E-learning versus face-to-face training: Comparison of two learning methods for Lyme borreliosis.

OBJECTIVES: To compare two learning methods for Lyme disease (e-learning versus face-to-face training) to assess knowledge and know-how. METHODS: The study population was volunteer general medicine residents and family physicians (FP). Face-to-face training on Lyme disease was offered to each group. E-learning training was then offered to those who had not attended the face-to-face training. Theoretical knowledge was assessed by an identical pre- and post-test questionnaire and know-how by a script concordance test. RESULTS: Seventy learners (47 FPs and 23 general medicine residents) were included in the face-to-face training group and 61 (33 FPs and 28 general medicine residents) in the e-learning group. The pre- and post-test scores were significantly improved in the FP group (difference of 29.3±1.9 [P<0.0001] out of 100) as well as in the general medicine resident group (difference of 38.2±2.7 [P<0.0001] out of 100). E-learning was more effective than face-to-face training, particularly among general medicine residents (progression of mean difference of 44.3±3.4/100 vs. 30.9±4.0/100; P=0.0138) and to a lesser extent among FPs (progression of 25.3±2.3/100 vs. 31.9±2.7/100; P=0.0757). Forty-six script concordance tests were completed by FPs and 20 by general medicine residents. Script concordance test results did not seem significant between the subgroups. CONCLUSIONS: E-learning seems to be a good alternative to face-to-face training for Lyme disease. It seems to be more effective than face-to-face training for the acquisition of theoretical knowledge. The script concordance test evaluation of know-how did not show any difference between the two learning methods.

Oyster hemolymph is a complex and dynamic ecosystem hosting bacteria, protists and viruses.

BACKGROUND: The impact of the microbiota on host fitness has so far mainly been demonstrated for the bacterial microbiome. We know much less about host-associated protist and viral communities, largely due to technical issues. However, all microorganisms within a microbiome potentially interact with each other as well as with the host and the environment, therefore likely affecting the host health. RESULTS: We set out to explore how environmental and host factors shape the composition and diversity of bacterial, protist and viral microbial communities in the Pacific oyster hemolymph, both in health and disease. To do so, five oyster families differing in susceptibility to the Pacific oyster mortality syndrome were reared in hatchery and transplanted into a natural environment either before or during a disease outbreak. Using metabarcoding and shotgun metagenomics, we demonstrate that hemolymph can be considered as an ecological niche hosting bacterial, protist and viral communities, each of them shaped by different factors and distinct from the corresponding communities in the surrounding seawater. Overall, we found that hemolymph microbiota is more strongly shaped by the environment than by host genetic background. Co-occurrence network analyses suggest a disruption of the microbial network after transplantation into natural environment during both non-infectious and infectious periods. Whereas we could not identify a common microbial community signature for healthy animals, OsHV-1 µVar virus dominated the hemolymph virome during the disease outbreak, without significant modifications of other microbiota components. CONCLUSION: Our study shows that oyster hemolymph is a complex ecosystem containing diverse bacteria, protists and viruses, whose composition and dynamics are primarily determined by the environment. However, all of these are also shaped by oyster genetic backgrounds, indicating they indeed interact with the oyster host and are therefore not only of transient character. Although it seems that the three microbiome components respond independently to environmental conditions, better characterization of hemolymph-associated viruses could change this picture.

Calcium citrate insolubilization drives the fouling of falling film evaporators during the concentration of hydrochloric acid whey.

When dairy powders are produced, the mineral fraction undergoes strong modifications during the vacuum concentration step, leading to the fouling of falling film evaporators. The objective of this study was to determine the nature of the deposits formed during the vacuum concentration of two fouling and highly mineralized products: hydrochloric acid whey and lactic acid whey. These products mainly differ in terms of their mineral composition: lactic acid whey contains a high level of lactic acid and traces of citrate, whereas hydrochloric acid whey contains citrate and no lactic acid. Concentrates at different concentration factors were produced using a pilot-scale falling film evaporator. The compositions of the fouling deposits as well as the precipitates present in the concentrates were deduced from the analytical determination of the composition of the concentrates and their respective diffusible phases. The behavior of the mineral fraction of both acid wheys during concentration was shown to be very different. In the case of hydrochloric acid whey, experimental results suggested a deposition of calcium and citrate ions in the evaporator as well as their precipitation in the highly concentrated products. On the contrary, neither mineral deposition nor precipitation occurred during the concentration of lactic acid whey. This study underlined the key role of citrate ions in the fouling of evaporators during the concentration of hydrochloric acid wheys.

[Unexplicated neuropsychiatric disorders: Do not ignore dysimmune encephalitis. A case report of a dysimmune encephalitis with anti-leucine rich glioma inactivated 1 (LGI-1) antibodies]. / Troubles neuropsychiatriques inexpliqués : penser aux encéphalites dysimmunitaires. À propos d'une observation d'encéphalite à anticorps anti-leucine rich glioma inactivated 1 (LGI-1).

INTRODUCTION: Anti-leucine rich glioma inactivated 1 encephalitis is a common and a treatable etiology of autoimmune encephalitis. Its diagnosis is a challenge because the initial diagnostic work-up is often normal. CASE REPORT: A 48-year-old man experienced cognitive and behavioral troubles, facio-brachial dystonic seizures and a syndrome of inappropriate antidiuretic hormone secretion. First line tests excluded infectious, neoplastic, systemic inflammatory, endrocrine or toxic etiologies. Cerebral (18)Fluoro-desoxy-glucose (FDG) position emission tomography and research of specific antibodies in cerebro-spinal fluid and serum led to diagnose an anti-leucine rich glioma inactivated 1 encephalitis. Intravenous immunoglobulins and corticosteroids were partially effective. Cyclophosphamid permitted a good recovery. CONCLUSION: In the presence of acute neuropsychiatric disorders with a negative etiologic research, physician should think about dysimmune encephalitis. Facio-brachial dystonic seizures and syndrome of inappropriate antidiuretic hormone secretion are highly evocative of anti-leucine rich glioma inactivated 1 encephalitis. The diagnosis needs specific diagnostic tests (cerebral (18)FDG position emission tomography and antibodies research in cerebro-spinal fluid and in serum), after the exclusion of alternative diagnoses. Extensive and repeated diagnostic work-up for neoplasia is required. Immunosupressive therapies are effective in most cases.

Detergent effects of kinetic properties of (Na+ +K+)-ATPase from kidney membranes.

Studies on (Na+ +K+)-ATPase generally employ detergents such as SDS and deoxycholate. Under such conditions, the purified enzyme possesses high specific activity. The (Na+ +K+)-ATPase from kidney membranes was unmasked by deoxycholate and SDS as described by Jlrgensen and its kinetic properties were studied. The results suggest that these detergents induce some irreversible alterations in the kinetic properties of the native enzyme. Another detergent, saponin, unmasked the (Na+ +K+)-ATPase as effectively as did SDS, but it seems to affect the kinetic properties of the native enzyme to a lesser extent.

Isolation and characterization of the rolipram-sensitive cyclic AMP-specific phosphodiesterase (type IV PDE) in human term myometrium.

On the basis of the potencies of classical selective modulators of cyclic nucleotide phosphodiesterase (PDE) activities, five cyclic nucleotide PDE isoforms have been isolated and characterized in the cytosolic fraction of human term myometrium. By means of successive ion-exchange chromatographies, a calcium-calmodulin sensitive isoform, a cyclic GMP-stimulated isoform, a cyclic GMP-inhibited isoform, a rolipram-sensitive cyclic AMP-specific isoform and a cyclic GMP-specific isoform, corresponding to PDE I, PDE II, PDE III, PDE IV and PDE V, respectively, have been identified. We found that near term, human myometrium contains a higher proportion of the rolipram-sensitive type IV PDE isoform (about 50% of total cyclic AMP hydrolytic activity) than the type III cyclic GMP-inhibited PDE isoform (only 10%). Type IV PDE displays simple Michaelis-Menten kinetics with a high affinity for cyclic AMP (Km approximately 4.4 microM) and is selectively and competitively inhibited by rolipram (K(i) approximately 0.9 microM) and Ro 20-1724 (K(i) approximately 2.6 microM). The predominance of type IV PDE at the end of pregnancy suggests that this isoform contributes, via a modulation of the intracellular cyclic AMP level, to local control of uterine motility and thus could help the myometrium prepare for pronounced contractile activity at the time of parturition.

Effect of pregnancy on PDE4 cAMP-specific phosphodiesterase messenger ribonucleic acid expression in human myometrium.

In light of the important role of the second messengers cAMP and cGMP in the mechanism of relaxation in the human myometrium, specific regulation of the phosphodiesterase (PDE) enzymatic system responsible for cyclic nucleotide inactivation is essential. We previously identified in the human myometrium PDE4 cAMP-specific PDE as by far the most abundant isoform. Here we have studied the expression patterns of mRNAs for the four cloned human PDE4 genes in the myometria of pregnant and non-pregnant women. Concurrent expression of the PDE4A, 4B, 4C and 4D genes is demonstrated. We found that the PDE4D transcripts are the most prominently expressed. PDE4A and PDE4B mRNAs also are markedly abundant, whereas lower expression is observed for PDE4C mRNAs. Interestingly, we showed that transcripts of PDE4B2 are more abundant in the myometria of pregnant women than in non-pregnant women, whereas no difference between the two tissues was detected for PDE4A, 4C and 4D mRNAs. Cultured human myometrial cells, which present a high level of PDE4 activity and express the four PDE4 mRNA subtypes, provide us with an appropriate model to further evaluate whether the level of expression of the PDE 4B2 mRNA subtype is under hormonal regulation.

[Leber congenital amaurosis: comprehensive survey of genetic heterogeneity. A clinical definition update]. / Amaurose congénitale de Leber: le point sur l'hétérogénéité génétique, actualisation de la définition clinique.

Leber congenital amaurosis (LCA) is the earliest and most severe form of all inherited retinal dystrophies, responsible for congenital blindness. Disease-associated mutations have been hitherto reported in seven genes. These genes are all expressed preferentially in the photoreceptor cells or the retinal pigment epithelium, but they are involved in strikingly different physiologic pathways, resulting in an unforeseeable pathophysiologic variety. This broad genetic and physiologic heterogeneity, which could greatly increase in the coming years, hinders molecular diagnosis in LCA patients. Genotyping is, however, required to establish genetically defined subgroups of patients ready for therapy. Here we report a comprehensive mutational analysis of all the known genes in 179 unrelated LCA patients, including 52 familial and 127 sporadic (27/127 consanguineous) cases. Mutations were identified in 47.5% of patients. GUCY2D accounted for by far the largest part of the LCA cases in our series (21.2%), followed by CRB1 (10%), RPE65 (6.1%), RPGRIP1 (4.5%), AIPL1 (3.4%), TULP1 (1.7%) and CRX (0.6%). The clinical history of all patients with mutations was carefully revisited in the search for phenotype variations. Genotype-phenotype correlations were found that made it possible to divide patients into two main groups. The first one includes patients whose symptoms fit the traditional definition of LCA, i.e., congenital or very early cone-rod dystrophy, while the second group gathers patients affected with severe yet progressive rod-cone dystrophy. In addition, objective ophthalmologic data subdivided each group into two subtypes. Based on these findings, we have drawn decisional flowcharts directing the molecular analysis of LCA genes in a given case. These flowcharts will hopefully lighten the onerous task of genotyping new patients, but only if the most precise clinical history since birth is available.

Selective up-regulation of phosphodiesterase-4 cyclic adenosine 3',5'-monophosphate (cAMP)-specific phosphodiesterase variants by elevated cAMP content in human myometrial cells in culture.

In human myometrium, the modulation of intracellular cAMP content resulting from agonist-mediated stimulation of the receptor-adenylyl cyclase complex is largely influenced by the rate of cAMP hydrolysis by phosphodiesterase (PDE) isoenzymes. We have previously shown that the PDE4 family contributes to the predominant cAMP-hydrolyzing activity in human myometrium and that elevation of the PDE4B2 messenger RNA steady state level occurs in pregnant myometrial tissue. In the present study, we used a model of human myometrial cells in culture to determine whether an elevated cAMP concentration could influence PDE expression. As in myometrial tissue, high levels of PDE4 activity were detected in these smooth muscle cells. Long term treatment with 8-bromo-cAMP or forskolin resulted in a selective induction of PDE4B and of PDE4D short form messenger RNA variants. Concurrently, an increased immunoreactive signal for the PDE4B- and PDE4D-related isoenzymes was detected. This induction was consistent with an observed significant up-regulation of PDE4 activity. Accordingly, our results demonstrate that in human cultured myometrial cells, cAMP-elevating agents manipulate PDE4 activity through selective induction of synthesis of PDE4B and PDE4D short forms. Such a mechanism might have physiological importance during pregnancy by dampening hormonal stimulation and could thereby be involved in tolerance to the tocolytic effect of beta-adrenoceptor agonists.

Is up-regulation of phosphodiesterase 4 activity by PGE2 involved in the desensitization of beta-mimetics in late pregnancy human myometrium?

Elevation of cAMP content resulting from stimulation of the receptor-adenylyl cyclase complex is involved in maintaining the quiescence of the human myometrium during pregnancy. The magnitude of this elevation is critically influenced by the rate of cAMP hydrolysis by phosphodiesterase (PDE) isoenzymes. In the present study we report that in term myometrium, enhanced cAMP-specific PDE4 activity takes part in the heterologous desensitization to the beta-mimetic, salbutamol. Indeed, pretreatment with a PDE4-selective inhibitor potentiates the relaxant effect of salbutamol on myometrial strips of women at term. Furthermore, the reduced relaxant effect of salbutamol after long-term treatment of myometrial strips with PGE2, a potent myometrial effector, can be reversed by PDE4 inhibition. Using a model of cultured myometrial cells, we also demonstrated that PGE2 is able to up-regulate PDE4 activity, at least through the induction of synthesis of PDE4B and PDE4D short forms, which, in turn, dampen the cAMP accumulation provoked by the stimulation of adenylyl cyclase. Such data suggest that in late pregnancy endogenous PGE2 might up-regulate PDE4 activity and lessen the responsiveness of myometrium to beta-mimetic activation. Accordingly, coapplication of a selective PDE4 inhibitor might greatly improve the usefulness of beta-mimetic in tocolysis.

Biochemical characterization and autoradiographic localization of [125I]endothelin-1 binding sites on trophoblast and blood vessels of human placenta.

The presence of endothelin binding sites in the human placenta raises the question of the precise localization of these receptors on well defined placental constituents. In order to find an answer to this problem various approaches were used. Specific binding sites for [125I] endothelin-1 (ET-1) were identified on human term placenta, not only on membranes of smooth muscles stem villi vessels, but also on trophoblastic plasma membranes prepared from trophoblast in culture. Scatchard analysis of binding data revealed a single class of high affinity binding sites with Kd values of 26 +/- 4 pmol/L for stem villi vessels and 126 +/- 4 pmol/L for trophoblast in culture, with maximum binding capacities of 681 +/- 61 and 224 +/- 53 fmol/mg protein, respectively. The anatomical localization of these binding sites was determined by in vitro autoradiography. Autoradiograms obtained from placental sections incubated with [125I]ET-1 indicate that [125I]ET-1 high affinity binding sites exist on placental stem villi vessels and on the trophoblastic layer of the villi. The latter localization was also found on autoradiograms of trophoblast in culture. The human placental syncytiotrophoblast is a polarized epithelium with the microvillous membrane, facing maternal blood space and the basal plasma membrane, facing fetal circulation. [125I]ET-1 high affinity binding sites are present on both membranes but the number of binding sites is higher on the basal plasma membrane. These findings lead to the suggestion that ET-1 may be involved in the regulation of the feto-placental circulation and may subserve specific trophoblastic functions.

Transient hypoparathyroidism induced by synthetic human parathyroid hormone-(1-34) treatment.

Daily injections of low doses of a synthetic fragment of human PTH [hPTH-(1-34) have increased iliac trabecular bone volume when used in the treatment of osteoporosis. In approximately 50 patients no major side-effects had occurred. However, during daily sc 100-micrograms injections of the peptide, one patient repeatedly developed parathyroid hypofunction which resolved each time treatment was stopped. Specific immunoglobulin G (IgG) antibodies binding [125I]hPTH-(1-34) were identified in the patient's serum, and positive immunohistochemical reactions were obtained when bovine parathyroid sections were exposed to the patient's IgG. After adsorption with PTH, the patient's IgG, free of anti-PTH antibodies, reacted with renal cell membranes, as demonstrated by indirect immunofluorescence and blocked renal PTH-dependent adenylate-cyclase activation in vitro. These results support the hypothesis that anti-PTH receptor as well as anti-PTH antibodies were generated during hPTH-(1-34) treatment, which led to the development of hypoparathyroidism when their titers were high.

[Use of SDS and saponin detergents for the demonstration and purification of (Na+K+)ATPase in sheep kidney]. / A propos de l'utilisation des détergents SDS et saponine pour le démasquage et la purification de la (Na+K+)ATPase de rein de mouton.

Incubation of membrane fragments from sheep kidney outer medulla in detergents such as SDS or saponin revealed increased specific (NA+) ATPase activity. Measurement of enzyme phosphorylation from [gamma 32P] ATP showed irreversible alteration of EP to (Na+) ATPase activity ratio when SDS is used as unmasking agent. These results were found with unmasked and purified enzyme.

Progesterone and estradiol in saliva after in vitro fertilization and embryo transfer.

The importance of the luteal function to ensure adequate implantation prompted us to assay salivary estradiol (SE2) and salivary progesterone (SP) concentration serially after embryo transfer by simple and rapid radioimmunoassays to allow a noninvasive easily repeatable approach. SE2, which has fallen 1 day after human chorionic gonadotropin injection, increased after reimplantation (day 3), plateaued during approximately 1 week, and returned to basal levels before menstruation in absence of conception or in chemical pregnancy, whereas it increased steadily in successful pregnancy. SP increased in all the cases, formed a plateau, and returned progressively to basal levels before menstruation, whereas in ongoing pregnancy there was a transitory decline in the midluteal phase followed by a rapid and continuous increase, with a significantly higher ratio day 13/day 10 in successful pregnancy.

The "dysharmonic luteal phase" syndrome: endometrial progesterone receptor and estradiol dehydrogenase.

The dysharmonic luteal phase (DLP) syndrome is defined by delayed endometrial maturation despite normal plasma progesterone (P) values. In ten patients with DLP the actual date of the endometrial biopsy, dated retrospectively, was 24.7 +/- 2.3 days, whereas the histologic date was 20.0 +/- 2.6 days. The concentration of cytosolic P receptor in DLP endometrium tended to be lower, whereas the concentration of nuclear receptor was significantly higher in DLP than in seven matched patients with normal luteal phases. Endometrial estradiol-dehydrogenase activities were identical in both groups. The DLP syndrome cannot be explained by a decreased sensitivity of the endometrium to P and is probably merely functional in nature.

Placental sulfatase deficiency: clinical and biochemical study of 16 cases.

Clinical and biochemical data of 16 typical cases of placental sulfatase deficiency have been observed. In vivo loading tests with DHA-S allowed us to make a prenatal diagnosis. In vitro experiments gave confirmation, showing zero or virtually zero placental sulfatase activity towards delta 5P or DHA sulfates Aromatase activities, when tested, were normal or more often less than standard values, the latter showing themselves rather large individual variations. All pregnancies were associated with the delivery of male neonates in good health but 3. The 15 living babies have been developing normally since then. These results, together with those reported in the literature, suggest that placental sulfatase deficiency is under control of an X-linked recessive character, this being supported by the recent observation of such a disorder in two sisters simultaneously pregnant. As to the high frequency problem of cesarian section, pointed out by several authors, we cannot conclude, from our own observations, that the defect has an obvious influence on the good outcome of labor, as 10 out of the 16 women delivered vaginally near term.

[Measurement of the quality of life in chronic hepatitis C: validation of a general index and specific index. First French results]. / Mesure de la qualité de vie chez les malades ayant une hépatite chronique virale C: validation d'un indicateur général et d'un indicateur spécifique.

OBJECTIVES: To report the validation of 2 questionnaires of quality of life in chronic hepatitis C and the first results in 100 patients. METHODS: The questionnaire included 118 items and took 30 to 45 minutes to answer. It included a general index, the Nottingham Health Profile, with 38 items in 6 themes (physical mobility, social isolation, emotional reactions, pain, sleep and energy) and a specific index, the Montpellier Specific Index, with 80 items in 7 themes: symptoms, food, alcohol and tobacco, work, relations with other people, perception of disease. RESULTS: The questionnaires were self-administered to the 100 first patients with chronic hepatitis C without cirrhosis before treatment; 55 men, 45 women, average age 40 year-old, median Knodell's score 8 and median METAVIR score A2 F1. Reduction in the quality of life was frequent and was not highly correlated with biological, virological and histological parameters; it was associated with psychological disorders, reduced sexuality and apprehension of the future. CONCLUSION: This study showed the feasibility, validation, sensitivity and agreement of a quality of life questionnaire, which included a general index and a specific index of chronic hepatitis C in France. These initial results must be confirmed in studies during antiviral treatment of patients.

[Change test with DHEA-S in vivo and in vitro. Hypotrophy and utero-placental blood flow (author's transl)]. / Test de charge au DHEA-S in vivo et in vitro. Hypotrophie et débit sanguin utéroplacentaire.

Using the method of Cedard and al., we perfused 18 placentas of women in which DHEA-S loading test has been performed during pregnancy. For each placenta, we measured the increase of estrogens in the perfusate (E1 + E2) 15 minutes after the injection of 10 mg of DHEA-S, and we calculated the half-life of the precursor in the system in well-standardized conditions. The comparison between: 1. Placentas of small for date babies and normal ones. 2. The increase of estrogens and the half-life of DHEA-S measured during pregnancy on the one hand and the same data obtained from the perfusion on the other, leads us to conclude that the capacity of the placenta to metabolize DHEA-S into estrogens is not diminished in small-for-date babies. The factor which modifies the response of the DHEA-S loading test in poor intrauterine growth seems to be due to a reduction of utero-placental blood flow.

[Placental sulfatase deficiency and sex-linked recessive ichthyosis. Two cases found in two sisters (author's transl)]. / Déficit en sulfatase placentaire et ichthyose récessive liée au sexe. Deux cas observés chez deux soeurs.

The diagnosis of placental sulfatase deficiency was made at the same time in two sisters who were pregnant. This is the first case history reported of two women who were carriers of this abnormality and who were linked by parentage. The inborn error of metabolism was able to be found in its post-natal state in two of the sons of one of the women in the form of retention cutaneous ichthyosis of a sex-linked type.

[Tertiary hyperparathyroidism after renal transplantation in man. Treatment by parathyroidectomy and auto-graft. Eight cases (author's transl)]. / Hyperparathyroïdisme tertiaire après transplantation rénale chez l'homme. Traitement par parathyroïdectomie et auto-greffe de parathyroïde. A propos de 8 cas.

In a series of 76 functional renal transplantations we noted 8 cases of hyperparthyroidism occurring in periods ranging from 2 months to 4 years. Hypercalcaemia was the most constant manifestation. PTH was raised in the 7 subjects in whom it was measured. Eight patients underwent total parathyroidectomy followed in 7 of them by auto-graft of a fragment of parathyroid into a forearm muscle according to the technique of Wells. The operation was followed in all cases by normalisation in blood calcium levels after the 1st month. Serum PTH levels also returned to normal apart from in one case where renal function was impaired because of rejection of the renal graft. Comparative estimations of PTH in venous blood from the side of the auto-graft and the opposite side showed that the parathyroid graft was functioning.