninety percent of the women reported disappearance or lessening of their symptoms, these changes mostly taking place within 15 days of starting homeopathic treatment. CONCLUSIONS: The results of this observational study suggest that homeopathic treatment for hot flushes in menopausal women is effective. Further studies including randomized controlled trials should be conducted.

Estudio de la concordancia de la Clasificación Internacional de Funcionamiento en pacientes con lumbalgia / Study on the concordance of the international classification of functioning in patients with lower back pain

Diseño. Estudio transversal comparativo. Objetivos. Determinación del grado de concordancia de los datos obtenidos aplicando la nueva Clasificación Internacional del Funcionamiento (CIF), de la Discapacidad y de la Salud de la Organización Mundial de la Salud, en pacientes con lumbalgia. Métodos. Se valoraron 10 categorías de dicha clasificación, por parte de dos observadores, en 10 sujetos (n = 10) afectos de lumbalgia. Las categorías se determinaron de forma paralela al test de Oswestry y abarcaron el área de Función Corporal y el de Actividades y Participación. El estudio se cegó de forma simple sin aleatorizar. Para la obtención del grado de concordancia, se realizó un estudio piloto inicial que determinó los porcentajes de acuerdo para cada categoría. Posteriormente, se determinó el valor del índice kappa simple y ponderado. Resultados. En la determinación del grado de concordancia (kappa ponderado cuadrático), los resultados mostraron un valor sin acuerdo (< 0,00), entre los dos observadores, en dos categorías; acuerdo insignificante (0,00-0,20) en otras dos categorías; acuerdo discreto (0,21-0,40) en otras dos, también; acuerdo moderado (0,41-0,60) en tres, y acuerdo sustancial (0,61-0,80) solamente en una categoría. Conclusión. Los datos obtenidos por dos observadores con la CIF no tienen concordancia, en las condiciones establecidas (AU)

In vivo efficacy of a bioartificial liver in improving spontaneous recovery from fulminant hepatic failure: a controlled study in pigs.

BACKGROUND: Bioartificial liver may be useful as a bridge to liver transplantation but there are no data of its efficacy in successfully bridging to spontaneous recovery in fulminant hepatic failure. The aim of our study was to evaluate the efficacy of a bioartificial liver in increasing the spontaneous recovery of pigs with hepatic failure. METHODS: The bioartificial liver consisted in a semipermeable dialyzer with 0.6 x 10(9) cryopreserved allogenic hepatocytes. Hepatic failure was induced by portacaval shunt plus 70% hepatectomy and 1 hour occlusion of the hepatic artery. Forty-one pigs were distributed 24 hr after liver failure induction to a group treated with the bioartificial liver (4 hr daily) until recovery or death (n=16), or to a control group (n=25). Intracranial pressure was monitored in 18 additional pigs, before and 4 hr after treatment with the bioartificial liver with (n=12) or without hepatocytes (n=6). RESULTS: Fifteen days after induction of hepatic failure, 44% of the treated animals had survived and recovered from liver failure versus 22% controls (P=0.030). Intracranial pressure decreased from 13.13+/-5.1 to 7.19+/-2.06 mmHg (P=0.02) in treated animals, and remained unchanged in sham-treated animals (14.08+/-1.92 to 12.54+/-3.82, ns). CONCLUSIONS: Bioartificial liver increases survival and allows spontaneous recovery in pigs with fulminant hepatic failure.

[Cognitive deficit, its prevalence and associated factors in the population over 74]. / Déficit cognitivo, prevalencia y factores asociados en la población mayor de 74 años.

OBJECTIVE: To know the proportion of people older than 74, who are not institutionalized and not immobilized with cognitive alteration and to analyze if there is any association with social demographic characteristics and health factors. DESIGN: Cross-sectional descriptive study, made by interview. LOCATION: In an urban environment: Getafe, Parla, Pinto and rural environment: Griñón. PARTICIPANTS: The study population included all the people older than 74, that was registered in data base of individual health card, INSALUD. The sample, consisted by 704 elderly, who compliment including criterion, accuracy +/- 3.4%, p < 0.05 It's evaluated 615 persons. MEASUREMENTS AND MAIN RESULTS: It's made by questionnaire that included social demographic variables, information about the necessity of help for basic activities in daily life (ADLs), perceived health status, illness, sensorial alterations, falls, stay in hospital, social support, rotation, architectonics obstacles. For evaluating the likely cognitive deterioration, it was used the Short Potable Mental Questionnaire (SPSMQ) with 2 cutting points: 2-4 errors and > 4 errors. The proportion of elderly people with cognitive deterioration (SPSMQ > 2) was 19% (95% CI, 16.2-22.4). This proportion grew with age, the same as men as in women (p < 0.0001), 11% (95% CI, 8-15) in < 80 years, 29% (95% CI, 23.8-34.8) in > 79 years. It's proved a significant statistically association between cognitive deficit (SPSMQ > 4), in age > 84 years OR = 4.1 (95% CI, 1.7-9.7), dependence degree for ADLs OR = 4.4 (95% CI, 2.2-8.8), and low cultural level, OR = 6.2 (95% CI, 2-18). CONCLUSION: The prevalence of cognitive deficit in elderly population who lives in community environment, it's associated with the degree of functional damage, advanced age and the absence of studies, without any difference between urban and rural environment.

Introducing infants to referential events: a development study of maternal ostensive marking in French.

It is well known that mothers give then infants lessons in conversational competence from an early age. This study considered how maternal gestures and prosody contribute to this developing competence. It examines how mothers use ostensive marking to point out common references at different stages of development. The corpus consisted of longitudinal observations of four mother-infant dyads during free play (infants aged 0;4 to 1;1), at three stages of sensorimotor development (III, IV and V). Four dimensions of ostensive marking were considered: (1) the span of the marked utterance (holistic vs. local); (2) the communication channel used (gestural vs. prosodic); (3) the type of gestural marker (oriented, iconic, conventional, beats); and (4) the type of prosodic marker (emphasis, prosodic cliché, reinforced nuclear stress, focal accent). Although there was no clear change in the patterns of specific types of gestural or prosodic markers, the results showed that mothers adapt their gestures to the infant's processing level. Between stages III and V, they move from holistic to local and from gestural to prosodic marking. Stage IV appears to be an excellent period for observing the transition.

Maintaining and reintroducing referents in French: cognitive constraints and development of narrative skills.

Seven- to eleven-year-old French-speaking children and adults told "silent" comic strip stories that differed by the frame display mode, by the explicitness of the links between depicted events, and whether the topic changed on the last frame. The results showed that (a) the character in the last frame was usually referred to as a given, with a definite pronoun when the topic was maintained and a definite noun phrase or a left dislocation when the topic changed; (b) joint display of frames triggered more pronouns and left dislocations, while single-frame display led to more definite noun phrases; and (c) explicit links gave rise to more pronouns. The production conditions manipulated turned out to be a good means of assessing speakers' acquisition of within-discourse referencing expressions and narrative skills: the children gradually refined and adjusted their use of definite expressions and pronouns, whereas the adults more readily used narration-specific devices.

[Interactions of infants with adults in day care centers. Evolutive dependencies vs. counter-evolutive risks and characteristics of the mother-infant relationship]. / Interactions du bébé avec les adultes de la crèche. Dépendances èvolutives/risques contre-évolutifs et caractéristiques de la relation mère-enfant.

As part of a broader research project on the construction of the self, six infants were observed longitudinally in day-care centers between the ages of five months and three years. Interviews were conducted with the six mothers in order to evaluate the intersubjective characteristics of the mother-infant relationship. For three of the six children, the mother was a caregiver in the center. This article deals with "propping" processes, defined as the affective-cognitive transformations by means of which infants develop networks of links with and between external and internal objects which are used for support during development and serve as a relay of the maternal object. The present analysis is limited to propping on the adults in the day-care center (caregivers, observer, and, for three of the children, mothers). Two factors were considered: the intersubjective quality of the mother-infant relation, and the presence or absence of the mother as a caregiver in the day-care center. The results showed that (1) even when very young, the infants under observation differentiated between the various functions of the adults, and adapted their behavior to them; (2) each child exhibited a unique and sometimes very creative way of using dependencies on an adult's psychic apparatus to construct his or her own modes of psychic functioning; and (3) the developmental dynamics and the richness of the observed transformations were found to depend on the quality of the contact and distancing in the mother-infant relationship and on the concrete conditions for its actualization, which can either promote or hinder, and sometimes even block, the construction of the mother's absence.

[Propafenone per os in ventricular arrhythmia]. / Propafénone per os dans les troubles du rythme ventriculaire.

Twenty-one patients presenting ventricular rhythm disorders and admitted to the Intensive Care Unit were treated with oral propafenone at the dosage of 450 to 900 mg/hours. The results of treatment were excellent in 13 cases, average in 2 cases, and nil in 4 cases. Worsening of arrhythmia was observed in 2 cases. Generally the drug was well tolerated, with treatment requiring to be discontinued in 1 case due to gastrointestinal upset and in another case due to broadening of the QRS complex. This study confirms that oral propafenone is well tolerated in ventricular arrhythmias regardless of their etiology.

Cytoplasmic progesterone receptors in uterine tissue of the snapping turtle (Chelydra serpentina).

A high affinity progesterone-binding component was detected in the cytosol of the uterus of the snapping turtle, Chelydra serpentina. Density gradient centrifugation indicated that binding of [3H]progesterone and [3H]promegestone (R5020) was to a fraction with a heavier sedimentation coefficient than bovine serum albumin (BSA) appearing as a broader peak in the 6-7 S region; it was not affected by excess cortisol. Another binding peak, lighter than BSA and appearing with [3H]R5020 and [3H]progesterone near the 4 S region, was affected by excess cortisol. Excess progesterone decreased both the heavier and lighter peaks. Analysis of steroid specificity revealed that, of the natural steroids, progesterone had the highest affinity for the uterine cytosol. This was followed by deoxycorticosterone, 5 alpha-pregnanedione, testosterone, oestradiol-17 beta, corticosterone, 5 alpha-dihydrotestosterone and cortisol. Non-linear regression analysis of saturation data indicated the presence of two classes of high affinity binding sites: progesterone-binding sites (R-sites) with equilibrium association constants (Ka) of 2.9 +/- 0.28 litres/nmol (mean +/- 95% confidence limit) for [3H]R5020 and 0.34 +/- 0.20 litres/nmol for [3H]progesterone, and corticosteroid-binding globulin-like sites (G-sites) with Ka of 4.5 +/- 1.6 litres/nmol for progesterone. The concentration of R-sites was between 0.66 +/- 0.10 and 2.6 +/- 0.55 pmol/mg protein while that of G-sites was between 0.73 +/- 0.05 and 5.0 +/- 0.27 pmol/mg protein. DEAE-cellulose filtration assay also confirmed the presence of R-sites and G-sites in the cytosol. R-sites were detectable without oestrogen priming during the preovulatory and vitellogenic phases (low progesterone, high oestrogen concentrations) when the ovarian follicles are mature (18-22 mm diameter).(ABSTRACT TRUNCATED AT 250 WORDS)

Binding of 5 alpha-dihydroprogesterone and other progestins to female rat anterior pituitary nuclear extracts.

The specific binding of 5 alpha-dihydroprogesterone (5 alpha-DHP), progesterone and R5020 to anterior pituitary nuclear extracts was studied using ovariectomized rats treated with estradiol benzoate and progesterone. The binding equilibrium association constant for 5 alpha-dihydroprogesterone with different preparations of nuclear extract ranged from 4.0 +/- 0.54 microM-1 to 59 +/- 10 microM-1. The association constants for progesterone and R5020 were 0.39 +/- 0.81 nM-1 and 1.5 +/- 0.15 nM-1, respectively. The binding of 5 alpha-DHP was specific in that it could be competed only by R5020, progesterone and 5 alpha-DHP and not by other progesterone metabolites and other hormonal steroids tested. With [3H]-progesterone and [3H]R5020 as ligands the most efficient competitors also were R5020, progesterone and 5 alpha-DHP. Estrogen priming of ovariectomized rats consistently and significantly increased the number of binding sites for all three progestins and subsequent progesterone treatment enabled their detection at higher levels in the nuclei.

Progesterone-induced glycogen accumulation in human endometrium during organ culture.

An organ culture system was used to evaluate the response of human proliferative endometrium to progesterone stimulation. The glycogen content of proliferative tissue was increased as much as thirteenfold during organ culture in media containing progesterone. The steroid-induced increase in tissue glycogen was detectable after 16 hours and reached a maximum at 48 and 72 hours of culture. Progesterone induced a significant increase in glycogen at a media concentration of 1.6 x 10(-8)M and a maximal increase at 3.2 x 10(-7) to 3.2 x 10(-6)M. At higher media concentrations of progesterone (1.6 x 10(-5)M), glycogen levels failed to reach the maximum obtainable. The extent of the response correlated poorly with the initial glycogen content of the tissue and not at all with the initial content of high-affinity progesterone-binding sites in cytosol. Addition of estradiol-17 beta to medium (10(-10)M to 10(-7)) has no effect on the progesterone-induced increase in tissue glycogen. Delaying the addition of progesterone to the cultures for 24 hours resulted in a diminished glycogen response; the reduced response may be related to a rapid decrease in high-affinity progesterone-binding sites as measured in cytosol prepared from tissues cultured in the absence of progesterone. High-affinity progesterone-binding sites in endometrial cytosol were found to decrease rapidly during the first 24 hours of culture. The addition of cycloheximide or actinomycin D to the culture media inhibited the increase in tissue glycogen caused by progesterone. These results demonstrate that progesterone can induce an in vitro response in human proliferative endometrium similar to that seen in vivo. The response of the endometrium is reproducible and allows for comparisons between grouped data obtained by using tissues from several different donors.

Feminizing adrenocortical carcinoma in a postmenopausal woman.

The successful surgical removal of a feminizing adrenal tumour in a postmenopausal woman is described. Most of these tumours are malignant and the pathological findings and the biological behaviour of the tumour frequently do not correlate, so that a careful follow-up is necessary. In the presence of vaginal bleeding in a postmenopausal woman endometrial carcinoma should be considered. If this has been ruled out and if oestrogens are elevated with low plasma gonadotrophins, a feminizing ovarian or adrenal tumour should be considered.

Synthetic progestins: in vitro potency on human endometrium and specific binding to cytosol receptor.

The relative potency of six commonly used synthetic progestins has been evaluated in an organ culture system for human endometrium. The affinities of these progestins for endometrial progesterone receptor were also evaluated after removing the CBG-like protein by spheroidal hydroxylapatite chromatography. All six progestins induced an increase in tissue glycogen during culture at lower concentrations than did progesterone; only one (medroxyprogesterone acetate) had a relative affinity greater than progesterone. The relative potencies and affinities of the synthetic progestins were found to have the same relative order but to differ in relative magnitude.