Association of Chorioamnionitis with Aberrant Neonatal Gut Colonization and Adverse Clinical Outcomes.

ObjectiveChorioamnionitis (inflammation of the placenta and fetal membranes) and abnormal gastrointestinal colonization have been associated with an increased risk of sepsis and death in preterm infants, but whether chorioamnionitis causes abnormal pioneering gastrointestinal colonization in infants is not known. We determined the relationship between chorioamnionitis, altered infant fecal microbiome indicating abnormal gastrointestinal colonization, and adverse outcomes.Study designPreterm infants ≤ 28 weeks at birth were enrolled from 3 level III NICUs in Cincinnati, Ohio and Birmingham, Alabama. Sequencing for 16S microbial gene was performed on stool samples in the first 3 weeks of life. Chorioamnionitis was diagnosed by placental histology. Late onset sepsis and death outcomes were analyzed in relation to fecal microbiota and chorioamnionitis with or without funisitis (inflammation of the umbilical cord).ResultsOf the 106 enrolled infants, 48 infants had no chorioamnionitis, 32 infants had chorioamnionitis but no funisitis (AC), and 26 infants had chorioamnionitis with funisitis (ACF). The fecal samples from ACF infants collected by day of life 7 had higher relative abundance of family Mycoplasmataceae (phylum Tenericutes), genus Prevotella (phylum Bacteroidetes) and genus Sneathia (phylum Fusobacteria). Further, AC and ACF infants had higher incidence of late-onset sepsis/death as a combined outcome. Presence of specific clades in fecal samples, specifically, order Fusobacteria, genus Sneathia or family Mycoplasmataceae, were significantly associated with higher risk of sepsis or death.ConclusionThe results support the hypothesis that specific alterations in the pioneering infant gastrointestinal microbiota induced by chorioamnionitis predispose to neonatal sepsis or death

EVALUATION OF PHYTASE PRODUCTION BY HYPOCREA LIXII SURT01 IN SUBMERGED AND SOLID-STATE FERMENTATIONS

Objective: Phytases have important applications in human and animal nutrition because they hydrolyze the phytate present in legumes, cereal grains and oil seeds to release inorganic phosphate. Supplementation of phosphate to the poultry causes a serious problem of eutrophication. This can be reduced by incorporating phytase in poultry feed. Present study explains extracellular phytase production by SmF and SSF from a fungal strain Hypocrea lixii SURT01. Methods: Extracellular phytase production by Hypocrea lixii SURT01 was evaluated in media containing various refined carbon sources (Fructose, Sucrose, Maltose and lactose in concentration ranging from 1.5% to 7.5%) along with standard medium under submerged fermentation (SmF). At the same time, phytase production was studied under Solid State Fermentation (SSF) with four different substrate such as barley, green gram, bengal gram and black gram. Results: In SmF out of different carbon sources in various concentrations, 6% sucrose showed maximum enzyme production (245U/ml). In SSF, barley showed highest phytase yield (1638 Units/ml) on 5th day of incubation. Conclusion: Evaluation of Solid state fermentation showed enhanced phytase production when compared to Submerged Fermentation

Generating Random Logic Programs Using Constraint Programming

Testing algorithms across a wide range of problem instances is crucial to ensure the validity of any claim about one algorithm's superiority over another. However, when it comes to inference algorithms for probabilistic logic programs, experimental evaluations are limited to only a few programs. Existing methods to generate random logic programs are limited to propositional programs and often impose stringent syntactic restrictions. We present a novel approach to generating random logic programs and random probabilistic logic programs using constraint programming, introducing a new constraint to control the independence structure of the underlying probability distribution. We also provide a combinatorial argument for the correctness of the model, show how the model scales with parameter values, and use the model to compare probabilistic inference algorithms across a range of synthetic problems. Our model allows inference algorithm developers to evaluate and compare the algorithms across a wide range of instances, providing a detailed picture of their (comparative) strengths and weaknesses.Comment: This is an extended version of the paper published in CP 202

Cancer cells adapt FAM134B/BiP mediated ER-phagy to survive hypoxic stress

In the tumor microenvironment, cancer cells experience hypoxia resulting in the accumulation of misfolded/unfolded proteins largely in the endoplasmic reticulum (ER). Consequently, ER proteotoxicity elicits unfolded protein response (UPR) as an adaptive mechanism to resolve ER stress. In addition to canonical UPR, proteotoxicity also stimulates the selective, autophagy-dependent, removal of discrete ER domains loaded with misfolded proteins to further alleviate ER stress. These mechanisms can favor cancer cell growth, metastasis, and long-term survival. Our investigations reveal that during hypoxia-induced ER stress, the ER-phagy receptor FAM134B targets damaged portions of ER into autophagosomes to restore ER homeostasis in cancer cells. Loss of FAM134B in breast cancer cells results in increased ER stress and reduced cell proliferation. Mechanistically, upon sensing hypoxia-induced proteotoxic stress, the ER chaperone BiP forms a complex with FAM134B and promotes ER-phagy. To prove the translational implication of our mechanistic findings, we identified vitexin as a pharmacological agent that disrupts FAM134B-BiP complex, inhibits ER-phagy, and potently suppresses breast cancer progression in vivo

Inhaled PGE1 in neonates with hypoxemic respiratory failure: two pilot feasibility randomized clinical trials.

BackgroundInhaled nitric oxide (INO), a selective pulmonary vasodilator, has revolutionized the treatment of neonatal hypoxemic respiratory failure (NHRF). However, there is lack of sustained improvement in 30 to 46% of infants. Aerosolized prostaglandins I2 (PGI2) and E1 (PGE1) have been reported to be effective selective pulmonary vasodilators. The objective of this study was to evaluate the feasibility of a randomized controlled trial (RCT) of inhaled PGE1 (IPGE1) in NHRF.MethodsTwo pilot multicenter phase II RCTs are included in this report. In the first pilot, late preterm and term neonates with NHRF, who had an oxygenation index (OI) of ≥15 and <25 on two arterial blood gases and had not previously received INO, were randomly assigned to receive two doses of IPGE1 (300 and 150 ng/kg/min) or placebo. The primary outcome was the enrollment of 50 infants in six to nine months at 10 sites. The first pilot was halted after four months for failure to enroll a single infant. The most common cause for non-enrollment was prior initiation of INO. In a re-designed second pilot, co-administration of IPGE1 and INO was permitted. Infants with suboptimal response to INO received either aerosolized saline or IPGE1 at a low (150 ng/kg/min) or high dose (300 ng/kg/min) for a maximum duration of 72 hours. The primary outcome was the recruitment of an adequate number of patients (n = 50) in a nine-month-period, with fewer than 20% protocol violations.ResultsNo infants were enrolled in the first pilot. Seven patients were enrolled in the second pilot; three in the control, two in the low-dose IPGE1, and two in the high-dose IPGE1 groups. The study was halted for recruitment futility after approximately six months as enrollment targets were not met. No serious adverse events, one minor protocol deviation and one pharmacy protocol violation were reported.ConclusionsThese two pilot RCTs failed to recruit adequate eligible newborns with NHRF. Complex management RCTs of novel therapies for persistent pulmonary hypertension of the newborn (PPHN) may require novel study designs and a longer period of time from study approval to commencement of enrollment.Trial registrationCLINICALTRIALS.GOV: Pilot one: NCT number: 00598429 registered on 10 January 2008. Last updated: 3 February 2011. Pilot two: NCT number: 01467076 17 October 2011. Last updated: 13 February 2013

Transpiration-based micropump for delivering continuous ultra-low flow rates

In this paper we describe the design, construction and operation of a micropump that delivers continuous, ultra-low flow velocities at ∼100 μm s−1. The pumping concept is based on the commonly observed phenomenon of transpiration in plant leaves. A liquid meniscus is pinned inside a microchannel by selective hydrophobic patterning and the evaporation rate of the liquid at the meniscus is controlled. The controlled evaporative flux results in a regulated flow of the liquid from a reservoir to the meniscus. Using this technique, precise flow control (5 nl min−1) has been achieved in several channel geometries for extended periods of time (∼2 h). Various factors affecting the performance of the pump were studied and theoretical predictions along with experimental results are presented. Such a micropump could find applications in emerging biological assays such as single-molecule studies of DNA and cell adhesion analyses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49039/2/jm3214.pd

ATP release from the human ureter on distension and P2X3 receptor expression on suburothelial sensory nerves

It is not clear how the increase in intraluminal pressure behind an obstructing ureteric calculus causes an increase in action potential frequency in ureteric sensory nerves so the pain messages are transmitted to the brain. It has been proposed that ureteric distension causes urothelial release of ATP, which activates purinoceptors on suburothelial nociceptive sensory nerves. The purpose of this study was to determine whether distension of the human ureter results in the release of ATP and whether the nociceptive P2 receptor, P2X3, is expressed on suburothelial sensory nerves in the human ureter. Human ureter segments were perfused with Krebs solution and intermittently distended to a range of pressures. Samples of perfusate were collected throughout and the ATP concentration ([ATP]) was determined using a luciferin-luciferase assay. Sections of ureter were stained using antibodies against P2X3 and capsaicin receptors (TRPV1). [ATP] rose to more than 10 times baseline levels after distension beyond a threshold of 25–30 cmH2O. Immunofluorescence studies on consecutive frozen sections showed that suburothelial nerves stained positively for P2X3 and capsaicin receptors, with no staining in controls. These findings are consistent with the hypothesis that purinergic signalling is involved in human ureteric mechanosensory transduction, leading to nociception

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured