Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients

Publication date: January 2018
Source:European Journal of Cancer, Volume 88
Author(s): S. Valpione, G. Gremel, P. Mundra, P. Middlehurst, E. Galvani, M.R. Girotti, R.J. Lee, G. Garner, N. Dhomen, P.C. Lorigan, R. Marais
IntroductionTumour burden is a prognostic biomarker in metastatic melanoma. However, tumour burden is difficult to measure and there are currently no reliable surrogate biomarkers to easily and reliably determine it. The aim of this study was to assess the potential of plasma total cell free DNA as biomarker of tumour burden and prognosis in metastatic melanoma patients.Materials and methodsA prospective biomarker cohort study for total plasma circulating cell-free DNA (cfDNA) concentration was performed in 43 metastatic melanoma patients. For 38 patients, paired blood collections and scan assessments were available before treatment and at first response evaluation. Tumour burden was calculated as the sum of volumes from three-dimensional radiological measurements of all metastatic lesions in individual patients.ResultsBaseline cfDNA concentration correlated with pre-treatment tumour burden (ρ = 0.52, P < 0.001). Baseline cfDNA levels correlated significantly with hazard of death and overall survival, and a cut off value of 89 pg/μl identified two distinct prognostic groups (HR = 2.22 for high cfDNA, P = 0.004). Patients with cfDNA ≥89 pg/μl had shorter OS (10.0 versus 22.7 months, P = 0.009; HR = 2.22 for high cfDNA, P = 0.004) and the significance was maintained when compared with lactic dehydrogenase (LDH) in a multivariate analysis. We also found a correlation between the changes of cfDNA and treatment-related changes in tumour burden (ρ = 0.49, P = 0.002). In addition, the ratio between baseline cfDNA and tumour burden was prognostic (HR = 2.7 for cfDNA/tumour volume ≥8 pg/(μl*cm³), P = 0.024).ConclusionsWe have demonstrated that cfDNA is a surrogate marker of tumour burden in metastatic melanoma patients, and that it is prognostic for overall survival.



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Prognostic impact of interval breast cancer detection in women with pT1a N0M0 breast cancer with HER2-positive status: Results from a multicentre population-based cancer registry study

Publication date: January 2018
Source:European Journal of Cancer, Volume 88
Author(s): A. Musolino, F. Falcini, A. Sikokis, D. Boggiani, A. Rimanti, B. Pellegrino, E.M. Silini, N. Campanini, E. Barbieri, C. Zamagni, R. Degli Esposti, L. Cortesi, G. Bisagni, L. Cavanna, A. Frassoldati, P. Sgargi, M. Michiara
BackgroundAlthough human epidermal growth factor receptor 2 (HER2) overexpression is associated with poor prognosis, patients (pts) with pT1a N0M0 breast cancers (BCs) have an excellent outcome across all subtypes. Interval cancers (ICs) have poorer survival than screen-detected (SD) tumours, and an association has been reported between ICs and HER2 overexpression. We aimed to determine, in a general population of pT1a N0M0 BCs with known screening status, whether HER2-positive ICs have a poorer outcome than HER2-positive SD cancers.MethodsWe evaluated all incident pT1a N0M0 BCs (n = 874) collected in the Emilia-Romagna region (Italy) from 2003 to 2009 and diagnosed in women aged 50–69. Pts unexposed to screening, with unknown HER2 status and/or treated with adjuvant trastuzumab were excluded from analysis.ResultsSixty-one percent of the BCs were SD, whereas 19% were ICs. BCs with high histologic grade, hormone receptor–negative or HER2-positive status (odds ratio=1.7; 95% confidence interval [CI]: 1.1–2.7) were more likely ICs. Median follow-up was 115 months. The 10-year invasive disease-free survival (iDFS) for HER2-positive ICs was lower than that for HER2-positive SD cancers: 75.0% (95% CI: 55.5%–94.5%) versus 93.8% (95% CI: 86.5%–100%). An interaction between ICs and HER2-positive status was found for poorer iDFS after adjusting for prognostic variables (HR = 5.3; 95% CI: 1.6–16.7).ConclusionsIC detection may identify pts with HER2-positive pT1a N0M0 tumours in whom the rate of recurrence justifies consideration for conventional, anti-HER2, adjuvant treatment.



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Corrigendum to “Loss of tight junction plaque molecules in breast cancer tissues is associated with a poor prognosis in patients with breast cancer” [Eur J Cancer 40 (18) (2004) 2717–2725]

Publication date: Available online 23 November 2017
Source:European Journal of Cancer
Author(s): Tracey A. Martin, Gareth Watkins, Robert E. Mansel, Wen G. Jiang




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Overall survival in MERiDiAN, a double-blind placebo-controlled randomised phase III trial evaluating first-line bevacizumab plus paclitaxel for HER2-negative metastatic breast cancer

Publication date: Available online 23 November 2017
Source:European Journal of Cancer
Author(s): David Miles, David Cameron, Magalie Hilton, Josep Garcia, Joyce O'Shaughnessy




http://ift.tt/2zyJuBO

In the Piriform Cortex, the Primary Impetus for Information Encoding through Synaptic Plasticity Is Provided by Descending Rather than Ascending Olfactory Inputs

Abstract

Information encoding by means of persistent changes in synaptic strength supports long-term information storage and memory in structures such as the hippocampus. In the piriform cortex (PC), that engages in the processing of associative memory, only short-term synaptic plasticity has been described to date, both in vitro and in anesthetized rodents in vivo. Whether the PC maintains changes in synaptic strength for longer periods of time is unknown: Such a property would indicate that it can serve as a repository for long-term memories. Here, we report that in freely behaving animals, frequency-dependent synaptic plasticity does not occur in the anterior PC (aPC) following patterned stimulation of the olfactory bulb (OB). Naris closure changed action potential properties of aPC neurons and enabled expression of long-term potentiation (LTP) by OB stimulation, indicating that an intrinsic ability to express synaptic plasticity is present. Odor discrimination and categorization in the aPC is supported by descending inputs from the orbitofrontal cortex (OFC). Here, OFC stimulation resulted in LTP (>4 h), suggesting that this structure plays an important role in promoting information encoding through synaptic plasticity in the aPC. These persistent changes in synaptic strength are likely to comprise a means through which long-term memories are encoded and/or retained in the PC.

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Walking, Gross Motor Development, and Brain Functional Connectivity in Infants and Toddlers

Abstract

Infant gross motor development is vital to adaptive function and predictive of both cognitive outcomes and neurodevelopmental disorders. However, little is known about neural systems underlying the emergence of walking and general gross motor abilities. Using resting state fcMRI, we identified functional brain networks associated with walking and gross motor scores in a mixed cross-sectional and longitudinal cohort of infants at high and low risk for autism spectrum disorder, who represent a dimensionally distributed range of motor function. At age 12 months, functional connectivity of motor and default mode networks was correlated with walking, whereas dorsal attention and posterior cingulo-opercular networks were implicated at age 24 months. Analyses of general gross motor function also revealed involvement of motor and default mode networks at 12 and 24 months, with dorsal attention, cingulo-opercular, frontoparietal, and subcortical networks additionally implicated at 24 months. These findings suggest that changes in network-level brain–behavior relationships underlie the emergence and consolidation of walking and gross motor abilities in the toddler period. This initial description of network substrates of early gross motor development may inform hypotheses regarding neural systems contributing to typical and atypical motor outcomes, as well as neurodevelopmental disorders associated with motor dysfunction.

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Coincidence of pollen season with the first fetal trimester together with early pet exposure is associated with sensitisation to cat and dog allergens in early childhood: a Finnish population-based study

Abstract

Background

Children whose 11^th fetal week falls in pollen season (spring) reportedly have an increased risk of sensitisation to food allergens. No such finding has been reported for pet allergens.

Objective

The aim of the study was to 1) evaluate the incidence of pet (dog and cat) sensitisation according to the season of the 11^th fetal week and 2) whether the association between pet exposure and respective sensitisation is modified by the coincidence of the 11^th fetal week with pollen season.

Methods

The study population comprised all children (born between 2001 and 2006) in the province of South Karelia, Finland (N=5920). Their data of IgE and skin prick tests to pet allergens (N=538) were collected from patient records and linked with questionnaire data on pet exposure.

Results

The seasonal incidence peak of cat sensitisation was observed in children whose 11^th fetal week occurred in June (7.4%) and that of dog sensitisation in April (3.8%) and June (4.7%). The relative rate (RR) for cat sensitisation was 2.92 (95% CI 1.40-6.08) in children with cat exposure alone, 8.53 (4.07−17.86) in children with cat and fetal pollen exposures, and 0.61 (0.20−1.83) in children exposed to pollen alone, compared with children without these exposures. The respective RRs for dog sensitisation were 2.17 (1.13-4.19), 4.40 (2.19−8.83) and 1.65 (0.77−3.53).

Conclusions and clinical relevance

Coincidence of the first fetal trimester with pollen season strengthens the association between pet exposure and respective sensitisation. Pollen exposure at early pregnancy may deviate immune system towards Th2 type reactivity promoting development of specific allergy in case allergen exposure occurred. Therefore, primary prevention of allergic diseases may need to begin during early pregnancy.

This article is protected by copyright. All rights reserved.

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Coincidence of pollen season with the first fetal trimester together with early pet exposure is associated with sensitisation to cat and dog allergens in early childhood: a Finnish population-based study

Abstract

Background

Children whose 11^th fetal week falls in pollen season (spring) reportedly have an increased risk of sensitisation to food allergens. No such finding has been reported for pet allergens.

Objective

The aim of the study was to 1) evaluate the incidence of pet (dog and cat) sensitisation according to the season of the 11^th fetal week and 2) whether the association between pet exposure and respective sensitisation is modified by the coincidence of the 11^th fetal week with pollen season.

Methods

The study population comprised all children (born between 2001 and 2006) in the province of South Karelia, Finland (N=5920). Their data of IgE and skin prick tests to pet allergens (N=538) were collected from patient records and linked with questionnaire data on pet exposure.

Results

The seasonal incidence peak of cat sensitisation was observed in children whose 11^th fetal week occurred in June (7.4%) and that of dog sensitisation in April (3.8%) and June (4.7%). The relative rate (RR) for cat sensitisation was 2.92 (95% CI 1.40-6.08) in children with cat exposure alone, 8.53 (4.07−17.86) in children with cat and fetal pollen exposures, and 0.61 (0.20−1.83) in children exposed to pollen alone, compared with children without these exposures. The respective RRs for dog sensitisation were 2.17 (1.13-4.19), 4.40 (2.19−8.83) and 1.65 (0.77−3.53).

Conclusions and clinical relevance

Coincidence of the first fetal trimester with pollen season strengthens the association between pet exposure and respective sensitisation. Pollen exposure at early pregnancy may deviate immune system towards Th2 type reactivity promoting development of specific allergy in case allergen exposure occurred. Therefore, primary prevention of allergic diseases may need to begin during early pregnancy.

This article is protected by copyright. All rights reserved.

http://ift.tt/2ArJL9s

Facilitated acquisition of the classically conditioned eyeblink response in active duty military expressing posttraumatic stress disorder symptoms

Publication date: 26 February 2018
Source:Behavioural Brain Research, Volume 339
Author(s): Justin D. Handy, Pelin Avcu, Nora Ko, Alejandro Ortiz, Michael J. Doria, Richard J. Servatius
ObjectiveLearning diathesis models underscore the role of hyper-conditioning in the development of PTSD following trauma exposure. Eyeblink classical conditioning is one method of examining associative learning biases independent of fear and threat produced by trauma. Facilitated learning is apparent in individuals self-expressing PTSD symptoms, as well as behaviorally inhibited (BI) temperament, a vulnerability factor for PTSD. Here, we examine eyeblink conditioning in active duty military personnel and relate learning with PTSD symptomology.MethodVolunteers were 83 active duty United States Coast Guard personnel (18 females) recruited from small boat stations. Personnel were administered the PTSD Checklist (PCL) to assess current PTSD symptoms using DSM-IV criteria. BI temperament was assessed with the Adult Measure of Behavioural Inhibition (AMBI). Eyeblink conditioning was conducted using a partial reinforcement schedule, whereby paired trials (500-ms pure tone conditioned stimulus co-terminating with a 50-ms air-puff unconditional stimulus) were interpolated with 50% CS-alone trials.ResultsConsistent with previous work, there was a high degree of concordance between BI and incidence of PTSD. Further, PTSD was associated with faster learning during the acquisition period, with conditioned responding sustained through the extinction period.ConclusionsThese results reinforce the relationship between BI and PTSD in an active duty military sample, supporting previous observations in veteran and civilian samples. The conditioning data are consistent with predictions derived from a learning diathesis model of stress and anxiety, suggesting facilitated associative learning may represent an additional vulnerability for the development and maintenance of stress-related pathology.



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Confirmed Ceylon krait (Bungarus ceylonicus) envenoming in Sri Lanka resulting in neuromuscular paralysis: a case report

Ceylon krait (Bungarus ceylonicus) is a venomous elapid snake endemic to Sri Lanka. It inhabits shaded home gardens and forests in the wet zone of Sri Lanka and might creep into houses in the night. Despite frequ...

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Oral keratinocytes synthesize CTACK: a new insight into the pathophysiology of the oral mucosa

Abstract

The skin-associated chemokine CTACK plays a key role in many inflammatory conditions and could be instrumental in the pathophysiology of tissue-specific immunological diseases such as oral lichen planus (OLP). In the present study, we investigated by RT-PCR, ELISA, chemotaxis assays, and fluorescence-activated cell sorting (FACS) the production of CTACK in oral keratinocytes, its expression in tissues from normal and OLP patients, and its role in T cell recruitment. CTACK was produced by the oral epithelium and it affects chemotaxis of memory CLA+ cells to the oral epithelium. CTACK mRNA was expressed constitutively in primary oral epithelium and was increased during pro-inflammatory IFN-γ treatment. We found a constitutive production of CTACK at a protein level in oral primary cells that increased after IFN-γ treatment. Moreover, we confirmed that CTACK attracts memory T cells and those T cells that express CLA above the level of basal migration.

This article is protected by copyright. All rights reserved.

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Tank bromeliads capture Saharan dust in El Yunque National Forest, Puerto Rico

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Dana L. Royer, Kylen M. Moynihan, Carolyn Ariori, Gavin Bodkin, Gabriela Doria, Katherine Enright, Rémy Hatfield-Gardner, Emma Kravet, C. Miller Nuttle, Lisa Shepard, Timothy C.W. Ku, Suzanne O'Connell, Phillip G. Resor
Dust from Saharan Africa commonly blows across the Atlantic Ocean and into the Caribbean. Most methods for measuring this dust either are expensive if collected directly from the atmosphere, or depend on very small concentrations that may be chemically altered if collected from soil. Tank bromeliads in the dwarf forest of El Yunque National Forest, Puerto Rico, have a structure of overlapping leaves used to capture rainwater and other atmospheric inputs. Therefore, it is likely that these bromeliads are collecting in their tanks Saharan dust along with local inputs. Here we analyze the elemental chemistry, including rare earth elements (REEs), of tank contents in order to match their chemical fingerprint to a provenance of the Earth's crust. We find that the tank contents differ from the local soils and bedrock and are more similar to published values of Saharan dust. Our study confirms the feasibility of using bromeliad tanks to trace Saharan dust in the Caribbean.



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Changes in oxidative potential of soil and fly ash after reaction with gaseous nitric acid

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Ying Zhan, Matthew Ginder-Vogel, Martin M. Shafer, Yinon Rudich, Michal Pardo, Itzhak Katra, David Katoshevski, James J. Schauer
The goal of this study was to examine the impact of simulated atmospheric aging on the oxidative potential of inorganic aerosols comprised primarily of crustal materials. Four soil samples and one coal fly ash sample were artificially aged in the laboratory through exposure to the vapor from 15.8 M nitric acid solution for 24 h at room temperature. Native and acid-aged samples were analyzed with a cellular macrophage and acellular dithionthreitol assays to determine oxidative potential. Additionally, the samples were analyzed to determine the concentration of 50 elements, both total and the water-soluble fraction of these elements by Sector Field Inductively Coupled Plasma Mass Spectrometry (SF-ICMS) and crystalline mineral composition using X-ray Diffraction (XRD). The results show that reactions with gaseous nitric acid increase the water-soluble fraction of many elements, including calcium, iron, magnesium, zinc, and lead. The mineral composition analysis documented that calcium-rich minerals present in the soils (e.g., calcite) are converted into different chemical forms, such as calcium nitrate (Ca(NO3)2). The nitric acid aging process, which can occur in the atmosphere, leads to a 200–600% increase in oxidative potential, as measured by cellular and acellular assays. This laboratory study demonstrates that the toxic effects of aged versus freshly emitted atmospheric dust may be quite different. In addition, the results suggest that mineralogical analysis of atmospheric dust may be useful in understanding its degree of aging.



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PAHs in Chinese atmosphere Part I: Concentration, source and temperature dependence

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Wan-Li Ma, Li-Yan Liu, Hong-Liang Jia, Meng Yang, Yi-Fan Li
The study on atmospheric polycyclic aromatic hydrocarbons (PAHs) in China has regional and global significance to understand the large scale atmospheric transport of PAHs. In this study, 16 US EPA priority PAHs were analyzed in more than 500 pairs of gas and particle phases samples, which were collected on the same schedule on a weekly basis from August 2008 to July 2009 at 11 urban sites (6 northern cities and 5 southern cities) across China. The average concentration was 239 ± 329 ng/m³ and 165 ± 164 ng/m³ for the northern cities and the southern cities, respectively. Different seasonal variations of atmospheric PAHs were observed between northern cities and southern cities, which were mainly caused by the different temperature effects in winter. Identified by principal component analysis, coal combustion and vehicle exhaust were the major sources of atmospheric PAHs in northern and southern cities of China, respectively. The temperature dependences of atmospheric PAHs were also different, which were caused by the different influences of temperature on identified sources. To our knowledge, this is the first comprehensive study to report the difference with concentrations, seasonal variations, sources and temperature dependences of atmospheric PAHs between northern cities and southern cities in China.

Graphical abstract

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The adverse effects of gas-burning CHP systems on the local air quality

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Javad Jazaeri, Mahdi Pahlevani
One of the benefits of the combined heat and power (CHP) systems is reducing greenhouse gases (GHG) in the national level. These systems are installed in the close vicinity of local communities and their pollution can directly affect the local environment. This paper studies the adverse environmental effects of a 2 MW gas-burning CHP (GB-CHP) system in a residential community in Mashhad, Iran. We compare the amount of CO2 and NOx emissions from the GB-CHP with the conventional choice of supplying electricity from the central power plants and heat from the locally installed boilers. The results show that the GB-CHP system increases local CO2 and NOx emissions by approximately two and six times, respectively. The NOx emission is increased from 3.1 tonnes to 18.7 tonnes. The CO2 emission increases from 3623 tonnes to 7238 tonnes. Furthermore, we use Gaussian Dispersion model to estimate the concentration of these emissions in the local area using the weather conditions of the most polluted times of the previous year. The results show that for a 3-meter stack, the maximum concentration of CO2 and NOx are 14.8 mg/m3 and 38.1 μg/m3, respectively. Our analysis shows that increasing the height of the GB-CHP stack from 3 meters to 10 meters reduces the concentration by 40%.



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Consistency and applicability of parameterization schemes for the size-resolved aerosol activation ratio based on field measurements in the North China Plain

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Jiangchuan Tao, Chunsheng Zhao, Nan Ma, Ye Kuang
Parameterization of the size-resolved particle activation ratio (AR) is useful for the prediction and analysis of the cloud condensation nuclei (CCN) number concentration (NCCN). Critical issues for the application of AR parameterizations in models are (1) the consistency of the different parameterization schemes in terms of fitting AR curves and (2) the applicability of the estimate of NCCN under different aerosol conditions. These issues are discussed in this study based on summertime measurements of the size-resolved AR in the North China Plain. By comparing parameterized AR curves, variations in the fitting parameters and application to NCCN calculations, the consistency of the three existing parameterization schemes is confirmed. Based on an analysis using representative AR fitting parameters, the method commonly used to calculate NCCN with a fixed AR was found to be accurate, except during periods affected by strong black carbon (BC) emissions or new particle formation (NPF) events. The NCCN value was overestimated by approximately 10% when BC aerosol emissions were abundant and deviated from the 1:1 line by 15% during NPF events. The bias of the calculated NCCN due to these significant emission or aerosol production events cannot be eliminated by using the appropriate representative fitting parameters. Under these circumstances, accurate prediction of NCCN requires real-time aerosol hygroscopicity data based on CCN measurements. This research furthers our understanding of the relationship between aerosol cloud activation and aerosol spectra.



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Analysis of patterns in the concentrations of atmospheric greenhouse gases measured in two typical urban clusters in China

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Lixin Liu, Pieter P. Tans, Lingjun Xia, Lingxi Zhou, Fang Zhang
China is the largest emitter of greenhouse gases, and urban clusters play an essential role in China's carbon emissions because of the country's unbalanced economic development. In this paper, the discrete air sample measurements of atmospheric CO2, CH4, and CO during the period between 2007 and 2013 from Shangdianzi (SDZ) station in Jing-Jin-Ji (JJJ) region and Linan (LAN) station in Yangtze River Delta (YRD) region, respectively, are presented and characterized. By backward trajectory cluster analysis, the low background CO2 mole fraction and similar long-term trends with Waliguan global station (WLG) were observed at SDZ because most of the air masses originate mostly from remote clean terrestrial areas in the north with limited information of anthropogenic emissions. But the background CH4 and CO are influenced mainly by ruminants and rice field emission from the surrounding regions and urban cluster emission in the JJJ region, which lead to the higher CH4 and CO in summer at SDZ. Whereas, the CO2, CH4 and CO background values observed at LAN are higher by the combined effects of long-distance atmospheric transportation from Northern and Central China and urban clusters emission from the YRD region. The observed polluted data at SDZ and LAN are all strongly affected by regional and local anthropogenic emissions, which lead to the higher GHGs concentrations compared to the background data. However, because the air mass transportation from the north is weak in winter and no winter heating is required and vegetation photosynthesis is still stronger in the south of China, the CO2 concentration at LAN is lower than that at SDZ in autumn and winter. The polluted CO value at SDZ is found considerably higher than that at LAN, especially in spring and winter. By analyzing the correlations of observed regional enhanced values of CO2, CH4 and CO at the two stations, we find the significant correlation between them, which means they may share the common-source of anthropogenic emissions from the regional fossil fuel and biomass burning in cold season. Moreover, the high coal-consumption proportion with the low CO2 emissions factors, and much biomass burning with low combustion efficiency in JJJ region lead to the higher slope values of △CO2 and △CO in spring and winter at SDZ and considerably higher than that at LAN. The results can provide a further understanding of regional/local features of atmospheric GHGs under the influence of human activities in the urban clusters in China.



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Public willingness to pay for urban smog mitigation and its determinants: A case study of Beijing, China

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Kangyin Dong, Xiangang Zeng
With the deteriorating air pollution in the urban areas of China, particularly the unprecedentedly high levels of smog, public demand for clean air is increasing. This study examines the values of public willingness to pay (WTP) for three smog mitigation scenarios in the urban areas of Beijing and investigates their determinants by employing the contingent valuation method (CVM) and interval regression model. The empirical results suggest that more than 80% of the respondents is willing to pay for smog mitigation. Respondents' WTP rises with an increasing smog mitigation percentage, and the amount of WTP for 30%, 45%, and 60% smog mitigation, respectively, is 615.13 CNY, 716.34 CNY, and 914.49 CNY, accounting for 0.55%, 0.64%, and 0.82% of their annual income. In contrast with other cities, the ratio of WTP to income in Beijing seems to situate inside a relatively moderate range. Moreover, respondents' knowledge, risk perception, and attitude toward government are positively and significantly correlated with their WTP, and other determinants such as age, health condition, and annual income also significantly affect the value of WTP. We further recommend several important policy implications, which offer new evidence for developing specific policies to tackle smog pollution.



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Correlation between glucuronidation and covalent adducts formation with proteins of nonsteroidal anti-inflammatory drugs

Publication date: 15 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 112
Author(s): Hiroaki Shimada, Yuri Kobayashi, Sakiko Tanahashi, Atsushi Kawase, Taro Ogiso, Masahiro Iwaki
Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause idiosyncratic liver injury. Mechanisms involved in NSAID-induced liver injury are complex. Previous studies have suggested that acyl glucuronide of NSAIDs (NSAIDs-Glu) plays an important role in the development of liver injury via covalently binds to proteins and the resultant adduct induces immunological toxicity. As only some NSAIDs-Glu are commercially available, the evaluation of covalent protein adduct formation using ready-made NSAIDs-Glu is difficult and inconvenient. Moreover, glucuronidation potency varies with the NSAID, including stereoisomers. Therefore, in this study, we simultaneously examined the glucuronidation and covalent adduct formation using enantiomers of parent NSAIDs (ibuprofen, naproxen, pranoprofen, ketoprofen, and flurbiprofen) in rat liver microsomes. Glucuronides and covalent adducts were quantified by HPLC. The amount of covalent adduct increased with NSAIDs-Glu formation in the rat liver microsomes in a time-dependent manner. A significant positive correlation was observed between the AUC of NSAIDs-Glu and that of covalent adduct, except ketoprofen. Although ketoprofen exhibited the highest glucuronidation rate among the NSAIDs investigated, the amount of covalent adduct was similar to that for pranoprofen, which had the lowest glucuronidation rate. Thus, it may be difficult for ketoprofen glucuronide to covalently bind with proteins in the rat liver microsomes. Our results suggested that the amount of glucuronide formed is a key factor in predicting covalent bond formation with protein in NSAIDs, in addition to degradability and bindability with proteins of NSAIDs-Glu. Further studies are required to confirm the relationship between the tendency of glucuronidation and the formation of covalent adducts of NSAIDs.

Graphical abstract

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Impact of processing methods on the dissolution of artemether from two non-ordered mesoporous silicas

Publication date: 15 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 112
Author(s): Hira Tahir, Yasser Shahzad, Laura J. Waters, Talib Hussain, Abid Mehmood Yousaf, Tariq Mahmood, Rizwan Sheikh
Poor aqueous solubility is often linked with a poor dissolution rate and ultimately, limited bioavailability of pharmaceutical compounds. This study describes the application of mesoporous materials (Syloid 244 and Syloid AL1) in improving the dissolution rate of a drug with poor aqueous solubility, namely artemether, utilising different processing methods including physical mixing, co-grinding and solid dispersions prepared by solvent evaporation and the lyophilisation technique. The prepared formulations were extensively characterised for their solid-state properties and the drug release attributes were studied. Differential scanning calorimetry and X-ray diffraction confirmed conversion of crystalline artemether into a disordered and amorphous form, whilst no intermolecular interactions were detected between artemether and silica. Both silica grades enhanced the dissolution rate of artemether in comparison with drug alone, for example from 17.43% (±0.87%) to 71.55% (±3.57%) after 120mins with lyophilisation and Syloid 244 at a 1:3 ratio. This enhancement was also dependant on the choice of processing method, for example, co-ground and lyophilised formulations prepared with Syloid 244 at 1:3 ratio produced the most extensive dissolution, thus endorsing the importance of materials as well as choice of formulation method.

Graphical abstract

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Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and 4vHPV vaccine administered according to two- or three-dose schedules in girls aged 9–14 years: Results to month 36 from a randomized trial

Publication date: Available online 23 November 2017
Source:Vaccine
Author(s): Ting Fan Leung, Anthony Pak-Yin Liu, Fong Seng Lim, Franck Thollot, Helen May Lin Oh, Bee Wah Lee, Lars Rombo, Ngiap Chuan Tan, Roman Rouzier, Stéphanie De Simoni, Pemmaraju Suryakiran, Marjan Hezareh, Florence Thomas, Nicolas Folschweiller, Frank Struyf
This observer-blind study (clinicaltrials.gov NCT01462357) compared the immunogenicity and safety of two doses (2D) of the HPV-16/18 AS04-adjuvanted vaccine (2D of AS04-HPV-16/18) vs. two or three doses of the 4vHPV vaccine [2D or 3D of 4vHPV] in 1075 healthy girls aged 9–14 years. Girls were randomized (1:1:1) to receive 2D of AS04-HPV-16/18 at months (M) 0, 6 (N = 359), 2D of 4vHPV at M0, 6 (N = 358) or 3D of 4vHPV at M0, 2, 6 (N = 358). 351, 339 and 346 girls, respectively, returned for the concluding visit at M36. Superiority was demonstrated at M7 and M12; comparison of the immune response to both vaccine antigens was made between 2D of AS04-HPV-16/18 and 2D or 3D of 4vHPV at subsequent time points in the according-to-protocol immunogenicity cohort (ATP-I; N = 958 at M36) and the total vaccinated cohort (TVC: N = 1036 at M36). HPV-16/18-specific T-cell- and B-cell-mediated immune responses and safety were also investigated. At M36, anti-HPV-16/18 ELISA responses in the 2D AS04-HPV-16/18 group remained superior to those of the 2D and 3D 4vHPV groups. In the M36 TVC, geometric mean titers were 2.78-fold (HPV-16) and 6.84-fold (HPV-18) higher for 2D of AS04-HPV-16/18 vs. 2D of 4vHPV and 2.3-fold (HPV-16) and 4.14-fold (HPV-18) higher vs. 3D of 4vHPV. Results were confirmed by vaccine pseudovirion-based neutralisation assay. Numbers of circulating CD4⁺ T cells and B cells appeared similar across groups. Safety was in line with the known safety profiles of both vaccines. In conclusion, superior HPV-16/18 antibody responses were elicited by 2D of the AS04-HPV-16/18 compared with 2D or 3D of the 4vHPV vaccine in girls aged 9–14 years.Clinical Trial Registration: NCT0146235.



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Prevalencia de alteraciones en el complejo estilohioideo y tonsilolitos en la tomografía computarizada de haz cónico realizada en individuos con fisura labiopalatina

Publication date: Available online 23 November 2017
Source:Acta Otorrinolaringológica Española
Author(s): Eymi Valery Cazas-Duran, Izabel Regina Fischer Rubira-Bullen, Otávio Pagin, Bruna Stuchi Centurion-Pagin
Introducción y objetivosLos tonsilolitos y alteraciones en el complejo estilohioideo pueden presentar similar sintomatología a otras de diferente etiología. Los individuos con fisura labiopalatina describen similares síntomas en razón de las repercusiones anatómicas propias de esta anomalía. El objetivo de este estudio fue determinar la prevalencia de alteraciones del complejo estilohioideo y tonsilolitos en exámenes de tomografía computarizada de haz cónico en individuos con fisura labiopalatina.MétodosSegún criterios de inclusión y exclusión fueron analizadas 66 tomografías de 2.794 tomografías, en el software i- Cat visión ® con índice Kappa 0,8 intraexaminador.ResultadosLa prevalencia total de osificación del complejo estilohioideo incompleto en individuos con fisura labiopalatina fue de 66,6%, la prevalencia de estos hallazgos en el género femenino fue de 75% y 61,9% en el género masculino. La prevalencia total de tonsilolitos fue de 7,5%.ConclusiónEs de relevancia constatar en el informe radiológico la presencia de la calcificación del complejo estilo-hioideo y tonsilolitos. Debido a la proximidad anatómica y similar sintomatología clínica con otras alteraciones orofaciales presentes en los individuos con fisura labiopalatina, haciendo énfasis en individuos con fisura labiopalatina del género femenino, pacientes con fisura tipo transformen incisivo y posforamen incisivo por presentar mayor prevalencia. Conocer más sobre la morfometría anatómica de individuos con fisura labiopalatina coadyuva relevantemente en la elección de conductas clínicas y calidad de vida de estos pacientes, teniendo presente que la fisura labiopalatina es una de las anomalías más comunes.Introduction and objectivesTonsilloliths and abnormal stylohyoid complex may have similar symptoms to others of different aetiology. Individuals with cleft lip and palate describe similar symptoms because of the anatomical implications that are peculiar to this anomaly. The aim of this study was to determine the prevalence of abnormal stylohyoid complex and tonsilloliths on cone beam computed tomography in individuals with cleft lip and palate.MethodsAccording to the inclusion and exclusion criteria, 66 CT scans out of of 2,794 were analysed, on i- Cat ® vision software with 0.8 index Kappa intra-examiner.ResultsThe total prevalence of ossification of the incomplete stylohyoid complex in individuals with cleft lip and palate was 66.6%; the prevalence of these findings in females was 75% and 61.9% in males. The total prevalence of tonsilloliths was 7.5%.ConclusionIt is important to ascertain calcification of the stylohyoid complex and tonsilloliths in the radiological report, due to the anatomical proximity and similarsymptomatology to other orofacial impairments inindividuals with cleft lip and palate, focusing on females with oral cleft formation, patients with incisive trans foramen cleft and incisive post foramen cleft because they are more prevalent. Greater knowledge of the anatomical morphometry of individuals with cleft lip and palate greatly contributes towards the selection of clinical behaviours and the quality of life of these patients, since cleft lip and palateis one of the most common anomalies.



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Reductions in prostatic doses are associated with less acute morbidity in patients undergoing Pd-103 brachytherapy: Substantiation of the rationale for focal therapy

Publication date: Available online 23 November 2017
Source:Brachytherapy
Author(s): Adam Ferro, Hee Joon Bae, Gayane Yenokyan, Yi Le, Todd McNutt, Omar Mian, Carol Gergis, Chloe Haviland, Theodore L. DeWeese, Daniel Y. Song
PurposeInterest in prostate dose reduction or focal treatment exists due to expected reductions in treatment morbidity. Prior analyses have not generally corroborated relationships between prostate or urethral dose and urinary toxicity after brachytherapy, but such analyses have been performed on cohorts all receiving the same prescribed dose. We analyzed patients treated to differing prescription doses to assess acute urinary morbidity with dose reduction.Methods and MaterialsPatients treated with Pd-103 to either 125 Gy or 90–100 Gy were compared using the International Prostate Symptom Score (IPSS) at 1-month postimplant. Patients in the 90–100 Gy cohort began external beam radiation therapy after their 1-month assessment; thus, toxicities were measured before contribution from external beam radiation therapy. Patient/treatment characteristics were compared to verify subgroup homogeneity. Dose and change in IPSS 1 month after treatment were assessed using a multivariate linear regression model.ResultsOne hundred ninety-one and 41 patients were treated with 125 Gy versus 90–100 Gy, respectively. Preimplant and postimplant prostate volumes and initial IPSS were similar between groups. Higher prescription dose and increased pretreatment IPSS were independent predictors of increased 1-month IPSS. In addition, every 10 percentage point additional prostate volume receiving a given dose was associated with increase in IPSS after treatment for the same level of pretreatment IPSS.ConclusionLower prescription dose and decreased volume of high-dose regions to the prostate correlated with reduced acute urinary morbidity after brachytherapy. Our findings suggest that focal treatment approaches with modest dose reductions to subregions of the prostate may reduce acute morbidity and potentially expand the number of patients eligible for brachytherapy.



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The impact of adjuvant vaginal brachytherapy in women with Stage II uterine endometrioid carcinoma: Results of a National Cancer Database analysis

Publication date: Available online 23 November 2017
Source:Brachytherapy
Author(s): Joon K. Lee, Ahmed I. Ghanem, Ankit Modh, Charlotte Burmeister, Omar Mahmoud, G. Larry Maxwell, Mohamed A. Elshaikh
PurposeTo report survival outcomes in women with Stage II uterine endometrioid carcinoma who received adjuvant radiation therapy (RT) without chemotherapy using the National Cancer Database.Methods and MaterialsThe National Cancer Database was queried for women with International Federation of Gynecology and Obstetrics Stage II uterine endometrioid carcinoma who underwent hysterectomy followed by adjuvant RT without chemotherapy. The χ² tests were performed to compare differences in outcome by type of adjuvant RT (external beam radiation therapy [EBRT] alone, vaginal brachytherapy [VBT] alone, or combination of EBRT and VBT). Overall survival (OS) was assessed by Kaplan–Meier and log-rank tests. Univariate and multivariate analyses were performed to identify predictors of OS.ResultsWe identified 2681 women. Simple hysterectomy was performed on 2261 women (84%). Adjuvant EBRT, VBT, and combination RT were administered to 27%, 36%, and 37%, respectively. There was a statistically significant difference in OS by modality of adjuvant RT (p = 0.01) favoring women who received VBT alone or in combination with EBRT. The 5-year OS was 80%, 87%, and 83% for women who received EBRT, VBT, and combination RT, respectively (p = 0.001). On multivariate analysis, old age, African-American race, no or fewer number of examined lymph nodes, and higher tumor grade were independent predictors of worse OS. RT modality did not sustain its independent prognostic significance as a predictor of OS.ConclusionsIn this nationwide hospital-based study of women with International Federation of Gynecology and Obstetrics Stage II uterine endometrioid carcinoma, adjuvant VBT alone provided excellent survival outcomes and may be a reasonable adjuvant RT modality for properly selected women with adequate lymph node dissection and low-grade tumors.



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Plesiobrachytherapy for chest wall recurrences of breast cancer after mastectomy and radiotherapy for breast cancer

Publication date: Available online 23 November 2017
Source:Brachytherapy
Author(s): Nadia Besson, Christophe Hennequin, Sophie Guillerm, Ingrid Fumagalli, Valentine Martin, Sophie Michaud, Luis Texeira, Laurent Quero
PurposeThe purpose of the study was to evaluate the results of high-dose-rate plesiobrachytherapy for local relapse after mastectomy and radiotherapy in terms of both local control and survival.MethodsWe reviewed retrospectively 43 patients who experienced a chest wall relapse of breast cancer after local excision (22 patients) or not (21 patients). Patients were treated with an individually designed mold with four to six fractions of 3–6 Gy high-dose-rate brachytherapy, two fractions per week. Mean total dose was 24 Gy.ResultsAfter surgical resection, the 3- and 5-year local control rates were 80% and 73%, respectively. For nonresectable patients, the overall response rate was 86%, and the 3-year infield local control and chest wall local control were 51% and 26%, respectively. The 5-year survival rate was 50.5% for the whole population, 62% after surgery, and 45.4% for irresectable patients. Acute Grade 2 or 3 toxicity occurred in 43% of the patients, resolving in a few days. Two patients had a local necrosis lasting 3 to 7 months. Late toxicity was observed in 5 patients.ConclusionsHigh-dose-rate plesiobrachytherapy is a simple outpatient technique to treat chest wall local relapse of breast cancer. As a reirradiation technique, its tolerance is acceptable. This technique may obtain long-term local control after incomplete surgery; in case of nonresectable disease, a high response rate was observed, which might improve the quality of life of these patients.



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TNFα induces tolerant production of CXC chemokines in colorectal cancer HCT116 cells via A20 inhibition of ERK signaling

Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Xin Zhou, Dongjian An, Xueting Liu, Manli Jiang, Chuang Yuan, Jinyue Hu
Ubiquitin editing enzyme A20 functions as a tumor suppressor in various cancer. However, the mechanism for A20 regulation of cancer progress is not fully understood. In this study, we found that in human colorectal cancer HCT116 cells, TNFα induced a tolerant production of CXC chemokines, including CXCL1, 2, and 8 in a dose and time dependent manner. TNFα pre-treatment of HCT116 cells down-regulated the chemokine production induced by TNFα re-treatment. TNFα induced the phosphorylation of MAPKs ERK, JNK, P38 and NF-κB P65, but only ERK inhibition decreased TNFα-induced chemokine production. Both RT-PCR and FACS results showed that TNFα treatment did not regulate the expression of TNF receptors. However, TNFα up-regulated the expression of A20 at both mRNA and protein levels significantly. TNFα pre-treatment inhibited the signal transduction of MAPKs induced by TNFα re-stimulation, and A20 over-expression decreased the signal transduction of ERK and P38. Meanwhile, A20 inhibition by RNA interference reversed chemokine down-regulation induced by TNFα re-stimulation after TNFα pre-treatment. Taken together, these results suggested that in human colorectal cancer cells, A20 may function to inhibit cancer progression via down-regulation of TNFα-induced chemokine production by suppression of ERK signaling.



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CD26 expression is down-regulated on CD8+ T cells in patients with Hashimoto's thyroiditis

Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Yalei Liu, Yuan Li, Yan Gong, Nan Yu, Yang Zhang, Ran You, Chenxue Qu, Guizhi Lu, Youyuan Huang, Ying Gao, Yanming Gao, Xiaohui Guo
The immune mechanism underlying Hashimoto's thyroiditis (HT) remains unclear. CD26, also known as dipeptidyl peptidase 4 (DPP-4), is a multifunctional molecule involved in the pathophysiology of autoimmune diseases. This study aimed to investigate the role of CD26 in the pathogenesis of HT. Peripheral blood was drawn from 20 healthy controls and 31 HT patients (19 mild HT patients and 12 severe HT patients). Plasma sCD26 concentrations were measured by ELISA, and sCD26 enzymatic activity was assessed using a luciferase-based assay. The expression levels of membrane-bound CD26 were analyzed by flow cytometry. Plasma sCD26 concentrations were lower in HT patients than in healthy controls, although the difference in sCD26 concentrations between the two groups did not reach statistical significance (P=0.07). The percentages of CD8⁺ T cells and Tc1 cells with CD26 expression were decreased in HT patients compared with those in healthy controls, and the mean fluorescence intensity (MFI) values of CD26 on CD8⁺ T cells and Tc17 cells in HT patients were significantly lower than in healthy controls (P<0.05). In HT patients, the expression of CD26 on CD8⁺ T cells and Tc subsets was decreased in the hypothyroidism group compared with that in the euthyroid group (P<0.05). These results suggest that the sCD26 concentrations and membrane-bound CD26 levels on CD8⁺ T cells are aberrant in HT and that the reduced CD26 expression may be involved in the progression of HT.



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The mast cell stabilizing activity of Chaga mushroom critical for its therapeutic effect on food allergy is derived from inotodiol

Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Thi Minh Nguyen Nguyet, Maria Lomunova, Ba Vinh Le, Ji Sun Lee, Seol Kyu Park, Jong Seong Kang, Young Ho Kim, Inkyu Hwang
While an anti-allergic effect of Chaga mushroom (Inonotus obliquus) has been indicated, its therapeutic effect on allergy and immunoregulatory mechanisms and chemical constituents directly responsible for that are hardly known. We examined the effect of 70% ethanol extract of Chaga mushroom (EE) and its dichloromethane (DF) and aqueous (AF) fractions using a mouse model of chicken ovalbumin (cOVA)-induced food allergy, and found that only EE and DF ameliorated allergy symptoms to a significant extent. The in vivo mast cell-stabilizing activity was also found only in EE and DF whereas the activities to suppress Th2 and Th17 immune responses and cOVA-specific IgE production in the small intestine were observed in all three treatment regimens, implying that inhibition of the mast cell function by lipophilic compounds was vital for the therapeutic effect. Results also indicated that inotodiol, a triterpenoid predominantly present in DF, played an active role as a mast cell stabilizer.



http://ift.tt/2A79elB

In vitro determination of Mexican Mestizo hair shaft diameter using optical coherence tomography

Abstract

Background

Mexican mestizo population has a pluriethnic mixture of Amerindian, European and African ancestry, predominant in most Latin American countries. Until now, there are no reports about hair characteristics in this population, necessary to define normal values, for hair diseases evaluation and comparison among other ethnic groups.

Methods

The VivoSight^® swept-source multibeam optical coherence tomography system was used to evaluate hair diameter and shape in 30 females. Three hair samples from each volunteer were measured transversely along three distances, generating nine cross-sectional images, two measurements per image and 18 measurements per patient for a total of 540 diameter measurements.

Results

Minimum hair diameter (n = 540) was 0.06 mm while maximum was 0.14 mm. Mean diameter was 0.10 ± 0.01 mm as compared with Asian hair, which ranges from 0.08 mm to 0.12 mm. On morphological analysis, Mexican Mestizo hair tends to have a round shape with homogenous diameters, resembling Caucasian and Asian hair.

Conclusion

Mexican hair is similar to Asian hair in diameter and shape and can be classified as 'thick' hair, which make it more resistant and with more volume. Cosmetic products intended to improve hair care in this population must to consider this characteristic.

http://ift.tt/2jU8GMa

Immunological differences between insect venom-allergic patients with and without immunotherapy and asymptomatically sensitized subjects

Abstract

Background

Currently available tests are unable to distinguish between asymptomatic sensitization and clinically relevant Hymenoptera venom allergy. A reliable serological marker to monitor venom immunotherapy (VIT) does also not exist. Our aim was to find reliable serological markers to predict tolerance to bee and vespid stings.

Methods

We included 77 asymptomatically-sensitized subjects, 85 allergic-patients with acute systemic sting reactions, and 61 allergic-patients currently treated with VIT. Levels of sIgE and sIgG₄ to bee and vespid venom, rApi-m-1 and rVes-v-5 were measured immediately after allergic sting-reactions or before sting-challenges and four weeks later. All sting challenges were tolerated. The inhibitory activity was determined using BAT-inhibition and ELIFAB-assay.

Results

Median sIgG₄ levels were 96-fold higher in VIT patients (p<0.001) while sIgE/sIgG₄ ratios were consistently lower (p<0.001). The ELIFAB-assay was paralleled by low sIgE/sIgG₄ ratios in VIT-patients, showing markedly higher allergen-blocking capacity (p<0.001). An almost complete inhibition of the basophil response was seen in all patients treated with vespid venom, but not in those treated with bee venom. Four weeks after the sting, sIgE and sIgG₄ levels were increased in allergic and asymptomatically-sensitized patients, but not in VIT-patients.

Conclusion

Immunological responses after stings varied in bee and vespid venom allergic patients. In patients under VIT, sIgE and sIgG₄ remained completely stable after sting-challenges. Monitoring VIT efficacy was only possible in vespid venom allergy and the sIgG₄ threshold for rVes-v-5 had the highest sensitivity to confirm tolerance. The BAT-inhibition test was the most reliable tool to confirm tolerance on an individual basis.

This article is protected by copyright. All rights reserved.

http://ift.tt/2A1jLRw

Immunological differences between insect venom-allergic patients with and without immunotherapy and asymptomatically sensitized subjects

Abstract

Background

Currently available tests are unable to distinguish between asymptomatic sensitization and clinically relevant Hymenoptera venom allergy. A reliable serological marker to monitor venom immunotherapy (VIT) does also not exist. Our aim was to find reliable serological markers to predict tolerance to bee and vespid stings.

Methods

We included 77 asymptomatically-sensitized subjects, 85 allergic-patients with acute systemic sting reactions, and 61 allergic-patients currently treated with VIT. Levels of sIgE and sIgG₄ to bee and vespid venom, rApi-m-1 and rVes-v-5 were measured immediately after allergic sting-reactions or before sting-challenges and four weeks later. All sting challenges were tolerated. The inhibitory activity was determined using BAT-inhibition and ELIFAB-assay.

Results

Median sIgG₄ levels were 96-fold higher in VIT patients (p<0.001) while sIgE/sIgG₄ ratios were consistently lower (p<0.001). The ELIFAB-assay was paralleled by low sIgE/sIgG₄ ratios in VIT-patients, showing markedly higher allergen-blocking capacity (p<0.001). An almost complete inhibition of the basophil response was seen in all patients treated with vespid venom, but not in those treated with bee venom. Four weeks after the sting, sIgE and sIgG₄ levels were increased in allergic and asymptomatically-sensitized patients, but not in VIT-patients.

Conclusion

Immunological responses after stings varied in bee and vespid venom allergic patients. In patients under VIT, sIgE and sIgG₄ remained completely stable after sting-challenges. Monitoring VIT efficacy was only possible in vespid venom allergy and the sIgG₄ threshold for rVes-v-5 had the highest sensitivity to confirm tolerance. The BAT-inhibition test was the most reliable tool to confirm tolerance on an individual basis.

This article is protected by copyright. All rights reserved.

http://ift.tt/2A1jLRw

Inhibition of intrinsic coagulation improves safety and tumor-targeted drug delivery of cationic solid lipid nanoparticles

Publication date: Available online 23 November 2017
Source:Biomaterials
Author(s): Xuan Wu, Hongmei Chen, Chenxi Wu, Jialiang Wang, Shi Zhang, Jing Gao, Hongda Wang, Tianmeng Sun, Yong-Guang Yang
Cationic solid lipid nanoparticles (cSLNs) are promising nanoparticles for controlled drug delivery. Increasing surface charge and/or reducing PEG density enhance cellular uptake of cSLNs in vitro, but for unknown reasons fail to improve drug delivery in vivo. Herein, we show that cSLNs present a risk for systemic platelet activation and aggregation in vivo, and this toxic effect can be significantly augmented by increasing the surface charge and reducing the PEG density. Furthermore, thrombotic toxicity significantly reduces blood circulation time and in vivo cellular uptake of cSLNs. Mechanistic studies revealed that the intrinsic coagulation pathway is responsible for cSLN-induced platelet activation. Importantly, pretreatment of the recipient mice with heparin, a clinically-approved intrinsic coagulation inhibitor, was highly effective in preventing toxicity, prolonging the circulation time of cSLNs, and improving cSLN-based antitumor drug delivery and therapeutic efficacy in tumor-bearing mice. This study offers a useful strategy for improving both the safety and efficacy of cSLN-based anticancer therapies.



http://ift.tt/2A2I9lC

Hydrothermal preparation and physicochemical studies of new copper nano-complexes for antitumor application

Publication date: 5 March 2018
Source:Journal of Molecular Structure, Volume 1155
Author(s): M. Saif, Hoda F. El-Shafiy, Mahmoud M. Mashaly, Mohamed F. Eid, A.I. Nabeel, R. Fouad
Two novel nano-complexes [(Cu)2(L) (NO3)2(OH2)] (CuH) and [Cu(HL) (OH2)2(NO3)] (CuCTH)were synthesized by hydrothermal method at 200 °C for 48 h in absence and presence of surfactant (CTAB), respectively. Introducing surfactant (CTAB) leads to changing stoichiometric metal/ligand ratio from binuclear (CuH) to mononuclear (CuCTH) nano-complexes. CuH shows irregular nano-flake shape while CuCTH have separately uniform nano-spherical morphology. Thermal analysis revealed that CuCTH is thermally stable in comparison with CuH Nano-complex. CuCTH absorption peak shifted to shorter wavelength (blue shift) and sharpness of the peak also decreased in presence of CTAB. The role of CTAB in the crystal growth is discussed. CuH and CuCTH nano-complexes were tested for their in vitro cytotoxicity against Ehrlich Ascites Carcinoma cell line (E.A.C.). Both nano-complexes effectively inhibited E.A.C. growth with IC50value of 37 and 25 μM for CuH and CuCTH, respectively. The high antitumor activity of CuCTH was attributed to several factors such as spherical morphology, smaller size, chemical structure, and geometry. The LD50 for high cytotoxic CuCTH nano-complex on mice was found to be 100 mg/kg with strong abscess in abdomen side effect. To overcome this side effect, different molar ratio of CuCTH and previously prepared ZnNano-complexes were tested for their in vitrocytotoxicity and in vivo toxicity. Obtained results show that the 2:8 M ratio between CuCTH and Zn nano-complexes gives very low toxicity without any side effects. Also, geometric optimization and conformational analysis were performed using semi-empirical PM3 method. Energy gap (ΔE), dipole moment, and structure activity relationship were performed and discussed.

Graphical abstract

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Heavy metals and lead isotopes in soils, road dust and leafy vegetables and health risks via vegetable consumption in the industrial areas of Shanghai, China

Publication date: 1 April 2018
Source:Science of The Total Environment, Volumes 619–620
Author(s): Chunjuan Bi, Ya Zhou, Zhenlou Chen, Jinpu Jia, Xinyi Bao
Vegetable fields have a high risk of heavy metal contamination from pollution sources in suburban and industrial areas of cities. Eighty-seven soil samples, 106 leafy vegetables and 48 road dust samples were collected from industrial areas of Shanghai, China. We studied the levels of heavy metals, health risk through consumption of leafy vegetables, and sources of Pb in soils, road dust and leafy vegetables. Soil Cd, Zn, Pb, Cu, Hg and As concentrations exceeded the soil background values in 73.6%, 97.7%, 52.3%, 37.8%, 95.1% and 20.2% soil samples, respectively, but were below the criteria for agricultural soil in China, with the exception of Hg. The concentrations of Cd, Zn, Pb, Cu and As in road dust were significantly higher than concentrations in soils, while Hg concentration in road dust was lower. Cd, Zn, Pb, Hg and Cu concentrations in soils and Zn, Pb and Cu concentrations in road dust were greatest near the municipal solid waste incineration power plant. Heavy metal concentrations in the edible tissues of vegetables were not correlated with their total values in soils and varied among vegetable species. The trends in transfer factors (TFs) in different vegetables were Cd>Zn>Cu>As>Hg>Pb. There was low health risk from heavy metal exposure by consumption of vegetables based on Hazard Quotients (HQM): As was the major contributor to HQM, followed by Cd and Pb. Parent material of the Yangtze River Estuary was the major source of Pb in soils, while coal-fired, stationary industrial emissions and municipal waste incineration emissions were the major sources of Pb in dust and vegetables based on use of the lead isotopic tracing method. Accumulation of Pb in leafy vegetables was through foliar uptake and directly related to atmospheric Pb.

Graphical abstract

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Ultrasensitive electrochemical immunosensor for procalcitonin with signal enhancement based on zinc nanoparticles functionalized ordered mesoporous carbon-silica nanocomposites

Publication date: 1 April 2018
Source:Sensors and Actuators B: Chemical, Volume 258
Author(s): Yishan Fang, Qiong Hu, Xiongtao Yu, Lishi Wang
A novel and sensitive strategy for procalcitonin (PCT) determination was developed based on zinc nanoparticles-functionalized ordered mesoporous carbon-silica nano-composites (OMCSi-Zn). This strategy combined an effectively designed trace tag and a simple immunosensor. The large amount of OMCSi-Zn materials as label greatly amplified the detection signals for the electrochemical detection of proteins, while the good biocompatibility of graphene-chitosan as sensor matrix retained excellent stability and accelerated electron transfer for the sandwich-type immunoassay. Without metal preconcentration, the zinc nanoparticles loading on the ordered mesoporous carbon-silica nano-composites (OMCSi) could directly be detected through electrochemical voltammetries, while the immunoreaction had a close relationship with the distinct voltammetric peaks. The proposed method exhibited high sensitivity and good stability for PCT detection, possessing an improved linear response range from 0.05pg/mL to 80ng/mL, with a detection limit of 0.013pg/mL (S/N=3). Moreover, the serum samples from clinic were accurately detected with the proposed method, indicating that the developed immunoassay possessed excellent potential application in clinical diagnostics for PCT.



http://ift.tt/2zhXDz8

Microstructure, phase evolution and interfacial effects in a new Zn0.9Mg0.1TiO3-ZnNb2O6 ceramic system with greatly induced improvement in microwave dielectric properties

Publication date: 15 March 2018
Source:Scripta Materialia, Volume 146
Author(s): Shenhui Lei, Huiqing Fan, Xiaohu Ren, Jiawen Fang, Longtao Ma, Hailin Tian
Zn0.9Mg0.1TiO3-ZnNb2O6 (ZMT-ZN) ceramics was synthesized and characterized successfully for the first time, and phase conversion to secondary phases was largely restrained due to the introduction of ZnO nano inhibitors. Excellent microwave dielectric properties and optimal combination were achieved for the ceramics sintered at 1100°C, i.e., εr=27.5, Q×f=75,000GHz, τf=−3.8ppm/°C. Particularly, the comparatively insulated interlayers were considered as the key mechanism to impede transportation or transfer of defects and surface polarization charges. Considering the merits of facile, low cost and simple process, this series of ZMT-ZN ceramics are promising new candidates for ultra-low microwave devices.

Graphical abstract

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Coordination of N,O-donor appended Schiff base ligand (H2L1) towards Zinc(II) in presence of pseudohalides: Syntheses, crystal structures, photoluminescence, antimicrobial activities and Hirshfeld surfaces

Publication date: 5 March 2018
Source:Journal of Molecular Structure, Volume 1155
Author(s): Dhrubajyoti Majumdar, Jayanta Kumar Biswas, Monojit Mondal, M.S. Surendra Babu, Ramesh K. Metre, Sourav Das, Kalipada Bankura, Dipankar Mishra
A series of dinuclear Zn(II) complexes [Zn2 (L¹) (CH3OH)2(SCN) (OAc)](1), [Zn2 (L¹) (CH3OH)2(N3)2](2) and [Zn2 (L¹) (Cl)2(CH3OH)]·CH3OH (3) have been synthesized by the reaction of compartmental Schiff base ligand (H2L¹) [N,N′-Bis(3-ethoxysalicylidenimino)-1,3-diaminopropane] with Zn(OAc)2·2H2O in presence of coligand like KSCN, NaN3 and NaCl respectively. X-ray diffraction analysis revealed that all the complexes are neutral and possess a 4-membered Zn2 (μ2-O)2 ring fastened by the unified coordination action of a doubly deprotonated ligand. In addition, solid state structure of the complexes display extensive intermolecular interaction which has been supported theoretically by Hirshfeld surface analysis with 2D Fingerprint plots. The synthesized Zn(II) metal complexes observed enhancement of luminescence emission compared to the parent Schiff base due to emanating ligand based intraligand (π→π^∗) fluorescence. Additionally, Zn(II) metal complexes exhibited considerable antimicrobial potency against some important Gram +ve and Gram -ve bacteria.

Graphical abstract

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Impact of hydration and nutrition on personal performance in the clinical workplace

As clinicians we sometimes fail to look after ourselves at work. We often do not drink enough during the day or miss lunch breaks while caring for patients, and this can be particularly evident during an all-day operating list when procedures are long and complex. Some operating theatre staff do not even eat breakfast regularly. Inadequate intake of fluids or nutrition can impair performance, lead to tiredness and headaches, and may compromise both our own health and the care we provide to patients.

http://ift.tt/2BhXsFn

Evaluation of the morphology of the genial tubercle using cone-beam computed tomography

The genial tubercle is a sharp projection of bone on the internal face of the mandible above the inferior border.1

http://ift.tt/2zkFPDv

Is routine holistic assessment with a prompt list feasible during consultations after treatment for oral cancer?

The head and neck cancer Patient Concerns Inventory (PCI-HN) is a holistic, self-reported list of items that can help patients to disclose their needs and concerns during routine follow-up consultations. The aim of this study was to report how often it was used during the first three years of follow up after treatment for oral cancer, and the range of issues that were raised. The sample comprised consecutive patients treated over a three-year period with curative intent. All clinic attendances were reviewed until October 2015 or until patients had a recurrence, a subsequent primary, metastases, or were discharged home or to follow up at a peripheral hospital, or started palliative care.

http://ift.tt/2Bin8Sm

Corrigendum to “Schneider membrane thickness classification evaluated by cone-beam computed tomography and its importance in the predictability of perforation. Retrospective analysis of 200 patients” [Br. J. Oral Maxillofac. Surg. 54 (10) (December 2016) 1106–1110]

The authors regret the errors in the membrane thickness in Table 1 of the above referenced paper. The correct table can be found below.

http://ift.tt/2zgYX5d

Tongue Pressure Production and Submental Surface Electromyogram Activities During Tongue-Hold Swallow with Different Holding Positions and Tongue Length

Abstract

Our previous study regarding the tongue-hold swallow (THS) demonstrated that the tongue-to-palate contact during THS could be influenced by the maximum tongue protrusion length (MTPL) of individual subjects, resulting in two different patterns of pressure generation. The present study further analyzed the influence of MTPL on the tongue pressure production along with submental surface electromyography (sEMG) during THS, in order to establish an index to better control THS effects. Tongue pressure using a sensor sheet system and concurrent submental sEMG activities were measured during swallowing tasks in 18 healthy young adults. Task conditions comprised THS at two different degrees of tongue protrusion and dry swallow. Tongue pressures and sEMG activities were compared among three task conditions, and correlations of MTPL with tongue pressure were also investigated. Additionally, a ROC curve was used to find a cut-off value for MTPL to predict changes (increases and decreases) in tongue pressure during THS. The duration and the amount of submental muscle activity increased concurrently during THS. Two trends were shown on the change in tongue pressure at the posterior-circumferential part of the hard palate during THS compared to dry swallow; the maximal magnitude and the integrated value of tongue pressure increased in some subjects, while these values decreased in others. Thirty-two millimeters was found to be the cut-off value of MTPL, which distinguishes increase/decrease pattern of tongue pressure with sensitivities of 60.0–85.7%. The present finding suggests that more reliable THS effects should be attainable using MTPL to set the tongue-hold position.

http://ift.tt/2BhmB37

Management of hypogammaglobulinemia and recurrent infections in a chronic lymphocytic leukemia patient receiving ibrutinib

Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disorder characterized by the progressive accumulation of monoclonal and functionally incompetent lymphocytes; it also is the most common adult leukemia in Western countries.1 In CLL, hypogammaglobulinemia is the predominant inherent immune defect and is often further exacerbated by immunosuppressive treatment.2 Nevertheless, neither antibiotic prophylaxis nor prophylactic immunoglobulin (Ig) replacement therapy (IRT) is routinely recommended for CLL.

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An exploratory open-label, investigator-initiated study to evaluate the efficacy and safety of combination sonidegib and buparlisib for advanced basal cell carcinomas

http://ift.tt/2mXGp8v

Management of hypogammaglobulinemia and recurrent infections in a chronic lymphocytic leukemia patient receiving ibrutinib

Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative disorder characterized by the progressive accumulation of monoclonal and functionally incompetent lymphocytes; it also is the most common adult leukemia in Western countries.1 In CLL, hypogammaglobulinemia is the predominant inherent immune defect and is often further exacerbated by immunosuppressive treatment.2 Nevertheless, neither antibiotic prophylaxis nor prophylactic immunoglobulin (Ig) replacement therapy (IRT) is routinely recommended for CLL.

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Diagnostic Accuracy of Digital Breast Tomosynthesis in the Evaluation of Palpable Breast Abnormalities

Publication date: Available online 23 November 2017
Source:Academic Radiology
Author(s): Jeffrey R. Hawley, Justine K. Kang-Chapman, Sarah E. Bonnet, Amy L. Kerger, Clayton R. Taylor, Barbaros S. Erdal
Rationale and ObjectivesThe role of digital breast tomosynthesis (DBT) in evaluating palpable abnormalities has not been evaluated and its accuracy compared to 2D mammography is unknown. The purpose of this study was to evaluate combined 2D mammography, DBT, and ultrasound (US) at palpable sites.Materials and MethodsTwo breast imagers reviewed blinded consecutive cases with combined 2D mammograms and DBT examinations performed for palpable complaints. By consensus, 2D and DBT findings were recorded and compared to US. Patient characteristics, demographics, subsequent workup, and outcome were recorded.ResultsA total of 229 sites in 188 patients were included, with 50 biopsies performed identifying 18 cancers. All 18 cancers were identified on 2D and US, whereas 17 cancers were identified on DBT. Cancer detection sensitivities for 2D, DBT, and US were 100.0%, 94.4%, and 100.0%. The negative predictive value, when combined with US, was 100% for both. The sensitivity and the specificity for both benign and malignant findings with 2D and DBT were 70.5% versus 75.4% (P = 0.07) and 95.3% versus 99.1% (P = 0.125). Palpable findings not identified by 2D and DBT were smaller than those identified (11.5 ± 8.3 mm vs 23.9 ± 12.8 mm, P < 0.001). Patients with dense breasts were more likely to have mammographically occult findings than patients with nondense breasts (27.4% vs 8.3%).ConclusionsDBT did not improve cancer detection over 2D or US. Both mammographic modalities failed to identify sonographically confirmed findings primarily in dense breasts. The diagnostic use of DBT at palpable sites provided limited benefit over combined 2D and US. When utilizing DBT, US should be performed to adequately characterize palpable sites.



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Impact of Radiation Dose Reduction in Abdominal Computed Tomography on Diagnostic Accuracy and Diagnostic Performance in Patients with Suspected Appendicitis

Publication date: Available online 23 November 2017
Source:Academic Radiology
Author(s): Corinna Storz, Manuel Kolb, Jong Hyo Kim, Jakob Weiss, Wolfgang G. Kunz, Konstantin Nikolaou, Fabian Bamberg, Ahmed E. Othman
Rationale and ObjectivesTo determine the intraindividual impact of radiation dose reduction in abdominal computed tomography (CT) on diagnostic performance in patients with suspected appendicitis.Materials and MethodsThis study was approved by the institutional review board. Seventy-five patients who underwent standard contrast-enhanced abdominal CT for suspected appendicitis between 2004 and 2009 were retrospectively included. Low-dose CT reconstructions with 75%, 50%, and 25% of the original radiation dose level were generated by applying realistic reduced-dose simulation. Two blinded, independent readers assessed image quality, signal-to-noise ratio, and diagnostic confidence on each dataset. Diagnostic accuracy for detection of appendicitis and complications were calculated for each reader. Paired univariate tests were used to determine intraindividual differences.ResultsAmong 75 subjects included in the analysis (57% female, mean age: 41 ± 18 years), the prevalence of histopathologically confirmed appendicitis was 59%. Signal-to-noise ratio and subjective image quality of 50% and 25% reduced-dose CTs were significantly lower than the reference datasets (all P < .005). Appendicitis was correctly identified in all reference and low-dose datasets (sensitivity: 100%, negative predictive value: 100%). Presence of complications was correctly detected in all reference, 75%, and 50% datasets, but was decreased in 25% datasets (sensitivity: 77.8% and negative predictive value: 97.4%). Diagnostic confidence was high for original and 75% datasets, but significantly lower for 50% and 25% datasets (P < .001).ConclusionsOur results indicate that diagnostic accuracy in abdominal CT acquisitions acquired at 75% and 50% of radiation dose is maintained in patients with suspected appendicitis, whereas further reduction of radiation exposition is associated with decreased diagnostic performance.



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Regional Heterogeneity of Lobar Ventilation in Asthma Using Hyperpolarized Helium-3 MRI

Publication date: Available online 23 November 2017
Source:Academic Radiology
Author(s): Wei Zha, Stanley J. Kruger, Robert V. Cadman, David G. Mummy, Michael D. Evans, Scott K. Nagle, Loren C. Denlinger, Nizar N. Jarjour, Ronald L. Sorkness, Sean B. Fain
Rationale and ObjectivesTo determine lobar ventilation patterns in asthmatic lungs with hyperpolarized ³He magnetic resonance imaging (HP ³He MRI).Materials and MethodsEighty-two subjects (14 normal, 48 mild-to-moderate asthma, and 20 severe asthma) underwent HP ³He MRI, computed tomography (CT), and pulmonary function testing. After registering proton to ³He images, we segmented the lungs from proton MRI and further segmented the five lung lobes (right upper lobe [RUL], right middle lobe [RML], and right lower lobe [RLL]; left upper lobe and left lower lobe [LLL]) by referring to the lobar segmentation from CT. We classified the gas volume into four signal intensity levels as follows: ventilation defect percent (VDP), low ventilation percent, medium ventilation percent, and high ventilation percent. The local signal intensity variations in the ventilated volume were estimated using heterogeneity score (Hs). We compared each ventilation level and Hs measured in the whole lung and lobar regions across the three subject groups.ResultsIn mild-to-moderate asthma, the RML and RUL showed significantly greater VDP than the two lower lobes (RLL and LLL) (P ≤ .047). In severe asthma, the pattern was more variable with the VDP in the RUL significantly greater than in the RLL (P = .026). In both asthma groups, the lower lobes (RLL and LLL) showed significantly higher high ventilation percent and Hs compared to the three upper lobes (all P ≤ .015).ConclusionsIn asthma, the RML and RUL showed greater ventilation abnormalities, and the RLL and LLL were more highly ventilated with greater local heterogeneity. These findings may facilitate guided bronchoscopic sampling and localized airway treatment in future studies.



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Expanding the Definition of a Benign Renal Cyst on Contrast-enhanced CT

Publication date: Available online 23 November 2017
Source:Academic Radiology
Author(s): Eric M. Hu, James H. Ellis, Stuart G. Silverman, Richard H. Cohan, Elaine M. Caoili, Matthew S. Davenport
Rationale and ObjectiveWe aimed to determine the frequency and clinical significance of homogeneous renal masses measuring 21–39 Hounsfield units on contrast-enhanced computed tomography (CT).MethodsSubjects 40–69 years old undergoing portal-venous-phase contrast-enhanced abdominal CT from January 1, 2006 to December 31, 2010 with slice thickness ≤5 mm and no prior CT or magnetic resonance imaging were identified (n = 1387) for this institutional review board-approved retrospective cohort study. Images were manually reviewed by three radiologists in consensus to identify all circumscribed homogeneous renal masses (maximum of three per subject) ≥10 mm with a measured attenuation of 21–39 Hounsfield units. Exclusion criteria were known renal cancer or imaging performed for a renal indication. The primary outcome was retrospective characterization as a clinically significant mass, defined as a solid mass, a Bosniak IIF/III/IV mass, or extirpative therapy or metastatic renal cancer within 5 years' follow-up.ResultsEligible masses (n = 74) were found in 5% (63/1387) of subjects. Of those with a reference standard (n = 42), none (0% [95% CI: 0.0%–8.4%]) were determined to be clinically significant.ConclusionIncidental renal masses on contrast-enhanced CT that are homogeneous and display an attenuation of 21–39 Hounsfield units are uncommon in patients 40–69 years of age, unlikely to be clinically significant, and may not need further imaging evaluation. If these results can be replicated in an independent and larger population, the practical definition of a benign cyst on imaging may be able to be expanded.



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Communicating Radiology Test Results

Publication date: Available online 23 November 2017
Source:Academic Radiology
Author(s): Zeeshaan S. Bhatti, Richard K.J. Brown, Ella A. Kazerooni, Matthew S. Davenport
Rationale and ObjectivesThis study aimed to determine the preferences of radiology and referring provider residents regarding direct communication of radiology test results.MethodsThis Health Insurance Portability and Accountability Act-compliant quality improvement effort was exempt from institutional review board oversight. An anonymous survey was emailed to 44 radiology residents and 364 referring resident providers who routinely provide or receive direct communication of test results at our quaternary care medical center. The survey focused on the frequency, indication, clinical utility, and methods of direct communication of radiology results. Proportions were compared to chi-square or Fisher exact test.ResultsThe response rates were 86% (37 of 43) (radiology) and 41% (151 of 364) (referring providers). Approximately half of radiology residents (49% [18 of 37]) thought the frequency of direct verbal communication was excessive, and none (0 of 37) thought more communication was needed. In contrast, only 1.3% (2 of 151; P < .001) of referring providers felt the frequency was excessive, and 24% (36 of 151; P < .001) desired more. The majority (66% [100 of 151]) of referring providers felt phone calls from radiologists often or always added value beyond a timely radiology report, and 59% (44 of 74) felt it is the radiologist's responsibility to call about abnormal findings. Furthermore, 83% (125 of 151) of referring providers preferred to receive a phone call about non-emergent unexpected findings, although preferences varied for various example abnormalities. For outpatients with non-emergent unexpected findings, most providers (90% [64 of 71]) prefer written communication rather than a phone call.ConclusionsReferring providers prefer direct communication of radiology results, even for non-urgent unexpected findings, whereas radiology residents prefer less direct communication and are more likely to consider radiologist-to-provider communication superfluous.



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Optical Coherence Tomography

Publication date: Available online 23 November 2017
Source:Academic Radiology
Author(s): Richard Ha, Lauren C. Friedlander, Hanina Hibshoosh, Christine Hendon, Sheldon Feldman, Soojin Ahn, Hank Schmidt, Margaret K. Akens, MaryAnn Fitzmaurice, Brian C. Wilson, Victoria L. Mango
Rationale and ObjectivesThis study aimed to assess whether different breast cancer subspecialty physicians can be trained to distinguish non-suspicious from suspicious areas of post-lumpectomy specimen margin in patients with breast cancer using optical coherence tomography (OCT) images (a near-infrared based imaging technique) with final histology as the reference standard.Materials and MethodsThis institutional review board-exempt, Health Insurance Portability and Accountability Act-compliant study was performed on 63 surgically excised breast specimens from 35 female patients, creating a 90-case atlas containing both non-suspicious and suspicious areas for cancer. OCT images of the specimens were performed, providing 6.5–15 µm resolution with tissue visualization 1–2 mm subsurface. From the 90-case atlas, 40 cases were chosen for training and 40 were randomly selected for reader assessment. Three breast imaging radiologists, two pathologists, two breast surgeons, and one non-clinical reader were trained and assessed for ability to distinguish non-suspicious from suspicious findings blinded to clinical data and corresponding histology slides. Duration of training and assessment, sensitivity, specificity, positive predictive value, negative predictive value, and the area under the curve for each reader were calculated as well as averages by subspecialty.ResultsThe average training time was 3.4 hours (standard deviation, 1.2). The average assessment time was 1.9 hours (standard deviation, 0.7). The overall average reader sensitivity, specificity, and accuracy for detecting suspicious findings with histologic confirmation of cancer at the surgical margin for all eight readers were 80%, 87%, and 87%, respectively. Radiologists demonstrated the highest average among the disciplines, 85%, 93%, and 94%, followed by pathologists, 79%, 90%, and 84%, and surgeons, 76%, 84%, and 82% respectively.ConclusionsWith relatively short training (3.4 hours), readers from different medical specialties were able to distinguish suspicious from non-suspicious OCT imaging findings in ex vivo breast tissue as confirmed by histology. These results support the potential of OCT as a real-time intraoperative tool for post-lumpectomy specimen margin assessment.



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Selective isolation and noninvasive analysis of circulating cancer stem cells through Raman imaging

Publication date: 15 April 2018
Source:Biosensors and Bioelectronics, Volume 102
Author(s): Hyeon-Yeol Cho, Md. Khaled Hossain, Jin-Ho Lee, Jiyou Han, Hun Joo Lee, Kyeong-Jun Kim, Jong-Hoon Kim, Ki-Bum Lee, Jeong-Woo Choi
Circulating cancer stem cells (CCSCs), a rare circulating tumor cell (CTC) type, recently arose as a useful resource for monitoring and characterizing both cancers and their metastatic derivatives. However, due to the scarcity of CCSCs among hematologic cells in the blood and the complexity of the phenotype confirmation process, CCSC research can be extremely challenging. Hence, we report a nanoparticle-mediated Raman imaging method for CCSC characterization which profiles CCSCs based on their surface marker expression phenotypes. We have developed an integrated combinatorial Raman-Active Nanoprobe (RAN) system combined with a microfluidic chip to successfully process complete blood samples. CCSCs and CTCs were detected (90% efficiency) and classified in accordance with their respective surface marker expression via completely distinct Raman signals of RANs. Selectively isolated CCSCs (93% accuracy) were employed for both in vitro and in vivo tumor phenotyping to identify the tumorigenicity of the CCSCs. We utilized our new method to predict metastasis by screening blood samples from xenograft models, showing that upon CCSC detection, all subjects exhibited liver metastasis. Having highly efficient detection and noninvasive isolation capabilities, we have demonstrated that our RAN-based Raman imaging method will be valuable for predicting cancer metastasis and relapse via CCSC detection. Moreover, the exclusion of peak overlapping in CCSC analysis with our Raman imaging method will allow to expand the RAN families for various cancer types, therefore, increasing therapeutic efficacy by providing detailed molecular features of tumor subtypes.

Graphical abstract

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A novel electrochemical sensor based on Cu@Ni/MWCNTs nanocomposite for simultaneous determination of guanine and adenine

Publication date: 15 April 2018
Source:Biosensors and Bioelectronics, Volume 102
Author(s): Dongyang Wang, Bintong Huang, Jie Liu, Xia Guo, Guzailinur Abudukeyoumu, Yang Zhang, Bang-Ce Ye, Yingchun Li
A novel electrochemical sensing platform based on combination of multi-walled carbon nanotubes and copper-nickel hybrid nanoparticles (Cu@Ni/MWCNTs) was developed for simultaneous detection of guanine (G) and adenine (A). The Ni/MWCNTs and Cu@Ni/MWCNTs nanocomposites were characterized by transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS). The electrochemical behaviors of G and A on the modified electrode were explored by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) in phosphate buffer with pH 3.0. Under the optimal conditions, electrical signals were linear over the concentration ranges from 5.0 to 180μM and 8.0 to 150μM for simultaneous determination G and A with the detection limit as low as 0.35μM and 0.56μM (S/N = 3), respectively. Furthermore, linear concentration ranges in individual determination are 1.0–180μM and 2.0–150μM with detection limits of 0.17μM and 0.33μM (S/N = 3) for G and A, respectively. The sensor was successfully used to quantify G and A in real samples. The Cu@Ni/MWCNTs composite presented here can serve as a promising candidate for developing electrochemical sensor devices and plays an important role in widespread fields.

Graphical abstract

http://ift.tt/2ji86nj

Superwettable microchips with improved spot homogeneity toward sensitive biosensing

Publication date: 15 April 2018
Source:Biosensors and Bioelectronics, Volume 102
Author(s): Yanxia Chen, Li-Ping Xu, Jingxin Meng, Shaohui Deng, Lulin Ma, Shudong Zhang, Xueji Zhang, Shutao Wang
The high-quality spots in microchips are prerequisites for sensitive and accurate detection of biomarkers. In this work, the superwettable micropattern was constructed by introducing superhydrophilic microwells onto a superhydrophobic substrate. The sample can distribute homogeneously within the well-designed superhydrophilic microwells after droplet evaporation and form homogeneous deposit spots, which can be ascribed to the enhanced Marangoni effect in superwettable micropattern and the suppressed outward flow by 3D nanodendritic silica structure. Based on the improved homogeneity of spots, sensitive and accurate fluorescence readout could be obtained. The free prostate-specific antigen (f-PSA) microchip based on the superwettable micropattern was developed. This superwettable f-PSA microchip exhibits high sensitivity, excellent specificity and long-term stability, and a limit of detection as low as 10fgmL⁻¹ is achieved. Moreover, the superwettable f-PSA microchip can accurately detect human serum samples with excellent correlations with chemiluminescence immunoassay in the clinic, demonstrating its great potential as a sensitive and reliable sensing platform for biological analysis and clinical diagnosis.

Graphical abstract

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A self-powered biosensing device with an integrated hybrid biofuel cell for intermittent monitoring of analytes

Publication date: 15 April 2018
Source:Biosensors and Bioelectronics, Volume 102
Author(s): Dominika Majdecka, Sylwia Draminska, Dariusz Janusek, Paweł Krysinski, Renata Bilewicz
In this work, we propose an integrated self-powered sensing system, driven by a hybrid biofuel cell (HBFC) with carbon paper discs coated with multiwalled carbon nanotubes. The sensing system has a biocathode made from laccase or bilirubin oxidase, and the anode is made from a zinc plate. The system includes a dedicated custom-built electronic control unit for the detection of oxygen and catechol analytes, which are central to medical and environmental applications. Both the HBFC and sensors, operate in a mediatorless direct electron transfer mode. The measured characteristics of the HBFC with externally applied resistance included the power-time dependencies under flow cell conditions, the sensors performance (evaluated by cyclic voltammetry), and chronoamperometry. The HBFC is integrated with analytical devices and operating in a pulse mode form long-run monitoring experiments. The HBFC generated sufficient power for wireless data transmission to a local computer.



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A novel screen-printed mast cell-based electrochemical sensor for detecting spoilage bacterial quorum signaling molecules (N-acyl-homoserine-lactones) in freshwater fish

Publication date: 15 April 2018
Source:Biosensors and Bioelectronics, Volume 102
Author(s): Donglei Jiang, Yan Liu, Hui Jiang, Shengqi Rao, Wu Fang, Mangang Wu, Limin Yuan, Weiming Fang
A novel screen-printed cell-based electrochemical sensor was developed to assess bacterial quorum signaling molecules, N-acylhomoserine lactones (AHLs). Screen-printed carbon electrode (SPCE), which possesses excellent properties such as low-cost, disposable and energy-efficient, was modified with multi-walled carbon nanotubes (MWNTs) to improve electrochemical signals and enhance the sensitivity. Rat basophilic leukemia (RBL-2H3) mast cells encapsulated in alginate/graphene oxide (NaAgl/GO) hydrogel were immobilized on the MWNTs/SPCE to serve as recognition element. Electrochemical impedance spectroscopy (EIS) was employed to record the cell impedance signal as-influenced by Pseudomonas aeruginosa quorum-sensing molecule, N−3-oxododecanoyl homoserine lactone (3OC12-HSL). Experimental results show that 3OC12-HSL caused a significant decrease in cell viability in a dose dependent manner. The EIS value decreased with concentrations of 3OC12-HSL in the range of 0.1–1μM, and the detection limit for 3OC12-HSL was calculated to be 0.094μM. These results were confirmed via cell viability, SEM, TEM analysis. Next, the sensor was successfully applied to monitoring the production of AHLs by spoilage bacteria in three different freshwater fish juice samples which efficiently proved the practicability of this cell based method. Therefore, the proposed cell sensor may serve as an innovative and effective approach to the measurement of quorum signaling molecule and thus provides a new avenue for real-time monitoring the spoilage bacteria in freshwater fish production.



http://ift.tt/2A6RkiZ

Ultrasensitive electrochemiluminescence assay of tumor cells and evaluation of H2O2 on a paper-based closed-bipolar electrode by in-situ hybridization chain reaction amplification

Publication date: 15 April 2018
Source:Biosensors and Bioelectronics, Volume 102
Author(s): Shenguang Ge, Jinge Zhao, Shaopeng Wang, Feifei Lan, Mei Yan, Jinghua Yu
In this manuscript, a disposable paper-based analytical device comprised of a closed bipolar electrode (BPE) was fabricated for the ultrasensitive electrochemiluminescence (ECL) detection of intracellular H2O2 and the number of cancer cells. In this approach, wax printing was used to fabricated reaction zone, and carbon ink-based BPE and driving electrodes were screen-printed into the paper. AuPd nanoparticles (NPs), which served as a carrier of the capture aptamer and as the catalyst for the ECL reaction of luminol and H2O2, were used to modify the BPE. Luminol/Au NPs were attached to the surface of the captured cells via hybridation chain reaction with two hairpin structure DNA labelled luminol/Au NPs. In the stimulation of phorbol myristate acetate, The coreactant H2O2 was released from the target cells. The ECL response of the luminol-H2O2 system was related to the number of cancer cells in the testing buffer, which served as a quantitative signal for the determination of cancer cells and the concentration of H2O2. In order to decrease the external voltage, K3[Fe(CN)6] was introduced in the cathode resevoir of BPE because it gained electrons at the cathode more easily than oxygen. The ECL intensity was quantitatively related to the concentration of MCF-7 in the range of 1.0 × 10²–1.0 × 10⁷ cells/mL. The detection limit was 40 cells/mL and it showed good specificity for cells with high overexpression of mucin-1 receptor, it was concluded that the developed protocol could be effectively utilized for the detection of MCF-7 cells.



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A multi-functional gold/iron-oxide nanoparticle-CNT hybrid nanomaterial as virus DNA sensing platform

Publication date: 15 April 2018
Source:Biosensors and Bioelectronics, Volume 102
Author(s): Jaewook Lee, Masahiro Morita, Kenshin Takemura, Enoch Y. Park
Nanoparticle (NP)-carbon nanomaterial hybrid structures have garnered significant attention due to their synergistic effects. Based on their interesting properties, hybrid nanomaterial-based sensing platforms have been investigated to achieve high sensitivity and selectivity detection. In our study, binary-NP-decorated carbon nanotubes (bNP-CNTs) were successfully synthesized through a simple two-step method and applied as a biosensing platform. Gold (Au)/iron-oxide magnetic NP-decorated CNTs (Au/MNP-CNT) were used for influenza and norovirus DNA sensing channels. To demonstrate biosensing, first, the Au/MNP-CNTs were magnetically aligned on a Pt-interdigitated electrode, and then, a thiol-group-functionalized probe DNA was attached to the Au NP surface on the bNP-CNT hybrid structure through thiol chemistry. DNA hybridization between the target influenza or norovirus DNA and probe DNA was measured to monitor an electrical conductivity change of the Au/MNP-CNTs. Various concentrations of target DNA from 1pM to 10nM were monitored, and the limits of detection for influenza virus and norovirus were calculated to be approximately 8.4pM and 8.8pM, respectively. The specificity was confirmed using different mismatched DNA sequences, showing high specificity. Therefore, this Au/MNP-CNT-based DNA sensing system exhibited excellent detection potential, and such hybrid materials could be universally applied as a highly sensitive and selective biosensing system.

Graphical abstract

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Climate mitigation, low-carbon society, and dynamism of educational institutes in a low-income country

Abstract

This paper aims to investigate carbon footprints of faculty members of University of Agriculture Faisalabad (UAF) associated with income and education in pursuance of a low-carbon society. For the study, 140 UAF faculty members (professors, associate professors, assistant professors, and lecturers) were selected using stratified random sampling technique, and a representative questionnaire was used to record primary data. Moreover, the ordinary least square (OLS) method was used to explain the statistical relationship between income, education, and carbon footprints. It was found that carbon footprints of UAF faculty members were 10.06 metric tons (mt) per year per person on an average. Our results further indicated that carbon footprints of assistant professors, associate professors, and professors were 10.83, 11.95, and 10.96 mt per person per annum, respectively. OLS estimates showed that an increase in one Doctor of Philosophy (Ph.D.) faculty member increases the carbon footprint by 1.15 mt per annum. Male faculty members emit more carbon footprints than females. Faculty members of Tenure Track System (TTS) had a higher income than those of Basic Pay Scale (BPS). Therefore, emissions of TTS faculty members were higher. Hence, in order to reduce carbon footprints and corroborate UAF campus environment-friendly, the attitude towards this aspect should be changed and awareness should be created. Furthermore, reduced car usage can be another bottom-up policy suggestion. As witnessed in green campuses of international universities, UAF should also be a motor-free campus (cycling and pedestrian only).

http://ift.tt/2mXD89d

Long-term outcomes of Universiti Kebangsaan Malaysia cochlear implant program among paediatric implantees

Cochlear implant (CI) greatly enhances auditory performance as compared to hearing aids and has dramatically affected the educational and communication outcomes for profoundly deaf children. Universiti Kebangsaan Malaysia (UKM) pioneered CI program in 1995 in the South East Asia. We would like to report the long-term outcomes of UKM paediatric cochlear implantation in terms of: the proportion of children who were implanted and still using the device, the children's modes of communication, their educational placements, and their functional auditory/oral performance.

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Pediatric laryngeal cleft repair and dysphagia

To describe changes in diet and swallow function in patients with a laryngeal cleft after surgical repair of the laryngeal cleft.

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Postoperative bradycardia following adenotonsillectomy in children: Does intraoperative administration of dexmedetomidine play a role?

Dexmedetomidine is a novel pharmacologic agent that has become a frequently used adjunct during care of pediatric patients with obstructive sleep apnea (OSA) undergoing tonsillectomy. While generally safe and effective, dexmedetomidine is associated with adverse effects of hypotension and bradycardia from its central sympatholytic effects. Due to safety concerns, our institution routinely admits patients with OSA for overnight cardiorespiratory monitoring following tonsillectomy. With such monitoring, we have anecdotally noted bradycardia in our patients and sought to investigate whether this was related to the increased use of intra-operative dexmedetomidine.

http://ift.tt/2A68htL

Sexsomnia: a diagnostic challenge, a case report

Marina Mioč, Elena Antelmi, Marco Filardi, Fabio Pizza, Francesca Ingravallo, Lino Nobili, Carlo Alberto Tassinari, Carlos H. Schenck and Giuseppe Plazzi have no financial relationships relevant to this article to disclose.

http://ift.tt/2mURO93

A not so incidental finding in a 12 year old with sleepiness and headaches

A 12-year-old girl presented with headaches and hypersomnolence. Her bedtime was 10 PM with a latency of 30 minutes. Reported sleeping for 12-16 hours. Upon awakening she felt sleepy and tired but this resolved as the day went on. There were no symptoms of snoring, parasomnias, hypnagogic hallucinations, cataplexy, sleep paralysis, or restless legs. Physical and neurologic exams were normal. Polysomnography was normal. Brain MRI showed a pineal cyst (Figure 1). Salivary melatonin levels (ELISA/EIA calibrated range 0.78-50 pg/ml) were collected by the parent; at home, under regular bedtime conditions.

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Differences in rapid eye movement (REM) sleep abnormalities between posttraumatic stress disorder (PTSD) and major depressive disorder patients: REM interruption correlated with nightmare complaints in PTSD

The presence of repeated nightmares in posttraumatic stress disorder (PTSD) has been hypothesized as a dysfunction of rapid eye movement (REM) sleep, but there has been remarkably little agreement about the pathophysiology. This presents a deterrent to more effective treatments. REM sleep abnormalities including elevated REM density also have been replicated in major depressive disorder (MDD). The purpose of this study was to clarify the difference of REM sleep abnormalities between the two disorders for understanding the pathophysiology of sleep disturbances in PTSD.

http://ift.tt/2mYa5SM

Elevated Tau and Interleukin-6 Concentrations in Adults with Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is characterized by apneas and hypopneas, resulting in hypoxia, cerebral hypoperfusion, endothelial dysfunction, inflammation, and oxidative stress. These pathophysiologic processes likely contribute to neuronal damage. Tau is a protein that stabilizes microtubules, which along with amyloid beta (Aβ), is linked to neurodegenerative processes. We sought to determine if tau, and other biomarkers of inflammation, were related to OSA severity.Concentrations of tau, Aβ40 and Aβ42, c-reactive protein (CRP), TNF-α, interleukin (IL)-6, and IL-10 were measured in blood and compared in participants with moderate-severe (n=28), mild OSA (n=22), and healthy controls (n=24).

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