Ιατρικά Άρθρα: 04/13/18

Παρασκευή 13 Απριλίου 2018

An epi(c)genetic war: Pathogens, cancer and human genome

Publication date: Available online 13 April 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Deepa Rajagopalan, Sudhakar Jha
Cancer is characterized by inter and intra-heterogeneity and this is also observed in the context of cancers caused by pathogens. Nearly 20% of all cancers are attributable to pathogenic organisms. Pathogenic infections result in deregulation of gene expression both by genetic and epigenetic mechanisms, thereby causing malignant transformation. Another characteristic of pathogen-induced cancers is the occurrence of chronic inflammation due to activation of the innate and adaptive arms of the immune system. This review focuses on the epigenetic changes induced by oncoviruses, parasites, cancer-causing bacteria and 'endogenous pathogens' to trigger host cell proliferation indefinitely as well as the inflammation associated with pathogen-induced cancers. The opportunity of targeting components of both pathogen and host epigenetic machinery to limit tumor progression is also discussed.

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Nervous system and primary liver cancer

Publication date: Available online 13 April 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Seogsong Jeong, Bo Zheng, Hongyang Wang, Qiang Xia, Lei Chen
Recent advances have found irregular activities of the nervous system-associated factors in the development and progression of primary liver cancer. These factors contributed in the regulation of migration, proliferation, and apoptosis of cancer cells, and took a role in modulating invasion, metastasis, and recurrence after curative treatment. In clinical researches, neural-related factors were found to be significant prognostic factors, suggesting that the interactions between nervous system and primary liver cancer are indispensable in understanding underlying biological mechanisms. Herein, we reviewed up-to-date achievements in this area and the future perspectives of the interactions between the nervous system and primary liver cancer.

Graphical abstract

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Protein restriction and cancer

Publication date: April 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1869, Issue 2
Author(s): Jie Yin, Wenkai Ren, Xingguo Huang, Tiejun Li, Yulong Yin
Protein restriction without malnutrition is currently an effective nutritional intervention known to prevent diseases and promote health span from yeast to human. Recently, low protein diets are reported to be associated with lowered cancer incidence and mortality risk of cancers in human. In murine models, protein restriction inhibits tumor growth via mTOR signaling pathway. IGF-1, amino acid metabolic programing, FGF21, and autophagy may also serve as potential mechanisms of protein restriction mediated cancer prevention. Together, dietary intervention aimed at reducing protein intake can be beneficial and has the potential to be widely adopted and effective in preventing and treating cancers.

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ILT4 functions as a potential checkpoint molecule for tumor immunotherapy

Publication date: April 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1869, Issue 2
Author(s): Aiqin Gao, Yuping Sun, Guangyong Peng
Immune checkpoint blockade therapy targeting CTLA4 and PD-1/PD-L1 is a promising strategy in the treatment of different types of cancers. However, the clinical success rates of these therapies are still moderate and varied among cancer types. Therefore, identification of alternative and novel checkpoint molecules or interrupting tolerogenic pathways is urgently needed for successful tumor immunotherapy. Immunoglobulin-like transcript 4 (ILT4) is as an immunosuppressive molecule predominantly expressed in myeloid cells, including monocytes, macrophages, dendritic cells and granulocytes. Recent studies revealed that ILT4 is also enriched in tumor cells and stroma cells in the tumor microenvironment of various malignancies, modulating the biological behaviors of tumor cells and promoting their immune escape. However, the underlying mechanisms responsible for ILT4-mediated tumor development and progression are still poorly understood. In this review, we explore the functional role of ILT4 as a novel checkpoint molecule in cancers. We specifically discuss the mechanisms mediated by ILT4 for controlling tumor malignant behaviors, impairing effector anti-tumor immune responses, and sustaining the tumor suppressive microenvironment. We also highlight the potential role of ILT4 as a novel immune checkpoint target for tumor immunotherapy. Improved understanding of these issues is critical for elucidation of the role of ILT4 in tumor pathogenesis and should open new avenues for cancer immunotherapy specifically targeting this novel and alternative checkpoint molecule.

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Age-related defects in short-term plasticity are reversed by acetyl-L-carnitine at the mouse calyx of Held

Publication date: July 2018
Source:Neurobiology of Aging, Volume 67
Author(s): Mahendra Singh, Pedro Miura, Robert Renden
Hearing acuity and sound localization are affected by aging and may contribute to cognitive dementias. Although loss of sensorineural conduction is well documented to occur with age, little is known regarding short-term synaptic plasticity in central auditory nuclei. Age-related changes in synaptic transmission properties were evaluated at the mouse calyx of Held, a sign-inverting relay synapse in the circuit for sound localization, in juvenile adults (1 month old) and late middle–aged (18–21 months old) mice. Synaptic timing and short-term plasticity were severely disrupted in older mice. Surprisingly, acetyl-l-carnitine (ALCAR), an anti-inflammatory agent that facilitates mitochondrial function, fully reversed synaptic transmission delays and defects in short-term plasticity in aged mice to reflect transmission similar to that seen in juvenile adults. These findings support ALCAR supplementation as an adjuvant to improve short-term plasticity and potentially central nervous system performance in animals compromised by age and/or neurodegenerative disease.

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APOE genotype modifies the association between central arterial stiffening and cognition in older adults

Publication date: July 2018
Source:Neurobiology of Aging, Volume 67
Author(s): Francis E. Cambronero, Dandan Liu, Jacquelyn E. Neal, Elizabeth E. Moore, Katherine A. Gifford, James G. Terry, Sangeeta Nair, Kimberly R. Pechman, Katie E. Osborn, Timothy J. Hohman, Susan P. Bell, J. David Sweatt, Thomas J. Wang, Joshua A. Beckman, John Jeffrey Carr, Angela L. Jefferson
Arterial stiffening is associated with cognitive impairment and prodromal Alzheimer's disease. This study tested the interaction between arterial stiffening and an Alzheimer's disease genetic risk factor (apolipoprotein E [APOE] genotype) on cognition among older adults. Vanderbilt Memory & Aging Project participants with normal cognition (n = 162, 72 ± 7 years, 29% APOE-ε4 carrier) and mild cognitive impairment (n = 121, 73 ± 8 years, 42% APOE-ε4 carrier) completed neuropsychological assessment and cardiac MRI to assess aortic stiffening using pulse wave velocity (PWV, m/s). Linear regression models stratified by cognitive diagnosis related aortic PWV × APOE-ε4 status to neuropsychological performances, adjusting for demographic and vascular risk factors. PWV × APOE-ε4 related to poorer performance on measures of lexical retrieval (β = −0.29, p = 0.01), executive function (β = −0.44, p = 0.02), and episodic memory (β = −3.07, p = 0.02). Among participants with higher aortic PWV, APOE-ε4 modified the association between central arterial stiffening and cognition, such that carriers had worse performances than noncarriers. Findings add to a growing body of evidence for APOE-vascular interactions on cognition in older adults and warrant further research into less heart-healthy cohorts where the association between PWV and cognition among older adults might be stronger.

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Muscle strength and size are associated with motor unit connectivity in aged mice

Publication date: July 2018
Source:Neurobiology of Aging, Volume 67
Author(s): Kajri A. Sheth, Chitra C. Iyer, Christopher G. Wier, Alexander E. Crum, Anna Bratasz, Stephen J. Kolb, Brian C. Clark, Arthur H.M. Burghes, W. David Arnold
In older adults, the loss of muscle strength (dynapenia) and the loss of muscle mass (sarcopenia) are important contributors to the loss of physical function. We sought to investigate dynapenia, sarcopenia, and the loss of motor unit function in aging mice. C57BL/6J mice were analyzed with cross-sectional (males: 3 vs. 27 months; males and females: 8 vs. 12 vs. 20 months) and longitudinal studies (males: 10–25 months) using in vivo electrophysiological measures of motor unit connectivity (triceps surae compound muscle action potential and motor unit number estimation), in vivo measures of plantar flexion torque, magnetic resonance imaging of hind limb muscle volume, and grip strength. Compound muscle action potential amplitude, motor unit number estimation, and plantar flexion torque were decreased at 20 months. In contrast, grip strength was reduced at 24 months. Motor unit number estimates correlated with muscle torque and hind limb muscle volume. Our results demonstrate that the loss of motor unit connectivity is an early finding in aging male and female mice and that muscle size and contractility are both associated with motor unit number.

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Escitalopram alleviates stress-induced Alzheimer's disease-like tau pathologies and cognitive deficits by reducing hypothalamic-pituitary-adrenal axis reactivity and insulin/GSK-3β signal pathway activity

Publication date: July 2018
Source:Neurobiology of Aging, Volume 67
Author(s): Chao Wu, Wei-Gang Gong, Yan-Juan Wang, Jun-Jun Sun, Hong Zhou, Zhi-Jun Zhang, Qing-Guo Ren
Chronic stress, a causal factor for depression, can also cause cognitive impairments and tau pathology. However, whether and how the selective serotonin reuptake inhibitor antidepressant escitalopram ameliorates these effects are still unclear. In the present study, rats were subjected to chronic mild unpredictable stress for 8 weeks. Following the initial 4 weeks, the stressed animals were separated into susceptible (depressive) and unsusceptible (resistant) groups based on behavioral tests. Then, escitalopram (10 mg/kg i.p.) was administered for 28 days. Pathophysiological changes were assessed by performing behavioral and biochemical analyses. The results showed that both depressive and resistant rats displayed spatial memory deficits and an accumulation of tau in the hippocampus. Increased levels of corticosterone and insulin and a decreased level of glucocorticoid receptor were found in both depressive and resistant rats. We also found that activity-dependent phosphorylated insulin receptor substrate and glycogen synthase kinase-3β (Ser9 site) were significantly decreased in both depressive and resistant rats. However, other important kinases, such as cyclin-dependent kinase 5 and mitogen-activated protein kinase kinase-1/2, did not change in our study. Furthermore, we found that the mRNA expression of tau was increased in depressive and resistant rats. No significant change in LC3B expression was found. Interestingly, almost all the pathological changes in depressive and resistant rats previously mentioned could be reversed by escitalopram. Our results suggested that escitalopram ameliorates cognitive impairments and selectively attenuates phosphorylated tau accumulation in stressed rats through the regulation of hypothalamic-pituitary-adrenal axis activity and the insulin receptor substrate/glycogen synthase kinase-3β signaling pathway.

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Evidence of Wnt/β-catenin alterations in brain and bone of a tauopathy mouse model of Alzheimer's disease

Publication date: July 2018
Source:Neurobiology of Aging, Volume 67
Author(s): Christine M. Dengler-Crish, Hope C. Ball, Li Lin, Kimberly M. Novak, Lisa Noelle Cooper
Low bone mineral density (BMD) is a significant comorbidity in Alzheimer's disease (AD) and may reflect systemic regulatory pathway dysfunction. Low BMD has been identified in several AD mouse models selective for amyloid-β or tau pathology, but these deficits were attributed to diverse mechanisms. In this study, we identified common pathophysiological mechanisms accounting for bone loss and neurodegeneration in the htau mouse, a tauopathy model with an early low BMD phenotype. We investigated the Wnt/β-catenin pathway—a cellular signaling cascade linked to both bone loss and neuropathology. We showed that low BMD persisted in male htau mice aged from 6 to 14 months, remaining significantly lower than tau-null and C57BL/6J controls. Osteogenic gene expression in female and male htau mice was markedly reduced from controls, indicating impaired bone remodeling. In both the bone and brain, htau mice showed alterations in Wnt/β-catenin signaling genes suggestive of increased inhibition of this pathway. These findings implicate dysfunctional Wnt signaling as a potential target for addressing bone loss in AD.

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BmSUC1 is essential for glycometabolism modulation in the silkworm, Bombyx mori

Publication date: Available online 14 April 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Quan Gan, Xinwei Zhang, Daobo Zhang, Liang Shi, Yue Zhou, Tongtong Sun, Song Jiang, Junshan Gao, Yan Meng
Sucrose is the most commonly transported sugar in plants and is easily assimilated by insects to fulfill the requirement of physiological metabolism. BmSuc1 is a novel animal β-fructofuranosidase (β-FFase, EC 3.2.1.26)-encoding gene that was firstly cloned and identified in silkworm, Bombyx mori. BmSUC1 was presumed to play an important role in the silkworm-mulberry enzymatic adaptation system by effectively hydrolyzing sucrose absorbed from mulberry leaves. However, this has not been proved with direct evidence thus far. In this study, we investigated sucrose hydrolysis activity in the larval midgut of B. mori by inhibition tests and found that sucrase activity mainly stemmed from β-FFase, not α-glucosidase. Next, we performed shRNA-mediated transgenic RNAi to analyze the growth characteristics of silkworm larvae and variations in glycometabolism in vivo in transgenic silkworms. The results showed that in the RNAi-BmSuc1 transgenic line, larval development was delayed, and their body size was markedly reduced. Finally, the activity of several disaccharidases alone in the midgut and the sugar distribution, total sugar and glycogen in the midgut, hemolymph and fat body were then determined and compared. Our results demonstrated that silencing BmSuc1 significantly reduced glucose and apparently activated maltase and trehalase in the midgut. Together with a clear decrease in both glycogen and trehalose in the fat body, we conclude that BmSUC1 acts as an essential sucrase by directly modulating the degree of sucrose hydrolysis in the silkworm larval midgut, and insufficient sugar storage in the fat body may be responsible for larval malnutrition and abnormal petite phenotypes.

Graphical abstract

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An improved inventory of polychlorinated biphenyls in China: A case study on PCB-153

Publication date: June 2018
Source:Atmospheric Environment, Volume 183
Author(s): Yue Xu, Chongguo Tian, Xiaoping Wang, Jianmin Ma, Jianhui Tang, Yingjun Chen, Jun Li, Gan Zhang
Emission inventory of pollutants is essential for the environmental fate study and management of the pollutant. To construct a reasonable PCB (polychlorinated biphenyls) inventory in China, this study estimates PCB usage and emission using power generating capacity, installed capacity of power plants and transformer substations, population density and GDP as surrogates. Inventory of representative PCB (PCB-153) with a resolution of 1/4° latitude × 1/4° longitude in China from 1952 to 2005 was generated and assessed as an example. Totally, about 20.3 kt PCBs were applied in China, of which 179 t were PCB-153. By the end of 2005, most of them (56.4%) were emitted into the soil, 2.7% entered the air, and about 20.8% was sealed in storage site or still in service. Historical emissions exhibited increasing trends after 1968, 1984 and 1994, which were mainly associated with usage or disposal processes. Although primary emission has been declined since 2005, the influence of secondary emission from soils, unintentionally produced PCBs (UP-PCB), and reemission from storage sites could be a long-lasting issue in the future. This new emission inventory improves previous PCB emission inventory significantly, which underestimated PCB emission in China considerably.

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Relative impact of short-term emissions controls on gas and particle-phase oxidative potential during the 2015 China Victory Day Parade in Beijing, China

Publication date: June 2018
Source:Atmospheric Environment, Volume 183
Author(s): Wei Huang, Dongqing Fang, Jing Shang, Zhengqiang Li, Yang Zhang, Peng Huo, Zhaoying Liu, James J. Schauer, Yuanxun Zhang
A field observation focusing on reactive oxygen species (ROS) was conducted before, during, and after the 2015 China Victory Day Parade to understand the influence of short-term emissions controls on atmospheric oxidative activity. The hourly average concentrations of PM2.5, SO2, NO, NO2, CO, O3, as well as gas and particle-phase ROS, were measured using a series of online instruments. PM2.5 concentrations during control days were significantly lower than non-control days, which directly lead to the "Parade Blue", yet reductions of most gaseous pollutants except SO2 were not so obvious as PM. Similarly, the control measures also led to a great loss of particle-phase ROS throughout the control period, while the reduction of ROS in gas phase was not obvious until the more stringent measures implemented since September 1. Furthermore, only weak positive correlations were observed among ROS and some other measured species, indicating ROS concentrations were affected by a number of comprehensive factors that single marker could not capture. Meanwhile, meteorological condition and regional transportation were also shown to be the minor factors affecting atmospheric oxidizing capacity. The results of this observation mainly revealed the control measures were conducive to reducing particle-related ROS. However, the reduction of gas-phase ROS activity was less effective given the menu of controls employed for the 2015 China Victory Day Parade. Therefore, short-term emissions controls only aimed to PM reduction and visibility improvement will produce the blue sky but will not equivalently reduce the gas-phase ROS. Supplemental control measures will be needed to further reduce gas-phase ROS concentrations.

Graphical abstract

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Characterizing the spatial variability of local and background concentration signals for air pollution at the neighbourhood scale

Publication date: June 2018
Source:Atmospheric Environment, Volume 183
Author(s): Kerolyn K. Shairsingh, Cheol-Heon Jeong, Jonathan M. Wang, Greg J. Evans
Vehicle emissions represent a major source of air pollution in urban districts, producing highly variable concentrations of some pollutants within cities. The main goal of this study was to identify a deconvolving method so as to characterize variability in local, neighbourhood and regional background concentration signals. This method was validated by examining how traffic-related and non-traffic-related sources influenced the different signals.Sampling with a mobile monitoring platform was conducted across the Greater Toronto Area over a seven-day period during summer 2015. This mobile monitoring platform was equipped with instruments for measuring a wide range of pollutants at time resolutions of 1 s (ultrafine particles, black carbon) to 20 s (nitric oxide, nitrogen oxides). The monitored neighbourhoods were selected based on their land use categories (e.g. industrial, commercial, parks and residential areas). The high time-resolution data allowed pollutant concentrations to be separated into signals representing background and local concentrations. The background signals were determined using a spline of minimums; local signals were derived by subtracting the background concentration from the total concentration.Our study showed that temporal scales of 500 s and 2400 s were associated with the neighbourhood and regional background signals respectively. The percent contribution of the pollutant concentration that was attributed to local signals was highest for nitric oxide (NO) (37–95%) and lowest for ultrafine particles (9–58%); the ultrafine particles were predominantly regional (32–87%) in origin on these days. Local concentrations showed stronger associations than total concentrations with traffic intensity in a 100 m buffer (ρ:0.21–0.44). The neighbourhood scale signal also showed stronger associations with industrial facilities than the total concentrations. Given that the signals show stronger associations with different land use suggests that resolving the ambient concentrations differentiates which emission sources drive the variability in each signal. The benefit of this deconvolution method is that it may reduce exposure misclassification when coupled with predictive models.

Graphical abstract

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Isoprene emission response to drought and the impact on global atmospheric chemistry

Publication date: June 2018
Source:Atmospheric Environment, Volume 183
Author(s): Xiaoyan Jiang, Alex Guenther, Mark Potosnak, Chris Geron, Roger Seco, Thomas Karl, Saewung Kim, Lianhong Gu, Stephen Pallardy
Biogenic isoprene emissions play a very important role in atmospheric chemistry. These emissions are strongly dependent on various environmental conditions, such as temperature, solar radiation, plant water stress, ambient ozone and CO2 concentrations, and soil moisture. Current biogenic emission models (i.e., Model of Emissions of Gases and Aerosols from Nature, MEGAN) can simulate emission responses to some of the major driving variables, such as short-term variations in temperature and solar radiation, but the other factors are either missing or poorly represented. In this paper, we propose a new modelling approach that considers the physiological effects of drought stress on plant photosynthesis and isoprene emissions for use in the MEGAN3 biogenic emission model. We test the MEGAN3 approach by integrating the algorithm into the existing MEGAN2.1 biogenic emission model framework embedded into the global Community Land Model of the Community Earth System Model (CLM4.5/CESM1.2). Single-point simulations are compared against available field measurements at the Missouri Ozarks AmeriFlux (MOFLUX) field site. The modelling results show that the MEGAN3 approach of using of a photosynthesis parameter (Vcmax) and soil wetness factor (βt) to determine the drought activity factor leads to better simulated isoprene emissions in non-drought and drought periods. The global simulation with the MEGAN3 approach predicts a 17% reduction in global annual isoprene emissions, in comparison to the value predicted using the default CLM4.5/MEGAN2.1 without any drought effect. This reduction leads to changes in surface ozone and oxidants in the areas where the reduction of isoprene emissions is observed. Based on the results presented in this study, we conclude that it is important to simulate the drought-induced response of biogenic isoprene emission accurately in the coupled Earth System model.

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The Association Between Heat Waves and Other Meteorological Parameters and Snakebites: Israel National Study

Publication date: Available online 13 April 2018
Source:The Journal of Emergency Medicine
Author(s): Sagi Shashar, Maayan Yitshak-Sade, Roman Sonkin, Victor Novack, Eli Jaffe
BackgroundPublished annual estimates report a global burden of 2.5 million snakebite cases and >100,000 deaths. In Israel, envenomations are the third most frequent cause of poisonings that are of moderate to major clinical severity. Most studies focus on the clinical descriptions of snakebites in tropical climates, and we sought to investigate the association between snakebite frequency and meteorological parameters.ObjectiveWe sought to investigate the seasonality of snakebites and evaluate the association between increasingly common heat waves and other meteorological parameters and snakebite frequency in a semiarid nontropical climate.MethodsWe obtained data for all medical evacuations (2008–2015) because of snakebites in Israel. Climate data included daily 24-hour average temperature (°C) and relative humidity (%). We used a time-stratified case crossover method, in which a conditional logistic regression was applied to estimate the association, and we also stratified our analysis by season and by region.ResultsWe identified 1234 snakebite cases over 8 years, of which most (74.2%) occurred in hot seasons and between 6 pm and 9 pm. The risk of snakebite was positively associated with temperature >23°C (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.01–1.53) and inversely with humidity >40% (OR 0.74, 95% CI 0.57–0.97). We also found an association with heat waves both in cold (OR 1.62, 95% CI 1.01–2.60) and hot seasons (OR 1.50, 95% CI 1.18–1.92).ConclusionsIn a semiarid nontropical climate, we observed an association between an increase in the number of snakebite cases and higher temperatures and lower humidity. Moreover, heat waves increased the frequency of snakebites in both cold and hot seasons.

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Is Transcellular Potassium Shifting With Insulin, Albuterol, or Sodium Bicarbonate in Emergency Department Patients With Hyperkalemia Associated With Recurrent Hyperkalemia After Dialysis?

Publication date: Available online 13 April 2018
Source:The Journal of Emergency Medicine
Author(s): Brian E. Driver, Lauren R. Klein, Chaitanya Chittineni, Ellen K. Cales, Nathaniel Scott
BackgroundEmergency department (ED) treatment of hyperkalemia often involves shifting potassium into the intracellular space. There is uncertainty whether transcellular shifting causes insufficient potassium removal during hemodialysis, resulting in a subsequent need for further medical therapy or multiple sessions of hemodialysis.ObjectiveWe sought to determine whether transcellular potassium shifting in ED patients with hyperkalemia who undergo hemodialysis is associated with recurrent hyperkalemia with or without repeat hemodialysis within 24 h.MethodsThis was a retrospective observational study of ED patients with a potassium value > 5.3 mmol/L and ≥1 hemodialysis run. Transcellular shifting medications were defined as albuterol, insulin, and sodium bicarbonate. Primary outcomes were recurrent hyperkalemia with and without repeat hemodialysis within 24 h of the initial dialysis run. Generalized estimating equation models were created for the outcomes using administration of a shifting medication as the primary predictor.ResultsFour hundred seventy-nine encounters were identified. In 238 (50%) encounters, a shifting medication was administered. There were 85 outcomes of recurrent hyperkalemia and 36 outcomes of recurrent hyperkalemia with repeat hemodialysis. After adjustment, administration of shifting medications was not associated with recurrent hyperkalemia (adjusted odds ratio 1.26, 95% confidence interval 0.71–2.23) or recurrent hyperkalemia with repeat dialysis (adjusted odds ratio 1.90, 95% confidence interval 0.80–4.48).ConclusionsAdministration of transcellular shifting medications for hyperkalemia in the ED was not associated with either recurrent hyperkalemia after hemodialysis or the need for a second dialysis session within 24 h. Our findings address the uncertainty regarding transcellular potassium shifting before emergent dialysis and support safe ED administration of medications that shift potassium to the intracellular space.

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Metal enhanced fluorescence (MEF) for biosensors: General approaches and a review of recent developments

Publication date: 15 July 2018
Source:Biosensors and Bioelectronics, Volume 111
Author(s): Yoon Jeong, Yun-Min Kook, Kangwon Lee, Won-Gun Koh
Fluorescence-based biosensor platforms have been intensively investigated not only to increase the sensitivity but also to improve the performance of biosensors. By exploiting metal from the macroscopic down to the nanoscopic surface, various architectures have been devised to manipulate fluorescence signals (enhancement, quenching) within near-optical fields. The interaction of a metallic surface with proximal fluorophores (in the range of 5–90 nm) has beneficial effects on optical properties such as an increased quantum yield, improved photostability and a reduced lifetime of fluorophores. This phenomenon called metal-enhanced fluorescence (MEF) has been extensively used in biosensory applications. However, their applications for biological analysis practically remain challenging in biological microenvironments. Therefore, this review primarily provides a general overview of MEF biosensor systems from the basic mechanism to state-of-the-art biological applications. The review also covers the pros and cons of MEF biosensor as well as discussions about further directions in biological perspectives.

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Real-time quartz crystal microbalance cytosensor based on a signal recovery strategy for in-situ and continuous monitoring of multiple cell membrane glycoproteins

Publication date: 15 July 2018
Source:Biosensors and Bioelectronics, Volume 111
Author(s): Bin Zhou, Yan Hao, Dongping Long, Peihui Yang
A real-time quartz crystal microbalance (QCM) cytosensor based on a signal recovery strategy was first developed for in-situ and continuous monitoring of multiple cell membrane glycoproteins. In this work, gold nanoparticles (AuNPs) were linked with ligands to fabricate ligand-functionalized mass nanoprobes with signal amplification for increasing monitoring sensitivity. The mass nanoprobes bound to cell surface could be eluted with glycine-hydrochloric acid buffer, which led to a quick recovery of resonance frequency. Using the strategy, folate receptors (FR), CD44 molecule and epidermal growth factor receptor (EGFR) on cell membrane as the models were monitored continuously. The quantification result of MDA-MB-231 cells showed a range of linearity of 3.0 × 10⁴ to 1.0 × 10⁶ cells and a detection limit of 5.0 × 10³ cells. Furthermore, the multianalyte cytosensor exhibited three sensitive and recoverable frequency shifts during continuous monitoring for in-situ and continuous evaluation of the expression levels of FR, CD44 and EGFR on cell membrane, which exhibited that the average numbers of molecules of FR, CD44 and EGFR per MDA-MB-231 cell were 0.5 × 10⁶, 0.2 × 10⁶ and 1.4 × 10⁵ with the relative standard deviation of 4.8%, 4.5% and 5.1%, respectively. Compared with monolithic multichannel QCM, the multianalyte cytosensor based on a single microbalance could not only exclude acoustic interference but also reduce instrumental cost. This work provided a simple and efficient QCM cytosensor for in-situ and continuous monitoring of multiple cell membrane glycoproteins that offered a new avenue for early diagnosis of cancer.

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Open external circuit for microbial fuel cell sensor to monitor the nitrate in aquatic environment

Publication date: 15 July 2018
Source:Biosensors and Bioelectronics, Volume 111
Author(s): Donglin Wang, Peng Liang, Yong Jiang, Panpan Liu, Bo Miao, Wen Hao, Xia Huang
This study employed an open external circuit, rather than a closed circuit applied in previous studies, to operate an microbial fuel cell (MFC) sensor for real-time nitrate monitoring, and achieved surprisingly greater sensitivity (4.42 ± 0.3–6.66 ± 0.4 mV/(mg/L)) when the nitrate was at a concentration of 10–40 mg/L, compared to that of the MFC sensor with a closed circuit (0.8 ± 0.05–1.6 ± 0.1 mV/(mg/L)). The MFC sensor operated in open circuit (O-MFC sensor) delivered much more stable performance than that operated in closed circuit (C-MFC sensor) when affected by organic matter (NaAc). The sensitivity of O-MFC sensor was twice that of C-MFC sensor at a low background concentration of organic matter. When organic matter reached a high concentration, the sensitivity of O-MFC sensor remained at an acceptable level, while that of C-MFC sensor dropped to almost zero. Challenged by a combined shock of organic matter and nitrate, O-MFC sensor delivered evident electrical signals for nitrate warning, while C-MFC failed. Another novel feature of this study lies in a new mathematical model to examine the bioanode process of nitrate monitoring. It revealed that lower capacitance of the bioanode in O-MFC was the major contributor to the improved sensitivity of the device.

Graphical abstract

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Highly stable and regenerative graphene–diamond hybrid electrochemical biosensor for fouling target dopamine detection

Publication date: 15 July 2018
Source:Biosensors and Bioelectronics, Volume 111
Author(s): Qilong Yuan, Ying Liu, Chen Ye, Hongyan Sun, Dan Dai, Qiuping Wei, Guosong Lai, Tianzhun Wu, Aimin Yu, Li Fu, Kuan W.A. Chee, Cheng-Te Lin
Graphene is widely recognized as a promising nanomaterial for the construction of high-performance electrochemical biosensors. However, the lack of strong interfacial forces between graphene and conductive substrates is a bottleneck in the fabrication of highly stable graphene electrodes. In this work, few-layer graphene was directly formed on a high pressure high temperature (HPHT) diamond substrate via sp³-to-sp² conversion by catalytic thermal treatment and using diamond itself as the carbon source. The hybrid electrode prototype was also highly conductive and had a linear electrochemical response to dopamine in the concentration range of 5 μM – 2 mM, with a low detection limit of 200 nM. After prolonged and repeated exposure to dopamine, electrode fouling was observed which led to sensitivity degradation. Based on the strong interfacial bonding between graphene and HPHT diamond, regeneration of the fouled electrode and full performance recovery would be easily achieved by ultrasonic cleaning. The hybrid electrode is highly robust, and shows potential in its application to the detection of biofouling molecules, food processing and wastewater treatment.

Graphical abstract

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AIE-based superwettable microchips for evaporation and aggregation induced fluorescence enhancement biosensing

Publication date: 15 July 2018
Source:Biosensors and Bioelectronics, Volume 111
Author(s): Yanxia Chen, Xuehong Min, Xiqi Zhang, Feilong Zhang, Simeng Lu, Li-Ping Xu, Xiaoding Lou, Fan Xia, Xueji Zhang, Shutao Wang
Superwettable microchips with superhydrophilic microwells on superhydrophobic substrate have attracted increasing attention in fluorescence-based biological and medical diagnostics. However, traditional fluorophores often suffer from the aggregation-caused quenching (ACQ) problem at high concentration or in aggregated state. Here, we developed an AIE-based superwettable microchip by combining the evaporation-induced enrichment of superwettable microchips and the aggregation-induced emission of AIEgens together into one chip. Benefitting from the synergistic effect of the above two mechanisms, the AIE molecules (TPE-Z, a tetraphenylethene salt) were enriched from the diluted solution via evaporation and aggregated within the superhydrophilic microwell and then realized the fluorescence enhancement. Based on the dual enhancement effect of the AIE-based superwettable microchip, microRNA-141 (miR-141) can be detected with excellent reproducibility, sensitivity and specificity. A low detection limit of 1 pM can be achieved with higher signal-to-noise ratio than the traditional fluorescent probes. The proposed AIE-based superwettable microchip will provide a simple fluorescence enhancement biosensing platform for rapid, multiplexed and high-throughput analysis of specific targets in environmental monitoring, food safety, medical diagnosis and related research areas.

Graphical abstract

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