Surface properties and bacterial adhesion on polyurethane central catheters: Impact of ethanol lock solution.

It was shown in the literature that ethanol locks have a positive effect on preventing catheter-related infections in patients with central venous catheters without causing any microbial resistance. However, ethanol is known to interact with polyurethanes. The consequences of this interaction on the catheter surface properties were studied as it can impact the biocompatibility of the material and the adhesion phenomena onto the surface. No physical and chemical degradation was put into evidence, but low molecular weight compounds such as additives were extracted from the catheter bulk or migrated and exudated onto its surface. Nevertheless, as far as bacterial adhesion is concerned, after the catheter was locked and the lock removed, the surface modifications promoted no adhesion.

Deep Chlorophyll Maxima in the Global Ocean: Occurrences, Drivers and Characteristics.

Stratified oceanic systems are characterized by the presence of a so-called Deep Chlorophyll a Maximum (DCM) not detectable by ocean color satellites. A DCM can either be a phytoplankton (carbon) biomass maximum (Deep Biomass Maximum, DBM), or the consequence of photoacclimation processes (Deep photoAcclimation Maximum, DAM) resulting in the increase of chlorophyll a per phytoplankton carbon. Even though these DCM (further qualified as either DBMs or DAMs) have long been studied, no global-scale assessment has yet been undertaken and large knowledge gaps still remain in relation to the environmental drivers responsible for their formation and maintenance. In order to investigate their spatial and temporal variability in the open ocean, we use a global data set acquired by more than 500 Biogeochemical-Argo floats given that DCMs can be detected from the comparative vertical distribution of chlorophyll a concentrations and particulate backscattering coefficients. Our findings show that the seasonal dynamics of the DCMs are clearly region-dependent. High-latitude environments are characterized by a low occurrence of intense DBMs, restricted to summer. Meanwhile, oligotrophic regions host permanent DAMs, occasionally replaced by DBMs in summer, while subequatorial waters are characterized by permanent DBMs benefiting from favorable conditions in terms of both light and nutrients. Overall, the appearance and depth of DCMs are primarily driven by light attenuation in the upper layer. Our present assessment of DCM occurrence and of environmental conditions prevailing in their development lay the basis for a better understanding and quantification of their role in carbon budgets (primary production and export).

Author Correction: Floats with bio-optical sensors reveal what processes trigger the North Atlantic bloom.

In the original version of this Article, the data accession https://doi.org/10.17882/42182 was omitted from the Data Availability statement.In the first paragraph of the Methods subsection entitled 'Float data processing', the WET Labs ECO-triplet fluorometer was incorrectly referred to as 'WETLabs ECO PUK'. In the final paragraph of this subsection, the WET Labs ECO-series fluorometer was incorrectly referred to as 'WETLabs 413 ECO-series'.In the Methods subsection 'Float estimates of phytoplankton carbon biomass', the average particulate organic carbon-bbp ratio of 37,537 mgC m-2 was incorrectly given as 37,357 mgC m-2.In the second paragraph of the Methods subsection 'Float estimates of population division rates', the symbol for Celsius (C) was omitted from the phrase 'a 10°C increase in temperature'.These errors have now been corrected in the PDF and HTML versions of the Article.

[Severe hypercalcemia of unusual cause, looking for the culprit: Case report and review of the literature]. / Hypercalcémie sévère de cause inhabituelle, à la recherche du coupable : cas clinique et revue de la littérature.

INTRODUCTION: Hypercalcemia is not a rare event and can lead to severe consequences. Its main etiologies are primary hyperparathyroidism and neoplasic conditions. The iatrogenic etiology by vitamin D intoxication is more rarely found. CASE PRESENTATION: A 76-year-old finish woman comes to the emergency room for chest pain. Her medical history is impossible to specify due to the language barrier and initial confusion. She has severe hypercalcaemia (4.14mmol/L), renal insufficiency, cardiac arrhythmia later complicated by an ischemic cardiac episode. Clinic and biologic examinations initially guided the research towards a hematological and neoplasic pathology. The iatrogenic etiology will be permitted by the contribution of details on its medical history and treatment learnt secondly. She was treated for post-surgical hypoparathyroidism by dihydrotachysterol, a vitamin D derivative. The cessation of substitution, treatment with hydration and biphosphonates allowed the rapid correction of hypercalcemia. DISCUSSION: Dihydrotachysterol intoxication is a rare etiology of hypercalcemia. Because of the longer half-life of this molecule, the risk of hypercalcemia seems to be greater than with other vitamin D derivatives. This molecule, withdrawn from the French market in 1982, is not detected by the dosage of 25 and 1.25 OH vitamin D. CONCLUSION: We report an original case of intoxication by dihydrotachysterol. The risk of hypercalcemia encountered with this molecule must be known. The close medical follow-up recommended in case of hypoparathyroidism seems to be particularly necessary in case of supplementation by this molecule.

Floats with bio-optical sensors reveal what processes trigger the North Atlantic bloom.

The North Atlantic bloom corresponds to a strong seasonal increase in phytoplankton that produces organic carbon through photosynthesis. It is still debated what physical and biological conditions trigger the bloom, because comprehensive time series of the vertical distribution of phytoplankton biomass are lacking. Vertical profiles from nine floats that sampled the waters of the North Atlantic every few days for a couple of years reveal that phytoplankton populations start growing in early winter at very weak rates. A proper bloom with rapidly accelerating population growth rates instead starts only in spring when atmospheric cooling subsides and the mixed layer rapidly shoals. While the weak accumulation of phytoplankton in winter is crucial to maintaining a viable population, the spring bloom dominates the overall seasonal production of organic carbon.

Presentation, diagnosis, and management of popliteal artery entrapment syndrome: 11 years of experience with 61 legs.

Popliteal artery entrapment syndrome (PAES) is still underdiagnosed yet it may significantly interfere with lifestyle, especially among young sportspeople, with symptoms like intermittent claudication. Although case reports and small case series are sometimes published, studies with larger populations are quite rare. This study summarizes our experience with PAES on 61 limbs (35 patients) over a period of 11 years, describing the demographics, the disease, and the diagnostic and therapeutic methods used with PAES patients. In a population of 327 consecutive explored symptomatic sportspersons, PAES was confirmed in 35 patients on 61 pathologic limbs. The median time with the symptoms before diagnosis was 34 months (range, 3-180 months). The mean age of patients was 30.5 years (range, 17-52 years) with 83% of males. The proportion of patients diagnosed with bilateral PAES was 74%. The main sports practiced were running (15 patients, 43%), soccer (nine patients, 26%), rugby (two patients), and athletics (two patients). Among 21 patients, intra-compartmental pressure measurements (ICP) found 18 (86%) to have an associated chronic exertional compartment syndrome (CECS). Among the patients followed up after PAES surgery, 80% were able to resume sport at a level comparable to that before the onset of pain. PAES could be sought earlier in young sportspeople who experience unexplained leg pain during exercise to diagnose the disease and avoid complications in a timely manner. Compartmental pressures should systematically be measured in the search for an associated CECS.

Extensive lymph node dissection during pancreaticoduodenectomy: a risk factor for hepatic steatosis?

PURPOSE: The first reports of hepatic steatosis following pancreaticoduodenectomy (PD) were published several years ago; however, clear risk factors remain to be identified. Therefore, the aim of this study was to identify the risk factors for hepatic steatosis post-PD. METHODS: We studied 90 patients who had undergone PD between September 2005 and January 2015. The inclusion criteria were as follows: available unenhanced CT within one month before PD and at least one unenhanced CT acquisition between PD and chemotherapy initiation. Using scanners, we studied the liver and spleen density as well as the surface areas of visceral (VF) and subcutaneous fat (SCF). These variables were previously identified by univariate and multivariate analyses. RESULTS: Hepatic steatosis occurred in 25.6% of patients at 45.2 days, on average, post-PD. Among the patients with hepatic steatosis, the average liver density was 52 HU before PD and 15.1 HU post-PD (p < 0.001). The Patients with hepatic steatosis lost more VF (mean, 28 vs. 11 cm2) and SCF (28.8 vs. 13.7 cm2) (p < 0.01 and p = 0.01, respectively). Portal vein resection and extensive lymph node dissection were independent risk factors in the multivariate analysis (odds ratio [OR] 5.29, p = 0.009; OR 3.38, p = 0.04, respectively). CONCLUSION: Portal vein resection and extensive lymph node dissection are independent risk factors for post-PD hepatic steatosis.

In vitro radiosensitizing effects of ultrasmall gadolinium based particles on tumour cells.

Since radiotherapy is widely used in cancer treatment, it is essential to develop strategies which lower the irradiation burden while increasing efficacy and become efficient even in radio resistant tumors. Our new strategy is relying on the development of solid hybrid nanoparticles based on rare-earth such as gadolinium. In this paper, we then evidenced that gadolinium-based particles can be designed to enter efficiently into the human glioblastoma cell line U87 in quantities that can be tuned by modifying the incubation conditions. These sub-5 nm particles consist in a core of gadolinium oxide, a shell of polysiloxane and are functionalized by diethylenetriaminepentaacetic acid (DTPA). Although photoelectric effect is maximal in the [10-100 keV] range, such particles were found to possess efficient in-vitro radiosensitizing properties at an energy of 660 keV by using the "single-cell gel electrophoresis comet assay," an assay that measures the number of DNA damage that occurs during irradiation. Even more interesting, the particles have been evidenced by MTT assays to be also efficient radiosensitizers at an energy of 6 MeV for doses comprised between 2 and 8 Gy. The properties of the gadolinium-based particles give promising opening to a particle-assisted radio-therapy by using irradiation systems already installed in the majority of hospitals.

Long-distance seed and pollen dispersal inferred from spatial genetic structure in the very low-density rainforest tree, Baillonella toxisperma Pierre, in Central Africa.

We analysed the spatial distribution of genetic diversity to infer gene flow for Baillonella toxisperma Pierre (Moabi), a threatened entomophilous pollinated and animal-dispersed Central African tree, with typically low density (5-7 adults trees/km(2)). Fifteen nuclear and three universal chloroplast microsatellites markers were used to type 247 individuals localized in three contiguous areas with differing past logging intensity. These three areas were within a natural forest block of approximately 2886 km(2) in Gabon. Expected heterozygosity and chloroplast diversity were He(nuc) = 0.570 and H(cp) = 0.761, respectively. F(IS) was only significant in one area (F(IS) = 0.076, P < 0.01) and could be attributed to selfing. For nuclear loci, Bayesian clustering did not detect discrete gene pools within and between the three areas and global differentiation (F(STnuc) = 0.007, P > 0.05) was not significant, suggesting that they are one population. At the level of the whole forest, both nuclear and chloroplast markers revealed a weak correlation between genetic relatedness and spatial distance between individuals: Sp(nuc) = 0.003 and Sp(cp) = 0.015, respectively. The extent of gene flow (σ) was partitioned into global gene flow (σ(g)) from 6.6 to 9.9 km, seed dispersal (σ(s)) from 4.0 to 6.3 km and pollen dispersal (σ(p)) from 9.8 to 10.8 km. These uncommonly high dispersal distances indicate that low-density canopy trees in African rainforests could be connected by extensive gene flow, although, given the current threats facing many seed disperser species in Central Africa, this may no longer be the case.

High-risk molecules or insufficient scientific data?

When I was invited to author an ethics policy piece on the "approach to high-risk molecules" as a contribution to the theme of "Innovation in Drug Development" of this Clinical Pharmacology & Therapeutics issue, I thought there was a need to evaluate whether questioning the transition from preclinical to clinical development after the TGN 1412 serious adverse event may freeze the development of innovating tools in drug development.

Acute immuno-allergic interstitial nephritis caused by fluindione.

Fluindione is a vitamin K antagonist that is commonly prescribed for the treatment of cardiovascular disease and venous thromboembolism in France. Bleeding is the most common side effect of fluindione, whereas hypersensitivity reactions are rare. We describe here a patient with acute immuno-allergic interstitial nephritis caused by fluindione. Initial symptoms included fever, eosinophilia, low albuminuria, microscopic hematuria, eosinophiluria and acute renal failure. Kidney biopsy showed severe interstitial nephritis with interstitial edema, inflammatory infiltrates and tubulorrhexis. Fluindione withdrawal and corticosteroid treatment resulted in rapid recovery of renal function. A review of the literature revealed a very low incidence of fluindione-induced interstitial nephritis, with variable renal and extra-renal signs. Early recognition of this rare complication may prevent the development of severe chronic renal injury.

Marker-based investigation of inbreeding depression in the endangered species Brassica insularis.

Various methods have been proposed to estimate inbreeding depression and to assess its consequences for natural populations. As an alternative to controlled crosses, the use of molecular markers has allowed direct investigation of inbreeding depression in natural populations, but usually suffers from low statistical power. Here, we investigated the effect of inbreeding depression on survival in two populations of the rare species Brassica insularis, using both controlled crosses and a marker-based approach. We compare the respective merits of the two approaches for studying inbreeding depression. We also use information from the molecular markers to dissect in detail patterns of inbreeding depression in this species. A posteriori, we find that combining the approaches was not necessary to obtain simple point estimates of inbreeding depression. However, using molecular markers may give insight into the genetic basis of inbreeding depression, such as the occurrence of epistatic interactions among deleterious alleles or purging.

[Viral cardiomyopathy]. / Cardiomyopathies virales. A propos de 4 observations d'infection myocardique à parvovirus B-19 et revue de la littérature.

In too many cases, the cause of dilated cardiomyopathy (DCM) remains undetermined. Coronary or valvular heart diseases, connective tissue disorders, toxic causes and signs of infection are systematically investigated. With the exceptions of coronary and sometimes valvular heart disease, the treatment of cardiac failure remains symptomatic treating the consequences but not the cause of DCM, which is therefore diagnosed as "idiopathic". This artericle reports the clinical history of 4 patients followed up for apparently "idiopathic" DCM in whom the presence of chronic Parvovirus B-19 infection was demonstrated. Based on these 4 cases, the hypothesis of an infectious cause of DCM and the role of myocardial biopsy, given the progress in molecular biology, are reconsidered. Parvovirus B-19 infection has recently been recognised not only as a cause of myocarditis but also of chronic viral cardiomyopathy, as in adeno and enteroviral infection. The authors conclude that the progress in molecular biology, the recognition of a viral aetiology and the efficacy of immuno-modulator therapy such as beta-interferon, may lead to a new management strategy of patients with DCM in cardiological referral centres.

Fine-scale genetic structure and gene dispersal in Centaurea corymbosa (Asteraceae) I. Pattern of pollen dispersal.

Pollen dispersal was characterized within a population of the narrowly endemic perennial herb, Centaurea corymbosa, using exclusion-based and likelihood-based paternity analyses carried out on microsatellite data. Data were used to fit a model of pollen dispersal and to estimate the rates of pollen flow and mutation/genotyping error, by developing a new method. Selfing was rare (1.6%). Pollen dispersed isotropically around each flowering plant following a leptokurtic distribution, with 50% of mating pairs separated by less than 11 m, but 22% by more than 40 m. Estimates of pollen flow lacked precision (0-25%), partially because mutations and/or genotyping errors (0.03-1%) could also explain the occurrence of offspring without a compatible candidate father. However, the pollen pool that fertilized these offspring was little differentiated from the adults of the population whereas strongly differentiated from the other populations, suggesting that pollen flow rate among populations was low. Our results suggest that pollen dispersal is too extended to allow differentiation by local adaptation within a population. However, among populations, gene flow might be low enough for such processes to occur.

Postmeiotic cytokinesis and pollen aperture number determination in eudicots: effect of the cleavage wall number.

In eudicot postmeiotic tetrads, apertures are usually joined in pairs in highly conserved areas. These appear to be located at the last points of contact persisting at the end of cytokinesis between the cytoplasm of the future microspores. In order to investigate the relationship between cytokinesis and aperture formation, aperture distribution within postmeiotic tetrads and the progression of meiosis were studied in Nicotiana tabacum cv. Ambalema. This variety (inbred line) produces about 85% tricolporate pollen and 15% tetracolporate pollen grains. In addition, about 7% of tetrads are composed of four equal-sized microspores and a supernumerary pseudomicrospore of small size and an equal proportion of tetrads exhibit unpaired apertures (these apertures are not joined in pairs within tetrads). Observation of cytokinesis indicates that both unpaired apertures and pseudomicrospores could result from the persistence of late communications between microsporocytes. Observations of tetrads indicate that an increase in the number of elements that are separated during cytokinesis is correlated with an increase in microspore aperture number. All data converge to support the hypothesis that aperture site determination is partly controlled by the number of walls formed to separate the different elements of the tetrad.

Inbreeding depression in small populations of self-incompatible plants.

Self-incompatibility (SI) is a widespread mechanism that prevents inbreeding in flowering plants. In many species, SI is controlled by a single locus (the S locus) where numerous alleles are maintained by negative frequency-dependent selection. Inbreeding depression, the decline in fitness of selfed individuals compared to outcrossed ones, is an essential factor in the evolution of SI systems. Conversely, breeding systems influence levels of inbreeding depression. Little is known about the joint effect of SI and drift on inbreeding depression. Here we studied, using a two-locus model, the effect of SI (frequency-dependent selection) on a locus subject to recurrent deleterious mutations causing inbreeding depression. Simulations were performed to assess the effect of population size and linkage between the two loci on the level of inbreeding depression and genetic load. We show that the sheltering of deleterious alleles linked to the S locus strengthens inbreeding depression in small populations. We discuss the implications of our results for the evolution of SI systems.

Pharmacokinetics of estradiol valerate 2mg + dienogest 2mg (climodien® 2/2) after single and repeated oral administration in healthy postmenopausal women.

OBJECTIVE: To evaluate the pharmacokinetics and tolerability of estradiol valerate 2.0mg plus dienogest 2.0mg (Climodien® 2/2). DESIGN AND SETTING: This was an open single-and multiple-dose study. STUDY PARTICIPANTS: 16 healthy postmenopausal women. INTERVENTIONS: Pharmacokinetic parameters were determined in plasma after single and multiple daily intake of Climodien® 2/2 for 12 weeks. Accumulation during multiple administration was calculated from the area under the plasma concentration-time curve (AUC). Changes in plasma levels of other hormones and sex hormone-binding globulin (SHBG) were also measured. RESULTS: The observed accumulation of estradiol (accumulation ratio R(1) = 3.3) and free estrone (R(1) = 2.4) was higher than that predicted from single-dose data (R(theor) = 1.7 and 2.0 for estradiol and free estrone, respectively). This was thought to be due to high interindividual variability in estrogen parameters, or the degree of extrapolation required when calculating the half-life (t1/2). The observed accumulation of total estrone after multiple-drug administration was as predicted from single-dose results (R(1) and R(theor) = 1.5). The pharmacokinetics of dienogest were not time dependent, the observed accumulation (AUC(0-24h) 627 vs 483 µg/L · h) was as predicted from single-dose results (R(1) and R(theor) = 1.3). Reduced total plasma testosterone levels confirmed the antiandrogenic effect of dienogest.The main adverse events with Climodien® 2/2 (breast tension in five participants and irregular vaginal bleeding in four) reflected its hormonal content, and laboratory screening tests revealed no tolerability concerns. CONCLUSIONS: Estradiol may accumulate in plasma during multiple-drug administration with Climodien® 2/2 more than predicted from single-dose results. However, dienogest kinetics after multiple-drug administration were as predicted from single-dose results. Climodien® 2/2 demonstrated antiandrogenic effects and was well tolerated.

Estradiol and estrone plasma levels during application of three strengths of a 7-day estradiol transdermal patch.

BACKGROUND: A new estradiol transdermal patch was developed for a once weekly application, with the aim to achieve an optimum practicability and to improve long-term compliance with estrogen replacement therapy. The pharmacokinetics of estradiol (CAS 50-28-2) and of estrone (CAS 53-16-7) during a 7-day application of the new patch is reported in this publication. METHODS: Unconjugated estradiol and estrone were assayed in plasma in a three-way crossover study on 18 postmenopausal women during and after a 7-day application of 3 strengths of the new patch, with daily release rates of 25, 50 and 75 micrograms of estradiol. RESULTS: During the 7-day application of the transdermal patches the concentration in plasma of unconjugated estradiol increased from less than 5 pg/ml, typical of postmenopause, to average concentrations of 26, 49 and 66 pg/ml under the patches with the release rates of 25, 50 and 75 micrograms/day of estradiol, respectively. The increases were linearly related and proportional to the strength of the patches. Upon removal of the patches, the estradiol concentrations returned to the basal postmenopausal values in 8-24 h. Retarded with regard to estradiol, there was also an increase of unconjugated estrone, from basal concentrations of 24 pg/ml to average concentrations of 39, 54 and 62 pg/ml, respectively. Estrone returned to its basal concentrations 24-48 h after removal of the patches. The estradiol/estrone ratio from the low pre-treatment values of 0.15-0.21 typical of postmenopause increased to average values of 0.51, 0.92 and respectively 1.09 during the application of the patches with the three strengths. The ratios are in the range of those of unconjugated hormones during the fertile age of women. The patches were well tolerated by the skin, with rare mild and transient reactions that disappeared spontaneously and did not cause interruption of treatment. Also the systemic tolerability was good, with occasional mild or moderate side effects typical of estradiol found especially under the application of the two higher strengths, i.e. with release of 50 and 75 micrograms/day of estradiol. CONCLUSIONS: The effective pharmacokinetic performance over the 7-day application, combined with the good general and local tolerability and the need to apply the patches only once weekly confer to the new patches a favorable practicability for the long-term estrogen replacement therapy needed to control the most severe postmenopausal disorders.

Pollen aperture heteromorphism. Variation in pollen-type proportions along altitudinal transects in Viola calcarata.

Some species produce pollen grains with different aperture numbers within a single individual (pollen aperture heteromorphism). In the pansy Viola diversifolia, aperture number is positively correlated with pollen germination speed, and negatively correlated with viability. In V. calcarata, young five-aperturate pollen grains germinate faster than four-aperturate ones. Heteromorphism could thus be favoured when pollination is unpredictable, as plants produce both very competitive and long-lived pollen grains. Depending on the efficiency of the pollinators, different proportions of pollen types will be optimal. In insect-pollinated species, such as V. calcarata, pollination efficiency generally decreases as elevation increases. We therefore expect a decrease in mean aperture number as altitude increases. This was found in four transects (out of six). Pollinator activity therefore has a potential impact on pollen morphology.