Demonstration of an erbium-doped fiber with annular doping for low gain compression in cladding-pumped amplifiers.

We present the design and characterization of a cladding-pumped amplifier with erbium doping located in an annular region near the core. This erbium-doped fiber is proposed to reduce gain saturation, leading to smaller gain compression when compared to uniform core doping. Through numerical simulations, we first compare the performance of three fibers with different erbium doping profiles in the core or the cladding. When the doped fibers are operated at the optimum length, results show that the smaller overlap of the signal mode field with the annular erbium doping region leads to higher gain and lower saturation of the amplifier. A single-core erbium-doped fiber with an annular doping and a D-shaped cladding was fabricated. Measurements demonstrate less than 4 dB of gain compression over the C-band for input power ranging from -40 dBm to 3 dBm. Small gain compression EDFAs are of interest for applications that require input channel reconfiguration. Higher gain and saturation output power are also key issues in cladding-pumped multi-core amplifiers.

Perfusion Pressure Is a Critical Determinant of the Intratumoral Extravasation of Oncolytic Viruses.

Antitumor efficacy of oncolytic virotherapy is determined by the density and distribution of infectious centers within the tumor, which may be heavily influenced by the permeability and blood flow in tumor microvessels. Here, we investigated whether systemic perfusion pressure, a key driver of tumor blood flow, could influence the intratumoral extravasation of systemically administered oncolytic vesicular stomatitis virus (VSV) in myeloma tumor-bearing mice. Exercise was used to increase mean arterial pressure, and general anesthesia to decrease it. A recombinant VSV expressing the sodium iodide symporter (NIS), which concentrates radiotracers at sites of infection, was administered intravenously to exercising or anesthetized mice, and nuclear NIS reporter gene imaging was used to noninvasively track the density and spatial distribution of intratumoral infectious centers. Anesthesia resulted in decreased intratumoral infection density, while exercise increased the density and uniformity of infectious centers. Perfusion state also had a significant impact on the antitumor efficacy of the VSV therapy. In conclusion, quantitative dynamic radiohistologic imaging was used to noninvasively interrogate delivery of oncolytic virotherapy, highlighting the critical importance of perfusion pressure as a driver of intratumoral delivery and efficacy of oncolytic viruses.

Maternal perinatal undernutrition modifies lactose and serotranferrin in milk: relevance to the programming of metabolic diseases?

A close link between intrauterine growth restriction and development of chronic adult diseases such as obesity, diabetes, and hypertension has been established both in humans and animals. Modification of growth velocity during the early postnatal period (i.e., lactation) may also sensitize to the development of metabolic syndrome in adulthood. This suggests that milk composition may have long-lasting programming/deprogramming metabolic effects in the offspring. We therefore assess the effects of maternal perinatal denutrition on breast milk composition in a food-restricted 50% (FR50) rat model. Monosaccharides and fatty acids were characterized by gas chromatography, and proteins were profiled by surface-enhanced laser desorption/ionization-time-of-flight analysis in milk samples from FR50 and control rat dams. Milk analysis of FR50 rats demonstrated that maternal undernutrition decreases lactose concentration and modulates lipid profile at postnatal day 10 by increasing the unsaturated fatty acids/saturated fatty acids and diminishes serotransferrin levels at postnatal day 21. Our data indicate that maternal perinatal undernutrition modifies milk composition both quantitatively and qualitatively. These modifications by maternal nutrition open new perspectives to identify molecules that could be used in artificial milk to protect from the subsequent development of metabolic diseases.

C-Reactive protein and procalcitonin for the early detection of postoperative complications after sleeve gastrectomy: preliminary study in 97 patients.

BACKGROUND: Fistula is the most fearsome complication after sleeve gastrectomy. The outcome depends on early and timely diagnosis. C-reactive protein (CRP) and procalcitonin (PCT) have not been extensively evaluated in this context. OBJECTIVE: This study aimed to evaluate the interest of C-reactive protein (CRP) and procalcitonin (PCT) assay for the early detection of gastric fistula after sleeve gastrectomy and to study the PCT as an adjunctive marker to the CRP. SETTING: Private Practice. PATIENTS AND METHODS: This is a retrospective analysis of data collected prospectively. This study was carried out in 97 patients who underwent sleeve gastrectomy between January 2011 and December 2012. The fistula is an abnormal connection between two organs. An abscess is a collection of pus. RESULTS: The rate of postoperative complications (fistulas and abscesses) was 7.2 %. The incidence of fistula was 2 % and the incidence of abscess was 5 %. Both CRP and PCT were significantly higher in patients with postoperative fistula or abscess. Mean CRP was 61.3 mg/l in patients without complications and 161.3 mg/l in case of complications (p = 0.02). Mean postoperative PCT was 0.062 ng/ml in uncomplicated patients versus 0.108 mg/l in those with complications (p = 0.0006). CRP and PCT measured during the postoperative period were correlated with the occurrence of postoperative complications. CONCLUSION: Early detection of fistula or abscess after sleeve gastrectomy simplifies the management of these complications. While the ideal biomarker of infection does not yet exist, this study shows that clinical observations in association with CRP and PCT measurements could be of help for the early detection of septic complications after sleeve gastrectomy.

Perinatal nutrition programs the hypothalamic melanocortin system in offspring.

Epidemiological studies initially suggested that maternal undernutrition leading to low birth weight may predispose for long-lasting energy balance disorders. High birth weight due to maternal obesity or diabetes, inappropriate early postnatal nutrition, and rapid catch-up growth, may also sensitize to increased risk of obesity. As stated by the Developmental Origin of Health and Disease concept, the perinatal perturbation of fetus/neonate nutrient supply might be a crucial determinant of individual programming of body weight set-point. The hypothalamic melanocortin system composed of the melanocortin receptor 4, its agonist α-melanin-stimulating hormone (α-MSH), and its antagonist agouti-related protein (AgRP) is considered as the main central anorexigenic pathway controlling energy homeostasis. Studies in numerous animal models demonstrated that this system is a prime target of developmental programming by maternal nutritional manipulation. In rodents, the perinatal period of life corresponds largely to the period of brain maturation (i. e., melanocortin neuronal differentiation and development of their neural projections). In contrast, these phenomena essentially take place before birth in bigger mammals. Despite these different developmental time windows, altricial and precocial species share several common offspring programming mechanisms. Offspring from malnourished dams present a hypothalamic melanocortin system with a series of alterations: impaired neurogenesis and neuronal functionality, disorganization of feeding pathways, modified glucose sensing, and leptin/insulin resistance. Overall, these alterations may account for the long-lasting dysregulation of energy balance and obesity. Following maternal malnutrition, hormonal and epigenetic mechanisms might be responsible for melanocortin system programming in offspring.

Workplace bullying and psychotropic drug use: the mediating role of physical and mental health status.

OBJECTIVES: The association between workplace bullying and psychotropic drug use is not well established. This study was aimed at exploring the association between workplace bullying, and its characteristics, and psychotropic drug use and studying the mediating role of physical and mental health. METHODS: The study population consisted of a random sample of 3132 men and 4562 women of the working population in the south-east of France. Workplace bullying, evaluated using the validated instrument elaborated by Leymann, and psychotropic drug use, as well as covariates, were measured using a self-administered questionnaire. Covariates included age, marital status, presence of children, education, occupation, working hours, night work, physico-chemical exposures at work, self-reported health, and depressive symptoms. Statistical analysis was performed using logistic regression analysis and was carried out separately for men and women. RESULTS: Workplace bullying was strongly associated with psychotropic drug use. Past exposure to bullying increased the risk for this use. The more frequent and the longer the exposure to bullying, the stronger the association with psychotropic drug use. Observing bullying on someone else at the workplace was associated with psychotropic drug use. Adjustment for covariates did not modify the results. Additional adjustment for self-reported health and depressive symptoms reduced the magnitude of the associations, especially for men. CONCLUSIONS: The association between bullying and psychotropic drug use was found to be significant and strong and was partially mediated by physical and mental health.

Shear stress affects the architecture and cohesion of Chlorella vulgaris biofilms.

The architecture of microalgae biofilms has been poorly investigated, in particular with respect to shear stress, which is a crucial factor in biofilm-based reactor design and operation. To investigate how microalgae biofilms respond to different hydrodynamic regimes, the architecture and cohesion of Chlorella vulgaris biofilms were studied in flow-cells at three shear stress: 1.0, 6.5 and 11.0 mPa. Biofilm physical properties and architecture dynamics were monitored using a set of microscopic techniques such as, fluorescence recovery after photobleaching (FRAP) and particle tracking. At low shear, biofilms cohesion was heterogeneous resulting in a strong basal (close to the substrate) layer and in more loose superficial ones. Higher shear (11.0 mPa) significantly increased the cohesion of the biofilms allowing them to grow thicker and to produce more biomass, likely due to a biological response to resist the shear stress. Interestingly, an acclimation strategy seemed also to occur which allowed the biofilms to preserve their growth rate at the different hydrodynamic regimes. Our results are in accordance with those previously reported for bacteria biofilms, revealing some general physical/mechanical rules that govern microalgae life on substrates. These results may bring new insights about how to improve productivity and stability of microalgae biofilm-based systems.

Workplace bullying and sleep disturbances: findings from a large scale cross-sectional survey in the French working population.

STUDY OBJECTIVES: The purpose of this study was to explore the associations between workplace bullying, the characteristics of workplace bullying, and sleep disturbances in a large sample of employees of the French working population. DESIGN: Workplace bullying, evaluated using the validated instrument developed by Leymann, and sleep disturbances, as well as covariates, were measured using a self-administered questionnaire. Covariates included age, marital status, presence of children, education, occupation, working hours, night work, physical and chemical exposures at work, self-reported health, and depressive symptoms. Statistical analysis was performed using logistic regression analysis and was carried out separately for men and women. SETTING: General working population. PARTICIPANTS: The study population consisted of a random sample of 3132 men and 4562 women of the working population in the southeast of France. RESULTS: Workplace bullying was strongly associated with sleep disturbances. Past exposure to bullying also increased the risk for this outcome. The more frequent the exposure to bullying, the higher the risk of experiencing sleep disturbances. Observing someone else being bullied in the workplace was also associated with the outcome. Adjustment for covariates did not modify the results. Additional adjustment for self-reported health and depressive symptoms diminished the magnitude of the associations that remained significant. CONCLUSIONS: The prevalence of workplace bullying (around 10%) was found to be high in this study as well was the impact of this major job-related stressor on sleep disturbances. Although no conclusion about causality could be drawn from this cross-sectional study, the findings suggest that the contribution of workplace bullying to the burden of sleep disturbances may be substantial.

Prenatal traffic-related air pollution exposures, cord blood adipokines and infant weight.

OBJECTIVE: Studies suggest that prenatal exposure to traffic-related air pollution (TRAP) may contribute to childhood obesity. While exact mechanisms for this association are unknown, circulating adipokines are hypothesized to contribute to early-life weight gain. METHODS: The Maternal and Child Health Study birth cohort included 136 women from the Los Angeles County + University of Southern California Medical Center. This study estimated prenatal residential TRAP exposure and used linear regression analysis to examine associations between adipokines with TRAP exposure and infant weight change (birth to 6 months). RESULTS: A one standard deviation (1-SD: 2 ppb) increase in prenatal non-freeway nitrogen oxides was associated with 33% (P = 0.01) higher leptin and 9% higher high molecular weight adiponectin levels (P = 0.07) in cord blood. Leptin levels were 71% higher in mothers who lived <75 m than those living >300 m from major roadways (P = 0.03). A 1-SD (10 ng mL-1 ) increase in leptin was associated with a significant increase in infant weight change in female infants (0.62 kg, P = 0.02) but not male infants (0.11 kg, P = 0.48). CONCLUSIONS: Higher TRAP exposures were associated with higher cord blood levels of leptin and high molecular weight adiponectin. These adipokines were associated with increased infant weight change in female infants, which may have implications for future obesity risk.

Structure/function studies of glycosyltransferases.

Glycosyltransferases are the enzymes that synthesize oligosaccharides, polysaccharides and glycoconjugates. The analysis of the wealth of sequences that are now available in databases allowed the determination of conserved peptide motifs for each class of enzyme. Recent experimental data demonstrated their importance in donor and acceptor substrate binding and in catalysis. Fold-recognition studies provided the first models of the catalytic domains of some of these enzymes, while the first successes in glycosyltransferase crystallography are opening new routes in structural glycobiology.

Maternal undernutrition programs the apelinergic system of adipose tissue in adult male rat offspring.

Based on the Developmental Origin of Health and Disease concept, maternal undernutrition has been shown to sensitize adult offspring to metabolic pathologies such as obesity. Using a model of maternal 70% food restriction in pregnant female rats throughout gestation (called FR30), we previously reported that obesity-prone adult male rat offspring displayed hyperleptinemia with modifications in leptin and leptin receptor messenger RNA (mRNA) levels in white adipose tissue (WAT). Apelin is a member of the adipokine family that regulates various aspects of energy metabolism and WAT functionality. We investigated whether apelin and its receptor APJ could be a target of maternal undernutrition. Adult male rat offspring from FR30 dams showed increased plasma apelin levels and apelin gene expression in WAT. Post-weaning high-fat diet led to marked increase in APJ mRNA and protein levels in offspring's WAT. We demonstrate that maternal undernutrition and post-weaning diet have long-term consequences on the apelinergic system of adult male rat offspring.

Characteristics of work related asthma: results from a population based survey.

OBJECTIVES: Many risk factors for asthma have been investigated, one of which is the workplace. Work related asthma is a frequently reported occupational respiratory disease yet the characteristics which distinguish it from non-work related asthma are not well understood. The purpose of this study was to examine differences between work related and non-work related asthma with respect to healthcare use and asthma control characteristics. METHODS: Data from the Massachusetts Behavioral Risk Factor Surveillance System for 2001 and 2002 were used for this analysis. Work related status of asthma was determined by self-report of ever having been told by a physician that asthma was work related. Healthcare measures evaluated were emergency room visits and physician visits for worsening asthma and for routine care. Characteristics of asthma control evaluated were frequency of asthma symptoms, asthma attacks, difficulty sleeping, and asthma medication usage in the last 30 days and limited activity in the past 12 months. RESULTS: The prevalence of lifetime and current asthma in Massachusetts were 13.0% and 9.2%, respectively. Approximately 6.0% (95% CI 4.8 to 7.3) of lifetime and 6.2% (95% CI 4.7 to 7.8) of current asthma cases were work related. In the past 12 months, individuals with work related current asthma were 4.8 times (95% CI 2.0 to 11.6) as likely to report having an asthma attack, 4.8 times (95% CI 1.8 to 13.1) as likely to visit the emergency room at least once, and 2.5 times (95% CI 1.1 to 6.0) as likely to visit the doctor at least once for worsening asthma compared to individuals with non-work related asthma. CONCLUSIONS: Work related asthma is associated with increased frequency of asthma attacks and use of healthcare services. A better understanding of factors that contribute to differences in healthcare use and asthma control is needed to improve prevention and control strategies for individuals suffering from the disease.

A single domain thermophilic xylanase can bind insoluble xylan: evidence for surface aromatic clusters.

A clone expressing xylanase activity in Escherichia coli has been selected from a genomic plasmid library of the thermophilic Bacillus strain D3. Subcloning from the 9-kb insert located the xylanase activity to a 2.7-kb HindII/BamHI fragment. The DNA sequence of this clone revealed an ORF of 367 codons encoding a single domain type-F or family 10 enzyme, which was designated as XynA. Purification of the enzyme following over-expression in E. coli produced an enzyme of 42 kDa with a temperature optimum of 75 degrees C which can efficiently bind and hydrolyse insoluble xylan. The pH optimum of the enzyme is 6.5, but it is active over a broad pH range. A homology model of the xylanase has been constructed which reveals a series of surface aromatic residues which form hydrophobic clusters. This unusual structural feature is strikingly similar to the situation observed in the structure determined for the type-G xylanase from the Bacillus D3 strain and may constitute a common evolutionary mechanism imposed on different structural frameworks by which these xylanases may bind potential substrates and exhibit thermostability.

Cell-surface estrogen receptors mediate calcium-dependent nitric oxide release in human endothelia.

BACKGROUND: Although estrogen replacement therapy has been associated with reduction of cardiovascular events in postmenopausal women, the mechanism for this benefit remains unclear. Because nitric oxide (NO) is considered an important endothelium-derived relaxing factor and may function to protect blood vessels against atherosclerotic development, we investigated the acute effects of physiological levels of estrogen on NO release from human internal thoracic artery endothelia and human arterial endothelia in culture. METHODS AND RESULTS: We tested the hypothesis that estrogen acutely stimulates constitutive NO synthase activity in human endothelial cells by acting on a cell-surface receptor. NO release was measured in real time with an amperometric probe. 17beta-Estradiol exposure to internal thoracic artery endothelia and human arterial endothelia in culture stimulated NO release within seconds in a concentration-dependent manner. 17beta-Estradiol conjugated to bovine serum albumin also stimulated NO release, suggesting action through a cell-surface receptor. Tamoxifen, an estrogen receptor inhibitor, antagonized this action. We further showed with the use of dual emission microfluorometry that 17beta-estradiol-stimulated release of endothelial NO was dependent on the initial stimulation of intracellular calcium transients. CONCLUSIONS: Physiological doses of estrogen immediately stimulate NO release from human endothelial cells through activation of a cell-surface estrogen receptor that is coupled to increases in intracellular calcium.

Ontogenesis and functional aspects of oxytocin and vasopressin gene expression in the thymus network.

Ontogenesis of oxytocin (OT) and vasopressin (VP) gene expression and function were investigated in murine thymus. OT and VP transcripts were detected in the thymus on embryonic days 13 and 15, respectively. Corresponding messenger RNAs were evidenced in thymic epithelial cells by in situ hybridization with a neurophysin probe. From all OT and VP receptors, only OTR was expressed by all T-cell subsets, while V1bR was found in double positive and single positive CD8 cells. In fetal thymic organ cultures, OTR antagonist d[D-Tyr(Et)2, Thr4]OVT increased early apoptosis of CD8 cells, while V1bR antagonist (Sanofi SSR149415) inhibited T-cell differentiation, and favored CD8 T-cell commitment.

Cloning, expression and pharmacological characterization of a vasopressin-related receptor in an annelid, the leech Theromyzon tessulatum.

In annelids, it has been established that arginine-vasopressin (AVP)/oxytocin (OT) superfamily peptides are involved in the maintenance of water and electrolyte homeostasis as well as reproduction. At present, there is little information on their receptors. In this study, we report the characterization of a 1.7 kb cDNA for an AVP-related receptor from the leech Theromyzon tessulatum. The open reading frame encodes a 435-aminoacid transmembrane protein that displays seven segments of hydrophobic amino acids, typical of G-protein-coupled receptors. The overall predicted protein exhibits about 30% amino-acid identities to other invertebrate, as well as vertebrate, AVP/OT receptor family members, and displays conserved characteristic features belonging to the AVP/OT receptor superfamily. RT-PCR expression experiments showed that mRNA is expressed in the genital tract, the ovary and the brain. The receptor expression is stage specific, showing a weak expression after the two first blood meals, increasing dramatically after the last blood meal during the period of sexual maturation and disappearing after egg laying. Thus, the leech AVP-related receptor may mediate reproductive functions. When expressed in COS-7 cells, the receptor binds ligands with the following rank order of potency: AVP= Arg-vasotocin >Arg-conopressin >mesotocin = OT = Lys-conopressin=isotocin>annetocin. This shows an AVP-like pharmacological profile. The transfected receptor mediates AVP-induced accumulation of inositol phosphates, indicating that the leech AVP-related receptor is functional. This study describes the characterization of a novel AVP/OT superfamily receptor in annelids, which are considered the most distant group of coelomate metazoans possessing a functional AVP/OT-related endocrine system.

Detection of intra-amniotic infection in a rabbit model by proteomics-based amniotic fluid analysis.

OBJECTIVE: This study was undertaken to identify intra-amniotic infection caused by several different organisms in a rabbit model by using proteomics. STUDY DESIGN: Twenty infected and 18 uninfected amniotic fluid samples were subjected to proteomic analysis by surface-enhanced laser desorption ionization (SELDI-TOF, Ciphergen Biosystems, Fremont, Calif), 1- and 2-dimensional gel electrophoresis, and tandem mass spectrometry (MS/MS). RESULTS: Detailed SELDI-TOF spectra revealed a constitutive 4.0 kd peak in all animals. Infected samples also displayed a signature double peak at 3.6 kd. A SELDI-TOF signature profile for intra-amniotic infection predicted positive amniotic fluid and/or fetal cultures with a sensitivity of 90% and specificity of 83%. Similar proteomic profiles were obtained regardless of the infecting organism. The 3.6 kd peak appeared to contain rabbit calgranulin C and rabbit calcyclin, members of the S100 family of calcium binding proteins. CONCLUSION: Amniotic fluid proteomic analysis was able to detect intra-amniotic infection in this experimental rabbit model. S100 proteins may be involved in the host inflammatory response to intra-amniotic infection.

Leishmaniosis due to Leishmania infantum in a FIV and FelV positive cat with a squamous cell carcinoma diagnosed with histological, serological and isoenzymatic methods.

Leishmaniosis caused by Leishmania infantum is an endemic zoonosis present in the Mediterranean area. Canidae (dog and fox) constitute the main reservoir hosts for the parasite, whilst wild rodents or the cat can be carriers of the protozoan and are considered as secondary potential reservoirs. This paper describes a case of disseminated feline leishmaniosis with cutaneous (ulcerative), visceral (spleen and lymph nodes) and blood involvement in a FIV-FelV positive cat. The microscopic identification of the Leishmania infection was initially made on a skin biopsy of the temporal area, where a squamous cell carcinoma was diagnosed. The diagnosis of the disease was achieved by several serological techniques (ELISA, IFAT and Western-blot). The strain was obtained by blood culture, characterized by electrophoresis of isoenzymes and identified as Leishmania infantum zymodeme MON-1. Since the infection due to L. infantum is a zoonosis, the potential feline reservoir should be more investigated. Serological analysis by Western blot on domestic cats provides a useful tool. In veterinary practice, feline leishmaniosis should be systematically included in the differential diagnosis when compatible cutaneous lesions are present, especially in the endemic areas of canine leishmaniosis.