Σάββατο 31 Δεκεμβρίου 2016

Advances in the controlled polymerization of conjugated polymers

Publication date: 13 January 2017
Source:Polymer, Volume 108
Author(s): Lize Verheyen, Pieter Leysen, Marie-Paule Van Den Eede, Ward Ceunen, Tine Hardeman, Guy Koeckelberghs
This article features recent advances in the synthesis of conjugated polymers via a controlled polymerization. These polymerizations typically rely on transition metal catalyzed cross coupling reactions. The mechanisms of the polymerization protocols are discussed in detail. An overview of all possible protocols and all homopolymers that have been investigated is given. Next, the synthesis of copolymers - random, gradient and block copolymers - is reviewed. Another advantage of a controlled polymerization is the possibility to introduce specific functional groups, either at the beginning of each polymer chain by the use of an external initiator, or at the end of the polymer chain using an endcapper. Finally, topologies different from simple linear polymer chains are discussed. This feature article is complementary to other recent review articles on this topic.[1,2]

Graphical abstract

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Graphical Contents list & Author index

Publication date: 13 January 2017
Source:Polymer, Volume 108





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Editorial board

Publication date: 13 January 2017
Source:Polymer, Volume 108





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Welcome to the first issue of polymer for 2017!

Publication date: 13 January 2017
Source:Polymer, Volume 108
Author(s): Rumen Duhlev




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Parameter Determination Using 3D FIB-SEM Images for Development of Effective Model of Shale Gas Flow in Nanoscale Pore Clusters

Abstract

A large amount of nano-pores exists in pore clusters in shale gas reservoirs. In addition to the multiple transport regimes that occur on the nanoscale, the pore space is another major factor that significantly affects the shale gas recoverability. An investigation of the pore-scale shale gas flow is therefore important, and the results can be used to develop an effective cluster-scale pore network model for the convenient examination of the process efficiency. Focused ion beam scanning electron microscope imaging, which enables the acquisition of nanometre-resolution images that facilitate nano-pore identification, was used in conjunction with a high-precision pore network extraction algorithm to generate the equivalent pore network for the simulation of Darcy and shale gas flows through the pores. The characteristic parameters of the pores and the gas transport features were determined and analysed to obtain a deeper understanding of shale gas flow through nanoscale pore clusters, such as the importance of the throat flux–radius distribution and the variation of the tortuosity with pressure. The best parameter scheme for the proposed effective model of shale gas flow was selected out of three derived schemes based on the pore-scale prediction results. The model is applicable to pore-scale to cluster-scale shale gas flows and can be used to avoid the multiple-solution problems in the study of gas flows. It affords a foundation for further study to develop models for shale gas flows on larger scales.



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A novel presenilin 1 mutation (F388L) identified in a Chinese family with early-onset Alzheimer's disease

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Yihong Zhan, Honghua Zheng, Chen Wang, Zhouyi Rong, Naian Xiao, Qilin Ma, Yun-wu Zhang
A subset of Alzheimer's disease (AD) occurrence shows autosomal dominant, familial inheritance patterns. Such familial AD (FAD) are caused by mutations in APP, PSEN1, and PSEN2 genes, which encode amyloid-β (Aβ) precursor protein, presenilin 1 (PS1), and presenilin 2 (PS2), respectively. Here, we report a novel PSEN1 mutation (c.1164C > G, p.F388L, mutation nomenclature according to National Center for Biotechnology Information Reference Sequence: NM_000021.3) occurring in a Chinese family with early-onset AD and cosegregating with affected family members. The average age at onset of this family was 43 years. The F388L mutation locates adjacent to the critical catalytic aspartate site (D385) of PS1. Overexpression of the F388L mutant significantly increased Aβ42 secretion and the ratio of Aβ42/Aβ40 when compared with wild type PS1, consisting with the notion that FAD-associated PS1 mutations induce disease pathogenesis by increasing Aβ42/Aβ40 ratio. Our results identify a novel pathogenic PS1 F388L mutation in a Chinese FAD family.



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Acute otitis media with spontaneous tympanic membrane perforation

Abstract

The principal aim of this review is to present the current knowledge regarding acute otitis media (AOM) with spontaneous tympanic membrane perforation (STMP) and to address the question of whether AOM with STMP is a disease with specific characteristics or a severe case of AOM. PubMed was used to search for all studies published over the past 15 years using the key words "acute otitis media" and "othorrea" or "spontaneous tympanic membrane perforation". More than 250 articles were found, but only those published in English and providing data on aspects related to perforation of infectious origin were considered. Early Streptococcus pneumoniae infection due to invasive pneumococcal strains, in addition to coinfections and biofilm production due mainly to non-typeable Haemophilus influenzae, seem to be precursors of STMP. However, it is unclear why some children have several STMP episodes during the first years of life that resolve without complications in adulthood, whereas other children develop chronic suppurative otitis media. Although specific aetiological agents appear to be associated with an increased risk of AOM with STMP, further studies are needed to determine whether AOM with STMP is a distinct disease with specific aetiological, clinical and prognostic characteristics or a more severe case of AOM than the cases that occur without STMP. Finally, it is important to identify preventive methods that are useful not only in otitis-prone children with uncomplicated AOM, but also in children with recurrent AOM and those who experience several episodes with STMP.



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Contents continued

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50





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Biology enters the scene—a new perspective on bilingualism, cognition, and dementia

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Thomas H. Bak, Ian Robertson
The question of whether bilingualism can influence cognitive functions in healthy aging as well as in brain diseases is currently a topic of an intense debate. In a study published in this issue of the "Neurobiology of Ageing", Estanga et al. are breaking new ground by combining cognitive and biological approaches. Based on the data from the Guipuzkoa Alzheimer Project, they report that, compared with monolinguals, early bilinguals are not only characterized by a better cognitive performance in several domains and a lower prevalence of Alzheimer's disease but also by lower levels of t-tau in their cerebrospinal fluid. We suggest that sustained activation of noradrenergic signaling pathways associated with bilingualism could provide a possible mechanism linking results of this study with previous observations of delayed onset of dementia in bilinguals.



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Brain tau deposition linked to systemic causes of death in normal elderly

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Keith A. Josephs, Nirubol Tosakulwong, Stephen D. Weigand, Melissa E. Murray, Jennifer L. Whitwell, Joseph E. Parisi, Dennis W. Dickson, Ronald C. Petersen
The relationship between causes of death and 4 major neurodegenerative brain proteins (beta-amyloid, tau, alpha-synuclein, and the TAR DNA-binding protein of 43 kDa (TDP-43) were assessed in 94 cognitively normal elderly participants that died without a neurodegenerative disease. There was an association between tau and causes of death (p = 0.01). Tau in the brain was associated with a reduced likelihood of dying from systemic cancers (p = 0.046), and with an increased likelihood of dying from pulmonary (p = 0.03) and gastrointestinal (p = 0.049) diseases. There were no associations between beta-amyloid, alpha-synuclein, or TDP-43 and causes of death. Tau deposition in the brain may have a relationship with systemic causes of death, including cancer, in the cognitively normal elderly.



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Novel presenilin 1 mutation (p.F386I) in a Chinese family with early-onset Alzheimer's disease

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Yat-Fung Shea, Angel On-Kei Chan, Leung-Wing Chu, Shui-Ching Lee, Chun-yin Law, Chung-him See, Kit-ling Yiu, Patrick Ka-Chun Chiu
Autosomal dominant familial Alzheimer's disease accounts for 0.5% of all Alzheimer's disease. A familial Alzheimer's disease Chinese family, with 7 affected family members, underwent PSEN1 screening in 3 affected family members. A heterozygous novel missense mutation in the PSEN1 gene c.1156T>A, altering phenylalanine to isoleucine at codon 386, was identified. Because the change occurred in conserved domains of this gene and cosegregated with affected family members, this change may have a mutagenic and probably pathogenic effect.



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Editorial Advisory Board

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50





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Lack of RAB39B mutations in early-onset and familial Parkinson's disease in a Taiwanese cohort

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Hsien-Han Lin, Ruey-Meei Wu, Han-I. Lin, Meng-Ling Chen, Chun-Hwei Tai, Chin-Hsien Lin
Loss of function mutations in RAB39B were recently linked to X-linked recessive early-onset Parkinsonism with variable degrees of intellectual dysfunction. Postmortem examination of the brain biopsy from a patient carrying the gene deletion revealed widespread α-synuclein pathology. However, subsequent analyses reported conflict results to replicate the role of RAB39B mutations in patients with early-onset Parkinsonism. The aim of this study was to address the genetic contribution of RAB39B in early-onset and familial Parkinson's disease (PD) in a Taiwanese population. Among 466 subjects, we sequenced both the exons and exon-intron boundaries of RAB39B from 235 patients with early-onset PD (age of onset <50 years), 119 probands with familial PD, and 112 ethnicity-matched control subjects. We did not find any coding variants or previously reported mutations, suggesting that RAB39B mutations are not a common cause of early-onset or familial PD in our Taiwanese population.



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Analysis of CHCHD2 gene in familial Parkinson's disease from Calabria

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Monica Gagliardi, Grazia Iannello, Carmela Colica, Grazia Annesi, Aldo Quattrone
Parkinson's disease (PD) is the most common form of degenerative Parkinsonism with a prevalence of 1% of those older than 65 years. PD is characterized by the combination of slowness of movement (bradykinesia), muscular rigidity, resting tremor, and postural instability. Recently, using a genome-wide linkage analysis and exome sequencing, a group identified a candidate gene (CHCHD2) in a large Japanese family with autosomal dominant Parkinson's disease. The aim of this study was to evaluate the presence of CHCHD2 mutations in a cohort of 165 familial patients with clinically diagnosed PD and 200 control subjects from South Italy. No mutations in CHCHD2 were found in our 165 PD patients. This result suggests that CHCHD2 mutations might not be the common cause of PD in South Italy.



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Genetic and functional analysis of TBK1 variants in Korean patients with sporadic amyotrophic lateral sclerosis

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Young-Eun Kim, Ki-Wook Oh, Min-Young Noh, Minyeop Nahm, Jinseok Park, Su Min Lim, Ja-Hyun Jang, Eun-Hae Cho, Chang-Seok Ki, Seungbok Lee, Seung Hyun Kim
The TANK-binding kinase 1 (TBK1) gene has recently been identified as a novel causative gene of amyotrophic lateral sclerosis (ALS). This study aims to determine the frequency and spectrum of TBK1 variants and their functional implications in Korean patients with sporadic ALS (sALS). TBK1 sequences were analyzed in 129 consecutive patients with sALS using either multigene panel or exome sequencing. One frameshift (c.1414delA) and 3 missense variants of uncertain significance in TBK1 were found in 4 patients each. In vitro functional studies revealed that the c.1414delA (p.Ile472Serfs*8) variant was associated with reduced mRNA expression of TBK1. Moreover, protein expression of this variant in patient-derived fibroblasts disrupted binding to autophagy adapter proteins and inhibited the function of TBK1 in HEK293T cells. In contrast, the 3 other missense variants of uncertain significance showed normal mRNA expression and no abnormalities in protein function. Based on these findings, the frequency of pathogenic TBK1 variants in Korean sALS patients was estimated to be 0.8% (1/129). In conclusion, pathogenic variants in TBK1 are rare but could be responsible for sALS in a small number of Korean patients.



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Genetic analysis of CHCHD2 in a southern Spanish population

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Cristina Tejera-Parrado, Silvia Jesús, Ismael Huertas-Fernández, Inmaculada Bernal-Bernal, Marta Bonilla-Toribio, Isabel Córdoba-Tevar, Irene Abreu-Rodríguez, Fátima Carrillo, Maravilla Bernal-Escudero, Laura Vargas-González, Manuel Carballo, Pilar Gómez-Garre, Pablo Mir
Researching genetic factors involved in Parkinson's disease (PD) is crucial to increase our knowledge about the pathophysiology of the disorder. A missense mutation has recently been reported within CHCHD2, a gene newly associated with autosomal dominant PD. Subsequent studies in different ethnic populations have not reached any conclusive result about the role of CHCHD2 in PD. Therefore, the aim of this study was to investigate the implication of this gene for a PD population from southern Spain (including 536 PD patients and 518 unrelated control subjects). We studied all 4 exons of CHCHD2 and their exon-intron boundary regions. Four variants were observed in non-coding regions. No significant differences were observed in the allele frequencies of these variants between patients and controls. Thus, our study suggests that CHCHD2 is probably not involved in the etiopathogenesis of PD in our population.



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SNCA mutation p.Ala53Glu is derived from a common founder in the Finnish population

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Petra Pasanen, Eino Palin, Risto Pohjolan-Pirhonen, Minna Pöyhönen, Juha O. Rinne, Markku Päivärinta, Mika H. Martikainen, Valtteri Kaasinen, Marja Hietala, Maria Gardberg, Anna Maija Saukkonen, Johanna Eerola-Rautio, Seppo Kaakkola, Jukka Lyytinen, Pentti J. Tienari, Anders Paetau, Anu Suomalainen, Liisa Myllykangas
Mutations in SNCA are rare causes of familial Parkinson's disease (PD). We have previously described a novel p.Ala53Glu mutation in 2 Finnish families. To assess this mutation's frequency among Finnish PD patients, we screened 110 PD patients (mean age-of-onset 60 years) from Western Finland by Sanger sequencing of the third coding exon of SNCA. In addition, a sample of 47 PD subjects (mean age-of-onset 53 years) originating from Southern and Eastern Finland were studied using next-generation sequencing covering SNCA. Only one new individual with the p.Ala53Glu mutation was identified, confirming that this mutation is a rare cause of PD in the Finnish population. To search for a possible common origin of the p.Ala53Glu mutation, haplotype analysis was conducted in 2 families and in a patient from a third family (6 affected subjects) using both STR markers and a genome-wide SNP array. The results show that patients with the p.Ala53Glu mutation share a haplotype spanning a minimum of 5.7 Mb suggesting a common founder.



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Lack of evidence for a role of genetic variation in TMEM230 in the risk for Parkinson's disease in the Caucasian population

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Anamika Giri, Kin Y. Mok, Iris Jansen, Manu Sharma, Christelle Tesson, Graziella Mangone, Suzanne Lesage, José M. Bras, Joshua M. Shulman, Una-Marie Sheerin, Mónica Díez-Fairen, Pau Pastor, María José Martí, Mario Ezquerra, Eduardo Tolosa, Leonor Correia-Guedes, Joaquim Ferreira, Najaf Amin, Cornelia M. van Duijn, Jeroen van Rooij, André G. Uitterlinden, Robert Kraaij, Michael Nalls, Javier Simón-Sánchez
Mutations in TMEM230 have recently been associated to Parkinson's disease (PD). To further understand the role of this gene in the Caucasian population, we interrogated our large repository of next generation sequencing data from unrelated PD cases and controls, as well as multiplex families with autosomal dominant PD. We identified 2 heterozygous missense variants in 2 unrelated PD cases and not in our control database (p.Y106H and p.I162V), and a heterozygous missense variant in 2 PD cases from the same family (p.A163T). However, data presented herein is not sufficient to support the role of any of these variants in PD pathology. A series of unified sequence kernel association tests also failed to show a cumulative effect of rare variation in this gene on the risk of PD in the general Caucasian population. Further evaluation of genetic data from different populations is needed to understand the genetic role of TMEM230 in PD etiology.



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Beneficial effect of bilingualism on Alzheimer's disease CSF biomarkers and cognition

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Ainara Estanga, Mirian Ecay-Torres, Almudena Ibañez, Andrea Izagirre, Jorge Villanua, Maite Garcia-Sebastian, M. Teresa Iglesias Gaspar, Ane Otaegui-Arrazola, Ane Iriondo, Monserrat Clerigue, Pablo Martinez-Lage
Bilingualism as a component of cognitive reserve has been claimed to delay the onset of Alzheimer's disease (AD). However, its effect on cerebrospinal fluid (CSF) AD-biomarkers has not been investigated. We assessed cognitive performance and CSF AD-biomarkers, and potential moderation effect of bilingualism on the association between age, CSF AD-biomarkers, and cognition. Cognitively healthy middle-aged participants classified as monolinguals (n = 100, nCSF = 59), early (n = 81, nCSF = 55) and late bilinguals (n = 97, nCSF = 52) were evaluated. Models adjusted for confounders showed that bilinguals performed better than monolinguals on digits backwards (early-bilinguals p = 0.003), Judgment of Line Orientation (JLO) (early-bilinguals p = 0.018; late-bilinguals p = 0.004), and Trail Making Test-B (late-bilinguals p = 0.047). Early bilingualism was associated with lower CSF total-tau (p = 0.019) and lower prevalence of preclinical AD (NIA-AA classification) (p = 0.02). Bilingualism showed a moderation effect on the relationship between age and CSF AD-biomarkers and the relationship between age and executive function. We conclude that bilingualism contributes to cognitive reserve enhancing executive and visual-spatial functions. For the first time, this study reveals that early bilingualism is associated with more favorable CSF AD-biomarker profile.



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Contents

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50





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Cognitive reserve moderates the association between functional network anti-correlations and memory in MCI

Publication date: February 2017
Source:Neurobiology of Aging, Volume 50
Author(s): Nicolai Franzmeier, Katharina Buerger, Stefan Teipel, Yaakov Stern, Martin Dichgans, Michael Ewers
Cognitive reserve (CR) shows protective effects on cognitive function in older adults. Here, we focused on the effects of CR at the functional network level. We assessed in patients with amnestic mild cognitive impairment (aMCI) whether higher CR moderates the association between low internetwork cross-talk on memory performance. In 2 independent aMCI samples (n = 76 and 93) and healthy controls (HC, n = 36), CR was assessed via years of education and intelligence (IQ). We focused on the anti-correlation between the dorsal attention network (DAN) and an anterior and posterior default mode network (DMN), assessed via sliding time window analysis of resting-state functional magnetic resonance imaging (fMRI). The DMN-DAN anti-correlation was numerically but not significantly lower in aMCI compared to HC. However, in aMCI, lower anterior DMN-DAN anti-correlation was associated with lower memory performance. This association was moderated by CR proxies, where the association between the internetwork anti-correlation and memory performance was alleviated at higher levels of education or IQ. In conclusion, lower DAN-DMN cross-talk is associated with lower memory in aMCI, where such effects are buffered by higher CR.



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Redo pullthrough for Hirschsprung disease

Abstract

Pullthrough procedures for Hirschsprung diseases typically have favorable results. However, some children experience long-term postoperative complications comprising stooling disorders, such as intermittent enterocolitis, severe stool retention, intestinal obstruction, as well as incontinence. Reoperative Hirschsprung Disease surgery is complex. This begins with the workup after the initial presentation following primary pullthrough, continues with the definitive surgical correction with redo pullthrough, and ends with long-term follow-up of individuals. The decision tree can be varied with each patient. The operating pediatric surgeon must be able to utilize different operations and treatment options available. While lesser procedures may provide relief in a select population, those with residual aganglionosis or transition zone pathology or mechanical problems will likely require a redo pullthrough. Thus, the diagnostic workup, treatment plan, and definitive surgical care should be coordinated, and executed by an experienced, specialized team at a pediatric referral center.



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Pulmonary lobectomy techniques in infants and children

Abstract

Thoracoscopic pulmonary lobectomy (TPL) techniques in infants and children are presented practically with concise descriptions and numerous illustrations. TPL is the treatment of choice for congenital pulmonary airway malformation and intralobar pulmonary sequestration, both now commonly diagnosed prenatally. Timing of surgery is somewhat controversial in asymptomatic cases with small isolated lesions. Incomplete fissures and history of chest infections are most problematic. Thorough understanding of anatomic relations preoperatively is vital for successful outcome and thin-slice computed tomography with 3D reconstruction of vessels is valuable. Judicious placement of trocars and switching instruments between trocars improves visualization and safety. Specific techniques for all commonly performed TPL are included.



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International validation of a urinary biomarker panel for identification of active lupus nephritis in children

Abstract

Background

Conventional markers of juvenile-onset systemic lupus erythematosus (JSLE) disease activity fail to adequately identify lupus nephritis (LN). While individual novel urine biomarkers are good at detecting LN flares, biomarker panels may improve diagnostic accuracy. The aim of this study was to assess the performance of a biomarker panel to identify active LN in two international JSLE cohorts.

Methods

Novel urinary biomarkers, namely vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein 1 (MCP-1), lipocalin-like prostaglandin D synthase (LPGDS), transferrin (TF), ceruloplasmin, alpha-1-acid glycoprotein (AGP) and neutrophil gelatinase-associated lipocalin (NGAL), were quantified in a cross-sectional study that included participants of the UK JSLE Cohort Study (Cohort 1) and validated within the Einstein Lupus Cohort (Cohort 2). Binary logistic regression modelling and receiver operating characteristic curve analysis [area under the curve (AUC)] were used to identify and assess combinations of biomarkers for diagnostic accuracy.

Results

A total of 91 JSLE patients were recruited across both cohorts, of whom 31 (34 %) had active LN and 60 (66 %) had no LN. Urinary AGP, ceruloplasmin, VCAM-1, MCP-1 and LPGDS levels were significantly higher in those patients with active LN than in non-LN patients [all corrected p values (p c) < 0.05] across both cohorts. Urinary TF also differed between patient groups in Cohort 2 (p c = 0.001). Within Cohort 1, the optimal biomarker panel included AGP, ceruloplasmin, LPGDS and TF (AUC 0.920 for active LN identification). These results were validated in Cohort 2, with the same markers resulting in the optimal urine biomarker panel (AUC 0.991).

Conclusion

In two international JSLE cohorts, urinary AGP, ceruloplasmin, LPGDS and TF demonstrate an 'excellent' ability for accurately identifying active LN in children.



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Emissions of ammonia, carbon dioxide and particulate matter from cage-free layer houses in California

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Publication date: March 2017
Source:Atmospheric Environment, Volume 152
Author(s): Xingjun Lin, Ruihong Zhang, Shumei Jiang, Hamed El-Mashad, Hongwei Xin
Cage-free housing systems have attracted considerable attention in the United States recently as they provide more space and other resources (such as litter area, perches, and nest boxes) for hens and are considered to be more favorable from the standpoint of hen welfare. This study was carried out to quantify emissions of aerial ammonia (NH3), carbon dioxide (CO2) and particulate matter (PM10 and PM2.5) from cage-free layer houses in California and compare the values with those for other types of layer houses. Two commercial cage-free houses with 38,000 hens each were monitored from March 1, 2012 to April 1, 2013. Results show that NH3 and CO2 concentrations in the houses were affected by ventilation rate, which was largely influenced by ambient air temperature. The PM10 and PM2.5 concentrations in the houses depended on the activity of birds, ventilation rate and relative humidity of the ambient air. The average emission rates of NH3, CO2, PM10 and PM2.5 were 0.29, 89.9, 0.163 and 0.020 g d−1 hen−1, respectively. The NH3 emission rate determined in this study was higher than those of aviary houses. The PM10 and PM2.5 emission rates were higher than those reported for high-rise layer houses.



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Magnetically controlled growing rod in early onset scoliosis: a 30-case multicenter study

Abstract

Purpose

Preliminary results of magnetically controlled growing rods (MCGR) are encouraging. However, only short case series of MCGR for the treatment of early onset scoliosis (EOS) have been reported. Our aim was to evaluate its effectiveness and complications.

Methods

We report a 30-case retrospective, consecutive, multicenter series of MCGR. Effectiveness was judged upon: deformity correction and difficulties to achieve desired distraction. Secondary endpoints included complications and revision surgeries.

Results

Median age at surgery was 9.1 years (5–13). Mean follow-up was 18.4 months (12–33.9). Mean Cobb angle was 66° preoperatively and 44° at latest follow-up. MCGR has avoided an average of 2.03 scheduled surgical procedures per patient compared to traditional growing rod (GR). The intended total length gain was 40.1 mm per patient (5–140) and the total measured length gain was 21.9 mm (45.5% discrepancy). There were 24 complications: 7 proximal pull-outs of the hooks, 3 rod breakages, 6 failures of the lengthening of which 4 complete blockages and 2 complete blockages followed by backtracking, 1 proximal junctional kyphosis, 1 wound dehiscence, 1 superficial infection, 1 deep infection requiring implant removal, 1 pulmonary embolism, 1 pulmonary insufficiency, 1 secondary lumbar scoliosis, and 1 painful outpatient distraction. Eight patients had a gradual loss of effectiveness of distractions. There were 13 revision surgeries in 9 patients.

Conclusions

MCGR provides satisfactory deformity correction and avoids repeated surgical procedures for lengthening. However, it has substantial complication rate. Although less frequent than in GR, the law of diminishing returns also applies to MCGR.



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Distal junctional kyphosis in patients with Scheuermann’s disease: a retrospective radiographic analysis

Abstract

Purpose

To investigate the relationship between preoperative and postoperative spinopelvic alignment and occurrence of DJK/DJF.

Study design/setting

This was a retrospective observational cohort study.

Patient sample

The sample included 40 patients who underwent posterior correction of SK from January 2006 to December 2014.

Outcome measures

Correlation analysis between the preoperative and postoperative spinopelvic alignment parameters and development of DJK over the course of the study period were studied.

Methods

Whole spine X-rays obtained before surgery, 3 months after surgery and at the latest follow-up were analyzed. The following parameters were measured: maximum of thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lower instrumented vertebra (LIV) and LIV plumb line. Development of DJK was considered as the primary end point of the study. The patient population was split into a control and DJK group, with 34 patients and 6 patients, respectively. Statistic analysis was performed using unpaired t test for normal contribution and Mann–Whitney test for skew distributed values. The significance level was set to 0.05.

Results

DJK occurred in 15% (n = 6) over the study period. There was a significantly lower postoperative TK for the group with DJK (42.4 ± 5.3 vs 49.8 ± 6.7, p = 0.015). LIV plumb line showed higher negative values in the DJK group (−43.6 ± 25.1 vs −2.2 ± 17.8, p = 0.0435). Furthermore, postoperative LL changes were lower for the DJK group (33.84 ± 13.86% vs 31.77 ± 14.05, p < 0.0001.) The age of the patients who developed DJK was also significantly lower than that of the control group (16.8 ± 1.7 vs 19.6 ± 4.9, p = 0.0024.)

Conclusions

SK patients who developed DJK appeared to have a significantly higher degree of TK correction and more negative LIV plumb line. In addition, there may be a higher risk for DJK in patients undergoing corrective surgery at a younger age.



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Cost-effectiveness of conservative versus surgical treatment strategies of lumbar spinal stenosis in the Swiss setting: analysis of the prospective multicenter Lumbar Stenosis Outcome Study (LSOS)

Abstract

Purpose

To evaluate the cost-effectiveness of conservative versus surgical treatment strategies for lumbar spinal stenosis (LSS).

Methods

Patients prospectively enrolled in the multicenter Lumbar Stenosis Outcome Study (LSOS) with a minimum follow-up of 12 months were included. Quality adjusted life years (QALY) were calculated based on EQ-5D data. Cost data were retrieved retrospectively. Cost-effectiveness was calculated via decision tree analysis.

Results

A total of 434 patients were included, treated surgically (n = 170) or conservatively (n = 264) for LSS. The majority of surgically treated patients underwent decompression (n = 141, 82.9%), and 17.1% (n = 29) additionally underwent fusion. A reoperation was required in 13 (7.6%) surgically treated patients. In 27 (10.2%) conservatively treated patients, a single infiltration was successful, with no further infiltration or surgery within the follow-up. However, 46 patients (17.4%) required multiple infiltrations, and in 191 (72.4%) initially conservatively treated patients a subsequent surgery was needed. The area under the curve was 0.776 QALY in the surgical arm (0.776 and 0.790, decompression or additional fusion, respectively), compared to 0.778 in the conservative arm. Treatment costs were estimated at CHF 12,958 and 13,637 (USD 13,465 and 14,169) in surgically and initially conservatively treated patients, respectively [base-case incremental cost-effectiveness ratio (ICER): CHF 392,145, USD 407,831], per QALY gained. Probabilistic sensitivity analysis identified surgery as the preferred strategy in 67.1%.

Conclusions

Both the surgical and the conservative treatment approach resulted in a comparable health-related quality of life within the first year after study inclusion. Due to slightly higher costs, mostly because the majority of initially conservatively treated patients underwent multiple infiltrations or a subsequent surgery, decompressive surgery was identified as the most cost-effective approach for LSS in this setting.



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Prevention of spinal cord injury using brain-evoked muscle-action potential (Br(E)-MsEP) monitoring in cervical spinal screw fixation

Abstract

Purpose

The goal of the study was to examine waveform deterioration in intraoperative monitoring during posterior fusion with a cervical screw. This surgery is useful for alignment correction, but worsening of neurological symptoms may occur in association with screw insertion and rod installation. Therefore, spinal cord monitoring is important for safe surgery.

Methods

The study included 25 cases treated with posterior fusion with a cervical screw. Waveform deterioration was defined as an intraoperative amplitude <50% of the control waveform. Comparisons were made between cases with normal and deteriorated waveforms.

Results

Intraoperative waveform deterioration occurred in nine cases, including after screw insertion in 8 and after rod installation in one. The nine patients with deteriorated waveforms had a significantly lower preoperative JOA score (8.8 vs. 11.2, P < 0.05) and a tendency for more frequent high signal intensity on MRI [67% (6/9) vs. 31% (5/16), P = 0.087]. Cases in which stenosis was greatest at the apex of the cervical lordosis had significantly more frequent intraoperative waveform deterioration [46% (6/13) vs. 0% (0/8), P < 0.05]. In cases in which the narrowest segment was at the apex of the cervical lordosis, screw insertion before compared to after decompression significantly increased waveform deterioration [67% (6/9) vs. 0% (0/4), P < 0.05].

Conclusion

Intraoperative waveform deterioration in posterior cervical screw fixation is associated with severe preoperative symptoms, location of the narrowest segment, and screw insertion before decompression. It is particularly desirable to perform decompression before screw insertion in cases with the narrowest segment at the apex of the cervical lordosis.



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Indeterminacy and the principle of need

Abstract

The principle of need—the idea that resources should be allocated according to need—is often invoked in priority setting in the health care sector. In this article, I argue that a reasonable principle of need must be indeterminate, and examine three different ways that this can be dealt with: appendicizing the principle with further principles, imposing determinacy, or empowering decision makers. I argue that need must be conceptualized as a composite property composed of at least two factors: health shortfall and capacity to benefit. When one examines how the different factors relate to each other, one discovers that this is sometimes indeterminate. I illustrate this indeterminacy in this article by applying the small improvement argument. If the relation between the factors are always determinate, the comparative relation changes by a small adjustment. Yet, if two needs are dissimilar but of seemingly equal magnitude, the comparative relation does not change by a small adjustment of one of the factors. I then outline arguments in favor of each of the three strategies for dealing with indeterminacy, but also point out that all strategies have significant shortcomings. More research is needed concerning how to deal with this indeterminacy, and the most promising path seems to be to scrutinize the position of the principle of need among a plurality of relevant principles for priority setting in the health care sector.



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Susan R. Holman: Beholden: religion, global health, and human rights



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The process of mammalian mitochondrial protein synthesis

Abstract

Oxidative phosphorylation (OXPHOS) is the mechanism whereby ATP, the major energy source for the cell, is produced by harnessing cellular respiration in the mitochondrion. This is facilitated by five multi-subunit complexes housed within the inner mitochondrial membrane. These complexes, with the exception of complex II, are of a dual genetic origin, requiring expression from nuclear and mitochondrial genes. Mitochondrially encoded mRNA is translated on the mitochondrial ribosome (mitoribosome) and the recent release of the near atomic resolution structure of the mammalian mitoribosome has highlighted its peculiar features. However, whereas some aspects of mitochondrial translation are understood, much is to be learnt about the presentation of mitochondrial mRNA to the mitoribosome, the biogenesis of the machinery, the exact role of the membrane, the constitution of the translocon/insertion machinery and the regulation of translation in the mitochondrion. This review addresses our current knowledge of mammalian mitochondrial gene expression, highlights key questions and indicates how defects in this process can result in profound mitochondrial disease.



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Mitochondrial translation and cellular stress response

Abstract

Mitochondria are organelles critical for the functionality of eukaryotic cells. One of their most prominent functions is energy conversion, thereby producing most of the cellular ATP. Energy conversion relies on the oxidative phosphorylation system, an ensemble of large protein complexes that include the respiratory chain and the ATP synthase. Biogenesis of this machinery requires the coordination of two separate genetic systems, namely nuclear and mitochondrial gene expression. Recent research into the molecular causes of aging have revealed a prominent contribution of mitochondrial gene expression on many aspects of degenerative processes that typically involve cellular stress signaling pathways. In this review, we summarize recent developments in attempting to identify the molecular mechanism by which dysfunction of mitochondrial gene expression activates cellular stress signaling pathways and how this affects organismal aging. By comparing data obtained in various model organisms, we identify conserved and species-specific aspects of this mitochondria-to-nucleus signaling.



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Incidence of bradycardia in pediatric patients receiving dexmedetomidine anesthesia: a meta-analysis

Abstract

Background Dexmedetomidine, an α2-receptor agonist, provides potent sedation, analgesia, and anxiolysis without respiratory depression and is used in a variety of surgical and procedural situations. Aim of the review The aim of this study was to estimate the incidence of bradycardia in pediatric patients who received dexmedetomidine as a sole agent for any procedural, intensive care or surgical sedation. Method Literature was searched in electronic databases and studies were selected by following pre-determined eligibility criteria. Meta-analyses were carried out by pooling the percent incidence of bradycardia to attain a weighted overall effect size. Age-wise subgroup analyses and meta-regression analyses for the identification of factors affecting the incidence were also performed. Results Data of 2835 patients from 21 studies were included. The mean age was 62.21 ± 35.68 months. Initial, maintenance and total doses of dexmedetomidine (mean ± standard deviation) were 1.63 ± 0.33 μg/kg body weight, 0.86 ± 0.68 μg/kg/h, and 26.7 ± 20.8 μg/kg. The overall incidence of bradycardia (95% confidence interval) was 3.067 (2.863, 3.270)%; P < 0.0001. However, range was wider (0–22%) with 9 studies observed 0% incidence. The mean change in the heart rate was −17.26 (−21.60, −12.92); P < 0.00001. In the meta-regression analyses, age, body weight and dexmedetomidine dose were not significantly associated with the incidence of bradycardia. The minimum heart rate observed during the dexmedetomidine treatment period was positively associated with baseline heart rate. Conclusion Incidence of bradycardia in dexmedetomidine treated pediatric patients is 3%.



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Simultaneous Separation and Determination of 15 Organic UV Filters in Sunscreen Cosmetics by HPLC-ESI-MS/MS

Abstract

Objective

A comprehensive methodology for the simultaneous determination of 15 multiclass organic UV filters in sunscreen cosmetics was developed using high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS).

Methods

Sunscreen cosmetics of various matrices, such as toning lotion, emulsion, cream, and lipstick, were analyzed. Ultrasound-assisted extraction (UAE) was utilized as the extraction technique for sample preparation. The 15 UV filters were chromatographically separated by two groups of mobile phase system on an XBridge C18 analytical column (150 mm × 2.1 mm I.D., 3.5 μm particle size) and quantified using HPLC-ESI-MS/MS. The quantitation was performed using the external calibration method.

Results

The established method was validated in terms of linearity, sensitivity, specificity, accuracy, stability, intra- and inter-day precisions, recovery, and matrix effect. The method was also applied for the determination of UV filters in commercial sunscreen cosmetics.

Conclusion

The experimental results demonstrated that the developed method was accurate, rapid, sensitive, and can be used for the analytical control of sunscreen cosmetics.

This article is protected by copyright. All rights reserved.



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Nipple Reconstruction with Dorsal Skin Provides Better Projection than Reconstruction with Abdominal or Breast Skin with Cartilage Grafting

Abstract

Nipple projection of a modified C–V flap with or without costal cartilage was compared on abdominal, breast, and dorsal skin. A total of 81 patients and 85 sites were studied. The nipple was reconstructed secondarily using a modified C–V flap. Patients were classified by breast mound skin into five groups: dorsal skin without cartilage (group A, n = 18); abdominal skin without cartilage (group B, n = 6); abdominal skin with cartilage (group C, n = 26); breast skin without cartilage (group D, n = 20); and breast skin with cartilage (group E, n = 15). Complications and nipple projection were evaluated over a mean follow-up of 18.5 months; there were no significant differences among the five groups. Minor flap necrosis occurred in 10/18, 0/6, 4/26, 1/20, and 2/15 of groups A, B, C, D, and E, respectively; the percentage was higher in group A than in group D. The average projection maintenance rate (postoperative nipple projection to V flap width) was 76.5, 50.1, 56.1, 46.1, and 52.3% for groups A, B, C, D, and E, respectively; the value in group A was higher than in all other groups. Despite more minor necrosis, the nipple reconstructed with dorsal skin maintained better projection than the nipple reconstructed with abdominal skin or breast skin combined with a cartilage graft.

Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the A3 online Instructions to Authors. http://ift.tt/18t7xNj.



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Comparison of Dexamethasone–Dimenhydrinate and Dexamethasone–Ondansetron in Prevention of Nausea and Vomiting in Postoperative Patients

Abstract

Introduction

Postoperative Nausea and Vomiting is one of the most common problems after implementation of general anesthesia. The incidence can reach 80% in high-risk patients, depending on the type of surgery. In our study, we aimed to compare dexamethasone–dimenhydrinate and dexamethasone–ondansetron combinations in prevention of nausea and vomiting in postoperative patients.

Method

Sixty 18–65-year-olds ASAI-II females who underwent rhinoplasty were included in the study. Patients were randomly included in two groups: Dexamethasone–dimenhydrinate group (group DD) and dexamethasone–ondansetron group (group DO). All patients received dexamethasone 8 mg iv after endotracheal intubation. Anesthesia continuation was established with sevoflurane, air–oxygen mixture and remifentanil infusion. At the 30th minute of the operation, group DO received ondansetron 4 mg iv and group DD received dimenhydrinate 1 mg/kg iv. For postoperative analgesia tramadol (1.5 mg/kg) iv, tenoksikam (20 mg) and afterward for postoperative patient-controlled tramadol was used. In the postoperative recovery room, nausea and vomiting were evaluated at the 30th, 60th, 120th minutes and at the end of 24 h. Total amount of tramadol was recorded. All results were statistically evaluated.

Observations

Demographics and Apfel risk scores of both groups were similar. Surgical operation duration (p = 0.038) and total preoperative remifentanil consumption were higher in group DD (p = 0.006). In group DO, nausea at 30 and 60 min (p = 0.001, p = 0.007), retching at 30 and 60 min (p = 0.002, p = 0.006) were higher than group DD. The additional antiemetic need in group DO was significantly higher at 30 min (p = 0.001). Postoperative analgesic consumption was similar in both groups.

Result

Our study revealed that dexamethasone–dimenhydrinate combination was more effective than dexamethasone–ondansetron in prevention of nausea and vomiting after rhinoplasty operations.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.



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Omega (Ω) Advancement Flap: A Circular Flap Design for the Aesthetic Closure of Circular Skin Defect

Abstract

Background

Most skin defects that require reconstruction with a local skin flap have a circular- or oval-shaped pattern. The majority of the skin flaps are planned in an angled shape. Therefore, it may be necessary to modify the shape of the defect or the distal flap border to minimize tissue distortion. We have designed a circular-shaped advancement flap to be compatible with the circular defect.

Methods

Eighteen cases of reconstruction of skin defects in the face, chest wall, hand and buttock area were performed using the omega advancement flap between 2010 and 2014. In this technique, a circular-shaped flap that has an equal diameter with the defect is planned adjacent to the defect. To facilitate the advancement of the flap and to avoid standing cones, deepithelialized equilateral triangular flaps are designed on both sides of the main circular flap. The circular flap is easily moved to the defect by pulling of the triangular flaps with minimal tension.

Results

All flaps survived without complication such as infection, hematoma or flap necrosis. No secondary surgery was required to correct contour deformities such as standing cones and trap-door deformities. The results were satisfactory aesthetically and functionally.

Conclusions

The omega advancement flap is an easy and reliable procedure for reconstruction of circular skin defects located on various anatomical regions.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.



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Does Postoperative Erythropoietin Reduce Transfusions and Hemodynamic Instability Following Liposuction, Either Alone or Associated with Abdominoplasty or Mammaplasty? A Comparative, Prospective Study of 50 Consecutive Patients

Abstract

Introduction

Erythropoietin (EPO) is a hematopoietic growth factor and an alternative to avoid blood transfusion in high-blood-loss surgeries. We evaluate EPO efficacy to reduce clinically relevant anemia and dehydration in patients undergoing liposuction.

Methods

We prospectively evaluated 50 consecutive patients subjected to liposuction greater than 2.5 L and alternately assigned into two comparable groups (25 patients each), except for the postoperative administration of erythropoietin (4000 UI per day subcutaneously) during five consecutive days. Incidence data for blood transfusion or parenteral hydration were collected. Statistical analyses were performed with significance at p value <5%.

Results

There was no significant difference between groups related to any preoperative feature or the incidence of dehydration (p = 0.1099) or transfusion (p = 1.0).

Conclusion

Postoperative erythropoietin administration was not effective in preventing blood transfusion for anemia or parenteral hydration for hemodynamic instability in patients undergoing major liposuction.

Level of Evidence III

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.



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Objective Outcome Measurement After Upper Blepharoplasty: An Analysis of Different Operative Techniques

Abstract

Background

Upper blepharoplasty is indicated in Asians for double-eyelid fold creation, periorbital rejuvenation, and functional visual field improvement. This article introduces a technical classification for blepharoplasty methods and investigates approaches to evaluate its outcomes.

Methods

Of 535 patients undergoing aesthetic upper blepharoplasty in our institution in 1998–2011, 136 patients who were well followed up were retrospectively reviewed and categorized into four groups according to the techniques employed. Blepharoplasty with skin excision only was indicated for upper eyelid-skin redundancy patients with prominent double eyelids (n = 20). Blepharoplasty with skin excision and nonburied suture fixation was indicated for patients with upper lid-skin redundancy and weak double eyelids (n = 15). Blepharoplasty with skin excision and buried suture fixation was indicated for patients with upper lid-skin redundancy but no double-eyelid folds (n = 46). Finally, blepharoplasty with simultaneous ptosis correction was utilized for patients with senile or subclinical ptosis requesting upper blepharoplasty (n = 55). The mean age was 48.7 years at surgery; the mean follow-up period was 6 months. Digital photographs were used to compare changes in marginal reflex distance 1 (MRD1), percentage of the area of corneal exposure (%ACE), and brow height.

Results

MRD1 increased from 1.92 to 2.84 mm in the whole patient group after upper blepharoplasty; it increased the most in blepharoplasty with simultaneous ptosis correction (1.22 mm). %ACE increased from 62.1 to 76.6% (14.5%), whereas brow height decreased from 29.4 to 26.7 mm (9.2%).

Conclusion

Upper blepharoplasty improves palpebral fissure. Numerically measured palpebral fissure changes facilitate operation outcome measurement.

Level of Evidence III

This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.



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Towards an automated analysis of bacterial peptidoglycan structure

Abstract

Peptidoglycan (PG) is an essential component of the bacterial cell envelope. This macromolecule consists of glycan chains alternating N-acetylglucosamine and N-acetylmuramic acid, cross-linked by short peptides containing nonstandard amino acids. Structural analysis of PG usually involves enzymatic digestion of glycan strands and separation of disaccharide peptides by reversed-phase HPLC followed by collection of individual peaks for MALDI-TOF and/or tandem mass spectrometry. Here, we report a novel strategy using shotgun proteomics techniques for a systematic and unbiased structural analysis of PG using high-resolution mass spectrometry and automated analysis of HCD and ETD fragmentation spectra with the Byonic software. Using the PG of the nosocomial pathogen Clostridium difficile as a proof of concept, we show that this high-throughput approach allows the identification of all PG monomers and dimers previously described, leaving only disambiguation of 3–3 and 4–3 cross-linking as a manual step. Our analysis confirms previous findings that C. difficile peptidoglycans include mainly deacetylated N-acetylglucosamine residues and 3–3 cross-links. The analysis also revealed a number of low abundance muropeptides with peptide sequences not previously reported.

Graphical Abstract

The bacterial cell envelope includes plasma membrane, peptidoglycan, and surface layer. Peptidoglycan is unique to bacteria and the target of the most important antibiotics; here it is analyzed by mass spectrometry.


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Diethylaminoethyl Sepharose (DEAE-Sepharose) microcolumn for enrichment of glycopeptides

Abstract

N-Glycosylation is one of the most prevalent protein post-translational modifications and is involved in many biological processes, such as protein folding, cellular communications, and signaling. Alteration of N-glycosylation is closely related to the pathogenesis of diseases. Thus, the investigation of protein N-glycosylation is crucial for the diagnosis and treatment of disease. In this research, we applied diethylaminoethanol (DEAE) Sepharose solid-phase extraction microcolumns for N-glycopeptide enrichment. This method integrated the advantages of Click Maltose and zwitterionic HILIC (ZIC-HILIC) and showed a relatively higher specificity for N-glycosylated peptides. This strategy was then applied to tryptic digests of normal human serum, followed by deglycosylation using peptide-N-glycosidase F (PNGase F) in H218O. Subsequent LC–MS/MS analysis allowed for the assignment of 219 N-glycosylation sites from 115 serum N-glycoproteins. This study provides an alternative approach for N-glycopeptide enrichment and the method employed is effective for large-scale N-glycosylation site identification.

Graphical abstract

Proposed mechanism of glycopeptides enrichment using DEAE-Sepharose


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Determination of azoxystrobin and chlorothalonil using a methacrylate-based polymer modified with gold nanoparticles as solid-phase extraction sorbent

Abstract

This paper describes a novel and sensitive method for extraction, preconcentration, and determination of two important widely used fungicides, azoxystrobin, and chlorothalonil. The developed methodology is based on solid-phase extraction (SPE) using a polymeric material functionalized with gold nanoparticles (AuNPs) as sorbent followed by high-performance liquid chromatography (HPLC) with diode array detector (DAD). Several experimental variables that affect the extraction efficiency such as the eluent volume, sample flow rate, and salt addition were optimized. Under the optimal conditions, the sorbent provided satisfactory enrichment efficiency for both fungicides, high selectivity and excellent reusability (>120 re-uses). The proposed method allowed the detection of 0.05 μg L−1 of the fungicides and gave satisfactory recoveries (75–95 %) when it was applied to drinking and environmental water samples (river, well, tap, irrigation, spring, and sea waters).



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Erratum to: Study of in-vitro metabolism of selected antibiotic drugs in human liver microsomes by liquid chromatography coupled with tandem mass spectrometry



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Analysis of heparin oligosaccharides by capillary electrophoresis–negative-ion electrospray ionization mass spectrometry

Abstract

Most hyphenated analytical approaches that rely on liquid chromatography–MS require relatively long separation times, produce incomplete resolution of oligosaccharide mixtures, use eluents that are incompatible with electrospray ionization, or require oligosaccharide derivatization. Here we demonstrate the analysis of heparin oligosaccharides, including disaccharides, ultralow molecular weight heparin, and a low molecular weight heparin, using a novel electrokinetic pump-based CE–MS coupling eletrospray ion source. Reverse polarity CE separation and negative-mode electrospray ionization were optimized using a volatile methanolic ammonium acetate electrolyte and sheath fluid. The online CE hyphenated negative-ion electrospray ionization MS on an LTQ Orbitrap mass spectrometer was useful in disaccharide compositional analysis and bottom-up and top-down analysis of low molecular weight heparin. The application of this CE–MS method to ultralow molecular heparin suggests that a charge state distribution and the low level of sulfate group loss that is achieved make this method useful for online tandem MS analysis of heparins.

Graphical abstract

Most hyphenated analytical approaches that rely on liquid chromatography–MS require relatively long separation times, produce incomplete resolution of oligosaccharide mixtures, use eluents that are incompatible with electrospray ionization, or require oligosaccharide derivatization. Here we demonstrate the analysis of heparin oligosaccharides, including disaccharides, ultralow molecular weight heparin, and a low molecular weight heparin, using a novel electrokinetic pump-based CE–MS coupling eletrospray ion source. Reverse polarity CE separation and negative-mode electrospray ionization were optimized using a volatile methanolic ammonium acetate electrolyte and sheath fluid. The online CE hyphenated negative-ion electrospray ionization MS on an LTQ Orbitrap mass spectrometer was useful in disaccharide compositional analysis and bottom-up and top-down analysis of low molecular weight heparin. The application of this CE–MS method to ultralow molecular heparin suggests that a charge state distribution and the low level of sulfate group loss that is achieved make this method useful for online tandem MS analysis of heparins


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Rapid classification of Chinese quince ( Chaenomeles speciosa Nakai) fruit provenance by near-infrared spectroscopy and multivariate calibration

Abstract

The quality of Chinese quince fruit is a significant factor for medicinal materials, influencing the quality of the medicine. However, it is difficult to distinguish different types of Chinese quince fruit. The main objective of this work was to use near-infrared (NIR) spectroscopy, which is a rapid and non-destructive analysis method, to classify the varieties of Chinese quince fruits. Raw spectra in the range of 1000 to 2500 nm were combined with linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), and support vector machines (SVMs) for classification. The first three principal component analysis (PCA) scores were used as input variables to build LDA, QDA, and SVM discriminant models. The results indicate that all three of these methods are effective for distinguishing the different types of Chinese quince fruit. The classification accuracies for LDA, QDA, and SVM are 94, 96, and 98 %, respectively. QDA led to high-level classification accuracy of Chinese quince fruit.



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Identification of individual red blood cells by Raman microspectroscopy for forensic purposes: in search of a limit of detection

Abstract

Traces of body fluids can be present at a variety of crime scenes. It is important that forensic investigators have a reliable and nondestructive method of identifying these traces. Of equal importance is establishing the limitations of any method in use, including its detection limit. We have previously reported on the use of Raman microspectroscopy and multivariate data analysis to identify and differentiate body fluids. While many studies use serial dilutions to establish limits of detection, we utilized a different approach and demonstrated that a single red blood cell is sufficient to be correctly identified as blood. The experimental Raman spectra of individual red blood cells were loaded into the previously reported models for body fluid identification, and all were correctly classified as peripheral blood. These results demonstrate that our model can be used to identify peripheral blood, even if there is only a single red blood cell present. Furthermore, a single red blood cell is 5000× smaller than the amount of peripheral blood required to perform DNA analysis in a modern crime laboratory. This means that if a bloodstain is large enough for DNA analysis, Raman microspectroscopy should be able to make a positive identification. Considering that the sample analysis reported here was carried out with a different instrument, not the one used for the previously reported method development, these results also represent a form of method validation. The model's ability to correctly classify spectra acquired on a different instrumental platform is crucial in preparing it for practical application.

Graphical Abstract

Peripheral blood is of great interest in forensic sciences. While many tests are available for the identification of peripheral blood at a crime scene, most are presumptive and destructive. Here we present results that show our new, nondestructive method can identify peripheral blood using as little as a single red blood cell


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Erratum to: Characterisation of the protein corona using tunable resistive pulse sensing: determining the change and distribution of a particle’s surface charge



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Redox titration challenge



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Reconstruction of undergraduate analytical chemistry laboratory course



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Rapid and sensitive MALDI MS analysis of oligosaccharides by using 2-hydrazinopyrimidine as a derivative reagent and co-matrix

Abstract

Sensitive analysis of oligosaccharides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is significantly hampered by the low ionization efficiency of oligosaccharides. Derivatization affords a feasible way to enhance the MALDI intensities of oligosaccharides by introducing an easily ionized and/or hydrophobic tag to their reducing ends. However, tagging and subsequent desalting processes are quite time-consuming. Herein, we develop a rapid and sensitive approach for oligosaccharide derivatization by using 2-hydrazinopyrimidine (2-HPM). As a result of the presence of an electron-withdrawing N-heterocycle, 2-HPM can quantitatively derivatize oligosaccharides within 15 min and selectively facilitate their ionization. Additionally, 2-HPM acts as co-matrix to enhance the MALDI signal of oligosaccharides, and therefore the tedious enrichment and purification processes prior to MALDI analysis are avoided. This approach is applied to the analysis of various oligosaccharides released from glycopeptides, glycoprotein, and biological samples. After derivatization, a significant increase of MALDI intensities (greater than 10-fold) was observed for all the tested neutral and sialylated oligosaccharides. Moreover, the enhanced fragmentation of MS/MS brings much convenience to the structural elucidation of oligosaccharides.

Graphical abstract

Improved MALDI MS analysis of oligosaccharides by using 2-hydrazinopyrimidine as a derivative tag and co-matrix


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A new immunoassay of serum antibodies against Peste des petits ruminants virus using quantum dots and a lateral-flow test strip

Abstract

A fast and ultrasensitive test-strip system combining quantum dots (QDs) with a lateral-flow immunoassay strip (LFIAS) was established for detection of Peste des petits ruminants virus (PPRV) antibody. The highly luminescent water-soluble carboxyl-functionalized QDs were used as the signal output and were conjugated to streptococcal protein G (SPG), which was capable of binding to immunoglobulin G (IgG) from many species through an amide bond to capture the target PPRV IgGs. The PPRV N protein, which was immobilized on the detection zone of the test strip, was expressed by transfecting recombinant Bacmid-PPRV-N with Lipofect into Sf9 insect cells. When exposed to PPRV IgG, QD-SPG bound to PPRV N protein, resulting in the formation of a complex that subsequently produced a bright fluorescent band in response to 365 nm ultraviolet excitation. Sensitivity evaluation showed that the QD-LFIAS limit of detection (LOD) for PPRV antibody was superior to competitive enzyme-linked immunosorbent assay (c-ELISA) and the immunochromatographic strip. No cross reaction was observed when the positive sera of bluetongue virus, canine distemper virus, goat pox virus, and foot-and-mouth disease virus were tested. Further evaluation using field samples indicated that the diagnostic specificity and sensitivity of the QD-LFIAS was 99.47 and 97.67 %, respectively, with excellent agreement between QD-LFIAS and c-ELISA. The simple analysis step and objective results that can be obtained within 15 min indicate that this new method shows great promise for rapid, sensitive detection of PPRV IgG for onsite, point-of-care diagnosis and post vaccination evaluation (PVE).

Graphical Abstract

Ultrasensitive fluorescent QD immunochromotography in combination with recombinant PPRV N protein could be used to detect PPRV antibody in serum


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Solution to isotope amount ratio measurement challenge



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A sensitive method for simultaneous quantitative determination of surfactin and iturin by LC-MS/MS

Abstract

Surfactin and iturin are antimicrobial lipopeptides produced from Bacillus spp. and have significant prospective applications in many fields. Therefore, accurate analysis of these lipopeptides in the fermented product of some Bacillus strains is important. A sensitive method for simultaneous quantitative determination of surfactin and iturin fermented by Bacillus natto NT-6 was developed and validated using liquid chromatography–tandem mass spectrometry. Crude extracts of antimicrobial lipopeptide samples were dissolved in a mixture of acetonitrile/water (7:3, v/v) in 0.1 % (v/v) formic acid and eluted with acetonitrile/water (7:3, v/v) containing 5 mmol L−1 ammonium acetate and 0.1 % (v/v) formic acid. The target compounds were detected by mass spectrometry (ESI+) using selective ion monitoring. A good linear regression in the range of 0.20–10.0 mg L−1 for both surfactin and iturin (R 2 ≥ 0.9995) was observed with spiked recoveries of 93.3–108.2 %, RSD values less than 15 %, precision 4.14–13.30 %, and a detection limit of 0.374 mg L−1. This method has a simple preprocessing operation, good repeatability, and provides an accurate quantitative analysis of surfactin and iturin.

Graphical Abstract

Surfactin and iturin from Bacillus natto NT-6 extraction and detection procedure


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Aptamer-based surface-enhanced Raman scattering (SERS) sensor for thrombin based on supramolecular recognition, oriented assembly, and local field coupling

Abstract

A supramolecular recognition and oriented assembly system was developed on chip for the highly selective surface-enhanced Raman scattering (SERS) detection of thrombin by means of the aptamer-based SERS tag method. A 15-base thrombin-binding aptamer (TBA15) with a thiol end was first immobilized on an Ag nanoprism array by the S–Ag bond. This aptamer has high binding affinity with thrombin when it folds into a G-quadruplex structure. After the recognition between the aptamer and thrombin, a bridge is built between the SERS tag (4-mercaptobenzoic acid marked Ag nanoparticle) and the fixed thrombin based on the activation of the carboxylic group of 4-mercaptobenzoic acid. Thus, the quantitative detection of thrombin can be achieved based on the SERS intensity of the immobilized SERS tags. The obvious advantages of this sensing method are as follows: (1) remarkable SERS enhancement due to the high electric field coupling effect via the gap structure formation, which improves the sensitivity of the SERS detection and the limit of detection of this method arrives in 1.6 × 10–11 M, (2) high selectivity based on the specific aptamer recognition toward thrombin, which can be extended to other enzymes easily by changing a proper sequence, (3) high repeatability of SERS signals according to a highly ordered structure, and (4) highly efficient oriented assembly of a sandwich structure over an Ag nanoprism array. The proposed method is expected to be a practical implement in medical diagnosis.

Graphical Abstract

Illustration of the aptamer-based SERS sensor for thrombin detection


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Application of organic acids for plant protection against phytopathogens

Abstract

The basic tendency in the field of plant protection concerns with reducing the use of pesticides and their replacement by environmentally acceptable biological preparations. The most promising approach to plant protection is application of microbial metabolites. In the last years, bactericidal, fungicidal, and nematodocidal activities were revealed for citric, succinic, α-ketoglutaric, palmitoleic, and other organic acids. It was shown that application of carboxylic acids resulted in acceleration of plant development and the yield increase. Of special interest is the use of arachidonic acid in very low concentrations as an inductor (elicitor) of protective functions in plants. The bottleneck in practical applications of these simple, nontoxic, and moderately priced preparations is the absence of industrial production of the mentioned organic acids of required quality since even small contaminations of synthetic preparations decrease their quality and make them dangerous for ecology and toxic for plants, animals, and human. This review gives a general conception on the use of organic acids for plant protection against the most dangerous pathogens and pests, as well as focuses on microbiological processes for production of these microbial metabolites of high quality from available, inexpensive, and renewable substrates.



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Male spider mites use chemical cues, but not the female mating interval, to choose between mates

Abstract

The choice of the partner an individual will mate with is expected to strongly impact its fitness. Hence, natural selection has favoured the evolution of cues to distinguish among mates that will provide different fitness benefits to the individual that is choosing. In species with first-male sperm precedence, this is particularly important for males, as mating with mated females will result in no offspring. In the spider mite Tetranychus urticae only the first mating is effective, except if the interval between first and second copulations is shorter than 24 h. In line with this, males prefer to mate with virgin over mated females. They do not, however, choose between females that have mated at different time intervals. Here, we tested which type of cues males use to distinguish between females with different mating status (virgin versus mated). To do so, we firstly confirmed that males prefer virgins over mated females and that they do not select females on the basis of their age or mating interval. Next, we tested whether contact and volatile compounds or chemical trails affected male discrimination between mated and virgin females, by systematically varying the exposure of males to these cues. We found that volatile compounds and chemical trails were sufficient to induce discrimination between virgin and mated females in males. Direct contact with females, however, does not seem to play a role in this discrimination. The composition of such chemical cues (trails and volatiles) remains to be identified.



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Carcinoma of buccal mucosa with metastasis to thigh

Squamous cell carcinoma of the oral cavity ranks as the twelfth most common cancer in the world and the eighth most frequent in males. In USA, cancers of oral cavity comprises approximately 3% of all cancers, the most common sub site for oral cavity carcinomas being the tongue followed by floor of mouth among all Head and Neck squamous cell carcinoma (HNSCC). Buccal mucosa is the most common oral cancer in men and the third most common oral cancer in women in India; and accounts for up to one-third of all tobacco-related cancers.

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“Hidden scar” submandibular gland excision using an endoscope-assisted hairline approach

Submandibular gland (SMG) excision is a well-established surgical technique, and it is performed using a cervical incision. However, external cervical incisions leave scars that can be great burdens for both patient and surgeon. Moreover, the psychological and social impacts of cervical scars have been documented [1]. Thus, many surgeons make the effort to minimize or hide the incision scars [2–12].

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“Hidden scar” submandibular gland excision using an endoscope-assisted hairline approach

Submandibular gland (SMG) excision is a well-established surgical technique, and it is performed using a cervical incision. However, external cervical incisions leave scars that can be great burdens for both patient and surgeon. Moreover, the psychological and social impacts of cervical scars have been documented [1]. Thus, many surgeons make the effort to minimize or hide the incision scars [2–12].

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Carcinoma of buccal mucosa with metastasis to thigh

Squamous cell carcinoma of the oral cavity ranks as the twelfth most common cancer in the world and the eighth most frequent in males. In USA, cancers of oral cavity comprises approximately 3% of all cancers, the most common sub site for oral cavity carcinomas being the tongue followed by floor of mouth among all Head and Neck squamous cell carcinoma (HNSCC). Buccal mucosa is the most common oral cancer in men and the third most common oral cancer in women in India; and accounts for up to one-third of all tobacco-related cancers.

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Smoking status regulates a novel panel of PIWI-interacting RNAs in head and neck squamous cell carcinoma

Head and neck squamous cell carcinomas (HNSCCs) represent the sixth deadliest cancer worldwide [1,2]. Despite advances in diagnosis and treatment, HNSCC patient mortality has improved minimally over the past three decades [3]. HNSCC risk factors include tobacco smoking, alcohol consumption, and more recently, HPV infection [4,5]; however, tobacco remains the most potent and longstanding etiological agent, increasing disease risk by up to 25-fold [6,7].

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Carcinoma of buccal mucosa with metastasis to thigh

Squamous cell carcinoma of the oral cavity ranks as the twelfth most common cancer in the world and the eighth most frequent in males. In USA, cancers of oral cavity comprises approximately 3% of all cancers, the most common sub site for oral cavity carcinomas being the tongue followed by floor of mouth among all Head and Neck squamous cell carcinoma (HNSCC). Buccal mucosa is the most common oral cancer in men and the third most common oral cancer in women in India; and accounts for up to one-third of all tobacco-related cancers.

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Smoking status regulates a novel panel of PIWI-interacting RNAs in head and neck squamous cell carcinoma

Head and neck squamous cell carcinomas (HNSCCs) represent the sixth deadliest cancer worldwide [1,2]. Despite advances in diagnosis and treatment, HNSCC patient mortality has improved minimally over the past three decades [3]. HNSCC risk factors include tobacco smoking, alcohol consumption, and more recently, HPV infection [4,5]; however, tobacco remains the most potent and longstanding etiological agent, increasing disease risk by up to 25-fold [6,7].

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Unraveling proteome changes of Holstein beef M. semitendinosus and its relationship to meat discoloration during post-mortem storage analyzed by label-free mass spectrometry

Publication date: 10 February 2017
Source:Journal of Proteomics, Volume 154
Author(s): Qianqian Yu, Wei Wu, Xiaojing Tian, Man Hou, Ruitong Dai, Xingmin Li
Label-free proteomics was applied to characterize the effect of post-mortem storage time (0, 4, and 9days at 4°C±1°C) on the proteome changes of M. semitendinosus (SM) in Holstein cattle, and correlations between differentially abundant proteins and meat color traits were investigated. The redness (a*) value decreased significantly (P<0.05) during post-mortem storage, meanwhile, the relative proportion of metmyoglobin increased significantly (P<0.05) from 16.99% at day 0 to 40.26% at day 9. A total of 118 proteins with significant changes (fold change>1.5, P<0.05) was identified by comparisons of day 4 vs. day 0, day 9 vs. day 0, and day 9 vs. day 4. Principal component and hierarchical cluster analyses of these proteins were performed, and results exhibited clear distinctions among samples from different storage times. Eighteen differentially abundant proteins were correlated closely with the a* value of meat. Bioinformatics analyses revealed that most of these proteins were involved in glycolysis and energy metabolism, electron-transfer processes, and the antioxidation function, which implied an underlying connection between meat discoloration and these biological processes.SignificanceIt is always a challenge for scientists to improve the stability of meat color during post-mortem storage and retail display. However, the mechanism involved in meat discoloration has not been unraveled completely, and the application of label-free proteomics in studying meat discoloration has not been reported. Our work discovers some key proteins in SM muscle of Holstein cattle that were correlated with a* value of meat via label-free proteomics. Bioinformatics analyses revealed that some of these differentially abundant proteins were involved in glycolysis and energy metabolism, electron-transfer processes, and the antioxidation function, which implied an underlying connection between meat discoloration and these biological processes. These results provide the theoretic basis on understanding of complicated biochemical changes and underlying molecular mechanisms responsible for meat discoloration.

Graphical abstract

image


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Antiplatelet Strategies and Outcomes in Patients with Noncardioembolic Ischemic Stroke from a Real-World Study with a Five-Year Follow-Up

Abstract

Aspirin and clopidogrel are both acceptable antiplatelet options for the secondary prevention of noncardioembolic ischemic stroke. Associations between Essen Stroke Risk Score (ESRS) and antiplatelet treatment in Chinese patients with noncardioembolic ischemic stroke were assessed. This retrospective study was taken in a tertiary care hospital located in eastern China. Patients with noncardioembolic ischemic stroke hospitalized during January 1, 2009, to December 31, 2011, were classified according to ESRS during index stroke hospitalization. Antiplatelet strategy at the time of discharge was categorized as aspirin (100 mg/day) vs. clopidogrel (75 mg/day). Patients received follow-up from July 1, 2014, to December 31, 2015, and the efficacy of clopidogrel and aspirin in different ESRS subgroups was assessed with respect to reducing the risk of a combined vascular event of recurrent stroke, myocardial infarction, or primary intracranial hemorrhage. Totally, 1175 non-cardiac stroke patients were included, among which 878 patients completed follow-up surveys. Of the patients who completed the follow-up, 458 (52.2%) had an ESRS > 3, and 621 (70.7%) received aspirin. Patients who received clopidogrel tended to be older, and more patients had hypertension, diabetes, and an ESRS > 3 than patients who received aspirin. Over a mean follow-up of 5.2 years, the rate of combined vascular events was 19.3% in the aspirin group and 16.7% in the clopidogrel group. Compared with clopidogrel-treated patients, a significant (P = 0.044) reduction in combined vascular events in aspirin-treated patients was observed in patients with an ESRS ≤ 3 (OR, odds ratio 0.5; 95% CI 0.3 to 0.9). However, a significant (P = 0.002) increase in combined vascular events was observed in patients with an ESRS > 3 (OR 2.2; 95% CI 1.3 to 3.8). More clopidogrel-treated patients with ESRS < 3 and ESRS = 3 discontinued treatment than their counterparts who took aspirin (P < 0.05). Adverse drug events, such as digestive discomfort and bleeding, were similar. In conclusion, clopidogrel is suggested for patients with an ESRS > 3 and aspirin for patients with an ESRS ≤ 3 for the secondary prevention of noncardioembolic ischemic stroke in Chinese patients.



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Unilateral partial oculomotor nerve palsy caused by Guillain–Barré syndrome



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F-wave of single firing motor units: correct or misleading criterion of motoneuron excitability in humans?

Abstract

Motoneuron excitability is a critical property for information processing during motor control. F-wave (a motoneuronal recurrent discharge evoked by a motor antidromic volley) is often used as a criterion of motoneuron pool excitability in normal and neuromuscular diseases. However, such using of F-wave calls in question. The present study was designed to explore excitability of single low-threshold motoneurons during their natural firing in healthy humans and to ascertain whether F-wave is a correct measure of motoneuronal excitability. Single motor units (MUs) were activated by gentle voluntary muscle contractions. MU peri-stimulus time histograms and motoneuron excitability changes within a target interspike interval were analysed during testing by motor antidromic and Ia-afferent volleys. It was found that F-waves could be occasionally recorded in some low-threshold MUs. However, during evoking F-wave, in contrast with the H-reflex, peri-stimulus time histograms revealed no statistically significant increase in MU discharge probability. Moreover, surprisingly, motoneurons appeared commonly incapable to fire a recurrent discharge within the most excitable part of a target interval. Thus, the F-wave, unlike the H-reflex, is the incorrect criterion of motoneuron excitability resulting in misleading conclusions. However, it does not exclude the validity of the F-wave as a clinical tool for other aims. It was concluded that the F-wave was first explored in low-threshold MUs during their natural firing. The findings may be useful at interpretations of changes in the motoneuron pool excitability in neuromuscular diseases.



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Estimated prevalence of multiple sclerosis in Italy in 2015

Abstract

Italy is a high risk area for multiple sclerosis (MS) as confirmed by the numerous prevalence and incidence studies conducted in several regions/districts of the country. Nevertheless, there are no recent published epidemiological data, nor studies about the total prevalence of MS in Italy. Our aim was to update as of 2015 the prevalence rates of MS in different geographical areas using already published epidemiological studies, and to estimate the overall prevalence of the disease in Italy. We made a search in MEDLINE database of all published studies on epidemiology of MS in Italy. Then, we applied, to the already published prevalence data, the last published incidence and mortality rates to recalculate, as of 2015, the prevalence of MS. So, we calculated the mean prevalence rate from our extrapolations, and we applied it to the population in 2015 to estimate the number of MS patients in Italy. Our prevalence extrapolations ranged from 122 to 232 cases/100,000 in the mainland and Sicily, with an average of 176/100,000, and from 280 to 317 cases/100,000 in Sardinia with an average of 299/100,000. Applying these media to the Italian population in 2015, we obtained an estimate of more than 109,000 MS patients in Italy. Our estimates were higher than the latest published rates but consistent with the annual increase of prevalence due to incidence that exceeds mortality, with the increase of survival and, maybe, with the probable increase of incidence.



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A wearable proprioceptive stabilizer for rehabilitation of limb and gait ataxia in hereditary cerebellar ataxias: a pilot open-labeled study

Abstract

The aim of this pilot study is to test the feasibility and effectiveness of a wearable proprioceptive stabilizer that emits focal mechanical vibrations in patients affected by hereditary cerebellar ataxias. Eleven adult patients with a confirmed genetic diagnosis of autosomal dominant spinocerebellar ataxia or Friedreich's ataxia were asked to wear an active device for 3 weeks. Assessments were performed at baseline, after the device use (T1), and 3 weeks after (T2). SARA, 9-HPT, PATA, 6MWT, and spatial and temporal gait parameters, measured with a BTS-G-Walk inertial sensor, were used as study endpoints. As expected, no adverse effects were reported. Statistically significant improvements in SARA, 9HPT dominant hand, PATA test, 6MWT, cadence, length cycle, support right/cycle, support left/cycle, flight right/cycle, flight left/cycle, double support right/cycle, double support left/cycle, single support right/cycle, and single support left/cycle were observed between T0 and T1. All parameters improved at T1 did not show statistically significant differences a T2, with the exception of length of cycle. This small open-labeled study shows preliminary evidence that focal mechanical vibration exerted by a wearable proprioceptive stabilizer might improve limb and gait ataxia in patients affected by hereditary cerebellar ataxias.



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Insights into the relationships between diabetes, prediabetes, and cancer

Abstract

Diabetes mellitus and cancer are two growing health problems. They have in common many modifiable risk factors including sex, age, obesity, physical activity, diet, alcohol, and smoking, and have a long latency before overtly manifesting. Patients with diabetes experience a roughly 20–25% higher cancer incidence compared to individuals without diabetes, and it depends on cancer site. Moreover, patients with diabetes who further develop cancer have increased early and late mortality in comparison with cancer patients without diabetes. Prediabetes and metabolic syndrome are also related to an increased risk of developing and die from cancer. Possible mechanisms linking diabetes and prediabetes with cancer include hyperglycemia (endogenous or exogenous), hyperinsulinemia, and alterations of insulin-like growth factor system, chronic subclinical inflammation, abnormalities in sex hormone metabolism, and adipokines. It becomes crucial to define the right orientation of the associations between diabetes and cancer in order to identify the modifiable pathogenic mechanisms. The common soil hypothesis claims that prediabetes and diabetes, as well as metabolic syndrome, may be considered a surrogate sign for dietary risk factors of cancer. The clepsydra of foods may help choose foods associated with healthy benefit while avoiding foods associated with harm, including cancer.



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Aldehyde dehydrogenase activity plays no functional role in stem cell-like properties in anaplastic thyroid cancer cell lines

Abstract

Recent studies have revealed that aldehyde dehydrogenase (ALDH) is a candidate marker for thyroid cancer stem cells, although its activity is flexible. The goal of this study is to clarify the functional significance of ALDH enzymatic activity on thyroid cancer stem cells properties in anaplastic thyroid cancer cell lines. In vitro sphere formation assay was used to judge the stemness of 4 anaplastic thyroid cancer cell lines (FRO, ACT1, 8505C, and KTC3). Two well-known ALDH inhibitors, N,N-diethylaminobenzaldehyde (DEAB) and disulfiram (DS), were first used. DEAB (50 μM) almost completely suppressed ALDH activity without affecting cell proliferation or spherogenicity. Lack of effect of ALDH suppression on spherogenicity was confirmed using shRNA for ALDH1A3, an ALDH isozyme predominantly expressed in anaplastic thyroid cancer cell lines. In contrast, an ALDH2 inhibitor DS (1 μM) inhibited spherogenicity but did not inhibit ALDH1A3 activity. Based on the recent article from another group reporting the importance of sonic hedgehog (Shh) signaling in ALDH activity and spherogenicity in thyroid cancer, the effects of the Shh inhibitor cyclopamine were also studied. Like DS, cyclopamine (1 μM) decreased spherogenicity but not ALDH activity. Finally, exogenous expression of ALDH1A3 in otherwise ALDH TPC1 cells (a papillary thyroid cancer cell line) revealed no effect on spherogenicity. In conclusion, we here show no functional role for ALDH activity in thyroid thyroid cancer stem cells properties. That is, ALDH activity and spherogenicity are clearly dissociable. Further understanding of thyroid cancer stem cells biology in thyroid cancers remains necessary for the future development of thyroid thyroid cancer stem cells-targeted therapies.



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Myofibroblast repair mechanisms post-inflammatory response: a fibrotic perspective

Abstract

Introduction

Fibrosis is a complex chronic disease characterized by a persistent repair response. Its pathogenesis is poorly understood but it is typically the result of chronic inflammation and maintained with the required activity of transforming growth factor-β (TGFβ) and extracellular matrix (ECM) tension, both of which drive fibroblasts to transition into a myofibroblast phenotype.

Findings

As the effector cells of repair, myofibroblasts migrate to the site of injury to deposit excessive amounts of matrix proteins and stimulate high levels of contraction. Myofibroblast activity is a decisive factor in whether a tissue is properly repaired by controlled wound healing or rendered fibrotic by deregulated repair. Extensive studies have documented the various contributing factors to an abrogated repair response. Though these fibrotic factors are known, very little is understood about the opposing antifibrotic molecules that assist in a successful repair, such as prostaglandin E2 (PGE2) and ECM retraction. The following review will discuss the general development of fibrosis through the transformation of myofibroblasts, focusing primarily on the prominent profibrotic pathways of TGFβ and ECM tension and antifibrotic pathways of PGE2 and ECM retraction.

Conclusions

The idea is to understand the ways in which the cell, after an injury and inflammatory response, normally controls its repair mechanisms through its homeostatic regulators so as to mimic them therapeutically to control abnormal pathways.



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Optimization and Rapid Prototyping of Catadioptric Omnidirectional Stereo Sensors

Abstract

Omnidirectional stereo imaging provides useful depth information for autonomous navigation. In principle, omnidirectional stereo images can be achieved at a low cost, using a single camera and two curved mirrors, but such systems are not widely deployed. Here we describe the optimization and rapid prototyping of a low-cost omnidirectional stereo sensor for a telepresence robot. We consider single-viewpoint and non-single-viewpoint designs. We present a new way of relaxing single-viewpoint constraints, while retaining the ability to vertically rectify images. We also present a method of optimizing the resulting design to minimize depth errors. However, we show that despite these steps, nonsingle-viewpoint designs produce stereo disparities over a more practical range of distances. The lack of a single viewpoint could potentially introduce distortions that affect stereo matching, but these distortions are removed by projecting rays through the mirror geometry. We also describe a new method for rapid prototyping of curved mirrors using 3D printing and vacuum forming.



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Environmental risk assessment of pesticides: state of the art and prospective improvement from science

Abstract

Pesticide risk assessment in the European regulatory framework is mandatory performed for active substances (pesticides) and the plant protection products they are constituents of. The aim is to guarantee that safe use can be achieved for the intended use of the product. This paper provides a feedback on the regulatory environmental risk assessment performed for pesticide registration at the EU and member state levels. The different steps of pesticide registration are addressed considering both exposure and hazard. In this paper, we focus on the environmental fate and behaviour in surface water together with the aquatic ecotoxicity of the substances to illustrate pesticide regulatory risk assessment performed for aquatic organisms. Current methodologies are presented along with highlights on potential improvements. For instance, as regards exposure aspects, moving from field based to landscape risk assessments is promising. Regarding ecotoxicology, ecological models may be valuable tools when applied to chemical risk assessment. In addition, interest and further developments to better take into account mitigation measures in risk assessment and management are also presented.



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Development of a Physiologically Based Pharmacokinetic Modelling Approach to Predict the Pharmacokinetics of Vancomycin in Critically Ill Septic Patients

Abstract

Background and Objectives

Sepsis is characterised by an excessive release of inflammatory mediators substantially affecting body composition and physiology, which can be further affected by intensive care management. Consequently, drug pharmacokinetics can be substantially altered. This study aimed to extend a whole-body physiologically based pharmacokinetic (PBPK) model for healthy adults based on disease-related physiological changes of critically ill septic patients and to evaluate the accuracy of this PBPK model using vancomycin as a clinically relevant drug.

Methods

The literature was searched for relevant information on physiological changes in critically ill patients with sepsis, severe sepsis and septic shock. Consolidated information was incorporated into a validated PBPK vancomycin model for healthy adults. In addition, the model was further individualised based on patient data from a study including ten septic patients treated with intravenous vancomycin. Models were evaluated comparing predicted concentrations with observed patient concentration–time data.

Results

The literature-based PBPK model correctly predicted pharmacokinetic changes and observed plasma concentrations especially for the distribution phase as a result of a consideration of interstitial water accumulation. Incorporation of disease-related changes improved the model prediction from 55 to 88% within a threshold of 30% variability of predicted vs. observed concentrations. In particular, the consideration of individualised creatinine clearance data, which were highly variable in this patient population, had an influence on model performance.

Conclusion

PBPK modelling incorporating literature data and individual patient data is able to correctly predict vancomycin pharmacokinetics in septic patients. This study therefore provides essential key parameters for further development of PBPK models and dose optimisation strategies in critically ill patients with sepsis.



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Data to inform a social media component for professional development and practices: A design-based research study

Publication date: February 2017
Source:Data in Brief, Volume 10
Author(s): Jeanette Novakovich, Steven Shaw, Sophia Miah
This DIB article includes the course artefacts, instruments, survey data, and descriptive statistics, along with in-depth correlational analysis for the first iteration of a design-based research study on designing curriculum for developing online professional identity and social media practices for a multi-major advanced professional writing course. Raw data was entered into SPSS software. For interpretation and discussion, please see the original article entitled, "Designing curriculum to shape professional social media skills and identity in virtual communities of practice" (J. Novakovich, S. Miah, S. Shaw, 2017) [1].



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