Label-free sensing and atomic force spectroscopy for the characterization of protein-DNA and protein-protein interactions: application to estrogen receptors.

In this paper we describe a new surface plasmon resonance (SPR) biosensor dedicated to potential estrogenic compounds prescreening, by developing an estrogen receptor (ER) specific DNA chip. Through the covalent binding of a DNA strain wearing the estrogen response element (ERE) to an activated 6-mercapto-1-hexadecanoic acid and 11-mercapto-1-undecanol self-assembled monolayer on gold surface, the SPR biosensor allows to detect specifically, quickly, and without any labeling the binding of ER in the presence of estrogen. In parallel, we investigated the ER interaction with itself, in order to study the formation of ER dimer apparently needed to activate the gene expression through ERE interaction. For that, we engaged force spectroscopy experiments that allowed us to prove that ER needs estrogen for its dimerization. Moreover, these ER/ER intermolecular measurements enabled to propose an innovative screening tool for anti-estrogenic compounds, molecules of interest for hormono-dependent cancer therapy.

High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer.

BACKGROUND: This study evaluates the relation of the early oestrogen-regulated gene gabarapl1 to cellular growth and its prognostic significance in breast adenocarcinoma. METHODS: First, the relation between GABARAPL1 expression and MCF-7 growth rate was analysed. Thereafter, by performing macroarray and reverse transcriptase quantitative-polymerase chain reaction (RT-qPCR) experiments, gabarapl1 expression was quantified in several histological breast tumour types and in a retrospective cohort of 265 breast cancers. RESULTS: GABARAPL1 overexpression inhibited MCF-7 growth rate and gabarapl1 expression was downregulated in breast tumours. Gabarapl1 mRNA levels were found to be significantly lower in tumours presenting a high histological grade, with a lymph node-positive (pN+) and oestrogen and/or progesterone receptor-negative status. In univariate analysis, high gabarapl1 levels were associated with a lower risk of metastasis in all patients (hazard ratio (HR) 4.96), as well as in pN+ patients (HR 14.96). In multivariate analysis, gabarapl1 expression remained significant in all patients (HR 3.63), as well as in pN+ patients (HR 5.65). In univariate or multivariate analysis, gabarapl1 expression did not disclose any difference in metastasis risk in lymph node-negative patients. CONCLUSIONS: Our data show for the first time that the level of gabarapl1 mRNA expression in breast tumours is a good indicator of the risk of recurrence, specifically in pN+ patients.

Bone micro-architecture and determinants of strength in the radius and tibia: age-related changes in a population-based study of normal adults measured with high-resolution pQCT.

SUMMARY: We recruited a population-based sample of 58 males and 74 females aged 20-79 from a primary care medical practice to provide normative and descriptive data for high-resolution peripheral quantitative computed tomography (pQCT) parameters. Important effects of ageing and contrasts in the effects of sex on the micro-architecture and strength of upper and lower limb bones were revealed. INTRODUCTION: The advent of high-resolution pQCT scanners has permitted non-invasive assessment of structural data on cortical and trabecular bone. METHODS: We investigated age-related changes in pQCT and finite element (FE) modelling parameters at the distal radius and distal tibia in a population-based cross-sectional study of 58 males and 74 females aged 20-79 years. Linear regression models including quadratic terms for age were used for inference. RESULTS: Age-related changes and sex differences were generally similar for pQCT parameters at the radius and tibia. At each site, mean values for bone density, cortical thickness and trabecular micro-architecture (number, separation and thickness) were lower (trabecular separation higher) in women than men. Changes with age were most apparent for bone density and cortical thickness, which declined with age, in contrast to trabecular micro-architecture parameters which were not significantly associated with age (p > 0.05) in either sex. Cortical bone density and thickness declined faster in women than men after age 50 and trabecular bone density was consistently lower in women. FE-analysis predicted failure load decreased with age and percentage of load carried by trabecular bone increased (p < 0.05). CONCLUSIONS: These data show contrasts in the effects of sex on the micro-architecture and strength of upper and lower limb bones with ageing. The faster decline in cortical bone thickness and density in women than men after age 50 and consistently lower trabecular bone density in women have implications for the excess risks of wrist and hip fractures in women.

[Analysis of a French female sexuality reference population]. / Analyse de la sexualité féminine dans une population féminine témoin française.

OBJECTIVES: To constitute and study a French female sexuality reference population database by means of the BISF-W self-administered questionnaire. MATERIALS AND METHODS: Retrospective study using the BISF-W self-administered questionnaire translated and validated in French, in a sample of one hundred women from Normandy. RESULTS: One hundred women aged 25 to 70 years answered the BISF-W self-administered questionnaire. Analysis of the results of this questionnaire showed that back and/or hip pain, age, and menopause influenced certain domains of sexuality. This study did not confirm the influence of smoking, HT, or parity on female sexuality. CONCLUSION: The results of this reference population are concordant with those reported in the literature. This database can be used to evaluate the impact of a surgical technique and/or the use of prosthetic materials on female sexuality by means of the BISF-W self-administered quality of life questionnaire, and compare it to other reference populations.

[Antibiotics at term. Questions about five severe allergic accidents]. / Antibiotiques en fin de grossesse. A propos de cinq réactions allergiques sévères.

We recently observed five cases of severe maternal allergic accident due to the administration of antibiotics near or at term in order to treat or prevent Early Onset Neonatal Group B Streptococcal Sepsis. We discuss the treatment of a severe maternal allergic reaction and these dramatic observations make us wonder about a reasonable use of antibiotics.

A satellite infrastructure for health early warning in post-disaster health management.

The risk of epidemics and emerging or re-emerging diseases such as avian flu, tuberculosis, malaria and other vector-borne diseases, is rising. These risks can be contained with prevention, early warning, and prompt management. Despite progress in information technology, communication is still a bottleneck for health early warning and response systems in post-disaster situations. This paper presents Satellites for Epidemiology (SAFE), a component-based interoperable architecture for health early warning that employs satellite, radio, and wireless networks, geographic information systems, integration technology, and data mining to promptly identify and respond to a disease outbreak. In a post-disaster situation, a mobile health emergency coordination center is established and integrated to public health services for health monitoring. The added-value of SAFE for post-disaster health management will be demonstrated as part of an earthquake readiness exercise regarding a typhoid fever epidemic, in the island of Crete. Advanced communication and data mining techniques in SAFE offer new tools to the "Epidemic Intelligence" and contribute to advanced preparedness and prompt response by lifting communication barriers, promoting collaboration, and reducing the isolation of affected areas.

Swope Supernova Survey 2017a (SSS17a), the optical counterpart to a gravitational wave source.

On 17 August 2017, the Laser Interferometer Gravitational-Wave Observatory (LIGO) and the Virgo interferometer detected gravitational waves (GWs) emanating from a binary neutron star merger, GW170817. Nearly simultaneously, the Fermi and INTEGRAL (INTErnational Gamma-Ray Astrophysics Laboratory) telescopes detected a gamma-ray transient, GRB 170817A. At 10.9 hours after the GW trigger, we discovered a transient and fading optical source, Swope Supernova Survey 2017a (SSS17a), coincident with GW170817. SSS17a is located in NGC 4993, an S0 galaxy at a distance of 40 megaparsecs. The precise location of GW170817 provides an opportunity to probe the nature of these cataclysmic events by combining electromagnetic and GW observations.

Electromagnetic evidence that SSS17a is the result of a binary neutron star merger.

Eleven hours after the detection of gravitational wave source GW170817 by the Laser Interferometer Gravitational-Wave Observatory and Virgo Interferometers, an associated optical transient, SSS17a, was identified in the galaxy NGC 4993. Although the gravitational wave data indicate that GW170817 is consistent with the merger of two compact objects, the electromagnetic observations provide independent constraints on the nature of that system. We synthesize the optical to near-infrared photometry and spectroscopy of SSS17a collected by the One-Meter Two-Hemisphere collaboration, finding that SSS17a is unlike other known transients. The source is best described by theoretical models of a kilonova consisting of radioactive elements produced by rapid neutron capture (the r-process). We conclude that SSS17a was the result of a binary neutron star merger, reinforcing the gravitational wave result.

Early spectra of the gravitational wave source GW170817: Evolution of a neutron star merger.

On 17 August 2017, Swope Supernova Survey 2017a (SSS17a) was discovered as the optical counterpart of the binary neutron star gravitational wave event GW170817. We report time-series spectroscopy of SSS17a from 11.75 hours until 8.5 days after the merger. Over the first hour of observations, the ejecta rapidly expanded and cooled. Applying blackbody fits to the spectra, we measured the photosphere cooling from [Formula: see text] to [Formula: see text] kelvin, and determined a photospheric velocity of roughly 30% of the speed of light. The spectra of SSS17a began displaying broad features after 1.46 days and evolved qualitatively over each subsequent day, with distinct blue (early-time) and red (late-time) components. The late-time component is consistent with theoretical models of r-process-enriched neutron star ejecta, whereas the blue component requires high-velocity, lanthanide-free material.

Light curves of the neutron star merger GW170817/SSS17a: Implications for r-process nucleosynthesis.

On 17 August 2017, gravitational waves (GWs) were detected from a binary neutron star merger, GW170817, along with a coincident short gamma-ray burst, GRB 170817A. An optical transient source, Swope Supernova Survey 17a (SSS17a), was subsequently identified as the counterpart of this event. We present ultraviolet, optical, and infrared light curves of SSS17a extending from 10.9 hours to 18 days postmerger. We constrain the radioactively powered transient resulting from the ejection of neutron-rich material. The fast rise of the light curves, subsequent decay, and rapid color evolution are consistent with multiple ejecta components of differing lanthanide abundance. The late-time light curve indicates that SSS17a produced at least ~0.05 solar masses of heavy elements, demonstrating that neutron star mergers play a role in rapid neutron capture (r-process) nucleosynthesis in the universe.

Impact of choice of treatment for bleeding episodes on inhibitor outcome in patients with mild/moderate hemophilia a and inhibitors.

Patients with mild/moderate hemophilia A (MHA) may develop inhibitors to factor VIII (FVIII). In this condition, FVIII clotting activity (FVIII:C) baseline levels may remain stable for some patients, but may be reduced to less than 0.01 U/mL for others. Several risk factors for the development of inhibitors in MHA have been proposed. Genetic factors, such as mutations in the FVIII gene, may play a central role; however, other influences, such as intensive treatment with FVIII products, may also be important. Optimal treatment regimens have yet to be determined, not only for the eradication of inhibitors, but also for the management or surgical prophylaxis of hemorrhages associated with this condition. Several treatment options for the control of bleeding in patients with MHA and inhibitors (MHAI) are currently available, and the choice of therapeutic strategy should be given careful consideration; some treatments may produce an anamnestic response, thus delaying the return to FVIII:C baseline levels and adversely affecting the duration of the severe bleeding phenotype. To increase our knowledge of MHAI, a retrospective collection of data is currently being performed among hemophilia centers in France and Belgium. Based on five examples of patients with MHAI collated from preliminary study data, we illustrate the impact on inhibitor outcome of the therapeutic choices used to treat bleeding episodes in these patients.

[Uterine rupture following operative hysteroscopy]. / Rupture utérine obstétricale après hystéroscopie opératoire.

The aim of this study was to attempt to identify factors predictive of uterine rupture following operative hysteroscopy. A MEDLINE and EMBASE search (1980 to April 2006) using the keywords "hysteroscopy", "uterine rupture" and "pregnancy" was performed with no limitations of languages. 18 cases of uterine rupture following operative hysteroscopy were retrieved. Hysteroscopic metroplasty (uterine septa and synechiae) was involved in 16 (89%) cases. Hysteroscopic resection was performed with monopolar current cutting, rigid scissors and laser in respectively 14 (78%), 3 (16.5%) and 1 (5.5%) cases. Uterine perforation occurred in 10 (55.5%) cases. The interval between hysteroscopy and subsequent pregnancies varied from 1 month to 5 years with an average delay of 16 months. Uterine rupture occurred between 19 and 41 weeks, with no labour in 12 (66.5%) cases. Four fetal and one maternal deaths followed uterine rupture. Hysteroscopic metroplasty may expose patients to an increased risk of uterine rupture in subsequent pregnancy. Uterine perforation and/or the use of current monopolar section during operative hysteroscopy increase this risk. Uncomplicated hysteroscopic resection of submucous myomas and endometrial polyps do not alter obstetrical outcome. Considering hysteroscopic metroplasty, the use of coaxial bipolar electrode should be preferred.

[Posthysterectomy posterior compartment prolapse: Preliminary results of a novel transvaginal surgical procedure using polypropylene mesh via the low transobturator route]. / Prolapsus isolé de l'étage postérieur posthystérectomie: résultats préliminaires d'une technique utilisant les voies vaginales et transobturatrice basses.

OBJECTIVE: The aim of this study is the description and anatomical and functional outcome assessment of a novel surgical procedure, based on rectovaginal fascia defect repair with polypropylene mesh using the tension-free transobturator and infracoccygeal route based on the integral theory developed by Petros. MATERIALS AND METHOD: Prospective, consecutive and single centre study performed between February 2003 and April 2005. Inclusion criteria were symptomatic posthysterectomy stage three to four regarding posterior compartment prolapse according to the Baden and Walker classification, with no anterior and/or apical prolapse. Principles and description of this new surgical procedure are described. RESULTS: Fourteen patients, with a mean age of 63.5 years and a mean body mass index of 29.2, were included in the study. All the patients had previous hysterectomy, 64.3% reported at least one previous surgery for pelvic organ prolapse, 44.5% reported at least one reoperation. All patients complained of rectocele and/or enterocele stage three. No perioperative or postoperative complication occurred. With a median follow-up of 13 months (range 3-32.9), no recurrence and no anterior or apical compartment prolapse occurred. No vaginal erosion an infection of the mesh was observed. The mean level of subjective satisfaction was 9.23 on a visual analogical scale (0-very disappointed, 10-very satisfied). CONCLUSION: This new surgical procedure is effective and safe for the repair of posthysterectomy large posterior compartment prolapse. A long-term follow-up is required to confirm these promising results.

Involvement of a calcium-dependent dephosphorylation of BAD associated with the localization of Trpc-1 within lipid rafts in 7-ketocholesterol-induced THP-1 cell apoptosis.

7-Ketocholesterol is a component of oxidized LDL, which plays a central role in atherosclerosis. It is a potent inducer of cell death towards a wide number of cells involved in atherosclerosis. In this study, it is reported that 7-ketocholesterol treatment induces an increase of cytosolic-free Ca(2+) in THP-1 monocytic cells. This increase is correlated with the induction of cytotoxicity as suggested from experiments using the Ca(2+) channel blockers verapamil and nifedipine. This 7-ketocholesterol-induced apoptosis appears to be associated with the dephosphorylation of serine 75 and serine 99 of the proapoptotic protein Bcl-2 antagonist of cell death (BAD). We demonstrated that this dephosphorylation results mainly from the activation of calcium-dependent phosphatase calcineurin by the oxysterol-induced increase in Ca(2+). Moreover, this Ca(2+) increase appears related to the incorporation of 7-ketocholesterol into lipid raft domains of the plasma membrane, followed by the translocation of transient receptor potential calcium channel 1, a component of the store operated Ca(2+) entry channel, to rafts.

A multicenter study on amidolytic factor X evaluation in oral anticoagulant therapy.

For laboratory control of oral anticoagulation, amidolytic factor X (F X) determination may offer an alternative to standardization difficulties of prothrombin time (PT). In order to validate this amidolytic assay on a large scale, a multicenter study was undertaken in 6 French laboratories using the same chromogenic substrate (Stachrom X Stago) and different automated instruments. Intra and between laboratory reproducibility of factor X was estimated on fresh and lyophilized patients plasmas and was found to be highly satisfactory. Standardization of the method did not seem to depend on the chromogenic substrate used, as investigated in two different centers. Results of PT and factor X were compared in over 500 patients on a long-term stabilized oral anticoagulant treatment: there was a strong positive correlation between the 2 tests in each center. The therapeutic range for factor X was evaluated from therapeutic PT values reported by Duckert and Marbet for the different thromboplastin reagents: the estimated mean range was 21 to 32%. Pooling the results of the six different centers a concordant information for prothrombin time and factor X amidolytic assay was found in 76% of patients and a fully discordant response was present in 0.6%. The results suggest that amidolytic factor X may be suitable for monitoring long-term anticoagulation. However, prospective trials are needed to evaluate its usefulness as compared to conventional methods.

Family resemblance in breakfast energy intake: the Stanislas Family Study.

BACKGROUND: There seems to be a consensus that family influences on dietary habits are important. However, no data relative to breakfast have been published yet. OBJECTIVE: To investigate whether and how breakfast energy intake aggregates within French families. DESIGN: A total of 398 families of the Stanislas Family Study who filled in a 3 day food consumption diary were selected. Absolute and relative breakfast energy intakes (BEI in kcal/day and RBEI in percentage of daily intake, respectively) were both studied. RESULTS: By using a variance component analysis, no genetic influence was shown in family aggregation of both BEI and RBEI. Intra-generation common environmental contribution to total phenotypic variance of BEI and RBEI was higher than inter-generation; both were increased with frequency of sharing breakfast. Furthermore frequency of sharing breakfast contributed to increase family resemblance in breakfast energy intake, particularly in offspring for BEI and RBEI, and in spouses for RBEI. Smoking habits, alcohol consumption, BMI or physical activity were related to family resemblance, but after adjustment on each factor degrees of resemblance were almost unchanged. CONCLUSION: General findings of this study were that family aggregation in breakfast absolute and relative energy intakes was significant within Stanislas families. Family resemblance depended on inter- and intra-generation components and was modified by the number of shared breakfasts. Our study confirmed that familial habits act on family resemblance in both absolute and relative breakfast energy intakes, so that family should be a favorite unit for health and diet promotion programs. SPONSORSHIP: Kellogg's PA, France.

[The new heparins]. / Les nouvelles héparines.

Low molecular weight heparins are increasingly prescribed in France. Prepared from standard heparin by depolymerisation, they show a markedly decreased anti IIa activity and a anti Xa/anti IIa ratio ranging from 2 to 4. Their mode of action in the coagulation system is still not well known and it is difficult to explain the mechanism of their antithrombotic effect, demonstrated in vivo. They seem to inhibit the first traces of thrombin and then counteract the priming and amplification of coagulation. Their fibrinolytic activity is also a disputed question, but seems to be lower than that of standard heparin. The pharmacological studies show a venous as well as arterial antithrombotic activity of a low molecular weight heparin on several animal models, a lower but not negligible bleeding risk as compared to unfractionated heparin. Furthermore heparin fragments have a weak interaction with platelets, which allow to foresee a greater efficacy of LMWH than standard heparin in arterial thrombosis. Some very rare cases of thrombocytopenia in patients treated with LMW heparins have been recently reported. The compared pharmacokinetics of heparins gave proof of a renal elimination of low molecular weight heparin and a bio availability of about 90% after subcutaneous injection. Many clinical studies allowed to define indications of heparin fragments in prophylactic treatment after surgery as well as in medical patients and in curative treatment in case of deep vein thrombosis. However, others studies must be carried out to define the real efficacy of such a treatment during pulmonary embolism, disseminated intravascular coagulation and myocardial infraction, or during thrombotic complications after vascular surgery.

[Voluntary poisoning with a rodenticide in an adolescent]. / Intoxication volontaire aux raticides chez une adolescente.

UNLABELLED: Suicide attempts are frequent during adolescence. Intentional ingestion of rat poison is not well known in France. The complications of this are prolonged and may be serious. CASE REPORT: An adolescent, 15 years old, with clinical hemorrhagic syndrome, had coagulation deficiency. Rat poison had been found in serum. The young girl recognized later that the ingestion of these toxins was intentional. CONCLUSION: Suicide attempt with rat poison is exceptional, but we have to mention it when vitamin K-dependent factors failed without any other explication.

[T lymphocytes in the circulating blood and pleural fluid of patients with tuberculosis or cancer]. / T lymphocytes du sang circulant et du liquide pleural chez des patients atteints de tuberculose évolutive ou de cancer.

Inflammatory pleurisies in the adult are particularly rich in CD4 lymphocytes, capable of inducing and facilitating the immune reaction. The aim of this study was to determine the percentage of CD4 and CD8 lymphocytes in pleural fluid and blood in 13 patients with tuberculous pleurisy and 12 patients with pleural neoplasms, to establish the diagnostic value of this analysis. Independent of the etiology of the effusion there is a concentration of CD4 T lymphocytes in the pleural fluid compared to the blood (49.52 +/- 12.36% and 39.28 +/- 6.74%, respectively, p value less than 0.001). However, there was a similar concentration for the two types of disorders studied with 59.92 +/- 7.26% for tuberculous pleurisies and 45.83 +/- 6.26% for neoplastic effusions, thus this technique does not make the diagnostic orientation any clearer.

[A case of Carrington's chronic eosinophilic pneumonia associated with bronchocentric granulomatosis in an asthmatic patient]. / A propos d'un cas de pneumonie chronique à éosinophiles de Carrington associée à une granulomatose broncho-centrique chez une asthmatique.

A case of Carrington's chronic eosinophilic pneumonia associated with bronchocentric granulomatosis in a young asthmatic woman is reported. Among the numerous forms of "eosinophilic lung", the characteristic features of these two diseases in asthmatic patients are briefly described. Concerning the association, the authors have found that some authors suggest a common nosological framework with many transitional forms.