Standard of Care Versus Octreotide in Angiodysplasia-Related Bleeding (the OCEAN Study): A Multicenter Randomized Controlled Trial.

BACKGROUND & AIMS: Gastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We investigated the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least 4 red blood cell (RBC) units or parental iron infusions, or both, in the year preceding randomization. Patients were allocated (1:1) to 40-mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was 1 year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least 1 octreotide injection or followed standard of care for at least 1 month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up. RESULTS: We enrolled 62 patients (mean age, 72 years; 32 men) from 17 Dutch hospitals in the octreotide (n = 31) and standard of care (n = 31) groups. Patients required a mean number of 20.3 (standard deviation, 15.6) transfusion units and 2.4 (standard deviation, 2.0) endoscopic procedures in the year before enrollment. The total number of transfusions was lower with octreotide (11.0; 95% confidence interval [CI], 5.5-16.5) compared with standard of care (21.2; 95% CI, 15.7-26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4-18.1; P = .012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3-1.5). CONCLUSIONS: Octreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia. CLINICALTRIALS: gov, NCT02384122.

Adhesion and colonization of potential probiont Pseudomonas aeruginosa FARP72 in the intestine of yellowtail catfish, Pangasius pangasius.

Adhesion is recognized as the first important step of a probiont for intestinal colonization. This study assessed the ability of an antagonistic Pseudomonas aeruginosa FARP72 to adhere and colonize the intestine of yellowtail catfish, Pangasius pangasius both in vitro and in vivo. For the in vitro assay, the whole intestines of each of two starved P. pangasius were introduced separately into tubes containing bluish-green pigment-producing P. aeruginosa FARP72 at 8.00 log10 CFU/mL and physiological saline (0.85% sodium chloride) and incubated for 1 h at 30 ± 1 °C. The homogenate mucus solutions from the intestine samples were serially diluted and plated onto Pseudomonas isolation agar to determine the counts of bluish-green pigment-producing P. aeruginosa (BPPAC). The difference between the numbers of BPPAC and presumptive Pseudomonas counts (PPC) in the treated and control intestines was attributed to the adherence of P. aeruginosa FARP72. The levels of BPPAC and PPC in the treated intestines were 6.09 ± 0.59 log10 CFU/g. Similarly, following 30 days of feeding P. pangasius with P. aeruginosa FARP72 supplemented diet, the intestine of catfish recorded the BPPAC of 5.83 ± 0.64 log CFU/g. In control samples, the BPPACs were recorded as < 3.00 log10 CFU/g. The scanning electron micrograph of the intestines of P. pangasius following the in vitro and in vivo adhesion assays confirmed the ability of this bacterium to strongly adhere to the intestine, thus making it most suitable candidate probiont for use in freshwater catfish aquaculture.

Predicting Mortality in COPD with Validated and Sensitive Biomarkers; Fibrinogen and Mid-Range-Proadrenomedullin (MR-proADM).

Although fibrinogen is a FDA qualified prognostic biomarker in COPD, it still lacks sufficient resolution to be clinically useful. Next to replication of findings in different cohorts also the combination with other validated biomarkers should be investigated. Therefore, the aim of this study was to confirm in a large well-defined population of COPD patients whether fibrinogen can predict mortality and whether a combination with the biomarker MR-proADM can increase prognostic accuracy. From the COMIC cohort study we included COPD patients with a blood sample obtained in stable state (n = 640) and/or at hospitalization for an acute exacerbation of COPD (n = 262). Risk of death during 3 years of follow up for the separate and combined biomarker models was analyzed with Cox regression. Furthermore, logistic regression models for death after one year were constructed. When both fibrinogen and MR-proADM were included in the survival model, a doubling in fibrinogen and MR-proADM levels gave a 2.2 (95% CI 1.3-3.7) and 2.1 (95% CI 1.5-3.0) fold increased risk of dying, respectively. The prediction model for death after 1 year improved significantly when MR-proADM was added to the model with fibrinogen (AUC increased from 0.78 to 0.83; p = 0.02). However, the combined model was not significantly more adequate than the model with solely MR-proADM (AUC 0.83 vs 0.82; p = 0.34). The study suggests that MR-proADM is more promising than fibrinogen in prediciting mortality. Adding fibrinogen to a model containing MR-proADM does not significantly increase the predictive capacity of the model.

Influence of Fluctuating Water Temperature and Dietary Oxytetracycline on the Safety of Monosex Nile Tilapia Oreochromis niloticus Fries.

The influence of fluctuating water temperature and dietary oxytetracycline (OTC) at 0 (0X), 80 (1X), 240 (3X), 400 (5X) and 800 mg (10X)/kg biomass/day for 30 consecutive days on the safety of monosex (all male) Nile tilapia Oreochromis niloticus fries in terms of feeding, growth, survival and histopathology of vital organs were assessed. A dose-dependent decline in feed intake and biomass was recorded. The OTC-dosed groups recorded higher mortalities than the control. The therapeutic OTC-dosing (1X) in conjunction with low temperature caused 75.56 ± 8.01% mortality and 25.75% reduced feed intake in 30 days. The mortalities increased with increasing OTC-doses from 85.19 ± 3.39% (1X) to 95.56 ± 2.22% (10X) and fluctuating temperature (12.00-21.50°C) even after the withdrawal of OTC. Relatively mild to moderate histopathological lesions were observed in the kidney, liver and intestine of OTC-dosed fries. These results suggested that dietary OTC and low water temperature may cause adverse effects on monosex O. niloticus fries.

Discontinuous spirals of stability in an optically injected semiconductor laser.

We report a new kind of discontinuous spiral with stable periodic orbits in the parameter space of an optically injected semiconductor laser model, which is a combination of the intercalation of fish-like and cuspidal-like structures (the two normal forms of complex cubic dynamics). The spiral has a tridimensional structure that rolls up in at least three directions. A turn of approximately 2π radians along the spiral and toward the center increases the number of peaks in the laser intensity by one, which does not occur when traversing the discontinuities. We show that as we vary the linewidth enhancement factor (α), discontinuities are created (destroyed) through disaggregation (collapses) from (into) the so-called shrimp-like structures. Future experimental verification and applications, as well as theoretical studies to explain its origin and relation with homoclinic spirals that exist in its neighborhood, are needed.

Tricorn-like structures in an optically injected semiconductor laser.

This study reports the existence of tricorn-like structures of stable periodic orbits in the parameter plane of an optically injected semiconductor laser model (a continuous-time dynamical system). These tricorns appear inside tongue-like structures that are created through simple Shi'lnikov bifurcations. As the linewidth enhancement factor-α of the laser increases, these tongues invade the laser locking zone and extends over the zone of stable period-1 orbits. This invasion provokes a rich overlap dynamics of the parameter planes that produces an abundant multistability. As α increases, the tricorn exhibits a phenomenon of codimension-3 rotating in the clockwise and counterclockwise directions in the plane of the injected field rate K vs its detuning ω. We hope that the numerical evidence of the tricorns presented herein motivates the study of mathematical conditions for their genesis. We also encourage the experimental verification of these tricorn-like structures because our results also open new possibilities for optical switching between several different laser outputs in the neighborhood of these structures.

Narrow Optical Line Widths in Erbium Implanted in TiO2.

Atomic and atomlike defects in the solid state are widely explored for quantum computers, networks, and sensors. Rare earth ions are an attractive class of atomic defects that feature narrow spin and optical transitions that are isolated from the host crystal, allowing incorporation into a wide range of materials. However, the realization of long electronic spin coherence times is hampered by magnetic noise from abundant nuclear spins in the most widely studied host crystals. Here, we demonstrate that Er3+ ions can be introduced via ion implantation into TiO2, a host crystal that has not been studied extensively for rare earth ions and has a low natural abundance of nuclear spins. We observe efficient incorporation of the implanted Er3+ into the Ti4+ site (>50% yield) and measure narrow inhomogeneous spin and optical line widths (20 and 460 MHz, respectively) that are comparable to bulk-doped crystalline hosts for Er3+. This work demonstrates that ion implantation is a viable path to studying rare earth ions in new hosts and is a significant step toward realizing individually addressed rare earth ions with long spin coherence times for quantum technologies.

Triclosan exposure induces varying extent of reversible antimicrobial resistance in Aeromonas hydrophila and Edwardsiella tarda.

Triclosan (TCS) is a biocide commonly used in household and personal care items to prevent the microbial growth and is currently considered as an emerging pollutant. It has a ubiquitous distribution which can substantially contribute towards antimicrobial resistance. The present study was designed to evaluate the effect of different concentrations of TCS exposure on the antibiotic sensitivity of aquatic bacteria. Aeromonas hydrophila ATCC® 49140™ and Edwardsiella tarda ATCC® 15947™ exposed to TCS for short (30 min) and long duration (serial passages). The agar-disc diffusion assay during the serial passages of TCS exposure and subsequent exposure withdrawal showed clinically insignificant changes in the zone of inhibition for six selected antibiotics in both bacterial strains at all exposure concentrations. Four folds concentration-dependent increase in the minimum inhibitory concentrations (MICs) of TCS was observed in both the strains following TCS exposure. Similarly, a concentration-dependent increase in the MICs of oxytetracycline (OTC) up to 4 folds in A. hydrophila, and up to 8 folds in E. tarda, was also documented during the TCS exposure. In all the cases, withdrawal of TCS exposure effectively reduced the MICs of TCS and OTC in blank passages suggesting a decline in acquired resistance. The frequencies of mutation during 30 min TCS exposure for E. tarda and A. hydrophila ranged between >10-6 and 10-7 levels. Nevertheless, the TCS exposure did not cause any detectable mutation on the fabV gene of A. hydrophila indicating that the TCS may elicit phenotypic adaptation or other resistance mechanism. Although the reduction in MICs due to exposure withdrawal did not restore the bacterial susceptibility up to the initial level, the study proved that the reduced TCS use could significantly help reduce the antimicrobial-resistance and cross-resistance in pathogenic bacteria.

Electrolyte transport pathways induced in the midgut epithelium of Drosophila melanogaster larvae by commensal gut microbiota and pathogens.

KEY POINTS: The digestive tract of larval and adult Drosophila is an excellent analogue of the mammalian gut. Enterocytes of the posterior midgut are separated by septa, with no paracellular path, and therefore perform both immune and transport functions. Using microperfusion electrophysiology, we show that larvae emerging from the embryo into sterile medium have symmetrical apical and basal membrane conductances while larvae emerging into non-sterile medium have apical membranes fivefold more conductive than basal membranes. The channels inserted into the apical membranes could originate in microbiata or host and mediate recognition of microbes. Entomopathogenic cyclic peptide toxins deplete intracellular ions reversibly, forming transient ion channels that do not conduct water, unlike an ionophore like nystatin that depletes ions irreversibly. We show the feasibility of studying the interaction of a single microbial species, or tractable combinatorials of microbial species, with only enterocytes in the primary epithelial barrier. ABSTRACT: Microbiota colonizing exposed epithelial surfaces are vital for sustenance of metazoan life, but communication between microbiota, epithelial cells and the host immune system is only beginning to be understood. We address this issue in the posterior midgut epithelium of Drosophila larvae where nutrient transport and immune functions are exclusively transcellular. We showed that larvae emerging into a sterile post-embryonic environment have symmetrical apical and basal membranes. In contrast, larvae emerging into non-sterile media, the source of microbiota, have markedly asymmetrical membranes, with apical membrane conductance more than fivefold higher than the basal membrane. As an example of pathogen action, we showed that the entomopathogenic fungal toxin destruxin A (Dx) depleted intracellular ions. Reversibility of action of Dx was verified by bilayer reconstitution in forming transient non-specific channels that conduct ions but not water. Dx was also less effective from the apical side as compared to the basal side of the epithelium. We also showed that intercellular septa are not conductive in non-sterile cells, even though most cells are isopotential. Luminal microbiota therefore impart asymmetry to the epithelium, by activation of apical membrane conductance, enhancing inter-enterocyte communication, separated by insulating septa, via the gut lumen. These results also open the possibility of studying the basis of bidirectional molecular conversation specifically between enterocytes and microbiota that enables discrimination between commensals and pathogens, establishment of the former, and elimination of the latter.

The American Urological Association Symptom Index for Benign Prostatic Hyperplasia.

A symptom index for benign prostatic hyperplasia (BPH) was developed and validated by a multidisciplinary measurement committee of the American Urological Association (AUA). Validation studies were conducted involving a total of 210 BPH patients and 108 control subjects. The final AUA symptom index includes 7 questions covering frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying and urgency. On revalidation, the index was internally consistent (Cronbach's α = 0.86) and the score generated had excellent test-retest reliability (r = 0.92). Scores were highly correlated with subjects' global ratings of the magnitude of their urinary problem (r = 0.65 to 0.72) and powerfully discriminated between BPH and control subjects (receiver operating characteristic area 0.85). Finally, the index was sensitive to change, with preoperative scores decreasing from a mean of 17.6 to 7.1 by 4 weeks after prostatectomy (p <0.001). The AUA symptom index is clinically sensible, reliable, valid and responsive. It is practical for use in practice and for inclusion in research protocols.

Superdeformed and Triaxial States in

Shape parameters of a weakly deformed ground-state band and highly deformed slightly triaxial sideband in ^{42}Ca were determined from E2 matrix elements measured in the first low-energy Coulomb excitation experiment performed with AGATA. The picture of two coexisting structures is well reproduced by new state-of-the-art large-scale shell model and beyond-mean-field calculations. Experimental evidence for superdeformation of the band built on 0_{2}^{+} has been obtained and the role of triaxiality in the A∼40 mass region is discussed. Furthermore, the potential of Coulomb excitation as a tool to study superdeformation has been demonstrated for the first time.

Reactivity of phenolic compounds towards free radicals under in vitro conditions.

The free radical scavenging activity and reducing power of 16 phenolic compounds including four hydroxycinnamic acid derivatives namely ferulic acid, caffeic acid, sinapic acid and p-coumaric acid, benzoic acid and its derivatives namely protocatechuic acid, gallic acid and vanillic acid, benzene derivatives namely vanillin, vanillyl alcohol, veratryl alcohol, veratraldehyde, pyrogallol, guaiacol and two synthetic antioxidants, butylated hydroxy anisole (BHA) and propyl gallate were evaluated using 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH(•)), 2,2'-Azinobis-3- ethylbenzothiazoline-6-sulfonic acid radical (ABTS(+•)), Hydroxyl radical ((•)OH) and Superoxide radical (O2 (•-)) scavenging assays and reduction potential assay. By virtue of their hydrogen donating ability, phenolic compounds with multiple hydroxyl groups such as protocatechuic acid, pyrogallol, caffeic acid, gallic acid and propyl gallate exhibited higher free radical scavenging activity especially against DPPH(•) and O2 (•-). The hydroxylated cinnamates such as ferulic acid and caffeic acid were in general better scavengers than their benzoic acid counter parts such as vanillic acid and protocatechuic acid. All the phenolic compounds tested exhibited more than 85 % scavenging due to the high reactivity of the hydroxyl radical. Phenolic compounds with multiple hydroxyl groups also exhibited high redox potential. Exploring the radical scavenging and reducing properties of antioxidants especially those which are found naturally in plant sources are of great interest due to their protective roles in biological systems.

Preventive and treatment effects of a hemp seed (Cannabis sativa L.) meal protein hydrolysate against high blood pressure in spontaneously hypertensive rats.

PURPOSE: This work determined the ability of hemp seed meal protein hydrolysate (HMH)-containing diets to attenuate elevated blood pressure (hypertension) development in spontaneously hypertensive rats (SHRs). Effects of diets on plasma levels of renin and angiotensin I-converting enzyme (ACE) in the SHRs were also determined. METHODS: Defatted hemp seed protein meal was hydrolyzed using simulated gastrointestinal tract digestion with pepsin followed by pancreatin, and the resulting HMH used as a source of antihypertensive peptides. The HMH was substituted for casein at 0.5 and 1.0% levels and fed to young growing rats for 8 weeks (preventive phase) or adult rats for 4 weeks (treatment phase). RESULTS: Feeding of young growing SHRs with HMH resulted in attenuation of the normal increases in systolic blood pressure (SBP) with an average value of ~120 mmHg when compared to the casein-only group of rats (control) with a maximum of 158 mm Hg (p < 0.05). Feeding adult rats (SBP ~145 mmHg) with same diets during a 4-week period led to significant (p < 0.05) reduction in SBP to ~119 mmHg in comparison with 150 mmHg for the control rats. Plasma ACE activity was significantly (p < 0.05) suppressed (0.047-0.059 U/mL) in HMH-fed rats when compared to control rats (0.123 U/mL). Plasma renin level was also decreased for HMH-fed rats (0.040-0.054 µg/mL) when compared to control rats that were fed only with casein (0.151 µg/mL). CONCLUSIONS: The results suggest that HMH with strong hypotensive effects in SHRs could be used as a therapeutic agent for both the prevention and treatment of hypertension.

Thermoase-derived flaxseed protein hydrolysates and membrane ultrafiltration peptide fractions have systolic blood pressure-lowering effects in spontaneously hypertensive rats.

Thermoase-digested flaxseed protein hydrolysate (FPH) samples and ultrafiltration membrane-separated peptide fractions were initially evaluated for in vitro inhibition of angiotensin I-converting enzyme (ACE) and renin activities. The two most active FPH samples and their corresponding peptide fractions were subsequently tested for in vivo antihypertensive activity in spontaneously hypertensive rats (SHR). The FPH produced with 3% thermoase digestion showed the highest ACE- and renin-inhibitory activities. Whereas membrane ultrafiltration resulted in significant (p < 0.05) increases in ACE inhibition by the <1 and 1-3 kDa peptides, only a marginal improvement in renin-inhibitory activity was observed for virtually all the samples after membrane ultrafiltration. The FPH samples and membrane fractions were also effective in lowering systolic blood pressure (SBP) in SHR with the largest effect occurring after oral administration (200 mg/kg body weight) of the 1-3 kDa peptide fraction of the 2.5% FPH and the 3-5 kDa fraction of the 3% FPH. Such potent SBP-lowering capacity indicates the potential of flaxseed protein-derived bioactive peptides as ingredients for the formulation of antihypertensive functional foods and nutraceuticals.

Predictive Value of Transrectal Ultrasonic Doppler and Elastographic Features in Prostate Cancer Detection in Lagos University Teaching Hospital.

Introduction: This study aimed at determining the predictive value (PV) of transrectal ultrasonic Doppler and elastographic features in prostate cancer (PCa) detection among patients in Lagos University Teaching Hospital. Materials and Methods: This prospective study involved patients that underwent evaluation for PCa. Participants had digital rectal examination (DRE), prostate-specific antigen (PSA) assay, and transrectal ultrasound-guided prostate biopsy using colour Doppler (CD) and elastography. All cores were sent for histopathology. Data were analysed using Statistical Package for the Social Sciences Version 22.0. CD and elastography PV in PCa detection and their relationships to the Gleason score (GS) were analysed (P < 0.05). Results: Seventy men (aged between 45 and 87 years) were enrolled. Forty-three (61.4%) patients had PCa with a mean age of 69.37 ± 8.22years. The sensitivity, specificity, positive PV (PPV), negative PV (NPV) and accuracy of CD were 8.50%, 97.44%, 64.10%, 66.42% and 66.31%, respectively. The sensitivity, specificity, PPV, NPV and accuracy of elastography were 84.21%, 94.59%, 88.89%, 92.11% and 91.07%, respectively. Conclusion: There is a significant association between decreased elasticity (elastography) and PCa detection but a weak association between increased vascularity (CD) and PCa detection. A positive correlation exists between extent of prostatic stiffness and GS.

Zinc deficiency and taste perception in the elderly.

Taste, one of the major senses in humans, is the ability to detect the flavor of substances such as food, certain minerals, and poisons. Taste distortions in human beings have been attributed to various physiological and environmental factors including aging and disease conditions. Given the fact that taste is one of the most important factors in food preference, selection, and consumption, the decreased appetite in the elderly, probably due to disease conditions, may lead to dietary restrictions that could negatively impact nutritional and health status. The role of zinc on taste distortion in the elderly population and taste impairment are described. Although several studies demonstrate the associative nature of taste degeneration with age, additional investigations are required to clarify the mechanisms by which taste perception is altered with age.

Aroma and taste perceptions with Alzheimer disease and stroke.

Chemosensory disorders of smell or taste in humans have been attributed to various physiological and environmental factors including aging and disease conditions. Aroma and taste greatly condition our food preference, selection and, consumption; the decreased appetite in patients with known neurodegenerative diseases may lead to dietary restrictions that could negatively impact nutritional and health status. The decline in olfactory and gustatory systems in patients with Alzheimer disease and various types of stroke are described.

Increased mast cell numbers in a calcaneal tendon overuse model.

Tendinopathy is often discovered late because the initial development of tendon pathology is asymptomatic. The aim of this study was to examine the potential role of mast cell involvement in early tendinopathy using a high-intensity uphill running (HIUR) exercise model. Twenty-four male Wistar rats were divided in two groups: running group (n = 12); sedentary control group (n = 12). The running-group was exposed to the HIUR exercise protocol for 7 weeks. The calcaneal tendons of both hind limbs were dissected. The right tendon was used for histologic analysis using Bonar score, immunohistochemistry, and second harmonic generation microscopy (SHGM). The left tendon was used for quantitative polymerase chain reaction (qPCR) analysis. An increased tendon cell density in the runners were observed compared to the controls (P = 0.05). Further, the intensity of immunostaining of protein kinase B, P = 0.03; 2.75 ± 0.54 vs 1.17 ± 0.53, was increased in the runners. The Bonar score (P = 0.05), and the number of mast cells (P = 0.02) were significantly higher in the runners compared to the controls. Furthermore, SHGM showed focal collagen disorganization in the runners, and reduced collagen density (P = 0.03). IL-3 mRNA levels were correlated with mast cell number in sedentary animals. The qPCR analysis showed no significant differences between the groups in the other analyzed targets. The current study demonstrates that 7-week HIUR causes structural changes in the calcaneal tendon, and further that these changes are associated with an increased mast cell density.

Reverse-phase HPLC separation of hemp seed (Cannabis sativa L.) protein hydrolysate produced peptide fractions with enhanced antioxidant capacity.

Hemp seed protein hydrolysate (HPH) was produced through simulated gastrointestinal tract (GIT) digestion of hemp seed protein isolate followed by partial purification and separation into eight peptide fractions by reverse-phase (RP)-HPLC. The peptide fractions exhibited higher oxygen radical absorbance capacity as well as scavenging of 2,2-diphenyl-1-picrylhydrazyl, superoxide and hydroxyl radicals when compared to HPH. Radical scavenging activities of the fractionated peptides increased as content of hydrophobic amino acids or elution time was increased, with the exception of hydroxyl radical scavenging that showed decreased trend. Glutathione (GSH), HPH and the RP-HPLC peptide fractions possessed low ferric ion reducing ability but all had strong (>60 %) metal chelating activities. Inhibition of linoleic acid oxidation by some of the HPH peptide fractions was higher at 1 mg/ml when compared to that observed at 0.1 mg/ml peptide concentration. Peptide separation resulted in higher concentration of some hydrophobic amino acids (especially proline, leucine and isoleucine) in the fractions (mainly F5 and F8) when compared to HPH. The elution time-dependent increased concentrations of the hydrophobic amino acids coupled with decreased levels of positively charged amino acids may have been responsible for the significantly higher (p < 0.05) antioxidant properties observed for some of the peptide fractions when compared to the unfractionated HPH. In conclusion, the antioxidant activity of HPH after simulated GIT digestion is mainly influenced by the amino acid composition of some of its peptides.