Prostaglandine E2 et mesures du flux mésentérique par Doppler à la suite d’un traitement du canal artériel à l’ibuprofène par voie intraveineuse et entérale chez les bébés prématurés

En dépit du nombre croissant d’études cliniques sur le canal artériel (CA), des failles méthodologiques entretiennent plusieurs incertitudes concernant l’efficacité et la sécurité des traitements chez les bébés nés prématurés. L’objectif de cette recherche était de comparer les concentrations de prostaglandine E2 (PGE2) et les mesures du flux mésentérique par échographie Doppler chez les enfants nés prématurément et ayant un canal artériel traité à l’ibuprofène par voie intraveineuse ou entérale, en utilisant la méthodologie randomisée contrôlée et à double insu. Dans notre étude pilote, 20 nouveau-nés prématurés de moins de 34 semaines ayant un CA symptomatique confirmé par échocardiographie, furent randomisés au traitement à l’ibuprofène par voie intraveineuse ou entérale. La voie d’administration fut maintenue à l’insu de l’équipe traitante, des cardiologues et des investigateurs. Des dosages des prostaglandines plasmatiques ont été mesurés avant le début du traitement ainsi que 3, 24 et 48 h après le début du traitement. Les mesures du flux mésentérique ont été effectuées avant le traitement à l’ibuprofène ainsi que 1 h et 3 h après le traitement. Nous avons démontré à partir de nos observations que les niveaux plasmatiques de prostaglandines E2 diminuent chez les patients ayant répondu au traitement à l’ibuprofène, indépendamment de la voie d’administration. Nous n’avons pas observé de changement dans l’évolution des dosages de PGE2 chez les patients qui n’ont pas répondu au traitement. Les paramètres mesurés par échographie Doppler au niveau de l’artère mésentérique supérieure n’étaient pas affectés par la voie d’administration du traitement à l’ibuprofène, intraveineuse ou entérale. La présente étude suggère ainsi que le traitement du CA par ibuprofène intraveineux ou entéral n’influe pas sur le flux sanguin mesuré par échographie Doppler. La baisse de la prostaglandine E2 coïncide avec la fermeture du CA, et son dosage pourrait jouer un rôle dans la gestion du traitement. Nous avons démontré la faisabilité d’une étude clinique randomisée à double insu dans le traitement du canal artériel; une méthodologie qui devrait désormait être employé dans la recherche clinique sur les traitements de la persistance du CA.Despite the growing body of research on the patent ductus arteriosus (PDA), issues with clinical research methodology impairs much of our understanding regarding treatment efficacy and safety in the preterm population. The purpose of this study was to determine plasma prostaglandin E2 (PGE2) concentrations in preterm infants with symptomatic persistence of the ductus arteriosus treated with IV and oral ibuprofen, and measure Doppler flow parameters in the superior mesenteric artery, utilizing randomized controlled and double-blind methodology. Twenty patients age < 34 wks with a symptomatic PDA confirmed by echocardiography randomized to oral vs intravenous ibuprofen regimen. Treating physician, cardiologists and study investigators were blinded to treatment allocation. Plasma PGE2 levels were measured prior to ibuprofen treatment and at 3, 24 and 48 h after treatment. Mesenteric Doppler measurements were taken prior to ibuprofen treatment, and 1 h and 3 h after treatment. Our results showed that plasma PGE2 levels decreased over time in patients that exhibited ductal closure after IV or oral ibuprofen treatment; no time-dependent changes in PGE2 were seen in subjects that failed to respond to ibuprofen. Superior mesenteric artery Doppler flow measurements were not affected by ibuprofen treatment (IV or oral), regardless of efficacy on ductal closure and of PGE2 changes. We conclude that treatment with oral or intravenous ibuprofen does not impact on superior mesenteric artery blood flow measured by Doppler ultrasound. Decreases in plasma PGE2 concentrations coincide with ibuprofen efficacy, and may be more cost-effective to monitor than ultrasound. This study also demonstrated the successful use of double blinded randomized controlled research methodology, which should be more strictly applied in future clinical research on PDA treatment

bRing: An observatory dedicated to monitoring the β\beta Pictoris b Hill sphere transit

Aims. We describe the design and first light observations from the $\beta$ Pictoris b Ring ("bRing") project. The primary goal is to detect photometric variability from the young star $\beta$ Pictoris due to circumplanetary material surrounding the directly imaged young extrasolar gas giant planet \bpb. Methods. Over a nine month period centred on September 2017, the Hill sphere of the planet will cross in front of the star, providing a unique opportunity to directly probe the circumplanetary environment of a directly imaged planet through photometric and spectroscopic variations. We have built and installed the first of two bRing monitoring stations (one in South Africa and the other in Australia) that will measure the flux of $\beta$ Pictoris, with a photometric precision of $0.5\%$ over 5 minutes. Each station uses two wide field cameras to cover the declination of the star at all elevations. Detection of photometric fluctuations will trigger spectroscopic observations with large aperture telescopes in order to determine the gas and dust composition in a system at the end of the planet-forming era. Results. The first three months of operation demonstrate that bRing can obtain better than 0.5\% photometry on $\beta$ Pictoris in five minutes and is sensitive to nightly trends enabling the detection of any transiting material within the Hill sphere of the exoplanet

Study of Sexual Functioning Determinants in Breast Cancer Survivors

Our goal was to identify the treatment, personal, interpersonal, and hormonal (testosterone) factors in breast cancer survivors (BCSs) that determine sexual dysfunction. The treatment variables studied were type of surgery, chemotherapy, radiation, and tamoxifen. The personal, interpersonal, and physiologic factors were depression, body image, age, relationship distress, and testosterone levels. A sample of 55 female breast cancer survivors seen for routine follow-up appointments from July 2002 to September 2002 were recruited to complete the Female Sexual Functioning Index (FSFI), Hamilton Depression Inventory (HDI), Body Image Survey (BIS), Marital Satisfaction Inventory-Revised (MSI-R), a demographic questionnaire, and have a serum testosterone level drawn. The average time since diagnosis was 4.4 years (SD 3.4 years). No associations were found between the type of cancer treatment, hormonal levels, and sexual functioning. BCS sexual functioning was significantly poorer than published normal controls in all areas but desire. The BCSs’ level of relationship distress was the most significant variable affecting arousal, orgasm, lubrication, satisfaction, and sexual pain. Depression and having traditional role preferences were the most important determinants of lower sexual desire. BCSs on antidepressants had higher levels of arousal and orgasm dysfunction. Women who were older had significantly more concerns about vaginal lubrication and pain. Relationship concerns, depression, and age are important influences in the development of BCS sexual dysfunction. The relationship of testosterone and sexual dysfunction needs further study with larger samples and more accurate assay techniques.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72034/1/j.1075-122X.2005.00131.x.pd

Dynamic clamp with StdpC software

Dynamic clamp is a powerful method that allows the introduction of artificial electrical components into target cells to simulate ionic conductances and synaptic inputs. This method is based on a fast cycle of measuring the membrane potential of a cell, calculating the current of a desired simulated component using an appropriate model and injecting this current into the cell. Here we present a dynamic clamp protocol using free, fully integrated, open-source software (StdpC, for spike timing-dependent plasticity clamp). Use of this protocol does not require specialist hardware, costly commercial software, experience in real-time operating systems or a strong programming background. The software enables the configuration and operation of a wide range of complex and fully automated dynamic clamp experiments through an intuitive and powerful interface with a minimal initial lead time of a few hours. After initial configuration, experimental results can be generated within minutes of establishing cell recording

Simple, Fast and Accurate Implementation of the Diffusion Approximation Algorithm for Stochastic Ion Channels with Multiple States

The phenomena that emerge from the interaction of the stochastic opening and closing of ion channels (channel noise) with the non-linear neural dynamics are essential to our understanding of the operation of the nervous system. The effects that channel noise can have on neural dynamics are generally studied using numerical simulations of stochastic models. Algorithms based on discrete Markov Chains (MC) seem to be the most reliable and trustworthy, but even optimized algorithms come with a non-negligible computational cost. Diffusion Approximation (DA) methods use Stochastic Differential Equations (SDE) to approximate the behavior of a number of MCs, considerably speeding up simulation times. However, model comparisons have suggested that DA methods did not lead to the same results as in MC modeling in terms of channel noise statistics and effects on excitability. Recently, it was shown that the difference arose because MCs were modeled with coupled activation subunits, while the DA was modeled using uncoupled activation subunits. Implementations of DA with coupled subunits, in the context of a specific kinetic scheme, yielded similar results to MC. However, it remained unclear how to generalize these implementations to different kinetic schemes, or whether they were faster than MC algorithms. Additionally, a steady state approximation was used for the stochastic terms, which, as we show here, can introduce significant inaccuracies. We derived the SDE explicitly for any given ion channel kinetic scheme. The resulting generic equations were surprisingly simple and interpretable - allowing an easy and efficient DA implementation. The algorithm was tested in a voltage clamp simulation and in two different current clamp simulations, yielding the same results as MC modeling. Also, the simulation efficiency of this DA method demonstrated considerable superiority over MC methods.Comment: 32 text pages, 10 figures, 1 supplementary text + figur

TOI-1431b/MASCARA-5b: an ultra-hot Jupiter orbiting one of the hottest & brightest known exoplanet host stars

Stars and planetary system

Listening In on the Past: What Can Otolith δ18O Values Really Tell Us about the Environmental History of Fishes?

Oxygen isotope ratios from fish otoliths are used to discriminate marine stocks and reconstruct past climate, assuming that variations in otolith δ18O values closely reflect differences in temperature history of fish when accounting for salinity induced variability in water δ18O. To investigate this, we exploited the environmental and migratory data gathered from a decade using archival tags to study the behaviour of adult plaice (Pleuronectes platessa L.) in the North Sea. Based on the tag-derived monthly distributions of the fish and corresponding temperature and salinity estimates modelled across three consecutive years, we first predicted annual otolith δ18O values for three geographically discrete offshore sub-stocks, using three alternative plausible scenarios for otolith growth. Comparison of predicted vs. measured annual δ18O values demonstrated >96% correct prediction of sub-stock membership, irrespective of the otolith growth scenario. Pronounced inter-stock differences in δ18O values, notably in summer, provide a robust marker for reconstructing broad-scale plaice distribution in the North Sea. However, although largely congruent, measured and predicted annual δ18O values of did not fully match. Small, but consistent, offsets were also observed between individual high-resolution otolith δ18O values measured during tag recording time and corresponding δ18O predictions using concomitant tag-recorded temperatures and location-specific salinity estimates. The nature of the shifts differed among sub-stocks, suggesting specific vital effects linked to variation in physiological response to temperature. Therefore, although otolith δ18O in free-ranging fish largely reflects environmental temperature and salinity, we counsel prudence when interpreting otolith δ18O data for stock discrimination or temperature reconstruction until the mechanisms underpinning otolith δ18O signature acquisition, and associated variation, are clarified

Risk-stratified approach to breast cancer screening in canada: Women’s knowledge of the legislative context and concerns about discrimination from genetic and other predictive health data

The success of risk-stratified approaches in improving population-based breast cancer screening programs depends in no small part on women’s buy-in. Fear of genetic discrimination (GD) could be a potential barrier to genetic testing uptake as part of risk assessment. Thus, the objective of this study was twofold. First, to evaluate Canadian women’s knowledge of the legislative context governing GD. Second, to assess their concerns about the possible use of breast cancer risk levels by insurance companies or employers. We use a cross-sectional survey of 4293 (age: 30–69) women, conducted in four Canadian provinces (Alberta, British Colombia, Ontario and Québec). Canadian women’s knowledge of the regulatory framework for GD is relatively limited, with some gaps and misconceptions noted. About a third (34.7%) of the participants had a lot of concerns about the use of their health information by employers or insurers; another third had some concerns (31.9%), while 20% had no concerns. There is a need to further educate and inform the Canadian public about GD and the legal protections that exist to prevent it. Enhanced knowledge could facilitate the implementation and uptake of risk prediction informed by genetic factors, such as the risk-stratified approach to breast cancer screening that includes risk levels

Identificação de espécies de Leishmania isoladas de casos humanos em Mato Grosso do Sul por meio da reação em cadeia da polimerase.

RESUMO - As leishmanioses são zoonoses endêmicas em Mato Grosso do Sul e têm por agentes etiológicos nessa região Leishmania (Leishmania) chagasi, Leishmania (Leishmania) amazonensis e Leishmania (Viannia) braziliensis. Como método para identificação de espécies de Leishmania, a reação em cadeia da polimerase é uma ferramenta com elevada especificidade e sensibilidade. Analisaram-se 39 isolados de Leishmania criopreservados, obtidos por meio de aspirado medular e/ou biópsia de lesão, conforme a suspeita clínica. Os isolados foram submetidos à extração de DNA e à reação em cadeia da polimerase com os iniciadores: RV1/RV2 para Leishmania (Leishmania) chagasi, a1/a2 para a identificação de Leishmania (Leishmania) amazonensis e b1/b2 para Leishmania (Viannia) braziliensis. Leishmania (Leishmania) chagasi foi a única espécie identificada em 37 casos de leishmaniose visceral. Leishmania (Leishmania) amazonensis foi identificada em dois isolados de pacientes com diagnóstico de leishmaniose tegumentar. Os resultados obtidos confirmam a possibilidade do uso dos três pares de iniciadores como uma ferramenta na caracterização de isolados de Leishmania. ABSTRACT - Leishmaniases are endemic zoonoses in the State of Mato Grosso do Sul. Their etiological agents in this region of Brazil are Leishmania (Leishmania) chagasi, Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis. The polymerase chain reaction (PCR) is a tool with high specificity and sensitivity for identifying Leishmania species. This study examined 39 cryopreserved isolates of Leishmania that had been collected by bone marrow aspiration and/or lesion biopsy, depending on the clinical suspicion. The isolates were subjected to DNA extraction and PCR using the following primers: RV1/RV2 for identifying Leishmania (Leishmania) chagasi, a1/a2 for Leishmania (Leishmania) amazonensis and b1/b2 for Leishmania (Viannia) braziliensis. Leishmania (Leishmania) chagasi was the only species identified in the 37 cases of visceral leishmaniasis. Leishmania (Leishmania) amazonensis was identified in two isolates from patients with a diagnosis of cutaneous leishmaniasis. The results obtained confirm that it is possible to use these three pairs of primers as a tool for characterizing Leishmania isolate