Efficacy of Radium 223 in Radioactive Iodine Refractory Bone Metastases From Differentiated Thyroid Cancer

Condition:   Thyroid Cancer
Intervention:   Radiation: Radium 223
Sponsor:   Gustave Roussy, Cancer Campus, Grand Paris
Recruiting - verified February 2016

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Phase III Trial Comparing Methotrexate and Cetuximab in First-line Treatment of Recurrent and/or Metastatic Squamous Cell Head and Neck Cancer

Condition:   Head Neck Cancer Squamous Cell Recurrent
Interventions:   Drug: Cetuximab;   Drug: Methotrexate
Sponsors:   Gustave Roussy, Cancer Campus, Grand Paris;   National Cancer Institute, France;   Ligue contre le cancer, France;   Merck Serono International SA
Recruiting - verified February 2016

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Differentiated Thyroid Cancer: is There a Need for Radioiodine Ablation in Low Risk Patients?

Condition:   Low Risk Differentiated Thyroid Cancer
Interventions:   Drug: rhTSH stimulation;   Drug: I131;   Other: Follow up
Sponsor:   Gustave Roussy, Cancer Campus, Grand Paris
Recruiting - verified February 2016

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Viruses, Vol. 8, Pages 42: Viruses Causing Gastroenteritis: The Known, The New and Those Beyond

The list of recently discovered gastrointestinal viruses is expanding rapidly. Whether these agents are actually involved in a disease such as diarrhea is the essential question, yet difficult to answer. In this review a summary of all viruses found in diarrhea is presented, together with the current knowledge about their connection to disease.

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Analgesic and Antipyretic Activities of Methanol Extract and Its Fraction from the Root of Schoenoplectus grossus

The study aims to evaluate analgesic and antipyretic activities of the methanol extract and its different fractions from root of Schoenoplectus grossus using acetic acid induced writhing and radiant heat tail flick method of pain models in mice and yeast induced pyrexia in rats at the doses of 400 and 200 mg/kg. In acetic acid writhing test, the methanol extract, petroleum ether, and carbon tetrachloride fractions produced significant ( and ) inhibition of writhing responses in dose dependent manner. The methanol extract at 400 and 200 mg/kg being more protective with 54% and 45.45% of inhibition compared to diclofenac sodium of 56% followed by petroleum ether fractions of 49.69% and 39.39% at the same doses. The extracts did not produce any significant antinociceptive activity in tail flick test except standard morphine. When studied on yeast induced pyrexia, methanol and petroleum ether fractions significantly lowered the rectal temperature time dependently in a manner similar to standard drug paracetamol and distinctly more significant () after second hour. These findings suggest that the root extracts of S. grossus possess significant peripherally acting analgesic potential and antipyretic property. The phytochemical screening showed the presence of flavonoids, alkaloids, and tannins.

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Effects of Dendritic Cell Subset Manipulation on Airway Allergy in a Mouse Model

Background: Two major distinct subsets of dendritic cells (DCs) are arranged to regulate immune responses: DEC-205+ DCs drive Th1 polarization and 33D1+ DCs establish Th2 dominancy. Th1 polarization can be achieved either by depletion of 33D1+ DCs with a 33D1-specific monoclonal antibody (mAb) or by activation of DEC-205+ DCs via intraperitoneal injection of α-galactosylceramide (α-GalCer). We studied the effect of 33D1+ DC depletion or DEC-205+ DC activation in vivo using an established mouse model of allergic rhinitis (AR). Methods: Mice were injected intraperitoneally with OVA plus alum and challenged 4 times with daily intranasal administration of OVA. Immediately after the last challenge, allergic symptoms such as sneezing and nasal rubbing as well as the number of cells in the bronchoalveolar lavage fluid (BALF) and nasal lavage fluid (NALF) were counted. The levels of serum OVA-specific IgG1, IgG2a, and IgE were also determined by ELISA. Results: The allergic symptom scores were significantly decreased in 33D1+ DC-depleted or DEC-205+ DC-activated AR mice. The levels of OVA-specific IgG1, IgG2a, and IgE, and the number of NALF cells, but not BALF cells, were reduced in 33D1+ DC-depleted but not in DEC-205+ DC-activated AR mice. Moreover, the activated DEC-205+ DCs suppressed histamine release from IgE-sensitized mast cells, probably through IL-12 secretion. Conclusions: The manipulation of innate DC subsets may provide a new therapeutic strategy for controlling various allergic diseases by reducing histamine release from IgE-sensitized mast cells by driving the immune response towards Th1 dominancy via activation of DEC-205+ DCs in vivo.
Int Arch Allergy Immunol 2015;168:219-232

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Concentration of Sindbis Virus with Optimized Gradient Insulator-based Dielectrophoresis

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C5AN02430G, Paper

Jie Ding, Robert Lawrence, Paul V Jones, Brenda G Hogue, Mark A Hayes
Biotechnology, separation science, and clinical research are impacted by microfluidic devices. Separation and manipulation bioparticles such as DNA, protein and viruses are performed on these platforms. Microfluidic systems provide many...
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Colchicine Treatment for Tracheobronchial Amyloidosis

Tracheobronchial amyloidosis is an infrequent disease characterized by the deposition of proteinaceous material in the tracheobronchial tree. The disease generally has a high morbidity and variable mortality in the years following diagnosis. There is no consensus on the optimal treatment. We report a case of a 63-year-old woman who presented with a diffuse tracheobronchial amyloidosis associated with laryngeal involvement, which required a percutaneous tracheostomy due to high-grade subglottic stenosis, with no evidence of systemic amyloidosis. After treatment exclusively with colchicine, she had a complete resolution of the stenotic area, with a very good response from the tracheobronchial amyloidosis disease, with only minor yellow plaques persisting. The patient has remained asymptomatic in the next 4 years of follow-up, with no evidence of endoscopic progression. This is the first documented case of this kind of response of tracheobronchial amyloidosis to colchicine treatment alone. A review of the available literature is presented.
Respiration

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Association of FEF25-75% Impairment with Bronchial Hyperresponsiveness and Airway Inflammation in Subjects with Asthma-Like Symptoms

Background: Forced expiratory flow at 25 and 75% of the pulmonary volume (FEF_25-75%) might be considered as a marker of early airway obstruction. FEF_25-75% impairment might suggest earlier asthma recognition in symptomatic subjects even in the absence of other abnormal spirometry values. Objectives: The study was designed in order to verify whether FEF_25-75% impairment in a cohort of subjects with asthma-like symptoms could be associated with the risk of bronchial hyperresponsiveness (BHR) and with airway inflammation expressed as fractional exhaled nitric oxide (FeNO) and eosinophil counts in induced sputum. Methods: Four hundred adults with a history of asthma-like symptoms (10.5% allergic) underwent spirometry, determination of BHR to methacholine (PD₂₀FEV₁), FeNO analysis and sputum induction. FEF_25-75%Results: All subjects had normal FVC, FEV₁ and FEV₁/FVC, while FEF_25-75% was abnormal in 27.5% of them. FEF_25-75% (z-score) was associated with PD₂₀FEV₁ (p NO (p 25-75% showed higher levels of FeNO and eosinophils in induced sputum than did patients with normal FEF_25-75% (p 25-75% had an increased probability of being BHR positive (OR = 13.38; 95% CI: 6.7-26.7; p Conclusions: Our data show that abnormal FEF_25-75% might be considered an early marker of airflow limitation associated with eosinophilic inflammation and BHR in subjects with asthma-like symptoms, indicating a role for FEF_25-75% as a predictive marker of newly diagnosed asthma.
Respiration

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The importance of the gastrorenal axis in the control of body sodium homeostasis

Hypertension develops with chronically increased sodium intake when sodium that accumulates in the body can no longer be sequestered, extracellular fluid is expanded, and compensatory neural, hormonal, and pressure-natriuresis mechanisms fail. Sensing the amount of ingested sodium, by the stomach, is one mechanism by which sodium balance is regulated. The natriuresis following the ingestion of a certain amount of sodium may be due to an enterokine, gastrin, secreted by G-cells in the stomach and duodenum and released into the circulation. Circulating gastrin levels are 10-20-fold higher than those for cholecystokinin. Of all the gut hormones circulating in the plasma, gastrin is the one that is reabsorbed to the greatest extent by renal tubules. Gastrin, via its receptor, the cholecystokinin type B receptor (CCKBR), is natriuretic, in mammals including humans, caused by inhibition of renal sodium transport. Germline deletion of gastrin (Gast) or Cckbr gene in mice causes salt-sensitive hypertension. Selective silencing of Gast in the stomach and duodenum impairs the ability to excrete an oral sodium load and also increases blood pressure. Thus, the gastro-renal axis, mediated by gastrin, can complement pronatriuretic hormones, such as dopamine to increase sodium excretion after an oral sodium load. These studies in mice may be translatable to humans because the chromosomal loci of CCKBR and GAST are linked to human essential hypertension. Understanding the role of genes in the regulation of renal function and blood pressure may lead to the tailoring of anti-hypertensive treatment based on genetic make-up.

This article is protected by copyright. All rights reserved

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Deficient attention modulation of lateralized alpha power in schizophrenia

Abstract

Modulation of 8–14 Hz (alpha) activity in posterior brain regions is associated with covert attention deployment in visuospatial tasks. Alpha power decrease contralateral to to-be-attended stimuli is believed to foster subsequent processing, such as retention of task-relevant input. Degradation of this alpha-regulation mechanism may reflect an early stage of disturbed attention regulation contributing to impaired attention and working memory commonly found in schizophrenia. The present study tested this hypothesis of early disturbed attention regulation by examining alpha power modulation in a lateralized cued delayed response task in 14 schizophrenia patients (SZ) and 25 healthy controls (HC). Participants were instructed to remember the location of a 100-ms saccade-target cue in the left or right visual hemifield in order to perform a delayed saccade to that location after a retention interval. As expected, alpha power decrease during the retention interval was larger in contralateral than ipsilateral posterior regions, and SZ showed less of this lateralization than did HC. In particular, SZ failed to show hemifield-specific alpha modulation in posterior right hemisphere. Results suggest less efficient modulation of alpha oscillations that are considered critical for attention deployment and item encoding and, hence, may affect subsequent spatial working memory performance.

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Event-related potential indices of congruency sequence effects without feature integration or contingency learning confounds

Abstract

The congruency effect in Stroop-like tasks (i.e., increased response time and reduced accuracy in incongruent relative to congruent trials) is often smaller when the previous trial was incongruent as compared to congruent. This congruency sequence effect (CSE) is thought to reflect cognitive control processes that shift attention to the target and/or modulate the response engendered by the distracter differently after incongruent relative to congruent trials. The neural signatures of CSEs are therefore usually attributed to cognitive control processes that minimize distraction from irrelevant stimuli. However, CSEs in previous functional neuroimaging studies were ubiquitously confounded with feature integration and/or contingency learning processes. We therefore investigated whether a neural CSE can be observed without such confounds in a group of healthy young adults (n = 56). To this end, we combined a prime-probe task that lacks such confounds with high-density ERPs to identify, for the first time, the neural time course of confound-minimized CSEs. Replicating recent behavioral findings, we observed strong CSEs in this task for mean response time and mean accuracy. Critically, conceptually replicating prior ERP results from confounded tasks, we also observed a CSE in both the parietal conflict slow potential (conflict SP) and the frontomedial N450. These findings indicate for the first time that neural CSEs as indexed by ERPs can be observed without the typical confounds. More broadly, the present study provides a confound-minimized protocol that will help future researchers to better isolate the neural bases of control processes that minimize distraction from irrelevant stimuli.

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Position-effect variegation revisited: HUSHing up heterochromatin in human cells

Much of what we understand about heterochromatin formation in mammals has been extrapolated from forward genetic screens for modifiers of position-effect variegation (PEV) in the fruit fly Drosophila melanogaster. The recent identification of the HUSH (Human Silencing Hub) complex suggests that more recent evolutionary developments contribute to the mechanisms underlying PEV in human cells. Although HUSH-mediated repression also involves heterochromatin spreading through the reading and writing of the repressive H3K9me3 histone modification, clear orthologues of HUSH subunits are not found in Drosophila but are conserved in vertebrates. Here we compare the insights into the mechanisms of PEV derived from genetic screens in the fly, the mouse and in human cells, review what is currently known about the HUSH complex and discuss the implications of HUSH-mediated silencing for viral latency. Future studies will provide mechanistic insight into HUSH complex function and reveal the relationship between HUSH and other epigenetic silencing complexes.

Chromosomal position-effects have been investigated through Drosophila screens for modifiers of position-effect variegation. An analogous gene-trap mutagenesis screen in near-haploid human KBM7 cells identified HUSH, an epigenetic silencing complex composed of FAM208A/TASOR, MPP8 and Periphilin, which mediates heterochromatin spreading through SETDB1 recruitment and deposition of the repressive H3K9me3 histone modification.

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Value thy postdoc, or s/he might be lost to gas fitting…

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Author response to Dr Wises letter

We welcome the opportunity to respond to the concerns of Dr Wise1 from the American Chemistry Council, regarding our report on the association between childhood infections and use of bleach at home.2

Dr Wise expresses disappointment with 'design flaws' and 'the speculative nature of our conclusions'. We do not agree that our study was badly designed, and the limitations have been carefully considered and discussed in our original paper. We relied on questionnaires for both exposure and outcome, but this does not imply flawed results or bad study design. Obviously, future studies are needed with better exposure and outcome assessment to further address the causal nature of the associations, as we acknowledge in the discussion.

Dr Wise is particularly concerned about the reliability of self-reported illnesses. Indeed, no further description of the targeted infections was given to the parents, nor were these illnesses confirmed by medical diagnosis. The...

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Neural FFA3 activation inversely regulates anion secretion evoked by nicotinic ACh receptor activation in rat proximal colon

Abstract

The proximal colonic mucosa is constantly exposed to high concentrations of microbially-produced short-chain fatty acids (SCFA). Although luminal SCFA evoke electrogenic anion secretion and smooth muscle contractility via neural and non-neural cholinergic pathways in the colon, the involvement of the SCFA receptor FFA3, one of the free fatty acid receptor (FFAR) family members, has not been clarified. We investigated the contribution of FFA3 to cholinergic-mediated secretory responses in rat proximal colon. FFA3 was immunolocalized to enteroendocrine cells and to the enteric neural plexuses. Most FFA3-immunoreactive nerve fibres and nerve endings were cholinergic, colocalized with PGP9.5, the vesicular ACh transporter, and the high-affinity choline transporter CHT1. In Ussing chambered mucosa-submucosa preparations (including the submucosal plexus) of rat proximal colon, carbachol (CCh)-induced Cl⁻ secretion was decreased by TTX, hexamethonium, and serosal FFA3 agonists acetate or propionate, but not by an inactive analogue 3-chloropropionate. Serosal application of the selective FFA3 agonist (N-[2-methylphenyl]-[4-furan-3-yl]-2-methyl-5-oxo-1,4,5,6,7,8-hexahydro-quinoline-3-carboxamide; MQC) dose-dependently suppressed the response to CCh, but not to forskolin, with an IC₅₀ of 13 μM. Pretreatment with MQC inhibited nicotine-evoked, but not bethanechol-evoked secretion. The inhibitory effect of MQC was reversed by pretreatment with pertussis toxin, indicating that FFA3 acts via the G_i/o pathway. Luminal propionate induced Cl⁻ secretion via the cholinergic pathway, which was reduced by MQC, as well as by TTX, hexamethonium, or by removal of the submucosal plexus. These results suggest that SCFA-FFA3 pathway has a novel antisecretory function in that it inhibits cholinergic neural reflexes in the enteric nervous system.

This article is protected by copyright. All rights reserved

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The interactive contributions of Na+/K+-ATPase and nitric oxide synthase to sweating and cutaneous vasodilation during exercise in the heat

Abstract

Nitric oxide (NO) synthase (NOS) contributes to the heat loss responses of sweating and cutaneous vasodilation. Given that NO can activate Na⁺/K⁺-ATPase, which also contributes to sweating and microvasculature regulation, we evaluated the separate and combined influence of Na⁺/K⁺-ATPase and NOS on sweating and cutaneous vasodilation. Thirteen young (23±3 years) males performed two 30-min semi-recumbent cycling bouts in the heat (35°C) at a fixed rate of metabolic heat production (500W) followed by 20- and 40-min recoveries, respectively. Local sweat rate (LSR) and cutaneous vascular conductance (CVC) were measured at four forearm skin sites continuously perfused via intradermal microdialysis with either: 1) lactated Ringer (Control); 2) 6mᴍ ouabain (Ouabain), Na⁺/K⁺-ATPase inhibitor; 3) 10mᴍ L-N^G-Nitroarginine methyl ester (_L-NAME), NOS inhibitor; or 4) 6mᴍ ouabain and 10mᴍ _L-NAME (Ouabain+_L-NAME). At the end of both exercise bouts relative to Control, LSR was attenuated with Ouabain (54-60%), _L-NAME (12-13%) and Ouabain+_L-NAME (68-74%; all P<0.05). Moreover, the sum of attenuations from Control induced by independent administration of Ouabain and _L-NAME was similar to the combined infusion of Ouabain+_L-NAME (both P≥0.74). Compared to Control, CVC at the end of both exercise bouts was similar with Ouabain (both P≥0.30), but attenuated with _L-NAME (%CVC_max reduction from Control, 24–25%). Further, CVC at the Ouabain+_L-NAME site (38-39%; all P<0.01) was attenuated compared to Control and did not differ from baseline resting values (both P≥0.81). We show that Na⁺/K⁺-ATPase and NOS do not synergistically mediate sweating, whereas they influence cutaneous blood flow in an interactive manner during exercise in the heat.

This article is protected by copyright. All rights reserved

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Nutrients, Vol. 8, Pages 84: Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge

Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS.

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Materials, Vol. 9, Pages 98: Increased Durability of Concrete Made with Fine Recycled Concrete Aggregates Using Superplasticizers

This paper evaluates the influence of two superplasticizers (SP) on the durability properties of concrete made with fine recycled concrete aggregate (FRCA). For this purpose, three families of concrete were tested: concrete without SP, concrete made with a regular superplasticizer and concrete made with a high-performance superplasticizer. Five volumetric replacement ratios of natural sand by FRCA were tested: 0%, 10%, 30%, 50% and 100%. Two natural gravels were used as coarse aggregates. All mixes had the same particle size distribution, cement content and amount of superplasticizer. The w/c ratio was calibrated to obtain similar slump. The results showed that the incorporation of FRCA increased the water absorption by immersion, the water absorption by capillary action, the carbonation depth and the chloride migration coefficient, while the use of superplasticizers highly improved these properties. The incorporation of FRCA jeopardized the SP's effectiveness. This research demonstrated that, from a durability point of view, the simultaneous incorporation of FRCA and high-performance SP is a viable sustainable solution for structural concrete production.

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Energies, Vol. 9, Pages 100: Joint Estimation of the Electric Vehicle Power Battery State of Charge Based on the Least Squares Method and the Kalman Filter Algorithm

An estimation of the power battery state of charge (SOC) is related to the energy management, the battery cycle life and the use cost of electric vehicles. When a lithium-ion power battery is used in an electric vehicle, the SOC displays a very strong time-dependent nonlinearity under the influence of random factors, such as the working conditions and the environment. Hence, research on estimating the SOC of a power battery for an electric vehicle is of great theoretical significance and application value. In this paper, according to the dynamic response of the power battery terminal voltage during a discharging process, the second-order RC circuit is first used as the equivalent model of the power battery. Subsequently, on the basis of this model, the least squares method (LS) with a forgetting factor and the adaptive unscented Kalman filter (AUKF) algorithm are used jointly in the estimation of the power battery SOC. Simulation experiments show that the joint estimation algorithm proposed in this paper has higher precision and convergence of the initial value error than a single AUKF algorithm.

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Children, Vol. 3, Pages 4: Averting the Legacy of Kidney Disease—Focus on Childhood

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy, including dialysis and transplantation, while only a minority of children may require this ultimate intervention.  Since there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. "For in every adult there dwells the child that was, and in every child there lies the adult that will be."—John Connolly, The Book of Lost Things.

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Micromachines, Vol. 7, Pages 25: Microfluidic-Based Droplet and Cell Manipulations Using Artificial Bacterial Flagella

Herein, we assess the functionality of magnetic helical microswimmers as basic tools for the manipulation of soft materials, including microdroplets and single cells. Their ability to perform a range of unit operations is evaluated and the operational challenges associated with their use are established. In addition, we also report on interactions observed between the head of such helical swimmers and the boundaries of droplets and cells and discuss the possibilities of assembling an artificial swimming microorganism or a motorized cell.

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Noncompetitive affinity assays of glucagon and amylin using mirror-image aptamers as affinity probes

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C5AN02468D, Paper

Lian Yi, Xue Wang, Lucas Bethge, Sven Klussmann, Michael G Roper
The ability to detect picomolar concentrations of glucagon and amylin using fluorescently labeled mirror-image aptamers, so-called Spiegelmers, is demonstrated. Spiegelmers rival the specificity of antibodies and overcome the problem of...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Effects of ethanol lock therapy on central line infections and mechanical problems in children with intestinal failure

Journal of Parenteral and Enteral Nutrition

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Oral nucleos(t)ide analogues reduce recurrence and death in chronic hepatitis B-related hepatocellular carcinoma

Alimentary Pharmacology and Therapeutics

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Novel c-Met inhibitor suppresses the growth of c-Met-addicted gastric cancer cells

BMC Cancer

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A proof-of-concept study showing antibiotics to be more effective in irritable bowel syndrome with than without small-intestinal bacterial overgrowth: a randomized, double-blind, placebo-controlled trial

European Journal of Gastroenterology & Hepatology

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Adverse events after surgery for benign colon polyps are common and associated with increased length of stay and costs

Gastrointestinal Endoscopy

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Real-world effectiveness of peginterferon α-2b plus ribavirin in a Canadian cohort of treatment-naïve chronic hepatitis C patients with genotypes 2 or 3: Results of the PoWer and RediPEN studies

European Journal of Clinical Microbiology & Infectious Diseases

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Intraileal casein infusion increases plasma concentrations of amino acids in humans: A randomized cross over trial

Clinical Nutrition

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Non-selective beta-blockers and survival in patients with cirrhosis and ascites: a systematic review and meta-analysis

Clinical Gastroenterology and Hepatology

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Assessment of beta-blocker response by expression of beta-Arrestin2 and RhoA/ROCK2 in antrum mucosa in cirrhotic patients

Journal of Hepatology

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Most children with eosinophilic esophagitis have a favorable outcome as young adults

Diseases of the Esophagus

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Blood loss and outcomes after resection of colorectal liver metastases

Journal of Surgical Research

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Prevalence of positive HIV, HBV, HCV and treponemal tests in blood donors in a rural hospital in southern Ethiopia

Journal of Clinical Virology

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Association between circulating levels of C-reactive protein and interleukin-6 and risk of inflammatory bowel disease

Clinical Gastroenterology and Hepatology

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National trends of acute kidney injury requiring dialysis in decompensated cirrhosis hospitalizations in the United States

Hepatology International

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Factors associated with colorectal cancer occurrence after colonoscopy that did not diagnose colorectal cancer

Gastrointestinal Endoscopy

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The dark cube: dark and light character profiles

Background. Research addressing distinctions and similarities between people's malevolent character traits (i.e., the Dark Triad: Machiavellianism, narcissism, and psychopathy) has detected inconsistent linear associations to temperament traits. Additionally, these dark traits seem to have a common core expressed as uncooperativeness. Hence, some researchers suggest that the dark traits are best represented as one global construct (i.e., the unification argument) rather than as ternary construct (i.e., the uniqueness argument). We put forward the dark cube (cf. Cloninger's character cube) comprising eight dark profiles that can be used to compare individuals who differ in one dark character trait while holding the other two constant. Our aim was to investigate in which circumstances individuals who are high in each one of the dark character traits differ in Cloninger's "light" character traits: self-directedness, cooperativeness, and self-transcendence. We also investigated if people's dark character profiles were associated to their light character profiles. Method. A total of 997 participants recruited from Amazon's Mechanical Turk (MTurk) responded to the Short Dark Triad and the Short Character Inventory. Participants were allocated to eight different dark profiles and eight light profiles based on their scores in each of the traits and any possible combination of high and low scores. We used three-way interaction regression analyses and t-tests to investigate differences in light character traits between individuals with different dark profiles. As a second step, we compared the individuals' dark profile with her/his character profile using an exact cell-wise analysis conducted in the ROPstat software (http://www.ropstat.com). Results. Individuals who expressed high levels of Machiavellianism and those who expressed high levels of psychopathy also expressed low self-directedness and low cooperativeness. Individuals with high levels of narcissism, in contrast, scored high in self-directedness. Moreover, individuals with a profile low in the dark traits were more likely to end up with a profile high in cooperativeness. The opposite was true for those individuals with a profile high in the dark traits. The rest of the cross-comparisons revealed some of the characteristics of human personality as a non-linear complex dynamic system. Conclusions. Our study suggests that individuals who are high in Machiavellianism and psychopathy share a unified non-agentic and uncooperative character (i.e., irresponsible, low in self-control, unempathetic, unhelpful, untolerant), while individuals high in narcissism have a more unique character configuration expressed as high agency and, when the other dark traits are high, highly spiritual but uncooperative. In other words, based on differences in their associations to the light side of character, the Dark Triad seems to be a dyad rather than a triad.

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Examining perceptions of the usefulness and usability of a mobile-based system for pharmacogenomics clinical decision support: a mixed methods study

Background. Pharmacogenomic testing has the potential to improve the safety and efficacy of pharmacotherapy, but clinical application of pharmacogenetic knowledge has remained uncommon. Clinical Decision Support (CDS) systems could help overcome some of the barriers to clinical implementation. The aim of this study was to evaluate the perception and usability of a web- and mobile-enabled CDS system for pharmacogenetics-guided drug therapy–the Medication Safety Code (MSC) system–among potential users (i.e., physicians and pharmacists). Furthermore, this study sought to collect data on the practicability and comprehensibility of potential layouts of a proposed personalized pocket card that is intended to not only contain the machine-readable data for use with the MSC system but also human-readable data on the patient's pharmacogenomic profile. Methods. We deployed an emergent mixed methods design encompassing (1) qualitative interviews with pharmacists and pharmacy students, (2) a survey among pharmacogenomics experts that included both qualitative and quantitative elements and (3) a quantitative survey among physicians and pharmacists. The interviews followed a semi-structured guide including a hypothetical patient scenario that had to be solved by using the MSC system. The survey among pharmacogenomics experts focused on what information should be printed on the card and how this information should be arranged. Furthermore, the MSC system was evaluated based on two hypothetical patient scenarios and four follow-up questions on the perceived usability. The second survey assessed physicians' and pharmacists' attitude towards the MSC system. Results. In total, 101 physicians, pharmacists and PGx experts coming from various relevant fields evaluated the MSC system. Overall, the reaction to the MSC system was positive across all investigated parameters and among all user groups. The majority of participants were able to solve the patient scenarios based on the recommendations displayed on the MSC interface. A frequent request among participants was to provide specific listings of alternative drugs and concrete dosage instructions. Negligence of other patient-specific factors for choosing the right treatment such as renal function and co-medication was a common concern related to the MSC system, while data privacy and cost-benefit considerations emerged as the participants' major concerns regarding pharmacogenetic testing in general. The results of the card layout evaluation indicate that a gene-centered and tabulated presentation of the patient's pharmacogenomic profile is helpful and well-accepted. Conclusions. We found that the MSC system was well-received among the physicians and pharmacists included in this study. A personalized pocket card that lists a patient's metabolizer status along with critically affected drugs can alert physicians and pharmacists to the availability of essential therapy modifications.

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The personality trait of behavioral inhibition modulates perceptions of moral character and performance during the trust game: behavioral results and computational modeling

Decisions based on trust are critical for human social interaction. We judge the trustworthiness of partners in social interactions based on a number of partner characteristics as well as experiences with those partners. These decisions are also influenced by personality. The current study examined how the personality trait of behavioral inhibition, which involves the tendency to avoid or withdraw from novelty in both social and non-social situations, is related to explicit ratings of trustworthiness as well as decisions made in the trust game. In the game, healthy young adults interacted with three fictional partners who were portrayed as trustworthy, untrustworthy or neutral through biographical information. Participants could choose to keep $1 or send $3 of virtual money to a partner. The partner could then choose to send $1.5 back to the participant or to keep the entire amount. On any trial in which the participant chose to send, the partner always reciprocated with 50% probability, irrespective of how that partner was portrayed in the biography. Behavioral inhibition was assessed through a self-report questionnaire. Finally, a reinforcement learning computational model was fit to the behavior of each participant. Self-reported ratings of trust confirmed that all participants, irrespective of behavioral inhibition, perceived differences in the moral character of the three partners (trustworthiness of good > neutral > bad partner). Decisions made in the game showed that inhibited participants tended to trust the neutral partner less than uninhibited participants. In contrast, this was not reflected in the ratings of the neutral partner (either pre- or post-game), indicating a dissociation between ratings of trustworthiness and decisions made by inhibited participants. Computational modeling showed that this was due to lower initial trust of the neutral partner rather than a higher learning rate associated with loss, suggesting an implicit bias against the neutral partner. Overall, the results suggest inhibited individuals may be predisposed to interpret neutral or ambiguous information more negatively which could, at least in part, account for the tendency to avoid unfamiliar people characteristic of behaviorally inhibited temperament, as well as its relationship to anxiety disorders.

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PhyloPythiaS+: a self-training method for the rapid reconstruction of low-ranking taxonomic bins from metagenomes

Background. Metagenomics is an approach for characterizing environmental microbial communities in situ, it allows their functional and taxonomic characterization and to recover sequences from uncultured taxa. This is often achieved by a combination of sequence assembly and binning, where sequences are grouped into 'bins' representing taxa of the underlying microbial community. Assignment to low-ranking taxonomic bins is an important challenge for binning methods as is scalability to Gb-sized datasets generated with deep sequencing techniques. One of the best available methods for species bins recovery from deep-branching phyla is the expert-trained PhyloPythiaS package, where a human expert decides on the taxa to incorporate in the model and identifies 'training' sequences based on marker genes directly from the sample. Due to the manual effort involved, this approach does not scale to multiple metagenome samples and requires substantial expertise, which researchers who are new to the area do not have. Results. We have developed PhyloPythiaS+, a successor to our PhyloPythia(S) software. The new (+) component performs the work previously done by the human expert. PhyloPythiaS+ also includes a new k-mer counting algorithm, which accelerated the simultaneous counting of 4–6-mers used for taxonomic binning 100-fold and reduced the overall execution time of the software by a factor of three. Our software allows to analyze Gb-sized metagenomes with inexpensive hardware, and to recover species or genera-level bins with low error rates in a fully automated fashion. PhyloPythiaS+ was compared to MEGAN, taxator-tk, Kraken and the generic PhyloPythiaS model. The results showed that PhyloPythiaS+ performs especially well for samples originating from novel environments in comparison to the other methods. Availability. PhyloPythiaS+ in a virtual machine is available for installation under Windows, Unix systems or OS X on: http://ift.tt/1SaK0bm.

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Sustainability, Vol. 8, Pages 164: A Novel Scheme to Relieve Parking Pressure at Tourist Attractions on Holidays

Parking is a key component of urban transportation managements and has become a severe problem at many tourist attractions during holidays in China. This paper presents a novel scheme to relieve the holiday parking pressure. Based on the perspectives of the activity-based travel characteristics, we propose an effort to develop parking alternatives by utilizing existing traffic facilities. A conceptual model is employed to explore the influence of additional leisure activity of parking and various options of transportation modes. The results indicate that compared to commuters, the scenery is the major factor affecting tourists' parking preference, besides parking time and cost. Based on the finding, a tourist-centered strategy is designed to satisfy the peak hours parking demands in order to relieve the parking pressure at tourist attractions during holidays.

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Molecules, Vol. 21, Pages 201: Design, Synthesis, and Biological Evaluation of Some Novel Pyrrolizine Derivatives as COX Inhibitors with Anti-Inflammatory/Analgesic Activities and Low Ulcerogenic Liability

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed anti-inflammatory and pain relief medications. However, their use is associated with many drawbacks, including mainly serious gastric and renal complications. In an attempt to circumvent these risks, a set of N-(4-bromophenyl)-7-cyano-6-substituted-H-pyrrolizine-5-carboxamide derivatives were designed, synthesized and evaluated as dual COX/5-LOX inhibitors. The structural elucidation, in vivo anti-inflammatory and analgesic activities using a carrageenan-induced rat paw edema model and hot plate assay, were performed, respectively. From the results obtained, it was found that the newly synthesized pyrrolizines exhibited IC50 values in the range of 2.45–5.69 µM and 0.85–3.44 µM for COX-1 and COX-2, respectively. Interestingly, compounds 12, 13, 16 and 17 showed higher anti-inflammatory and analgesic activities compared to ibuprofen. Among these derivatives, compounds 16 and 19 displayed better safety profile than ibuprofen in acute ulcerogenicity and histopathological studies. Furthermore, the docking studies revealed that compound 17 fits nicely into COX-1 and COX-2 binding sites with the highest binding affinity, while compound 16 exerted the highest binding affinity for 5-LOX. In light of these findings, these novel pyrrolizine-5-carboxamide derivatives represent a promising scaffold for further development into potential dual COX/5-LOX inhibitors with safer gastric profile.

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IJMS, Vol. 17, Pages 227: Therapeutic Effect of Losartan, an Angiotensin II Type 1 Receptor Antagonist, on CCl4-Induced Skeletal Muscle Injury

TGF-β1 is known to inhibit muscle regeneration after muscle injury. However, it is unknown if high systemic levels of TGF-β can affect the muscle regeneration process. In the present study, we demonstrated the effect of a CCl4 intra-peritoneal injection and losartan (an angiotensin II type 1 receptor antagonist) on skeletal muscle (gastrocnemius muscle) injury and regeneration. Male C57BL/6 mice were grouped randomly as follows: control (n = 7), CCl4-treatment group (n = 7), and CCl4 + losartan treatment group (n = 7). After CCl4 treatment for a 16-week period, the animals were sacrificed and analyzed. The expression of dystrophin significantly decreased in the muscle tissues of the control group, as compared with that of the CCl4 + losartan group (p < 0.01). p(phospho)-Smad2/3 expression significantly increased in the muscles of the control group compared to that in the CCl4 + losartan group (p < 0.01). The expressions of Pax7, MyoD, and myogenin increased in skeletal muscles of the CCl4 + losartan group compared to the corresponding levels in the control group (p < 0.01). We hypothesize that systemically elevated TGF-β1 as a result of CCl4-induced liver injury causes skeletal muscle injury, while losartan promotes muscle repair from injury via blockade of TGF-β1 signaling.

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IJMS, Vol. 17, Pages 229: Sanger Sequencing for BRCA1 c.68_69del, BRCA1 c.5266dup and BRCA2 c.5946del Mutation Screen on Pap Smear Cytology Samples

Three sets of polymerase chain reaction (PCR) primers were designed for heminested PCR amplification of the target DNA fragments in the human genome which include the site of BRCA1 c.68_69del, BRCA1 c.5266dup and BRCA2 c.5946del respectively, to prepare the templates for direct Sanger sequencing screen of these three founder mutations. With a robust PCR mixture, crude proteinase K digestate of the fixed cervicovaginal cells in the liquid-based Papanicolaou (Pap) cytology specimens can be used as the sample for target DNA amplification without pre-PCR DNA extraction, purification and quantitation. The post-PCR products can be used directly as the sequencing templates without further purification or quantitation. By simplifying the frontend procedures for template preparation, the cost for screening these three founder mutations can be reduced to about US $200 per test when performed in conjunction with human papillomavirus (HPV) assays now routinely ordered for cervical cancer prevention. With this projected price structure, selective patients in a high-risk population can be tested and each provided with a set of DNA sequencing electropherograms to document the absence or presence of these founder mutations in her genome to help assess inherited susceptibility to breast and ovarian cancer in this era of precision molecular personalized medicine.

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IJMS, Vol. 17, Pages 228: Identification of Novel Pathways in Plant Lectin-Induced Cancer Cell Apoptosis

Plant lectins have been investigated to elucidate their complicated mechanisms due to their remarkable anticancer activities. Although plant lectins seems promising as a potential anticancer agent for further preclinical and clinical uses, further research is still urgently needed and should include more focus on molecular mechanisms. Herein, a Naïve Bayesian model was developed to predict the protein-protein interaction (PPI), and thus construct the global human PPI network. Moreover, multiple sources of biological data, such as smallest shared biological process (SSBP), domain-domain interaction (DDI), gene co-expression profiles and cross-species interolog mapping were integrated to build the core apoptotic PPI network. In addition, we further modified it into a plant lectin-induced apoptotic cell death context. Then, we identified 22 apoptotic hub proteins in mesothelioma cells according to their different microarray expressions. Subsequently, we used combinational methods to predict microRNAs (miRNAs) which could negatively regulate the abovementioned hub proteins. Together, we demonstrated the ability of our Naïve Bayesian model-based network for identifying novel plant lectin-treated cancer cell apoptotic pathways. These findings may provide new clues concerning plant lectins as potential apoptotic inducers for cancer drug discovery.

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Sustainability, Vol. 8, Pages 165: Liner Shipping Fleet Deployment with Sustainable Collaborative Transportation

Facing sharp competition in the market for shipping companies, it is necessary to make reasonable and efficient decisions to optimize the container shipping line network so as to improve the shipping efficiency and reduce the transportation cost, as well as to realize the transportation sustainability. Therefore, the liner ship fleet deployment problem with collaborative transportation is proposed in this paper. This problem is formulated as a mixed-integer linear programming model that takes collaborative transportation into consideration. The model includes fixed cost, variable cost, berth cost, transport cost, penalty, compensation cost, and so on. To achieve the sustainable development of collaborative transportation, the shipping companies could make a selection between the internal routes and the external routes to serve each task by comparing the distance between the above routes. A real Asia-Europe-Oceania numerical experiment shows that the proposed sustainable collaborative transportation model can be efficiently solved by C++ calling ILOG CPLEX. Results demonstrate that the optimized shipping line network with sustainable collaborative transportation can improve the service efficiency, as well as the service level of shipping companies.

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Remote Sensing, Vol. 8, Pages 137: Assessment of the Suomi NPP VIIRS Land Surface Albedo Data Using Station Measurements and High-Resolution Albedo Maps

Land surface albedo (LSA), one of the Visible Infrared Imaging Radiometer Suite (VIIRS) environmental data records (EDRs), is a fundamental component for linking the land surface and the climate system by regulating shortwave energy exchange between the land and the atmosphere. Currently, the improved bright pixel sub-algorithm (BPSA) is a unique algorithm employed by VIIRS to routinely generate LSA EDR from VIIRS top-of-atmosphere (TOA) observations. As a product validation procedure, LSA EDR reached validated (V1 stage) maturity in December 2014. This study summarizes recent progress in algorithm refinement, and presents comprehensive validation and evaluation results of VIIRS LSA by using extensive field measurements, Moderate Resolution Imaging Spectroradiometer (MODIS) albedo product, and Landsat-retrieved albedo maps. Results indicate that: (1) by testing the updated desert-specific look-up-table (LUT) that uses a stricter standard to select the training data specific for desert aerosol type in our local environment, it is found that the VIIRS LSA retrieval accuracy is improved over a desert surface and the absolute root mean square error (RMSE) is reduced from 0.036 to 0.023, suggesting the potential of the updated desert LUT to the improve the VIIRS LSA product accuracy; (2) LSA retrieval on snow-covered surfaces is more accurate if the newly developed snow-specific LUT (RMSE = 0.082) replaces the generic LUT (RMSE = 0.093) that is employed in the current operational LSA EDR production; (3) VIIRS LSA is also comparable to high-resolution Landsat albedo retrieval (RMSE < 0.04), although Landsat albedo has a slightly higher accuracy, probably owing to higher spatial resolution with less impacts of mixed pixel; (4) VIIRS LSA retrievals agree well with the MODIS albedo product over various land surface types, with overall RMSE of lower than 0.05 and the overall bias as low as 0.025, demonstrating the comparable data quality between VIIRS and the MODIS LSA product.

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Sensors, Vol. 16, Pages 217: Design and Analysis of a Single—Camera Omnistereo Sensor for Quadrotor Micro Aerial Vehicles (MAVs)

We describe the design and 3D sensing performance of an omnidirectional stereo (omnistereo) vision system applied to Micro Aerial Vehicles (MAVs). The proposed omnistereo sensor employs a monocular camera that is co-axially aligned with a pair of hyperboloidal mirrors (a vertically-folded catadioptric configuration). We show that this arrangement provides a compact solution for omnidirectional 3D perception while mounted on top of propeller-based MAVs (not capable of large payloads). The theoretical single viewpoint (SVP) constraint helps us derive analytical solutions for the sensor's projective geometry and generate SVP-compliant panoramic images to compute 3D information from stereo correspondences (in a truly synchronous fashion). We perform an extensive analysis on various system characteristics such as its size, catadioptric spatial resolution, field-of-view. In addition, we pose a probabilistic model for the uncertainty estimation of 3D information from triangulation of back-projected rays. We validate the projection error of the design using both synthetic and real-life images against ground-truth data. Qualitatively, we show 3D point clouds (dense and sparse) resulting out of a single image captured from a real-life experiment. We expect the reproducibility of our sensor as its model parameters can be optimized to satisfy other catadioptric-based omnistereo vision under different circumstances.

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