Acellular bovine pericardium in implant-based breast reconstruction: A systematic review of the literature

Abstract

Background

The use of bovine acellular pericardium as a pectoral extender is a relatively newer biologic in prosthetic breast reconstruction. Fewer studies with smaller sample sizes have been conducted on the outcome and complications of its use lacking comprehensive data. We therefore reviewed the published literature and conducted a systematic review to summarise both aesthetic benefits and reported complications.

Methods

A literature search of electronic databases (Medline/PubMed and Embase) between January 2010 and July 2016 was conducted. The search terms breast reconstruction, Veritas®, bovine pericardial patch, bovine pericardium and acellular collagen matrix were used. Inclusion criteria were restricted to articles containing data on bovine pericardial collagen matrix used in breast reconstruction either immediate or delayed. Graph Pad Prism statistical software was used for summarising and depicting results.

Results

Data from 87 patients included in five articles which met the inclusion criteria were collated. In total, 135 procedures were performed using Veritas®. Sixty-six patients' procedures were immediate reconstruction, 57 procedures were delayed reconstruction, and seven patients lack the details of the type of reconstruction. Complications were reported for 80 patients seroma was noticed in 12 patients (15%); skin necrosis was noticed in 5 patients (6.25%); infection was noticed in 6 patients (7.5%); and haematoma was noticed in 3 patients (3.75%). No patient presented with a capsular contracture. In total, 9 patients have received radiotherapy.

Conclusion

Use of acellular bovine pericardium is safe according to the results published in the literature so far. Randomised controlled study comparing acellular dermal matrix with acellular bovine pericardium using a similar group of patients with minimal or no inter surgeon variance are warranted to compare and contrast outcomes.

Level of Evidence: Not ratable

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Cell membrane-derived nanomaterials for biomedical applications

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Ronnie H. Fang, Yao Jiang, Jean C. Fang, Liangfang Zhang
The continued evolution of biomedical nanotechnology has enabled clinicians to better detect, prevent, manage, and treat human disease. In order to further push the limits of nanoparticle performance and functionality, there has recently been a paradigm shift towards biomimetic design strategies. By taking inspiration from nature, the goal is to create next-generation nanoparticle platforms that can more effectively navigate and interact with the incredibly complex biological systems that exist within the body. Of great interest are cellular membranes, which play essential roles in biointerfacing, self-identification, signal transduction, and compartmentalization. In this review, we explore the major ways in which researchers have directly leveraged cell membrane-derived biomaterials for the fabrication of novel nanotherapeutics and nanodiagnostics. Such emerging technologies have the potential to significantly advance the field of nanomedicine, helping to improve upon traditional modalities while also enabling novel applications.

Graphical abstract

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Selective Deletion of Apolipoprotein E in Astrocytes Ameliorates the Spatial Learning and Memory Deficits in Alzheimer’s Disease (APP/PS1) mice by Inhibiting TGF-β/Smad2/STAT3 Signaling

Publication date: Available online 11 March 2017
Source:Neurobiology of Aging
Author(s): Jin-yu Zheng, Jian Sun, Chun-mei Ji, Lin Shen, Zhong-jun Chen, Peng Xie, Yuan-zhao Sun, Ru-tong Yu
Astrocytes and apolipoprotein E (apoE) play critical roles in cognitive function, not only under physiological conditions but also in some pathological situations, particularly in the pathological progression of Alzheimer's disease (AD). The regulatory mechanisms underlying the effect of apoE, derived from astrocytes, on cognitive deficits during AD pathology development are unclear. In this study, we generated APP/apoE^KO and APP/GFAP-apoE^KO mice (the AD mice model used in this study was based on the APP-FAD overexpression) to investigate the role of apoE, derived from astrocytes, in AD pathology and cognitive function. To explore the mechanism, we investigated the amyloidogenic process related TGF-β/Smad2/STAT3 signaling pathway and further confirmed by administering TGF-β-overexpression AAV (specific to astrocytes) to APP/GFAP-apoE^KO mice and TGF-β-inhibition AAV (specific to astrocytes) to APP/WT mice. Whole body deletion of apoE significantly ameliorated the spatial learning and memory impairment, reduced Aβ production and inhibited astrogliosis in APP/apoE^KO mice, as well as specific deletion apoE in astrocytes in APP/GFAP-apoE^KO mice. Moreover, Aβ accumulation was increased due to promotion of amyloidogenesis of APP, and astrogliosis was upregulated by activation of TGF-β/Smad2/STAT3 signaling. Furthermore, the overexpression of TGF-β in astrocytes in APP/GFAP-apoE^KO mice abrogated the effects of apoE knockout. In contrast, repression of TGF-β in astrocytes of APP/WT mice exerted a therapeutic effect similar to apoE knockout. These data suggested that apoE derived from astrocytes contributes to the risk of AD through TGF-β/Smad2/STAT3 signaling activation. These findings enhance our understanding of the role of apoE, derived from astrocytes, in AD and suggest it to be a potential biomarker and therapeutic target for AD.



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Resting-state networks associated with cognitive processing show more age-related decline than those associated with emotional processing

Publication date: Available online 11 March 2017
Source:Neurobiology of Aging
Author(s): Kaoru Nashiro, Michiko Sakaki, Meredith N. Braskie, Mara Mather
Correlations in activity across disparate brain regions during rest reveal functional networks in the brain. Although previous studies largely agree that there is an age-related decline in the "default mode network," how age affects other resting-state networks, such as emotion-related networks, is still controversial. Here we used a dual regression approach to investigate age-related alterations in resting-state networks. The results revealed age-related disruptions in functional connectivity in all five identified cognitive networks, namely the default mode network, cognitive-auditory, cognitive-speech (or speech-related somatosensory) and right and left fronto-parietal networks, whereas such age effects were not observed in the three identified emotion networks. In addition, we observed age-related decline in functional connectivity in three visual and three motor/visuospatial networks. Older adults showed greater functional connectivity in regions outside four out of the five identified cognitive networks, consistent with the dedifferentiation effect previously observed in task-based fMRI studies. Both reduced within-network connectivity and increased out-of-network connectivity were correlated with poor cognitive performance, providing potential biomarkers for cognitive aging.



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Currents of Memory: Recent Progress, Translational Challenges, and Ethical Considerations in Fornix Deep Brain Stimulation Trials for Alzheimer’s Disease

Publication date: Available online 11 March 2017
Source:Neurobiology of Aging
Author(s): John Noel M. Viaña, James C. Vickers, Mark J. Cook, Frederic Gilbert
The serendipitous discovery of triggered autobiographical memories and eventual memory improvement in an obese patient who received fornix deep brain stimulation (fDBS) in 2008 paved the way for several Phase I and Phase II clinical trials focused on the safety and efficacy of this potential intervention for people with Alzheimer's disease. In this paper, we summarize clinical trials and case reports on fDBS for Alzheimer's disease and review experiments on animal models evaluating the physiological or behavioral effects of this intervention. Based on information from these reports and studies, we identify potential translational challenges of this approach and determine practical and ethical considerations for clinical trials, focusing on issues regarding selection criteria, trial design, and outcome evaluation. Based on initial results suggesting greater benefit for those with milder disease stage, we find it essential that participant expectations are carefully managed to avoid treatment disenchantment and/or frustration from participants and caregivers. Finally, we urge for collaboration between centers to establish proper clinical standards and to promote better trial results comparison.



http://ift.tt/2mVumaE

Comparative analysis data of SF1 and SF2 helicases from three domains of life

Publication date: April 2017
Source:Data in Brief, Volume 11
Author(s): Wafi Chaar, Hiba Ibrahim, Juliana Kozah, Hala Chamieh
SF1 and SF2 helicases are important molecular motors that use the energy of ATP to unwind nucleic acids or nucleic-acid protein complexes. They are ubiquitous enzymes and found in almost all organisms sequenced to date. This article provides a comparative analysis for SF1 and SF2 helicase families from three domains of life archaea, human, bacteria. Seven families are conserved in these three representatives and includes Upf1-like, UvrD-like, Rad3-like, DEAD-box, RecQ-like. Snf2 and Ski2-like. The data highlight conservation of the helicase core motifs for each of these families. Phylogenetic analysis presented on certain protein families are essential for further studies tracing the evolutionary history of helicase families. The data supplied in this article support publication "Genome-wide identification of SF1 and SF2 helicases from archaea" (Chamieh et al., 2016) [1].



http://ift.tt/2nhC8sF

Synthesis of polythiophene derivative bearing methoxy and pyridine groups at the β-position and formation of an intramolecular hydrogen bonding through the polymer reaction

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Koji Takagi, Ryo Kouchi, Junpei Kawai
Two 4-pyridylthiophene monomers M1 (2,5-dibromo derivative) and M2 (5-bromo-2-iodo derivative) having the methoxy group at the 3-position were synthesized. The Grignard metathesis reaction of M1 using i-PrMgCl·LiCl demonstrated the highest monomer conversion (87%) and regioselectivity (GM1/GM1′ = 76/24). The following Kumada coupling polymerization by Ni(dppe)Cl2 gave P1-OMe with the number-averaged molecular weight ranging from 3000 to 4600. Likewise, P2-OMe was obtained from M2. On the basis of ¹H-NMR spectra, the regiorandom structure of P1-OMe and P2-OMe were suggested. The transformation from the methoxy group to the hydroxy one was then carried out using P1-OMe by treating with BBr3 to afford P1-OH. By measuring the UV-vis absorption spectra of polymers in CHCl3 and film along with the DFT calculation of model compounds, it was found that 1) the formation of an intramolecular hydrogen bonding between the pyridine and hydroxy groups brings about the significant red-shift of the absorption maxima from 476 nm (P1-OMe) to 662 nm (P1-OH) and 2) P1-OH has the less planar conformation resulting in the ineffective π-π stacking of polymer chains in the solid state. The proton doping experiments and CV measurements revealed the hydrogen bonding characteristic in P1-OH.

Graphical abstract

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Controlling MWCNT partitioning and electrical conductivity in melt compounded polypropylene/poly(ethylene-co-octene) blends

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Kyle G. Petrie, Osayuki Osazuwa, Aristides Docoslis, Marianna Kontopoulou
Composites containing multi-walled carbon nanotubes (MWCNTs) within polypropylene (PP)/poly (ethylene-co-octene) (EOC) blends are prepared using different melt compounding strategies, in the presence of polypropylene-graft-maleic anhydride (PP-g-MA) and polypropylene-graft- aminomethylpyridine (PP-g-Py) compatibilizers. Experimental evidence that MWCNTs are thermodynamically driven to localize preferentially in the EOC phase agrees with estimates of the partition coefficient using measured surface energy values. Addition of PP-g-Py alters the interfacial tension between the PP matrix and the MWCNTs; as a result some nanotubes remain in the PP phase. All blend compositions display lower electrical percolation thresholds compared to the neat matrix, with a minimum at 0.5 wt% MWCNTs for blends having a co-continuous blend morphology. A kinetic approach, involving pre-mixing the MWCNTs with PP and adding the EOC phase, is employed to monitor the evolution of morphology, MWCNT migration and the ensuing electrical conductivity, as a function of residence time. The morphology is fully developed and MWCNT migration is complete within 2 min of melt mixing with the EOC. The electrical conductivity is reduced considerably after 2 min of compounding, due to the migration of the MWCNTs within the dispersed EOC phase.

Graphical abstract

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Oculomotor Prediction: A Window into the Psychotic Mind

Publication date: Available online 11 March 2017
Source:Trends in Cognitive Sciences
Author(s): Katharine N. Thakkar, Vaibhav A. Diwadkar, Martin Rolfs
Psychosis – an impaired contact with reality – is a hallmark of schizophrenia. Many psychotic symptoms are associated with disruptions in agency – the sense that 'I' cause my actions. A failure to predict sensory consequences of one's own actions may underlie agency disturbances. Such predictions rely on corollary discharge (CD) signals, 'copies' of movement commands sent to sensory regions prior to action execution. Here, we make a case that the oculomotor system is a promising model for understanding CD in psychosis, building on advances in our understanding of the behavioral and neurophysiological correlates of CD associated with eye movements. In this opinion article, we provide an overview of recent evidence for disturbed oculomotor CD in schizophrenia, potentially linking bizarre and disturbing psychotic experiences with basic physiological processes.



http://ift.tt/2lP7F87

Cell membrane-derived nanomaterials for biomedical applications

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Ronnie H. Fang, Yao Jiang, Jean C. Fang, Liangfang Zhang
The continued evolution of biomedical nanotechnology has enabled clinicians to better detect, prevent, manage, and treat human disease. In order to further push the limits of nanoparticle performance and functionality, there has recently been a paradigm shift towards biomimetic design strategies. By taking inspiration from nature, the goal is to create next-generation nanoparticle platforms that can more effectively navigate and interact with the incredibly complex biological systems that exist within the body. Of great interest are cellular membranes, which play essential roles in biointerfacing, self-identification, signal transduction, and compartmentalization. In this review, we explore the major ways in which researchers have directly leveraged cell membrane-derived biomaterials for the fabrication of novel nanotherapeutics and nanodiagnostics. Such emerging technologies have the potential to significantly advance the field of nanomedicine, helping to improve upon traditional modalities while also enabling novel applications.

Graphical abstract

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Indenocinnoline derivatives as G-quadruplex binders, topoisomerase IIα inhibitors and antiproliferative agents

Publication date: Available online 11 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Grigoris Zoidis, Alice Sosic, Silvia Da Ros, Barbara Gatto, Claudia Sissi, Fausta Palluotto, Angelo Carotti, Marco Catto
DNA intercalating agents are a consolidated therapeutic option in the treatment of tumor diseases. Starting from previous findings in the antiproliferative efficacy of a series of indeno[1,2-c]cinnoline-11-one derivatives, we performed a suitable decoration of this scaffold by means of a simple and straightforward chemistry, aiming to a) enlarge the planar core to a pentacyclic benzo[h]indeno[1,2-c]cinnoline-13-one and b) introduce a basic head tethered through a simple polymethylene chain. In fluorescence melting and fluorescence intercalator displacement assays, these new compounds displayed fair to very good intercalating properties on different nucleic acid strands, with preference for G-quadruplex sequences. Inhibition of human topoisomerase IIα and antiproliferative assays on HeLa and MCF7 tumor cell lines outlined a multitarget antiproliferative profile for tetracyclic 6 and pentacyclic derivative 20, both bearing a N,N-dimethylamine as the protonatable moiety. Particularly, compound 6 displayed a very potent inhibition of tumor cell proliferation, while 20 returned the highest thermal stabilization in melting experiments. In summary, these results outlined a potential of such highly planar scaffolds for nucleic acid binding and antiproliferative effects.

Graphical abstract

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The Majority of Children with Epilepsy Experience Postictal Phenomena, Often Preventing a Return to Normal Activities of Childhood

Publication date: Available online 11 March 2017
Source:Pediatric Neurology
Author(s): Sarah J. MacEachern, Sabrina D'Alfonso, Roman J. McDonald, Nancy Thornton, Nils D. Forkert, Jeffrey R. Buchhalter
ObjectiveFollowing a seizure, patients with epilepsy have reported diverse symptoms in the postictal period, especially motor and cognitive dysfunction. However, these phenomena have not been well characterized in children, and their impact on patient well-being is not understood. We hypothesized that in a subset of epilepsy patients, postictal symptoms would affect their ability to return to normal childhood activities.MethodsTo test our hypothesis, a survey-based approach was used to characterize the type, frequency, and duration as well as the impact of these symptoms on the ability of these children to return their normal activities.ResultsIn this prospective study, data was analyzed from 208 patients seen in the outpatient Pediatric Neurology Clinic at the Alberta Children's Hospital. It was found that 86% (179/208) of respondents reported postictal symptoms, with the most common symptom category being Fatigue/Sleepiness/Tiredness (90%; 161/179), and the greatest impact being Weakness/Unable to move normally, which prevented 78% of those affected (71/91) from returning to normal activities after a seizure. Children who had focal seizures were more likely to experience postictal fatigue, sleepiness, and/or tiredness (P=0.01 [Bonferroni corrected]), but no other postictal symptoms were significantly associated with a specific seizure type or epilepsy syndrome.InterpretationThe results of this study further our understanding of the frequency, type and duration of symptoms experienced in the postictal period and how these symptoms impact children with epilepsy. It is clear that postictal phenomena are often experienced following epileptic seizures and have a significant impact on the lives of children with epilepsy.



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Death in pediatric mitochondrial disorders

Publication date: Available online 11 March 2017
Source:Pediatric Neurology
Author(s): Josef Finsterer, Sinda Zarrouk-Mahjoub




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Test-retest reproducibility of quantitative binding measures of [11C]Ro15-4513, a PET ligand for GABAA receptors containing alpha5 subunits

Publication date: 15 May 2017
Source:NeuroImage, Volume 152
Author(s): Colm J. McGinnity, Daniela A. Riaño Barros, Lula Rosso, Mattia Veronese, Gaia Rizzo, Alessandra Bertoldo, Rainer Hinz, Federico E. Turkheimer, Matthias J. Koepp, Alexander Hammers
IntroductionAlteration of γ-aminobutyric acid "A" (GABAA) receptor-mediated neurotransmission has been associated with various neurological and psychiatric disorders. [¹¹C]Ro15-4513 is a PET ligand with high affinity for α5-subunit-containing GABAA receptors, which are highly expressed in limbic regions of the human brain (Sur et al., 1998). We quantified the test-retest reproducibility of measures of [¹¹C]Ro15-4513 binding derived from six different quantification methods (12 variants).MethodsFive healthy males (median age 40 years, range 38–49 years) had a 90-min PET scan on two occasions (median interval 12 days, range 11–30 days), after injection of a median dose of 441 MegaBequerels of [¹¹C]Ro15-4513. Metabolite-corrected arterial plasma input functions (parent plasma input functions, ppIFs) were generated for all scans.We quantified regional binding using six methods (12 variants), some of which were region-based (applied to the average time-activity curve within a region) and others were voxel-based: 1) Models requiring arterial ppIFs – regional reversible compartmental models with one and two tissue compartments (2kbv and 4kbv); 2) Regional and voxelwise Logan's graphical analyses (Logan et al., 1990), which required arterial ppIFs; 3) Model-free regional and voxelwise (exponential) spectral analyses (SA; (Cunningham and Jones, 1993)), which also required arterial ppIFs; 4) methods not requiring arterial ppIFs – voxelwise standardised uptake values (Kenney et al., 1941), and regional and voxelwise simplified reference tissue models (SRTM/SRTM2) using brainstem or alternatively cerebellum as pseudo-reference regions (Lammertsma and Hume, 1996; Gunn et al., 1997).To compare the variants, we sampled the mean values of the outcome parameters within six bilateral, non-reference grey matter regions-of-interest. Reliability was quantified in terms of median absolute percentage test-retest differences (MA-TDs; preferentially low) and between-subject coefficient of variation (BS-CV, preferentially high), both compounded by the intraclass correlation coefficient (ICC). These measures were compared between variants, with particular interest in the hippocampus.ResultsTwo of the six methods (5/12 variants) yielded reproducible data (i.e. MA-TD <10%): regional SRTMs and voxelwise SRTM2s, both using either the brainstem or the cerebellum; and voxelwise SA. However, the SRTMs using the brainstem yielded a lower median BS-CV (7% for regional, 7% voxelwise) than the other variants (8–11%), resulting in lower ICCs. The median ICCs across six regions were 0.89 (interquartile range 0.75–0.90) for voxelwise SA, 0.71 (0.64–0.84) for regional SRTM-cerebellum and 0.83 (0.70–0.86) for voxelwise SRTM-cerebellum. The ICCs for the hippocampus were 0.89 for voxelwise SA, 0.95 for regional SRTM-cerebellum and 0.93 for voxelwise SRTM-cerebellum.ConclusionQuantification of [¹¹C]Ro15-4513 binding shows very good to excellent reproducibility with SRTM and with voxelwise SA which, however, requires an arterial ppIF. Quantification in the α5 subunit-rich hippocampus is particularly reliable. The very low expression of the α5 in the cerebellum (Fritschy and Mohler, 1995; Veronese et al., 2016) and the substantial α1 subunit density in this region may hamper the application of reference tissue methods.



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High sensitive detection method for protein by combining the magnetic separation with cation exchange based signal amplification

Publication date: 1 June 2017
Source:Talanta, Volume 168
Author(s): Jin Xu, Qian-mei Zhang, Dong-xu Zhao, Ya-ru Liu, Ping Chen, Gui-hong Lu, Hai-yan Xie
PSA is a member of low abundance proteins and serves as a critical indicator of the development and therapy efficacy for prostate cancer. In this study, a facile and high sensitive method was developed for serum PSA detection by integrating the immunomagnetic separation and cation exchange based signal amplification. On the basis of nanoparticle preparation and immunoprobe construction, PSA in serum was captured, separated by the immunomagnetic probe and then interacted with the quantum dots (QDs) based immunofluorescence probe; Zn²⁺ inside QDs was replaced by Ag⁺ within seconds, after which fluorescence signal was amplified by Fluozin-3, the Zn²⁺ responsive dye. Under optimized conditions, low detection limit (1.56pg/mL), wide linear range (1.56–25ng/mL) and good repeatability (intra-coefficient variation=3.18%) were achieved, which is superior to commercialized ELISA kit. These results demonstrated the potential of our high sensitive method for PSA detection in clinical.

Graphical abstract

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Sleep regulation of the distribution of cortical firing rates

Publication date: June 2017
Source:Current Opinion in Neurobiology, Volume 44
Author(s): Daniel Levenstein, Brendon O Watson, John Rinzel, György Buzsáki
Sleep is thought to mediate both mnemonic and homeostatic functions. However, the mechanism by which this brain state can simultaneously implement the 'selective' plasticity needed to consolidate novel memory traces and the 'general' plasticity necessary to maintain a well-functioning neuronal system is unclear. Recent findings show that both of these functions differentially affect neurons based on their intrinsic firing rate, a ubiquitous neuronal heterogeneity. Furthermore, they are both implemented by the NREM slow oscillation, which also distinguishes neurons based on firing rate during sequential activity at the DOWN→UP transition. These findings suggest a mechanism by which spiking activity during the slow oscillation acts to maintain network statistics that promote a skewed distribution of neuronal firing rates, and perturbation of that activity by hippocampal replay acts to integrate new memory traces into the existing cortical network.



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A giant oropharyngeal synovial sarcoma threatening the supraglottic airway – A case report

Publication date: Available online 11 March 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Santosh K. Swain, Alok Das, Mitali Madhumita Rath, Mahesh C. Sahu
Oropharyngeal synovial sarcoma is a rare malignant tumour. It has an aggressive nature and poor prognosis. The treatment of the synovial sarcoma is essentially surgical followed by postoperative chemoradiation. The giant oropharyngeal synovial sarcoma obstructing the airway may create threatening to the patient's airway and challenge to the surgeon. Before treating the patient, safe airway is vital for management of the disease. The appropriate diagnosis and treating the lesion with negative margin can improve the prognosis and survival of the patient. We report a case of oropharyngeal synovial sarcoma obstructing the supraglottic airway in a 29year old man, who undergone tracheostomy for safe airway followed by surgery and chemoradiation.



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Enhanced levofloxacin removal from water using zirconium (IV) loaded corn bracts

Abstract

The presence of antibiotics in the environment has attracted considerable attention due to their toxicity. In this study, agricultural waste corn bracts (CBs) modified by zirconium cations were utilized to remove levofloxacin (LEV) from wastewater. Zr-modified CBs exhibited a strong adsorption capacity (Q_max = 73 mg/g), and their desorption rate could reach 89% by simply adjusting the pH to 11. FTIR and XPS analyses indicated that the mechanism of LEV adsorption included the complexation between the ketone/carboxyl groups of LEV and the Zr atoms and the π-π electron-donor-acceptor interaction. Zr-modified CBs are economic, effective and nontoxic adsorbents. This material not only removes antibiotics from wastewater but also enables recycling and reuse of agricultural waste.

http://ift.tt/2lOJ17C

Sediment heavy metals and benthic diversities in Hun-Tai River, northeast of China

Abstract

In aquatic ecosystems, metal contamination in sediments has become a ubiquitous environmental problem, causing serious issues. Hun-Tai River, located in northeast of China, flows through an important heavy industry region and metropolitan area. This study examined the heavy metals (Cd, Cr, Cu, Fe, Mn, Pb, Ni, and Zn) of sediments and diversities (taxa richness, Shannon diversity, and evenness) of benthic assemblages (benthic algae and macroinvertebrate) in Hun-Tai River. The results clearly described the spatial patterns of metal contamination in terms of geo-accumulation index and contamination factor, as well as the spatial patterns of benthic diversities in terms of taxa richness, Shannon index, and evenness by kriging interpolation. The sediments were largely contaminated by Cd, followed by Cu, Fe, Zn, Mn, and Ni. Cd and Zn had similar spatial patterns and similar sources. Cu, Fe, Mn, and Ni showed similar spatial patterns and similar sources. The surface sediments were unpolluted by Cr and Pb. The metal mines and the heavy industry in the major cities were the potential pollution sources. Benthic algae and macroinvertebrate responded similarly to the heterogeneous environment and metal contamination, with high taxa richness and Shannon index in middle-upper reaches of Hun-Tai River. Evenness showed complex spatial patterns. Under low contamination, both taxa richness, Shannon diversity, and evenness had a large variation range. However, under the moderate and high contamination, the taxa richness and Shannon diversity kept to a low level but the evenness had a high level. This study provided insights into the sediment heavy metal contamination in Hun-Tai River.

http://ift.tt/2mec0Om

Adsorption behavior of Sudan I-IV on a coastal soil and their forecasted biogeochemical cycles

Abstract

Sudan I–IV as synthetic azo dyes have been concerned worldwide and ever caused a panic on food safety because of illegal addition into foodstuffs. In the past decades, various methods are being developed to identify and determine Sudan dyes in foodstuffs. However, relevant studies about their biogeochemical behaviors and potential environmental effects are rarely reported, although it is of great importance and necessity accounting for their potential environmental contamination from various sources. In this work, the experimental studies on adsorption behavior of Sudan I–IV acting on soil (10, 25, 50, 75, and 100 mg/L) were carried out, and their transport in soil compartments and between soil-water, and air-soil interfaces were discussed. Results showed that the amount of Sudan I–IV adsorbed on soil increased accordingly with the increasing concentration of Sudan dyes in aqueous solution, and Sudan II and IV were more likely adsorbed on the tested soils than Sudan I and III based on their maximum adsorption amount. However, for Sudan I, III, and IV, in some high concentrations (under the treatment of 75 mg/L for Sudan III, 100 mg/L for Sudan I and IV), the adsorption was significantly increased, and then came back to the "normal" level (under the treatment of 100 mg/L for Sudan III). It is expected that relevant researches on their biogeochemical behaviors in soil compartments, and between soil-water and air-soil interfaces would be concerned and addressed.

http://ift.tt/2lOIiDA

Caregivers had neighbourhood support but perceived it unsatisfactory and worsened: England Community Life Survey, 2012–2014

Abstract

There has been limited research studying neighbourhood support for caregivers. Therefore, the aim of the present study was to investigate the support from neighbourhoods between both caregivers and non-caregivers in a country-wide and population-based setting. Data were retrieved from England Community Life Survey, 2012–2014, a new annual household survey conducted by face-to-face interview since 2012, with a representative sample size of 5–6000 adult (aged 16 years and over) resident per year in England. Chi-square test and logistic regression modelling were performed to examine the variance in support from and perception toward neighbourhoods between caregivers and non-caregivers. Of 15,320 study participants, 2315 (16.0%) had a caring responsibility. There was not much variance in feeling belonging, comfortably asking neighbours to keep keys, comfortably asking neighbours to mind children, believing neighbours pulling together and trusting people in the neighbourhood between caregivers and non-caregivers. However, caregivers seemed to be more likely to chat to neighbours (OR 0.77, 95% CI 0.69–0.87, P < 0.001) and comfortably ask neighbours to help collect grocery (OR 0.89, 95% CI 0.81–0.98, P = 0.023). In addition, caregivers tended to perceive their neighbourhoods unsatisfactory (OR 1.17, 95% CI 1.05–1.32, P = 0.007) and worsened in the last 2 years (OR 1.36, 95% CI 1.22–1.51, P < 0.001). For future research, a longitudinal neighbourhood monitoring surveillance for all people would be suggested. For practice and policy, environmental health and nursing programs might need to extend education trainings and interventions to cover all neighbourhoods at different time points that can lessen both disease and caregiving burden and therefore optimize health and quality of life.

http://ift.tt/2me0Zg2

15th EuCheMS International Conference on Chemistry and the Environment—ICCE 2015 Leipzig, 20–24 September 2015

http://ift.tt/2lOOcEL

A new insight to adsorption and accumulation of high lead concentration by exopolymer and whole cells of lead-resistant bacterium Acinetobacter junii L. Pb1 isolated from coal mine dump

Abstract

A lead-resistant bacterial strain was isolated from coal mine dump and identified as Acinetobacter junii Pb1 on basis of 16S rRNA (ribosomal ribonucleic acid) gene sequencing. The minimum inhibitory concentration of lead for the strain was 16,000 mg l⁻¹ and it showed antibiotic and multi metal resistance. In aqueous culture, at an initial lead (Pb(II)) concentration of 100 and 500 mg l⁻¹, lead adsorption and accumulation by the isolate was 100 and 60%, at pH 7 at 30 °C after 48 and 120 h, respectively. The two fractions of exopolysaccharide (EPS), loosely associated EPS (laEPS) and bound EPS (bEPS), and whole cells (devoid of EPS) showed high binding affinity towards Pb(II). The binding affinity of laEPS towards Pb(II) (1071 mg Pb g⁻¹) was three times higher than that of bEPS (321.5 mg Pb g⁻¹) and 6.5 times higher than that of whole cells (165 mg Pb g⁻¹). The binding affinity of EPS and whole cells with Pb(II), reported in the current study, is considerably higher as compared to that reported in the literature, till date. SEM analysis, showed an increase in thickness of cells on exposure to Pb(II) and TEM analysis, revealed its accumulation (interior of cell) and its adsorption (with the external cell surface). The isolate was also found to be positive for indole acetic acid (IAA) and 1-aminocyclopropane-1-carboxylate (ACC) deaminase production which helps in promoting plant growth. Thus, this study provides a new understanding towards Pb(II) uptake by A. junii Pb1, highlighting its potential on the restoration of Pb(II) contaminated repositories.

http://ift.tt/2medqsf

Do shallow soil, low water availability, or their combination increase the competition between grasses with different root systems in karst soil?

Abstract

Uneven soil depth and low water availability are the key limiting factors to vegetation restoration and reconstruction in limestone soils such as in vulnerable karst regions. Belowground competition will possibly increase under limited soil resources. Here, we investigate whether low resource availability (including shallow soil, low water availability, and shallow soil and low water availability combined) stimulates the competition between grasses with different root systems in karst soil, by assessing their growth response, biomass allocation, and morphological plasticity. In a full three-way factorial blocked design of soil depth by water availability by neighbor identity, we grew Festuca arundinacea (deep-rooted) and Lolium perenne (shallow-rooted) under normal versus shallow soil depth, high versus low water availability, and in monoculture (conspecific neighbor) versus mixture (neighbor of the other species). The key results were as follows: (1) total biomass and aboveground biomass in either of the species decreased with reduction of resources but were not affected by planting patterns (monoculture or mixture) even at low resource levels. (2) For F. arundinacea, root biomass, root mass fraction, total root length, and root volume were higher in mixture than in monoculture at high resource level (consistent with resource use complementarity), but lower in mixture than in monoculture at low resource levels (consistent with interspecific competition). In contrast for L. perenne, either at high or low resource level, these root traits had mostly similar values at both planting patterns. These results suggest that deep-rooted and shallow-rooted plant species can coexist in karst regions under current climatic regimes. Declining resources, due to shallow soil, a decrease in precipitation, or combined shallow soil and karst drought, increased the root competition between plants of deep-rooted and shallow-rooted species. The root systems of deep-rooted plants may be too small to get sufficient water and nutrients from dry, shallow soil, while shallow-rooted plants will maintain a dominant position with their already adaptive strategy in respect of root biomass allocation and root growth.

http://ift.tt/2lOyB7P

Effect of silicon fertilizers on cadmium in rice ( Oryza sativa ) tissue at tillering stage

Abstract

Silicon has been found to enhance the plants' tolerance to heavy metal stress. In a field study, the effect of different types of Si-rich soil amendments (slag, ground slag, and diatomaceous earth) and fertilizers (activated slag, ground activated slag, and commercial Si fertilizer) on the distribution of soluble and insoluble forms of Cd in the rice plant organs grown on long-term cultivated paddy soil contaminated with Cd (central part of Hunan Province, China) was investigated. The soluble Si and Cd were tested in the apoplast and symplast of the roots, stems, and leaves of rice at a tillering stage. The Si-rich materials increased rice biomass by up to 15.5% and reduced the total leaf Cd by 8.5 to 21.9%. Commercial Si fertilizer was the most effective. Three main locations of the most active Si-Cd interactions were distinguished in the soil-plant system: soil, where monosilicic acid affords adsorption and fixation of the bioavailable Cd and root apoplast and apoplast above roots, where monosilicic acid can precipitate Cd. The transport of Cd to stems and leaves and the mobility of Cd in the soil depend on the content of monosilicic acid in the system.

http://ift.tt/2me98Ba

Parthenium weed ( Parthenium hysterophorus L.) and climate change: the effect of CO 2 concentration, temperature, and water deficit on growth and reproduction of two biotypes

Abstract

Climate change will have a considerable impact upon the processes that moderate weed invasion, in particular to that of parthenium weed (Parthenium hysterophorus L.). This study evaluated the performance of two Australian biotypes of parthenium weed under a range of environmental conditions including soil moisture (100 and 50% of field capacity), atmospheric carbon dioxide (CO₂) concentration (390 and 550 ppm), and temperature (35/20 and 30/15 °C/day/night). Measurements were taken upon growth, reproductive output, seed biology (fill, viability and dormancy) and soil seed longevity. Parthenium weed growth and seed output were significantly increased under the elevated CO₂ concentration (550 ppm) and in the cooler (30/15 °C) and wetter (field capacity) conditions. However, elevated CO₂ concentration could not promote growth or seed output when the plants were grown under the warmer (35/20 °C) and wetter conditions. Warm temperatures accelerated the growth of parthenium weed, producing plants with greater height biomass but with a shorter life span. Warm temperatures also affected the reproductive output by promoting both seed production and fill, and promoting seed longevity. Dryer soil conditions (50% of field capacity) also promoted the reproductive output, but did not retain high seed fill or promote seed longevity. Therefore, the rising temperatures, the increased atmospheric CO₂ concentration and the longer periods of drought predicted under climate change scenarios are likely to substantially enhance the growth and reproductive output of these two Australian parthenium weed biotypes. This may facilitate the further invasion of this noxious weed in tropical and sub-tropical natural and agro-ecosystems.

http://ift.tt/2lOIjal

Estimation of the PM 2.5 health effects in China during 2000–2011

Abstract

Exposure to fine particulate matter (PM_2.5) has been associated with mortality, but the extent of the adverse impacts differs across various regions. A quantitative estimation of health effects attributed to PM_2.5 in China is urgently required, particularly because it has the largest population and high air pollution levels. Based on the remote sensing-derived PM_2.5 and grid population data, we estimated the acute health effects of PM_2.5 in China using an exposure-response function. The results suggest the following: (1) The proportion of the population exposed to high PM_2.5 concentrations (>35 μg/m³) increased consistently from 2000 to 2011, and the population exposed to concentrations above the threshold defined by World Health Organization (WHO) (>10 μg/m³) rose from 1,191,191,943 to 1,290,562,965. (2) The number of deaths associated with PM_2.5 exposure increased steadily from 107,608 in 2000 to 173,560 in 2010, with larger numbers in the eastern region. (3) PM_2.5 health effects decreased in three pollution control scenarios estimated for 2017, i.e., the Air Pollution Prevention and Control Action Plan (APPCAP) scenario, the APPCAP under WHO IT-1 scenario (35 μg/m³), and the APPCAP under WHO IT-3 scenario (15 μg/m³), which indicates that pollution control can effectively reduce PM_2.5 effects on mortality.

http://ift.tt/2mdYqui

The effects of lead stress on photosynthetic function and chloroplast ultrastructure of Robinia pseudoacacia seedlings

Abstract

In this experiment, the effects of different lead (Pb) concentrations (0, 200, 600, 1000, 1400 mg kg⁻¹) on photosynthesis and chlorophyll fluorescence in Robinia pseudoacacia seedlings were examined. As Pb concentration increased, chlorophyll a, chlorophyll b, total chlorophyll content, net photosynthetic rate, transpiration rate, stomatal conductance (g _s), and mesophyll intercellular carbon dioxide concentration were gradually reduced. Maximal photochemical efficiency, photochemical quenching, and quantum yield also decreased. However, the initial fluorescence and nonphotochemical quenching gradually increased. Chloroplasts swelled owing to local plasmolysis and lost most of their starch content, and their thylakoid lamellae gradually became disordered and loosely packed. When the chloroplast envelope was lost under high Pb stress (≥1000 mg kg⁻¹), lipid globules were released into the surrounding mesophyll cell. Multiple regression analysis showed that g _s and inactivity of the PSII reaction center had the greatest effect on photosynthetic function, whereas inhibition of electron transport had minimal effects on black locust seedlings under Pb stress.

http://ift.tt/2lOIkep

Intensification of constructed wetlands for land area reduction: a review

Abstract

The large land area requirement of constructed wetlands (CWs) is a major limitation of its application especially in densely populated and mountainous areas. This review paper provides insights on different strategies applied for the reduction of land area including stack design and intensification of CWs with different aeration methods. The impacts of different aeration methods on the performance and land area reduction were extensively and critically evaluated for nine wetland systems under three aeration strategies such as tidal flow (TF), effluent recirculation (ER), and artificial aeration (AA) applied on three types of CWs including vertical flow constructed wetland (VFCW), horizontal flow constructed wetland (HFCW), and hybrid constructed wetland (HCW). The area reduction and pollutant removal efficiency showed substantial variation among different types of CWs and aeration strategies. The ER-VFCW designated the smallest footprint of 1.1 ± 0.5 m² PE⁻¹ (population equivalent) followed by TF-VFCW with the footprint of 2.1 ± 1.8 m² PE⁻¹, and the large footprint was of AA-HFCW (7.8 ± 4.7 m² PE⁻¹). When footprint and removal efficiency both are the major indicators for the selection of wetland type, the best options for practical application could be TF-VFCW, ER-HCW, and AA-HCW. The data and results outlined in this review could be instructive for futures studies and practical applications of CWs for wastewater treatment, especially in land-limited regions.

http://ift.tt/2mefYXp

Removal of traces of toluene and p -xylene in indoor air using biofiltration and a hybrid system (biofiltration + adsorption)

Abstract

Biofiltration technology and the hybrid system combining biofiltration and adsorption (onto activated carbon) were compared as possible methods to toluene and p-xylene at parts per million concentration levels (2–45 and 1–33 ppb, respectively). An organic material was used as packing material for the biofiltration process. Even at low empty bed residence times (EBRTs) and concentrations, toluene removal efficiency reached 100% and p-xylene showed an increasing trend on their removal efficiency over the time using biofiltration. The assessment of by-products and particle generation by the biofilter and the hybrid system were taken into account. Acetone and acetic acid were identified as by-products of the biofilter. Particle emissions in the range of 0.03 to 10 μm were recorded for both systems.

http://ift.tt/2lOKFGc

Alleviating the environmental heat burden on laying hens by feeding on diets enriched with certain antioxidants (vitamin E and selenium) individually or combined

Abstract

The present study was designed to alleviate the negative biohazards of high ambient temperature on the productive performance and physiological status of laying hens. A total of 135 Bovans laying hens were distributed into nine groups in a 3 × 3 factorial design experiment. Basal diet was supplemented with vitamin E at levels of 0, 250, and 500 mg /kg diet. Within each dietary vitamin E level, each diet was supplemented with sodium selenite as a source of selenium (Se) to supply 0, 0.25, and 0.50 mg Se/kg diet. Results showed that supplementing layer's diet with 500 mg vitamin E/kg was accompanied with the lowest feed consumption (FC) and feed conversion ratio (FCR). The interaction among vitamin E and Se levels exerted significant effects only on FC and FCR. Insignificant differences were observed in egg quality criteria due to the treatments studied. Increasing vitamin E level was associated with a gradual decrease in basophil count and an increase in monocytes. A gradual decrease in the count of each of heterophils, monocytes, and eosinophils was observed with the elevation in the dietary Se level. The combination among vitamin E and Se levels produced a significant effect on all hematological parameters studied. As vitamin E increased, a marked decrease in serum AST and a gradual increase in total lipids, total cholesterol, and calcium were observed. As the level of dietary Se increased, serum total protein, albumin, T₄, total cholesterol, and total lipids increased. No significant impacts were detected for the interaction among vitamin E and Se levels on any of blood constituents determined except serum globulin, ALT, and calcium. In conclusion, the combination between vitamin E and Se showed a good ability to alleviate the harmful impacts of heat stress and produced the highest productive performance when compared with the other groups, which exhibit the synergistic effect between the two antioxidants.

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Functionalized Single-Walled Carbon Nanotubes: Cellular Uptake, Biodistribution and Applications in Drug Delivery

Publication date: Available online 11 March 2017
Source:International Journal of Pharmaceutics
Author(s): Zixian Li, Andre Luis Branco de Barros, Daniel Cristian Ferreira Soares, Sara Nicole Moss, Laleh Alisaraie
The unique properties of single-walled carbon nanotubes (SWNTs) enable them to play important roles in many fields. One of their functional roles is to transport cargo into the cell. SWNTs are able to traverse amphipathic cell membranes due to their large surface area, flexible interactions with cargo, customizable dimensions, and surface chemistry. The cargoes delivered by SWNTs include peptides, proteins, nucleic acids, as well as drug molecules for therapeutic purpose. The drug delivery functions of SWNTs have been explored over the past decade. Many breakthrough studies have shown the high specificity and potency of functionalized SWNT-based drug delivery systems for the treatment of cancers and other diseases. In this review, we discuss different aspects of drug delivery by functionalized SWNT carriers, diving into the cellular uptake mechanisms, biodistribution of the delivery system, and safety concerns on degradation of the carriers. We emphasize the delivery of several common drugs to highlight the recent achievements of SWNT-based drug delivery.

Graphical abstract

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Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041)

Abstract

Purpose

This phase I b study evaluated the safety and anti-tumor activity of pembrolizumab in Japanese patients with advanced melanoma.

Methods

Pembrolizumab (2 mg/kg) was given every 3 weeks (Q3W) for up to 2 years or until confirmed progression or unacceptable toxicity. The tumor response was assessed as per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by both investigator review and central review.

Results

Forty-two patients with advanced melanoma received pembrolizumab. A primary cutaneous histology was observed in 34 patients (81.0%), while a primary mucosal histology was observed in 8 patients (19.0%). Thirty-four patients (81.0%) experienced treatment-related adverse events (AEs). The most common treatment-related AEs were pruritus, maculopapular rash, malaise, and hypothyroidism. Grade 3–5 treatment-related AEs occurred in 8 patients (19.0%). The only grade 3–5 treatment-related AE reported in at least two patients was anemia. There were two treatment-related deaths (unknown cause and cerebral hemorrhage). Among the 37 evaluable patients, the confirmed overall response rates (ORRs) determined by central review were 24.1% (95% CI 10.3–43.5) for cutaneous melanoma and 25.0% (95% CI 3.2–65.1) for mucosal melanoma. The responses were durable, and the median duration of response was not reached in either population. The median overall survival (OS) was not reached, with a 12-month OS of 82.7% for cutaneous melanoma and 51.4% for mucosal melanoma.

Conclusion

The safety profile of pembrolizumab in Japanese patients was similar to that reported in the previous clinical studies. Pembrolizumab provided promising anti-tumor activity in Japanese patients with advanced melanoma.

http://ift.tt/2mwrgbW

Luhong formula inhibits myocardial fibrosis in a paracrine manner by activating the gp130/JAK2/STAT3 pathway in cardiomyocytes

Publication date: 18 April 2017
Source:Journal of Ethnopharmacology, Volume 202
Author(s): Huiyan Qu, Yong Wang, Yingjie Wang, Tao Yang, Zhou Feng, Yang Qu, Hua Zhou
Ethnopharmacological relevanceLuhong formula (LHF)—a traditional Chinese medicine containing Cervus nippon Temminck, Carthamus tinctorius L., Cinnamomum cassia Presl, Codonopisis pilosula( Franch.) Nannf., Astragalus membranaceus ( Fisch.) Bge. var. mongholicus ( Bge.) Hsiao, Lepidium apetalum Willd—is used in the treatment of heart failure.Aim of the studyTo investigate the antifibrotic efficacy of LHF in a myocardial infarction-induced rat model of heart failure and to determine its mechanism of action.Material and methodsMyocardial infarction was induced in rats by coronary artery ligation, and cardiac fibroblasts were isolated. Neonatal rat cardiomyocytes (NRCMs) were isolated from 2 to 3-day-old Sprague-Dawley male rats, and cardiomyocyte hypertrophy was induced by isoprenaline. Histological examination was carried out to estimate the degree of myocardial fibrosis. Expression of gp130/JAK2/STAT3 pathway proteins was measured by western blot. The mRNA levels of downstream genes of gp130/JAK2/STAT3 pathway (i.e., CTGF, TSP-1, and TIMP1) were determined by RT-PCR; while CTGF, TSP-1, and TIMP1 protein levels were measured by ELISA. To investigate paracrine effects, cell proliferation and collagen synthesis was measured after treating cardiac fibroblasts with the conditioned media from isoprenaline-treated NRCMs.ResultsHistopathological changes showed that LHF inhibited myocardial fibrosis in heart failure rats. Treatment with LHF up-regulated gp130, JAK2, and STAT3 protein expression in heart tissue, and down-regulated CTGF, TSP-1, and TIMP1 gene expression. Isoprenaline-treated NRCMs displayed lower expression of the gp130, JAK2, and STAT3 pathway proteins and higher secretion of its downstream signaling molecules (CTGF, TSP-1, TIMP1). LHF inhibited cardiac fibroblast proliferation and collagen synthesis after treatment with the conditioned media from isoprenaline-treated NRCMs.ConclusionLHF treatment attenuates myocardial fibrosis in vivo. LHF inhibits cardiac fibroblasts proliferation and collagen synthesis in a paracrine manner by activating the gp130/JAK2/STAT3 pathway in cardiomyocytes, thereby inhibiting the secretion of downstream profibrogenic cytokines.

Graphical abstract

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Epithelial cell-enhanced metabolism by low-level laser therapy and epidermal growth factor

Abstract

Reepithelialization and wound closure are the desired outcome for several ulcerative conditions. Such resolution reduces the possibility of wound contamination and maintenance of the injury and improves the reestablishment of tissue morphology and functions. Investigators are seeking adjuvant therapies that can accelerate wound healing and are developing new strategies for clinical applications. This study compared the effects of epidermal growth factor (EGF) application and low-level laser therapy (LLLT) on cultured epithelial cells. Cells were seeded in 24-well plates. After a 24-h incubation, the epithelial cells were either treated with EGF (100 μM in serum-free DMEM for 72 h) or subjected to LLLT (780 nm, 25 mW, 0.5, 1.5, and 3 J/cm²) by three applications every 24 h. Seventy-two hours after cells were treated with EGF or LLLT, cell migration, viability, proliferation, and collagen synthesis were assessed. Cells treated with EGF showed increased cell viability, proliferation, and collagen synthesis compared with those cells that received no treatment. LLLT enhanced cell migration; however, no significant effects of laser irradiation on other cell functions were observed. Comparison of both therapies demonstrated that EGF and LLLT enhanced specific epithelial cell activities related to wound healing.

http://ift.tt/2nh95VW

Expression patterns of prune2 is regulated by Notch and retinoic acid signaling pathways in the zebrafish embryogenesis

Publication date: Available online 11 March 2017
Source:Gene Expression Patterns
Author(s): Mrudhula Anuppalle, Sateesh Maddirevula, Ajeet Kumar, Tae-Lin Huh, Joonho Choe, Myungchull Rhee
PRUNE2 has been identified as a susceptible gene for Alzheimer's disease and a marker for leiomyosarcomas. Isoforms of Prune2 regulate neuronal cell differentiation and synaptogenesis. Although expression pattern of Prune2 has been reported in the murine brain, its expression patterns and regulation along vertebrate embryogenesis remain to be further investigated. We thus defined the expression profiles and transcriptional regulation of prune2 in zebrafish embryos. prune2 exhibits maternal expression, but is increased in later embryonic stages, and expressed in the telencephalon, epiphysis cluster, nucleus of the tract of the post optic commissure, spinal cord, cerebellum, tegmentum, anterior lateral line ganglion, posterior lateral line ganglion and rhombomeres 2 through 5. Two color WISH with a post-mitotic neuron specific marker, huC defined that prune2 is expressed in the post mitotic neurons. The level of prune2 transcripts is upregulated in Notch signaling homozygous mutant, mib1^−/−(mib^ta52b), indicating that Notch signaling regulates transcription of prune2. Interestingly, in silico analysis of prune2 promoter found retinoic acid (RA) response elements (AGGTCAcaTGACCA) located at −3 to −16 relative to the first exon. It turned out that RA signaling altered the expression pattern of prune2 in the hindbrain. We further propose that Prune2 might be a putative regulator for CNS development in zebrafish embryogenesis.



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Vitexin alleviates ox-LDL-mediated endothelial injury by inducing autophagy via AMPK signaling activation

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Shaoli Zhang, Changlei Guo, Zhigang Chen, Peiyong Zhang, Jianhua Li, Yan Li
Endothelial cell injury plays a crucial role in the development and pathogenesis of cardiovascular disease. Vitexin is a natural flavonoid characterized by anti-oxidative and anti-inflammatory properties. The purpose of this study was to investigate the effects of vitexin on ox-LDL-induced endothelial dysfunction and to explore the underlying molecular mechanisms. In the present study, vitexin was found to play a protective role against ox-LDL-induced endothelial injury. Vitexin significantly promoted cell viability and inhibited apoptosis in ox-LDL-treated HUVECs. The up-regulation of cleaved Caspase-3, cleaved Caspase-9 and Bax induced by ox-LDL were inhibited by treatment with vitexin; meanwhile, the down-regulation of Bcl-2 was suppressed by vitexin. Pretreatment with vitexin was found to inhibit the ox-LDL-induced overexpression of IL-1β, IL-6, TNF-α, E-selectin, ICAM1 and VCAM1. Moreover, vitexin reduced ox-LDL-induced oxidative stress by inhibiting the production of ROS and MDA, and by promoting the expression of SOD. Furthermore, we had shown that vitexin protected against the ox-LDL induced cell injury by activating autophagy. The protective effects of vitexin in ox-LDL-treated HUVECs were all reversed following treatment with the autophagy inhibitor 3-MA. In addition, we found that vitexin increased the expression of p-AMPK and decreased the expression of p-mTOR. The combination of the AMPK inhibitor Compound C plus vitexin significantly reversed the effects of vitexin in ox-LDL-treated HUVECs, such as the inhibition of autophagy, reduction in cell viability, increase in apoptosis and ROS production. In conclusion, these data suggest that vitexin ameliorates ox-LDL-mediated endothelial injury by inducing autophagy via AMPK signaling.



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Frontmatter

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 3
Pages: i-iii

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Adrenocortical neoplasms in adulthood and childhood: distinct presentation. Review of the clinical, pathological and imaging characteristics

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 3
Pages: 253-276

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Assessment of health-related quality of life in Egyptian adolescents with type 1 diabetes: DEMPU survey

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 3
Pages: 277-283

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Non-HDL-cholesterol and C-reactive protein in children and adolescents with type 1 diabetes

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 3
Pages: 285-288

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Nutritional status and metabolic profile in neurologically impaired pediatric surgical patients

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 3
Pages: 289-300

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Vascular risk factors are associated with retinal arteriolar narrowing and venular widening in children and adolescents with type 1 diabetes

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 3
Pages: 301-309

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Are aromatase inhibitors in boys with predicted short stature and/or rapidly advancing bone age effective and safe?

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 3
Pages: 311-317

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Increased prevalence of bicuspid aortic valve in Turner syndrome links with karyotype: the crucial importance of detailed cardiovascular screening

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 3
Pages: 319-325

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Resting energy expenditure in girls with Turner syndrome

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 3
Pages: 327-332

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AMH levels in girls with various pubertal problems

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 3
Pages: 333-335

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Bone age in unilateral spastic cerebral palsy: is there a correlation with hand function and limb length?

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 3
Pages: 337-341

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Novel germline mutation (Leu512Met) in the thyrotropin receptor gene (TSHR) leading to sporadic non-autoimmune hyperthyroidism

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 3
Pages: 343-347

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A novel DAX-1 mutation in two male siblings presenting with precocious puberty and late-onset hypogonadotropic hypogonadism

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 3
Pages: 349-353

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Adrenarche unmasks compound heterozygous 3β-hydroxysteroid dehydrogenase deficiency: c.244G>A (p.Ala82Thr) and the novel 931C>T (p.Gln311*) variant in a non-salt wasting, severely undervirilised 46XY

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 3
Pages: 355-360

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Three cases of Gordon syndrome with dominant KLHL3 mutations

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 3
Pages: 361-364

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Unexplained cyanosis caused by hepatopulmonary syndrome in a girl with APECED syndrome

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 3
Pages: 365-369

http://ift.tt/2mxRaw5

Long-term Outcome after Thrombolysis for Acute Lower Limb Ischaemia

Publication date: Available online 11 March 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): O. Grip, A. Wanhainen, S. Acosta, M. Björck
ObjectivesThe purpose was to study long-term outcome after thrombolysis for acute arterial lower limb ischaemia, and to evaluate the results depending on the underlying aetiology of arterial occlusion.MethodsThis was a retrospective study of patients entered into a prospective database. Patients were identified in prospective databases from two vascular centres, including a large number of variables. Case records were analysed retrospectively. Through cross linkage with the Population Registry 100% accurate survival data were obtained. Between January 2001 and December 2013, 689 procedures were included. The aetiology of ischaemia was graft/stent/stent graft occlusion in 39.8%, arterial thrombosis in 27.7%, embolus in 25.1% and popliteal aneurysm in 7.4%.ResultsThe mean follow-up was 59.4 months (95% CI, 56.1–62.7), during which 32.9% needed further re-interventions, 16.4% underwent amputation without re-intervention, and 50.7% had no re-intervention. The need for re-intervention during follow-up was 48.0% in the graft/stent occlusions group, 34.0% of the popliteal aneurysm group, 25.4% in the thrombosis group, and 16.3% in the embolus group (p < .001). The overall primary patency rates were 69.1% and 55.9% at 1 and 5 years, respectively. Primary patency at 5 years was higher for the embolus group (83.3%, p = .002) and lower for the occluded graft/stent group (43.3%, p < .001). Secondary patency rates were 80.1% and 75.2% at 1 and 5 years, respectively, without difference between the subgroups. The amputation rate was lower in the embolic group at 1 and 5 years (8.1% and 11.1%, respectively, p = .001). Survival was higher in the group with occluded popliteal aneurysms at 5 years (83.3%, p = 0.004). Amputation free survival was 72.1% and 45.2% at 1 and 5 years; lower in the occluded graft/stent group at five years (37.9%, p = .007).ConclusionIntra-arterial thrombolytic therapy achieves good medium and long-term clinical outcome, reducing the need of open surgical treatment in most patients.



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Jesper Swedenborg In Memoriam

Publication date: Available online 11 March 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): U. Hedin, R. Hultgren




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Choices of Stent and Cerebral Protection in the Ongoing ACST-2 Trial: A Descriptive Study

Publication date: Available online 11 March 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): D.D. de Waard, A. Halliday, G.J. de Borst, R. Bulbulia, A. Huibers, R. Casana, L.H. Bonati, V. Tolva
Objective/BackgroundSeveral plaque and lesion characteristics have been associated with an increased risk for procedural stroke during or shortly after carotid artery stenting (CAS). While technical advancements in stent design and cerebral protection devices (CPD) may help reduce the procedural stroke risk, and anatomy remains important, tailoring stenting procedures according to plaque and lesion characteristics might be a useful strategy in reducing stroke associated with CAS. In this descriptive report of the ongoing Asymptomatic Carotid Surgery Trial-2 (ACST-2), it was assessed whether choice for stent and use or type of CPD was influenced by plaque and lesion characteristics.MethodsTrial patients who underwent CAS between 2008 and 2015 were included in this study. Chi-square statistics were used to study the effects of plaque echolucency, ipsilateral preocclusive disease (90–99%), and contralateral high-grade stenosis (>50%) or occlusion of the carotid artery on interventionalists' choice for stent and CPD. Differences in treatment preference between specialties were also analysed.ResultsIn this study, 831 patients from 88 ACST-2 centres were included. Almost all procedures were performed by either interventional radiologists (50%) or vascular surgeons (45%). Plaque echolucency, ipsilateral preocclusive disease (90–99%), and significant contralateral stenosis (>50%) or occlusion did not affect the choice of stent or either the use of cerebral protection and type of CPD employed (i.e., filter/flow reversal). Vascular surgeons used a CPD significantly more often than interventional radiologists (98.6% vs. 76.3%; p < .001), but this choice did not appear to be dependent on patient characteristics.ConclusionIn ACST-2, plaque characteristics and severity of stenosis did not primarily determine interventionalists' choice of stent or use or type of CPD, suggesting that other factors, such as vascular anatomy or personal and centre preference, may be more important. Stent and CPD use was highly heterogeneous among participating European centres.



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Long-term survival of patients aged 80 years or older treated with radical prostatectomy for prostate cancer

Publication date: Available online 10 March 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Paolo Dell'Oglio, Emanuele Zaffuto, Katharina Boehm, Vincent Trudeau, Alessandro Larcher, Zhe Tian, Marco Moschini, Shahrokh F. Shariat, Markus Graefen, Fred Saad, Umberto Capitanio, Alberto Briganti, Francesco Montorsi, Pierre I. Karakiewicz
BackgroundRadical prostatectomy (RP) is the gold standard for clinically localized prostate cancer (PCa) patients with life expectancy (LE) of at least 10 years. We examined long-term survival of men aged 80 years or older treated with RP and we attempted to identify criteria based on age and comorbidities that could predict survival of at least 10 years after RP, to identify those that might be considered for RP.Patients and MethodsIn Surveillance Epidemiology and End Results (SEER)-Medicare-linked database, we identified 234 octo- and nonagenarians with clinical T1, T2 or T3 PCa treated with RP between 1991 and 2009. Kaplan-Meier analyses examined 10-year survival patterns. Multivariable Cox regression analyses focused on the combined effect of age and/or Charlson Comorbidity Index (CCI) after adjusting for different confounders.ResultsThe 10-year overall survival (OS) and cancer specific mortality (CSM) rates in the overall population were 51 and 9.9%. In individuals aged 80-81 years old, the 10-year OS was 62.4 vs. 39.6% in older patients (p=0.001). Moreover, combination of age 80-81 with CCI=0 yielded 10-year OS of 67.9 vs. 28.5% in older and sicker patients (p<0.001). Age 80-81, absence of comorbidities and the combination of age 80-81 with CCI=0, represented independent predictors of lower overall mortality (all p≤0.01).ConclusionsTwo out of three individuals selected for RP aged 80 to 81 years and without comorbidities, fulfill the criterion of LE of 10 years or more. Therefore, elderly PCa individuals can be suitable for surgical management, if appropriately selected, based on LE criterion.



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Changes in nationwide use of preoperative radiotherapy for rectal cancer after revision of the national colorectal cancer guideline

Publication date: Available online 10 March 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Lieke Gietelink, Michel W.J.M. Wouters, C.A.M. Marijnen, Julia van Groningen, Nicoline van Leersum, R.G.H. Beets-Tan, Rob A.E.M. Tollenaar, Pieter J. Tanis
BackgroundThe rate of preoperative radiotherapy (RT) for rectal cancer in the Netherlands has been the highest among European countries. Revision of the national guideline on colorectal cancer, officially published in 2014, specifically focussed on the indication for RT and MRI criteria to evaluate mesorectal lymph nodes. The objective of this study was to evaluate implementation of the revised guideline using a national audit.MethodsData of the Dutch Surgical Colorectal Audit (DSCA) between 2009 and 2014 were used to evaluate RT use and RT regimen for relevant subgroups of cM0 rectal cancer patients, as well as accuracy of pre-operative MRI.Results14,018 patients were included for analysis. Overall RT use in cT1-4N0-2M0 stage ranged from 81.4% to 84.2% between 2009 and 2013, and decreased to 64.4% in 2014. The absolute decrease in RT use from 2013 to 2014 for cT1N0, cT2N0 and cT3N0 stage was 32.8%, 43.5% and 31.6%, respectively. Short course RT with delayed surgery was used as an alternative to chemoradiotherapy up to 2013 in 30.6% of patients over 80 years, and in 12.1% of patients with an ASA score > 2; these percentages increased to 45.8% and 19.9% in 2014, respectively. Specificity of MRI for N-stage decreased from 82.9% in 2009 to 62.9% in 2013, with an increase to 73.2% in 2014.ConclusionThe revised national guideline on colorectal cancer was rapidly implemented in the Netherlands with a substantial decrease in RT use for low risk resectable rectal cancer, and increased specificity of MRI for N-staging.



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Pyoderma gangrenosum avec anticorps anti-cytoplasme des neutrophiles de type anti-protéinase 3 (PR3-ANCA) induits par le propylthiouracile

Publication date: Available online 11 March 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): A. Coster, J.-L. Dargent, N. de Visscher, P. Levecque, P.-P. Roquet-Gravy
IntroductionLes antithyroïdiens de synthèse peuvent être responsables du développement d'anticorps anti-cytoplasme des neutrophiles (ANCA) et de vasculites liées à la présence de ces ANCA, ou de dermatoses neutrophiliques. Le propylthiouracile (PTU) est l'antithyroïdien de synthèse le plus souvent incriminé et ces ANCA sont surtout de type anti-myélopéroxydase (MPO-ANCA). À notre connaissance, aucune publication n'a rapporté d'association entre pyoderma gangrenosum (PG) et ANCA anti-protéinase 3 (PR3-ANCA) induits par le PTU.ObservationUne femme de 68 ans était traitée par du PTU pour un goitre multinodulaire toxique. Elle se présentait en raison d'une ulcération nécrotique étendue de la partie inférieure de l'abdomen. L'anamnèse, la clinique, les prélèvements bactériologiques et histologiques permettaient de poser le diagnostic de pyoderma gangrenosum. Celui-ci était accompagné d'ANCA de spécificité antigénique anti-protéinase 3. L'arrêt du PTU, associé à une courte cure de corticothérapie générale et de ciclosporine, permettait une résolution rapide et complète du pyoderma gangrenosum, parallèlement à une décroissance des ANCA. Aucune rechute n'était objectivée à un an de l'arrêt de tout traitement.DiscussionNous rapportons un cas de PG accompagné de PR3-ANCA induits par le PTU, en l'absence de toute vasculite démontrable.BackgroundSynthetic antithyroid drugs are often used in the treatment of hyperthyroidism, regardless of aetiology. They may cause various side effects, including the development of anti-neutrophil cytoplasmic antibodies (ANCA), ANCA-associated vasculitis, and neutrophilic dermatoses. Propylthiouracil (PTU) is the antithyroid drug most frequently implicated in ANCA-associated diseases specifically involving anti-myeloperoxidase ANCA (MPO-ANCA). To our knowledge, there are no clinical reports describing the association of pyoderma gangrenosum (PG) and anti-proteinase3-ANCA (PR3-ANCA) induced by PTU, with ANCA levels decreasing after antithyroid drug withdrawal.Patients and methodsA 68-year-old woman was treated with propylthiouracil (PTU) for toxic multinodular goitre. She presented necrotic ulceration of the lower abdomen. The patient's history, physical examination, and bacteriological and histological samples led to a diagnosis of pyoderma gangrenosum. This pyoderma involved ANCA with antigenic specificity for proteinase 3. Withdrawal of PTU and a short course of corticosteroids and cyclosporine resulted in rapid and complete resolution of the pyoderma gangrenosum as well as a decrease in ANCA. No relapse was observed one year after cessation of treatment.DiscussionWe report a case of PG associated with PR3-ANCA induced by PTU, without any demonstrable vasculitis.



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Bioinformatic approaches to interrogating vitamin D receptor signaling

Publication date: Available online 10 March 2017
Source:Molecular and Cellular Endocrinology
Author(s): Moray J. Campbell
Bioinformatics applies unbiased approaches to develop statistically-robust insight into health and disease. At the global, or "20,000 foot" view bioinformatic analyses of vitamin D receptor (NR1I1/VDR) signaling can measure where the VDR gene or protein exerts a genome-wide significant impact on biology; VDR is significantly implicated in bone biology and immune systems, but not in cancer. With a more VDR-centric, or "2000 foot" view, bioinformatic approaches can interrogate events downstream of VDR activity. Integrative approaches can combine VDR ChIP-Seq in cell systems where significant volumes of publically available data are available. For example, VDR ChIP-Seq studies can be combined with genome-wide association studies to reveal significant associations to immune phenotypes. Similarly, VDR ChIP-Seq can be combined with data from Cancer Genome Atlas (TCGA) to infer the impact of VDR target genes in cancer progression. Therefore, bioinformatic approaches can reveal what aspects of VDR downstream networks are significantly related to disease or phenotype.



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Restored Plasma Anandamide and Endometrial Expression of Fatty Acid Amide Hydrolase in Women With Polycystic Ovary Syndrome by the Combination Use of Diane-35 and Metformin

Publication date: Available online 11 March 2017
Source:Clinical Therapeutics
Author(s): Na Cui, Xiaoye Feng, Zhiming Zhao, Jie Zhang, Yueming Xu, Luning Wang, Guimin Hao
PurposePolycystic ovary syndrome (PCOS) is a metabolic and endocrinal disorder affecting a number of women of reproductive age. We aimed to reveal the correlation between the endocannabinoid system and PCOS, which may provide a new therapeutic target for PCOS treatment.MethodsSerum levels of anandamide and 2-arachidonoylglycerol andexpression of cannabinoid receptors and fatty acid amide hydrolase (FAAH) in the endometrium were compared between women with PCOS and infertile women without PCOS, as well as women with PCOS before and after treatment with Diane-35 and metformin. Cannabinoid receptors and FAAH in the endometrium were stained using the immunohistochemical method. Results were analyzed by calculating integrated optical density.FindingsPlasma anandamide was increased significantly in women with PCOS compared with infertile women without PCOS. Treatment with Diane-35 and metformin reversed this increase in women with PCOS. No significant difference in 2-arachidonoylglycerol was observed between the infertile women with or without PCOS. The women with PCOS had lower endometrial expression of FAAH compared with infertile women without PCOS, whereas no significant difference in endometrial expression of cannabinoid receptors was observed between the women with PCOS and infertile women without PCOS. We found that after treatment with Diane-35 and metformin, FAAH expression tended toward a significant increase compared with women before the treatment.ImplicationsEndocannabinoid system may be involved in the progression of PCOS, and serum anandamide could serve as a potential biomarker of clinical diagnosis of PCOS.



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A Real-world Cost-effectiveness Analysis of Sevelamer Versus Calcium Acetate in Korean Dialysis Patients

Publication date: Available online 11 March 2017
Source:Clinical Therapeutics
Author(s): Jang-Hee Cho, Hye Min Jang, Hee-Yeon Jung, Ji-Young Choi, Sun-Hee Park, Chan-Duck Kim, Chul Woo Yang, Dong-Chan Jin, Yong-Lim Kim
PurposeSevelamer, a noncalcium phosphate binder, has been shown to attenuate the progression of vascular calcification and improve survival in patients with chronic kidney disease undergoing dialysis compared with calcium-based binders. Using real-world data from a cohort study and the Health Insurance Review and Assessment Service database, we conducted a cost-effectiveness analysis comparing sevelamer with calcium acetate in dialysis patients from the perspective of the National Health Insurance Service in South Korea.MethodsData (demographic, diagnostic, laboratory, and survival) from 4674 patients undergoing dialysis enrolled in a multicenter prospective cohort study conducted in South Korea between September 2008 and December 2012 were linked to phosphate binder use, hospitalization, and cost data available from the Health Insurance Review and Assessment Service database. After propensity score matching, a dataset comprising comparable patients treated with either sevelamer (n = 501) or calcium acetate (n = 501) was used in the cost-effectiveness analysis. A Markov model was used to estimate costs, life years, quality-adjusted life years (QALYs), and cost-effectiveness over each patient's lifetime. Forty-month treatment-specific overall survival (OS) data available from the dataset were extrapolated to lifetime survival with the use of regression analysis.FindingsPatients had a mean age of 56.3 years and were treated with dialysis for a mean duration of 67.6 months. Compared with calcium acetate, sevelamer was associated with an incremental cost of South Korean Won (₩) 12,246,911 ($10,819) and a gain of 1.758 life years and 1.108 QALYs per patient. This outcome yielded incremental cost-effectiveness ratios of ₩6,966,350 ($6154) and ₩11,057,699 ($9768) per life year and QALY gained, respectively. Conclusions regarding sevelamer's cost-effectiveness were insensitive to alternative assumptions in time horizon, discount rate, hospitalization rate, costs, and health utility estimates, and they remained consistent in 100% of the model iterations, considering a willingness-to-pay threshold of ₩31,894,720 ($28,176) per QALY gained.ImplicationsThis analysis of real-world data found that sevelamer's higher cost relative to calcium acetate was adequately offset by improved survival among patients undergoing dialysis in South Korea. As such, sevelamer offers good value for money, representing a cost-effective alternative to calcium-based binders.



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Health professional feedback on HPV vaccination roll-out in a developing country

Publication date: Available online 11 March 2017
Source:Vaccine
Author(s): Collette Venturas, Kanayo Umeh
BackgroundWorldwide, Zambia has the highest cervical cancer incidence rates (58.4/100,000 per year) and mortality rates (36.2/100,000 per year). The human papilloma virus (HPV) vaccine is considered a vital preventative measure against cervical cancer, particularly in sub-Saharan countries, such as Zambia. Past research suggests health professionals' experiences with HPV vaccination rollout can have practical implications for effective delivery.ObjectiveTo explore health professionals' perspectives on the HPV vaccination programme in Zambia.MethodsResearcher travelled to Zambia and conducted semi-structured interviews with fifteen health professionals working in private, government, and missionary clinics/hospitals. Observation was conducted for triangulation purposes. Thematic analysis was used to analyse the data.FindingsFive main themes emerged; medical misconceptions about the HPV vaccination, particularly with regards to infertility; fear of the unknown, including possible side effects and inadequate empirical research; need for prior desensitisation to resolve cultural barriers prior to vaccination rollout; a rural-urban divide in health awareness, particularly in relation to cancer vaccines; and economic concerns associated with access to the HPV vaccination for most of the Zambian population.ConclusionOverall, the findings indicate that an essential avenue for facilitating HPV vaccination rollout in Zambia is by implementing a pre-rollout community effort that removes or softens cultural barriers, particularly in rural areas. It is also essential to correct erroneous HPV presumptions health professionals may have around infertility. Affordability remains a seemingly intractable hindrance that hampers HPV vaccination rollout in Zambia.



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Does seasonal vaccination affect the clinical presentation of influenza among the elderly? A cross-sectional analysis in the outpatient setting in France, 2003–2014

Publication date: Available online 11 March 2017
Source:Vaccine
Author(s): Anne Mosnier, Isabelle Daviaud, Saverio Caini, Hervé Berche, Jean-Michel Mansuy, Sylvie van der Werf, Jean Marie Cohen, Bruno Lina
Vaccine-induced protection against influenza is not optimal, however it has been suggested that the vaccine may reduce the severity of symptoms among those who develop illness despite being vaccinated. We tested this hypothesis within a countrywide, sentinel general practitioners-based surveillance system in France. We included 2277 individuals aged 65years or older (of whom 1293 had been vaccinated against influenza, 56.8%) who consulted a general practitioner because of an acute respiratory infection (ARI) during 2003–2014. All patients were taken a nasopharyngeal swab, and information was collected on demographic characteristics and symptoms at disease onset. All specimens were tested for respiratory viruses and, if positive for influenza, the virus type and subtype were determined. We compared the average maximum temperature and the frequency of each symptom, between non-vaccinated and vaccinated influenza patients. We then used logistic regression models to calculate the odds of presenting with each symptom between vaccinated vs. non-vaccinated patients, adjusting by age group, virus (sub)type and season. Overall, 675 ARI patients (29.6%) tested positive for influenza. The A(H3) virus caused the majority of cases (55.1%), followed by influenza B (22.9%), A not-subtyped (11.7%), and A(H1) (10.3%) viruses. Compared to non-vaccinated influenza patients, those who had been vaccinated had a slightly reduced maximum temperature and presented less frequently with myalgia, shivering and headache. In stratified analyses, the observed effect was limited to patients infected with A(H3) or type B viruses. After adjusting by age group, virus (sub)type and season, the difference remained statistically significant only for headache, which was less frequent among vaccinated individuals (odds ratio 0.69, 95% confidence intervals 0.48–0.98). In conclusion, the vaccine was found to be modestly associated with less severe clinical presentation of influenza among the elderly. Our findings reinforce the need for influenza vaccines providing better protection.



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Combining stable insect cell lines with baculovirus-mediated expression for multi-HA influenza VLP production

Publication date: Available online 11 March 2017
Source:Vaccine
Author(s): Daniela P. Sequeira, Ricardo Correia, Manuel J.T. Carrondo, António Roldão, Ana P. Teixeira, Paula M. Alves
Safer and broadly protective vaccines are needed to cope with the continuous evolution of circulating influenza virus strains and promising approaches based on the expression of multiple hemagglutinins (HA) in a virus-like particle (VLP) have been proposed. However, expression of multiple genes in the same vector can lead to its instability due to tandem repetition of similar sequences. By combining stable with transient expression systems we can rationally distribute the number of genes to be expressed per platform and thus mitigate this risk. In this work, we developed a modular system comprising stable and baculovirus-mediated expression in insect cells for production of multi-HA influenza enveloped VLPs. First, a stable insect High Five cell population expressing two different HA proteins from subtype H3 was established. Infection of this cell population with a baculovirus vector encoding three other HA proteins from H3 subtype proved to be as competitive as traditional co-infection approaches in producing a pentavalent H3 VLP. Aiming at increasing HA expression, the stable insect cell population was infected at increasingly higher cell concentrations (CCI). However, cultures infected at CCI of 3×10⁶cells/mL showed lower HA titers per cell in comparison to standard CCI of 2×10⁶cells/mL, a phenomenon named "cell density effect". To lessen the negative impact of this phenomenon, a tailor-made refeed strategy was designed based on the exhaustion of key nutrients during cell growth. Noteworthy, cultures supplemented and infected at a CCI of 4×10⁶cells/mL showed comparable HA titers per cell to those of CCI of 2×10⁶cells/mL, thus leading to an increase of up to 4-fold in HA titers per mL. Scalability of the modular strategy herein proposed was successfully demonstrated in 2L stirred tank bioreactors with comparable HA protein levels observed between bioreactor and shake flasks cultures. Overall, this work demonstrates the suitability of combining stable with baculovirus-mediated expression in insect cells as an efficient platform for production of multi-HA influenza VLPs, surpassing the drawbacks of traditional co-infection strategies and/or the use of larger, unstable vectors.



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Low-dose aspirin use and survival in breast cancer patients: A nationwide cohort study

Publication date: Available online 11 March 2017
Source:Cancer Epidemiology
Author(s): Úna Mc Menamin, Chris Cardwell, Carmel Hughes, Liam Murray




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Assessment for the impact of dust events on measles incidence in western China

Publication date: May 2017
Source:Atmospheric Environment, Volume 157
Author(s): Yuxia Ma, Jianding Zhou, Sixu Yang, Yuxin Zhao, Xiaodong Zheng
Dust events affect human health in both drylands and downwind environments. In this study, we used county-level data during the period of 1965–2005 to assess the impact of dust events on measles incidence in Gansu province in Western China. We used Fast Fourier Transform (FFT) to set up the cyclical regression model; in particular, we set the model to downwind direction for the typical cities in the Hexi Corridor as well as the capital city Lanzhou. The results showed that Spring measles incidence was the highest in the Hexi Corridor, where dust events occur the most frequently over Gansu province. Measles incidence declined on the pathway of dust storms from west to east due to the weakening of both intensity and duration in dust storms. Measles incidence was positively correlated with monthly wind speed and negatively correlated with rainfall amount, relative humidity, and air pressure. Measles incidence was significantly (p ≤ 0.01) positively correlated with daily coarse particles, e.g., TSP and PM10. According to the cyclical regression model, average monthly excess measles that is related to dust events was 39.1 (ranging from 17.3 to 87.6), 149.9 (ranging from 7.1 to 413.4), and 31.3 (ranging from 20.6 to 63.5) in Zhangye, Lanzhou, and Jiuquan, respectively.



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Factors controlling particle number concentration and size at metro stations

Publication date: May 2017
Source:Atmospheric Environment, Volume 156
Author(s): C. Reche, T. Moreno, V. Martins, M.C. Minguillón, T. Jones, E. de Miguel, M. Capdevila, S. Centelles, X. Querol
An extensive air quality campaign was performed at differently designed station platforms in the Barcelona metro system, aiming to investigate the factors governing airborne particle number (N) concentrations and their size distributions. The study of the daily trends of N concentrations by different size ranges shows that concentrations of N0.3–10 are closely related with the schedule of the metro service. Conversely, the hourly variation of N0.007–10 (mainly composed of ultrafine particles) could be partly governed by the entrance of particles from outdoor emissions through mechanical ventilation. Measurements under different ventilation settings at three metro platforms reveal that the effect on air quality linked to changes in the tunnel ventilation depends on the station design. Night-time maintenance works in tunnels are frequent activities in the metro system; and after intense prolonged works, these can result in higher N concentrations at platforms during the following metro operating hours (by up to 30%), this being especially evident for N1–10. Due to the complex mixture of factors controlling N, together with the differences in trends recorded for particles within different size ranges, developing an air quality strategy at metro systems is a great challenge. When compared to street-level urban particles concentrations, the priority in metro air quality should be dealing with particles coarser than 0.3 μm. In fact, the results suggest that at narrow platforms served by single-track tunnels the current forced tunnel ventilation during operating hours is less efficient in reducing coarse particles compared to fine.



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Targeted exome sequencing and chromosomal microarray for the molecular diagnosis of nevoid basal cell carcinoma syndrome

Publication date: Available online 11 March 2017
Source:Journal of Dermatological Science
Author(s): Yoshihiro Matsudate, Takuya Naruto, Yumiko Hayashi, Mitsuyoshi Minami, Mikiko Tohyama, Kenji Yokota, Daisuke Yamada, Issei Imoto, Yoshiaki Kubo
BackgroundNevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder mainly caused by heterozygous mutations of PTCH1. In addition to characteristic clinical features, detection of a mutation in causative genes is reliable for the diagnosis of NBCCS; however, no mutations have been identified in some patients using conventional methods.ObjectiveTo improve the method for the molecular diagnosis of NBCCS.MethodsWe performed targeted exome sequencing (TES) analysis using a multi-gene panel, including PTCH1, PTCH2, SUFU, and other sonic hedgehog signaling pathway-related genes, based on next-generation sequencing (NGS) technology in 8 cases in whom possible causative mutations were not detected by previously performed conventional analysis and 2 recent cases of NBCCS. Subsequent analysis of gross deletion within or around PTCH1 detected by TES was performed using chromosomal microarray (CMA).ResultsThrough TES analysis, specific single nucleotide variants or small indels of PTCH1 causing inferred amino acid changes were identified in 2 novel cases and 2 undiagnosed cases, whereas gross deletions within or around PTCH1, which are validated by CMA, were found in 3 undiagnosed cases. However, no mutations were detected even by TES in 3 cases. Among 3 cases with gross deletions of PTCH1, deletions containing the entire PTCH1 and additional neighboring genes was detected in 2 cases, one of which exhibited atypical clinical features, such as severe mental retardation, likely associated with genes located within the 4.3 Mb deleted region, especially.ConclusionTES-based, simultaneous evaluation of sequences and copy number status in all targeted coding exons by NGS is likely to be more useful for the molecular diagnosis of NBCCS than conventional methods. CMA is recommended as a subsequent analysis for validation and detailed mapping of deleted regions, which may explain the atypical clinical features of NBCCS cases.



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Topical application of Glycolic acid suppresses the UVB induced IL-6, IL-8, MCP-1 and COX-2 inflammation by modulating NF-κB signaling pathway in keratinocytes and mice skin

Publication date: Available online 11 March 2017
Source:Journal of Dermatological Science
Author(s): Sheau-Chung Tang, Pei-Yun Liao, Sung-Jen Hung, Jheng-Siang Ge, Shiou-Mei Chen, Ji-Ching Lai, Yu-Ping Hsiao, Jen-Hung Yang
BackgroundGlycolic acid (GA), commonly present in fruits, has been used to treat dermatological diseases. Extensive exposure to solar ultraviolet B (UVB) irradiation plays a crucial role in the induction of skin inflammation. The development of photo prevention from natural materials represents an effective strategy for skin keratinocytes.ObjectiveThe aim of this study was to investigate the molecular mechanisms underlying the glycolic acid (GA)-induced reduction of UVB-mediated inflammatory responses.MethodsWe determined the effects of different concentrations of GA on the inflammatory response of human keratinocytes HaCaT cells and C57BL/6J mice dorsal skin. After GA was topically applied, HaCaT and mice skin were exposed to UVB irradiation.ResultsGA reduced the production of UVB-induced nuclear factor kappa B (NF-κB)-dependent inflammatory mediators [interleukin (IL)-1β, IL-6, IL-8, cyclooxygenase (COX)-2, tumor necrosis factor-α, and monocyte chemoattractant protein (MCP-1)] at both mRNA and protein levels. GA inhibited the UVB-induced promoter activity of NF-κB in HaCaT cells. GA attenuated the elevation of senescence associated with β-galactosidase activity but did not affect the wound migration ability. The topical application of GA inhibited the genes expression of IL-1β, IL-6, IL-8, COX-2, and MCP-1 in UVB-exposed mouse skin. The mice to UVB irradiation after GA was topically applied for 9 consecutive days and reported that 1%–1.5% of GA exerted anti-inflammatory effects on mouse skin.ConclusionWe clarified the molecular mechanism of GA protection against UVB-induced inflammation by modulating NF-κB signaling pathways and determined the optimal concentration of GA in mice skin exposed to UVB irradiation.

Graphical abstract

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Ultraviolet B inhibition of DNMT1 activity via AhR activation dependent SIRT1 suppression in CD4+ T cells from systemic lupus erythematosus patients

Publication date: Available online 10 March 2017
Source:Journal of Dermatological Science
Author(s): Zhouwei Wu, Xingyu Mei, Zuolin Ying, Yue Sun, Jun Song, Weimin Shi
BackgroundPrevious studies have reported that ultraviolet B (UVB) inhibits DNA methyltransferase1 (DNMT1) activity in CD4+ T cells from systemic lupus erythematosus (SLE) patients. Silent mating type information regulation 2 homolog 1 (SIRT1) is a type of Class III histone deacetylases (HDACs), and has been reported to play roles in the pathogenesis of different autoimmune diseases and can modulate DNMT1 activity. Moreover, aryl hydrocarbon receptor (AhR) has been reported to link UVB with SLE. However, the exact mechanisms by which DNMT1 activity is inhibited by UVB in lupus CD4+ T cells remain largely unknown.ObjectiveTo elucidate the exact mechanisms by which DNMT1 activity is inhibited by UVB in lupus CD4+ T cells.MethodsTwenty-two newly diagnosed active SLE patients and 30 healthy controls were enrolled in the study. CD4+ T cells were isolated, cultured and treated. DNMT1 activity assay, quantitative real-time PCR (qRT-PCR), Western blotting, RNA interference using small interfering RNA and Chromatin Immunoprecipitation (ChIP) assay were employed.ResultsDNMT1 activity was inhibited in si-SIRT1-transfected CD4+ T cells, and increased by the established SIRT1 activator, SRT1720. Moreover, the mRNA and protein expression of SIRT1 were suppressed by UVB exposure in lupus CD4+ T cells. UVB-inhibited DNMT1 activity was reversed by SRT1720 in si-control-transfected lupus CD4+ T cells, but not in si-SIRT1-transfected lupus CD4 + T cells. Furthermore, AhR activation by VAF347 reduced the mRNA and protein expression of SIRT1. ChIP using an antibody against AhR in normal CD4+ T cells revealed a 16-fold stronger signal at the site about 1.6kb upstream from the translation start site of the SIRT1 promoter. Finally, UVB could activate AhR and inhibit the mRNA and protein expression of SIRT1. AhR knockdown abrogated the inhibition of UVB-mediated SIRT1 mRNA and protein expression and DNMT1 activity in lupus CD4+ T cells.ConclusionUVB suppressed SIRT1 expression via activating AhR, and subsequently inhibited DNMT1 activity in CD4+ T cells from SLE patients.



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Agrimonia pilosa leaf extract accelerates skin barrier restoration by activation of transient receptor potential vanilloid 3

Publication date: Available online 10 March 2017
Source:Journal of Dermatological Science
Author(s): Yu-Ran Nam, Hyun Jong Kim, Young-Mi Kim, Young-Won Chin, Hyo Sang Bae, Woo Kyung Kim, Joo Hyun Nama




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A possible role for CD26/DPPIV enzyme activity in the regulation of psoriatic pruritus

Publication date: Available online 10 March 2017
Source:Journal of Dermatological Science
Author(s): Eriko Komiya, Ryo Hatano, Haruna Otsuka, Takumi Itoh, Hiroto Yamazaki, Taketo Yamada, Nam H. Dang, Mitsutoshi Tominaga, Yasushi Suga, Utako Kimura, Kenji Takamori, Chikao Morimoto, Kei Ohnuma
BackgroundPsoriasis (PSO) is one of the most common chronic inflammatory skin diseases, and pruritus affects approximately 60-90% of patients with PSO. However, the pathogenesis of pruritus in PSO remains unclear. Dipeptidyl peptidase IV (DPPIV) enzyme activity is involved in the regulation of peptide hormones, chemokines and neurotransmitters.ObjectivesOur aim is to evaluate for a potential association between DPPIV and an increased risk of pruritus, and to identify possible underlying treatment targets in affected patients.Methodsutilizing clinical serum samples of PSO patients and in vivo experimental pruritus models, we evaluated for a potential association between DPPIV and an increased risk for pruritus, and attempted to identify possible underlying treatment targets in pruritus of PSO.ResultsWe first showed that levels of DPPIV enzyme activity in sera of patients with PSO were significantly increased compared to those of healthy controls. We next evaluated levels of substance-P (SP), which is a neurotransmitter for pruritus and a substrate for DPPIV enzyme. Truncated form SP cleaved by DPPIV was significantly increased in sera of PSO. In an in vivo pruritus model induced by SP, scratching was decreased by treatment with a DPPIV inhibitor. Moreover, DPPIV-knockout mice showed attenuation of scratching induced by SP. Finally, scratching was decreased following the administration of a DPPIV inhibitor in an imiquimod-induced PSO model. On the other hand, scratching induced by imiquimod was increased in DPPIV overexpressing-mice.ConclusionsThese results suggest that inhibition of DPPIV enzyme activity regulates pruritus in PSO.



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With the Help of MOM: Mitochondrial Contributions to Cellular Quality Control

Publication date: Available online 11 March 2017
Source:Trends in Cell Biology
Author(s): Ralf J. Braun, Benedikt Westermann
Mitochondria are essential organelles because they have key roles in cellular energy metabolism and many other metabolic pathways. Several quality control systems have evolved to ensure that dysfunctional mitochondria are either repaired or eliminated. The activities of these pathways are crucial for cellular health because they maintain functional mitochondria. In addition, the cytosolic ubiquitin–proteasome system (UPS) and the mitochondria-associated degradation pathway (MAD) share some of their core components, are functionally tightly interconnected, and mutually modulate their activities. Thus, the mitochondrial outer membrane (MOM) actively supports quality control systems in extramitochondrial compartments. Furthermore, mitochondrial quality surveillance systems also act on cytosolic or endoplasmic reticulum (ER) substrates and modulate immune responses. Therefore, mitochondria contribute to cellular quality control and homeostasis on several levels.



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Identification of carbamylated alpha 1 anti-trypsin (A1AT) as an antigenic target of anti-CarP antibodies in patients with rheumatoid arthritis

Publication date: Available online 11 March 2017
Source:Journal of Autoimmunity
Author(s): Marije K. Verheul, Alvin Yee, Andrea Seaman, George M. Janssen, Peter A. van Veelen, Jan W. Drijfhout, Rene E.M. Toes, Michael Mahler, Leendert A. Trouw
In 2011 a novel autoantibody system, anti-carbamylated protein (anti-CarP) antibodies, was described in rheumatoid arthritis (RA) patients. Anti-CarP antibody positivity associates with a more severe disease course, is observed years before disease onset, and may predict the development of RA in arthralgia patients. Although many clinical observations have been carried out, information on the antigenic targets of anti-CarP antibodies is limited. Most studies on anti-CarP antibodies utilize an ELISA-based assay with carbamylated fetal calf serum (Ca-FCS) as antigen, a complex mixture of proteins. Therefore, we analysed the molecular identity of proteins within Ca-FCS that are recognized by anti-CarP antibodies.Ca-FCS was fractionated using ion exchange chromatography, selecting one of the fractions for further investigation. Using mass-spectrometry, carbamylated alpha-1-antitrypsin (Ca-A1AT) was identified as a potential antigenic target of anti-CarP antibodies in RA patients. A1AT contains several lysines on the protein surface that can readily be carbamylated.A large proportion of the RA patients harbour antibodies that bind human Ca-A1AT in ELISA, indicating that Ca-A1AT is indeed an autoantigen for anti-CarP antibodies. Next to the Ca-A1AT protein, several homocitrulline-containing peptides of A1AT were recognized by RA sera. Moreover, we identified a carbamylated peptide of A1AT in the synovial fluid of an RA patient using mass spectrometry.We conclude that Ca-A1AT is not only a target of anti-CarP antibodies but is also present in the synovial compartment, suggesting that Ca-A1AT recognized by anti-CarP antibodies in the joint may contribute to synovial inflammation in anti-CarP-positive RA.



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