Mannosyl electrochemical impedance cytosensor for label-free MDA-MB-231 cancer cell detection

Publication date: 30 September 2018
Source:Biosensors and Bioelectronics, Volume 116
Author(s): Yi-Hsuan Tang, Han-Chen Lin, Chiao-Ling Lai, Po-Yu Chen, Chian-Hui Lai
A label-free and ultrasensitive electrochemical impedance cytosensor was developed to specifically detect the breast cancer cells MDA-MB-231 via the interaction between the mannosyl glassy carbon electrode (GCE) and the overexpressed mannose receptors on the target cell surface. The mannosyl GCE was prepared through electrografting of the amino-functionalized mannose derivatives on GCE surface in which a covalent bond was formed between carbon of the electrode and the amino group of the mannose derivative. The fluorescent microscopy indicated that the electrode is specific for MDA-MB-231 cells, with good biocompatibility for viable captured cells. The derivative with a shorter alkyl linker, mannose-C2NH2, showed a better sensitivity than that with a longer linker, mannose-C6NH2. GCE modified with amino-functionalized galactose derivative, galactose-C2NH2, shows no function to the detection of MDA-MB-231 cells. The specific interaction between the mannosyl GCE and Con A (a mannose-binding lectin) or MDA-MB-231 breast cancer cells with overexpressed mannose receptors was determined through the change of peak separation in the cyclic voltammogram or the change of charge transfer resistance in the electrochemical impedance spectra (Nyquist plot) in the electrolytes containing a reversible redox couple [Fe(CN)6]³⁻/[Fe(CN)6]⁴⁻. The charge transfer resistance in the Nyquist plots linearly depended on the concentration of MDA-MB-231 cells (1.0 × 10–1.0 × 10⁵ cells mL⁻¹, with 10 cells mL⁻¹ being the lower detection limit). Introducing 0.1% polyethylene glycol-200 (PEG-200) was able to prevent the interference caused by 1.0 × 10³ HEK-293T cells mL⁻¹, a non-cancer cell line (control).

Graphical abstract

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Ultrasensitive dual probe immunosensor for the monitoring of nicotine induced-brain derived neurotrophic factor released from cancer cells

Publication date: 30 September 2018
Source:Biosensors and Bioelectronics, Volume 116
Author(s): Mahmood H. Akhtar, Khalil K. Hussain, N.G. Gurudatt, Pranjal Chandra, Yoon-Bo Shim
Brain-derived neurotrophic factor (BDNF) was detected in the extracellular matrix of neuronal cells using a dual probe immunosensor (DPI), where one of them was used as a working and another bioconjugate loading probe. The working probe was fabricated by covalently immobilizing capture anti-BDNF (Cap Ab) on the gold nanoparticles (AuNPs)/conducting polymer composite layer. The bioconjugate probe was modified by drop casting a bioconjugate particles composed of conducting polymer self-assembled AuNPs, immobilized with detection anti-BDNF (Det Ab) and toluidine blue O (TBO). Each sensor layer was characterized using the surface analysis and electrochemical methods. Two modified probes were precisely faced each other to form a microfluidic channel structure and the gap between inside modified surfaces was about 19 µm. At optimized conditions, the DPI showed a linear dynamic range from 4.0 to 600.0 pg/ml with a detection limit of 1.5 ± 0.012 pg/ml. Interference effect of IgG, arginine, glutamine, serine, albumin, and fibrinogene were examined and stability of the developed biosensor was also investigated. The reliability of the DPI sensor was evaluated by monitoring the extracellular release of BDNF using exogenic activators (ethanol, K⁺, and nicotine) in neuronal and non-neuronal cells. In addition, the effect of nicotine onto neuroblastoma cancer cells (SH-SY5Y) was studied in detail.



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Parameters of skull vibration-induced nystagmus in normal subjects

Abstract

Hypothesis

The knowledge of vibration-induced nystagmus test (SVINT) values in the normal population is highly relevant to provide a rapid orientation on the diagnosis attitude in a patient with vertigo.

Background

Although mastoid bone vibration should only induce nystagmus in the presence of vestibular asymmetry, it has also been reported in normal individuals raising doubts as to how to interpret the SVINT. To date, no population studies involving the use of the SVINT and that establish normative values have been published.

Methods

This study was carried out at two tertiary healthcare centres on a total of 122 subjects. We stimulated at three frequencies (30, 60 and 100 Hz), in increasing order, first stimulating the right mastoid and then the left mastoid, and waiting for 30 s between each stimulus. The response was recorded with a videonystagmography system. The following variables were evaluated in each subject: the mean and maximum speed of the slow phase of nystagmus, the frequency of the nystagmatic response (NR) and the component and direction of the rapid phase of nystagmus.

Results

Only 26 subjects (20.5%) of the subjects studied here (122 subjects) developed any kind of nystagmatic response and 96 subjects (79.5%) did not display any response. Stimulation at 100 Hz provoked the largest number of responses (p = 0.04), while there was no difference in the number of responses induced by 30 and 60 Hz stimulations (p = 0.85). The frequency of nystagmus was ≤ 0.7 n/s in 80.8% of the positive responses. The mean velocity of the horizontal component of the NR was 2.2°/s (SD 1.6) and that of the vertical component was 1.3°/s (SD 1.2).

Conclusions

Healthy subjects do not generally develop to NR upon vibratory stimulation and only 20% of the subjects studied here developed any kind of NR, this being a slow and inconsistent response of low frequency. The establishment of normal values contributes to improve the orientation in clinical practice in the pathological population and this opens possibilities for tackling more reliable studies in this population.

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HER1-based vaccine: simultaneous activation of humoral and cellular immune response

Publication date: Available online 31 May 2018
Source:Seminars in Oncology
Author(s): Gretchen Bergado Báez, Diana R. Hernández Fernández, Zaima Mazorra Herrera, Belinda Sánchez Ramírez
The human epidermal growth factor receptor 1 (HER1) is a tumor associated antigen that has been validated as a clinical target for several passive, non-immune therapies currently approved for the treatment epithelial tumors. HER1 is an oncogene that not only promotes tumor progression and survival, but also immune-escape. Its overexpression in some epithelial malignancies has been correlated with a poor prognosis. We developed an approach to target HER1 by specific active immunotherapy, recognizing the extracellular domain of the receptor, using a combination of VSSP and Montanide ISA 51 as adjuvants. We summarize the results obtained with this vaccine in both the preclinical and clinical settings, emphasizing the importance of the induction of both humoral and cellular responses for the success of cancer vaccines, as safe therapeutic alternatives for the treatment of cancer.



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Molecular mechanisms underlying the neuroprotective role of atrial natriuretic peptide in experimental acute ischemic stroke

Publication date: 5 September 2018
Source:Molecular and Cellular Endocrinology, Volume 472
Author(s): Mikahela A. López-Morales, María Castelló-Ruiz, María C. Burguete, Teresa Jover-Mengual, Alicia Aliena-Valero, José M. Centeno, Enrique Alborch, Juan B. Salom, Germán Torregrosa, Francisco J. Miranda
Along with its role in regulating blood pressure and fluid homeostasis, the natriuretic peptide system could be also part of an endogenous protective mechanism against brain damage. We aimed to assess the possibility that exogenous atrial natriuretic peptide (ANP) could protect against acute ischemic stroke, as well as the molecular mechanisms involved. Three groups of rats subjected to transient middle cerebral artery occlusion (tMCAO, intraluminal filament technique, 60 min) received intracerebroventricular vehicle, low-dose ANP (0.5 nmol) or high-dose ANP (2.5 nmol), at 30 min reperfusion. Neurofunctional condition, and brain infarct and edema volumes were measured at 24 h after tMCAO. Apoptotic cell death and expression of natriuretic peptide receptors (NPR-A and NPR-C), K⁺ channels (KATP, KV and BKCa), and PI3K/Akt and MAPK/ERK1/2 signaling pathways were analyzed. Significant improvement in neurofunctional status, associated to reduction in infarct and edema volumes, was shown in the high-dose ANP group. As to the molecular mechanisms analyzed, high-dose ANP: 1) reduced caspase-3-mediated apoptosis; 2) did not modify the expression of NPR-A and NPR-C, which had been downregulated by the ischemic insult; 3) induced a significant reversion of ischemia-downregulated KATP channel expression; and 4) induced a significant reversion of ischemia-upregulated pERK2/ERK2 expression ratio. In conclusion, ANP exerts a significant protective role in terms of both improvement of neurofunctional status and reduction in infarct volume. Modulation of ANP on some molecular mechanisms involved in ischemia-induced apoptotic cell death (KATP channels and MAPK/ERK1/2 signaling pathway) could account, at least in part, for its beneficial effect. Therefore, ANP should be considered as a potential adjunctive neuroprotective agent improving stroke outcome after successful reperfusion interventions.



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Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis

Publication date: Available online 31 May 2018
Source:Cell Metabolism
Author(s): Elahu G. Sustarsic, Tao Ma, Matthew D. Lynes, Michael Larsen, Iuliia Karavaeva, Jesper F. Havelund, Carsten H. Nielsen, Mark P. Jedrychowski, Marta Moreno-Torres, Morten Lundh, Kaja Plucinska, Naja Z. Jespersen, Trisha J. Grevengoed, Barbara Kramar, Julia Peics, Jakob B. Hansen, Farnaz Shamsi, Isabel Forss, Ditte Neess, Susanne Keipert, Jianing Wang, Katharina Stohlmann, Ivan Brandslund, Cramer Christensen, Marit E. Jørgensen, Allan Linneberg, Oluf Pedersen, Michael A. Kiebish, Klaus Qvortrup, Xianlin Han, Bente Klarlund Pedersen, Martin Jastroch, Susanne Mandrup, Andreas Kjær, Steven P. Gygi, Torben Hansen, Matthew P. Gillum, Niels Grarup, Brice Emanuelli, Søren Nielsen, Camilla Scheele, Yu-Hua Tseng, Nils J. Færgeman, Zachary Gerhart-Hines
Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show that synthesis of the mitochondrial phospholipid cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Mimicking this response through overexpression of cardiolipin synthase (Crls1) enhances energy consumption in mouse and human adipocytes. Crls1 deficiency in thermogenic adipocytes diminishes inducible mitochondrial uncoupling and elicits a nuclear transcriptional response through endoplasmic reticulum stress-mediated retrograde communication. Cardiolipin depletion in brown and beige fat abolishes adipose thermogenesis and glucose uptake, which renders animals insulin resistant. We further identify a rare human CRLS1 variant associated with insulin resistance and show that adipose CRLS1 levels positively correlate with insulin sensitivity. Thus, adipose cardiolipin has a powerful impact on organismal energy homeostasis through thermogenic fat bioenergetics.

Graphical abstract

Teaser

Sustarsic et al. reveal that synthesis of the mitochondrial phospholipid cardiolipin is a hallmark of brown and beige fat activation by cold temperature. This single lipid species in thermogenic fat not only shapes adipose mitochondrial bioenergetics but also exerts profound control over whole-body insulin sensitivity and metabolic flexibility.


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Ubiquitination of ABCE1 by NOT4 in Response to Mitochondrial Damage Links Co-translational Quality Control to PINK1-Directed Mitophagy

Publication date: Available online 31 May 2018
Source:Cell Metabolism
Author(s): Zhihao Wu, Yan Wang, Junghyun Lim, Boxiang Liu, Yanping Li, Rasika Vartak, Trisha Stankiewicz, Stephen Montgomery, Bingwei Lu
Translation of mRNAs is tightly regulated and constantly surveyed for errors. Aberrant translation can trigger co-translational protein and RNA quality control processes, impairments of which cause neurodegeneration by still poorly understood mechanism(s). Here we show that quality control of translation of mitochondrial outer membrane (MOM)-localized mRNA intersects with the turnover of damaged mitochondria, both orchestrated by the mitochondrial kinase PINK1. Mitochondrial damage causes stalled translation of complex-I 30 kDa subunit (C-I30) mRNA on MOM, triggering the recruitment of co-translational quality control factors Pelo, ABCE1, and NOT4 to the ribosome/mRNA-ribonucleoprotein complex. Damage-induced ubiquitination of ABCE1 by NOT4 generates poly-ubiquitin signals that attract autophagy receptors to MOM to initiate mitophagy. In the Drosophila PINK1 model, these factors act synergistically to restore mitophagy and neuromuscular tissue integrity. Thus ribosome-associated co-translational quality control generates an early signal to trigger mitophagy. Our results have broad therapeutic implications for the understanding and treatment of neurodegenerative diseases.

Graphical abstract

Teaser

Removal of damaged mitochondria is essential for maintaining cellular vitality, but the earliest signal that initiates the mitophagy process is not well defined. Wu et al. show that mitochondrial damage causes stalled translation of OXPHOS-related mRNAs on the mitochondrial surface. Co-translational quality control of stalled ribosomes generates ubiquitin-containing signals that trigger mitophagy.


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Chrono-pharmacological Targeting of the CCL2-CCR2 Axis Ameliorates Atherosclerosis

Publication date: Available online 31 May 2018
Source:Cell Metabolism
Author(s): Carla Winter, Carlos Silvestre-Roig, Almudena Ortega-Gomez, Patricia Lemnitzer, Hessel Poelman, Ariane Schumski, Janine Winter, Maik Drechsler, Renske de Jong, Roland Immler, Markus Sperandio, Michael Hristov, Tanja Zeller, Gerry A.F. Nicolaes, Christian Weber, Joana R. Viola, Andres Hidalgo, Christoph Scheiermann, Oliver Soehnlein
Onset of cardiovascular complications as a consequence of atherosclerosis exhibits a circadian incidence with a peak in the morning hours. Although development of atherosclerosis extends for long periods of time through arterial leukocyte recruitment, we hypothesized that discrete diurnal invasion of the arterial wall could sustain atherogenic growth. Here, we show that myeloid cell recruitment to atherosclerotic lesions oscillates with a peak during the transition from the activity to the resting phase. This diurnal phenotype is regulated by rhythmic release of myeloid cell-derived CCL2, and blockade of its signaling abolished oscillatory leukocyte adhesion. In contrast, we show that myeloid cell adhesion to microvascular beds peaks during the early activity phase. Consequently, timed pharmacological CCR2 neutralization during the activity phase caused inhibition of atherosclerosis without disturbing microvascular recruitment. These findings demonstrate that chronic inflammation of large vessels feeds on rhythmic myeloid cell recruitment, and lay the foundation for chrono-pharmacology-based therapy.

Graphical abstract

Teaser

Winter et al. identify an oscillatory myeloid cell recruitment pattern to atherosclerotic lesions regulated, in part, by rhythmic deposition of CCL2 on arterial endothelium. These findings lay the foundation for a chrono-pharmacological treatment strategy targeting early lesion development without disturbing microvascular recruitment of myeloid cells.


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Patients with Obesity Caused by Melanocortin-4 Receptor Mutations Can Be Treated with a Glucagon-like Peptide-1 Receptor Agonist

Publication date: Available online 31 May 2018
Source:Cell Metabolism
Author(s): Eva W. Iepsen, Jinyi Zhang, Henrik S. Thomsen, Elizaveta L. Hansen, Mette Hollensted, Sten Madsbad, Torben Hansen, Jens J. Holst, Jens-Christian Holm, Signe S. Torekov
Pathogenic mutations in the appetite-regulating melanocortin-4 receptor (MC4R) represent the most common cause of monogenic obesity with limited treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) cause weight loss by reducing appetite. We assessed the effect of the GLP-1 RA liraglutide 3.0 mg for 16 weeks in 14 obese individuals with pathogenic MC4R mutations (BMI 37.5 ± 6.8) and 28 matched control participants without MC4R mutation (BMI 36.8 ± 4.8). Liraglutide decreased body weight by 6.8 kg ± 1.8 kg in individuals with pathogenic MC4R mutations and by 6.1 kg ± 1.2 kg in control participants. Total body fat, waist circumference, and fasting and postprandial glucose concentrations similarly decreased in both groups. Thus, liraglutide induced an equal, clinically significant weight loss of 6% in both groups, indicating that the appetite-reducing effect of liraglutide is preserved in MC4R causal obesity and that liraglutide acts independently of the MC4R pathway. Thus, liraglutide could be an effective treatment of the most common form of monogenic obesity.

Graphical abstract

Teaser

Iepsen et al. show that the diabetes and obesity drug liraglutide, which has appetite-suppressing effects, caused weight loss in obese patients with mutations in the appetite-regulating melanocortin-4 receptor (MC4R). These results show that the appetite effects of liraglutide are independent of the MC4R pathway and offer therapeutic opportunities for patients with MC4R causal obesity.


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Cancer Lipid Metabolism Confers Antiangiogenic Drug Resistance

Publication date: Available online 31 May 2018
Source:Cell Metabolism
Author(s): Hideki Iwamoto, Mitsuhiko Abe, Yunlong Yang, Dongmei Cui, Takahiro Seki, Masaki Nakamura, Kayoko Hosaka, Sharon Lim, Jieyu Wu, Xingkang He, Xiaoting Sun, Yongtian Lu, Qingjun Zhou, Weiyun Shi, Takuji Torimura, Guohui Nie, Qi Li, Yihai Cao
Intrinsic and evasive antiangiogenic drug (AAD) resistance is frequently developed in cancer patients, and molecular mechanisms underlying AAD resistance remain largely unknown. Here we describe AAD-triggered, lipid-dependent metabolic reprogramming as an alternative mechanism of AAD resistance. Unexpectedly, tumor angiogenesis in adipose and non-adipose environments is equally sensitive to AAD treatment. AAD-treated tumors in adipose environment show accelerated growth rates in the presence of a minimal number of microvessels. Mechanistically, AAD-induced tumor hypoxia initiates the fatty acid oxidation metabolic reprogramming and increases uptake of free fatty acid (FFA) that stimulates cancer cell proliferation. Inhibition of carnitine palmitoyl transferase 1A (CPT1) significantly compromises the FFA-induced cell proliferation. Genetic and pharmacological loss of CPT1 function sensitizes AAD therapeutic efficacy and enhances its anti-tumor effects. Together, we propose an effective cancer therapy concept by combining drugs that target angiogenesis and lipid metabolism.

Graphical abstract

Teaser

Antiangiogenic drug (AAD) resistance is a frequent problem in cancer patients. Iwamoto et al. show that vascularization is not a limiting factor. Instead, AAD triggered a lipid-dependent metabolic reprogramming, resulting in increased free fatty acid and cancer cell proliferation. Inhibition of fatty acid oxidation enhanced the therapeutic efficacy of AAD.


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Control of Feeding Behavior by Cerebral Ventricular Volume Transmission of Melanin-Concentrating Hormone

Publication date: Available online 31 May 2018
Source:Cell Metabolism
Author(s): Emily E. Noble, Joel D. Hahn, Vaibhav R. Konanur, Ted M. Hsu, Stephen J. Page, Alyssa M. Cortella, Clarissa M. Liu, Monica Y. Song, Andrea N. Suarez, Caroline C. Szujewski, Danielle Rider, Jamie E. Clarke, Martin Darvas, Suzanne M. Appleyard, Scott E. Kanoski
Classical mechanisms through which brain-derived molecules influence behavior include neuronal synaptic communication and neuroendocrine signaling. Here we provide evidence for an alternative neural communication mechanism that is relevant for food intake control involving cerebroventricular volume transmission of the neuropeptide melanin-concentrating hormone (MCH). Results reveal that the cerebral ventricles receive input from approximately one-third of MCH-producing neurons. Moreover, MCH cerebrospinal fluid (CSF) levels increase prior to nocturnal feeding and following chemogenetic activation of MCH-producing neurons. Utilizing a dual viral vector approach, additional results reveal that selective activation of putative CSF-projecting MCH neurons increases food intake. In contrast, food intake was reduced following immunosequestration of MCH endogenously present in CSF, indicating that neuropeptide transmission through the cerebral ventricles is a physiologically relevant signaling pathway for energy balance control. Collectively these results suggest that neural-CSF volume transmission signaling may be a common neurobiological mechanism for the control of fundamental behaviors.

Graphical abstract

Teaser

Noble et al. identify a biological signaling mechanism whereby the neuropeptide melanin-concentrating hormone is transmitted via the brain cerebrospinal fluid (CSF) to increase feeding behavior. These findings suggest that neuropeptide transmission through the CSF may be an important signaling mechanism through which the brain regulates fundamental behaviors.


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Weight Gain and Impaired Glucose Metabolism in Women Are Predicted by Inefficient Subcutaneous Fat Cell Lipolysis

Publication date: Available online 31 May 2018
Source:Cell Metabolism
Author(s): Peter Arner, Daniel P. Andersson, Jesper Bäckdahl, Ingrid Dahlman, Mikael Rydén
Adipocyte mobilization of fatty acids (lipolysis) is instrumental for energy expenditure. Lipolysis displays both spontaneous (basal) and hormone-stimulated activity. It is unknown if lipolysis is important for future body weight gain and associated disturbed glucose metabolism, and this was presently investigated in subcutaneous adipocytes from two female cohorts before and after ≥10-year follow-up. High basal and low stimulated lipolysis at baseline predicted future weight gain (odds ratios ≥4.6) as well as development of insulin resistance and impaired fasting glucose/type 2 diabetes (odds ratios ≥3.2). At baseline, weight gainers displayed lower adipose expression of several established lipolysis-regulating genes. Thus, inefficient lipolysis (high basal/low stimulated) involving altered gene expression is linked to future weight gain and impaired glucose metabolism and may constitute a treatment target. Finally, low stimulated lipolysis could be accurately estimated in vivo by simple clinical/biochemical measures and may be used to identify risk individuals for intensified preventive measures.

Graphical abstract

Teaser

Although differences in energy metabolism may promote weight gain, the involved tissue(s) are unknown. Here, Arner et al. report that altered subcutaneous fat cell lipolysis is independently linked to long-term weight gain and disturbed glucose metabolism. This may depend on primary defects in the expression of specific lipolytic regulators.


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The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma

Publication date: Available online 31 May 2018
Source:Cancer Cell
Author(s): Matthew J. McBride, John L. Pulice, Hannah C. Beird, Davis R. Ingram, Andrew R. D'Avino, Jack F. Shern, Gregory W. Charville, Jason L. Hornick, Robert T. Nakayama, Enrique M. Garcia-Rivera, Dejka M. Araujo, Wei-Lien Wang, Jen-Wei Tsai, Michelle Yeagley, Andrew J. Wagner, P. Andrew Futreal, Javed Khan, Alexander J. Lazar, Cigall Kadoch
Synovial sarcoma (SS) is defined by the hallmark SS18-SSX fusion oncoprotein, which renders BAF complexes aberrant in two manners: gain of SSX to the SS18 subunit and concomitant loss of BAF47 subunit assembly. Here we demonstrate that SS18-SSX globally hijacks BAF complexes on chromatin to activate an SS transcriptional signature that we define using primary tumors and cell lines. Specifically, SS18-SSX retargets BAF complexes from enhancers to broad polycomb domains to oppose PRC2-mediated repression and activate bivalent genes. Upon suppression of SS18-SSX, reassembly of BAF47 restores enhancer activation, but is not required for proliferative arrest. These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations.

Graphical abstract

Teaser

Incorporation of the synovial sarcoma SS18-SSX fusion into BAF complexes results in concomitant eviction of BAF47. McBride et al. show that SS18-SSX retargets BAF complexes from enhancers to polycomb domains to oppose PRC2-mediated repression. Reincorporation of BAF47 upon suppression of SS18-SSX restores enhancer activation but is not required for proliferative arrest.


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Cancer cachexia: Diagnosis, assessment, and treatment

Publication date: July 2018
Source:Critical Reviews in Oncology/Hematology, Volume 127
Author(s): Mohammadamin Sadeghi, Mahsa Keshavarz-Fathi, Vickie Baracos, Jann Arends, Maryam Mahmoudi, Nima Rezaei
Cancer cachexia is a multi-factorial syndrome, which negatively affects quality of life, responsiveness to chemotherapy, and survival in advanced cancer patients. Our understanding of cachexia has grown greatly in recent years and the roles of many tumor-derived and host-derived compounds have been elucidated as mediators of cancer cachexia. However, cancer cachexia remains an unmet medical need and attempts towards a standard treatment guideline have been unsuccessful. This review covers the diagnosis, assessment, and treatment of cancer cachexia; the elements impeding the formulation of a standard management guideline; and future directions of research for the improvement and standardization of current treatment procedures.



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Acoustic Field-Assisted Particle Patterning for Smart Polymer Composite Fabrication in Stereolithography

3D Printing and Additive Manufacturing, Ahead of Print.


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Editorial Board

Publication date: June–July 2018
Source:DNA Repair, Volumes 66–67





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Diagnosis and Management of Hepatitis in Patients on Checkpoint Blockade

AbstractMany human tumors are recognized by the adaptive immune system, but these spontaneous antitumor responses are typically inadequate to mediate regression. Blockade of immune regulatory "checkpoint" receptors such as cytotoxic T‐lymphocyte‐associated antigen 4 and programmed cell death 1 can unleash antitumor immunity, resulting in tumor responses that can be durable. Alongside the enormous promise of immunotherapy for cancer, the immune dysregulation of checkpoint blockade has led to a plethora of new autoimmune adverse events. Hepatic toxicity occurs in 1%–17% of patients on immune checkpoint inhibitors, with the precise incidence dependent on both the drug used and the underlying malignancy. Hepatitis is most commonly a low‐grade toxicity, but grade 3 and 4 hepatotoxicity does occur. Here we will answer frequently asked questions regarding immune‐related hepatitis to assist in the recognition and management of this important condition. The Oncologist 2018

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E4206: AMG 706 and Octreotide in Patients with Low‐Grade Neuroendocrine Tumors

AbstractLessons Learned. Rate of progression‐free survival at a particular point in time, i.e., a landmark analysis, is a difficult endpoint for a heterogenous malignancy such as neuroendocrine cancer.Landmark analyses can also be complicated by evolution in the standard of care during the conduct of a clinical trial.Improvements in biomarker development would be useful in developing future clinical trials in NET to better tailor individualized therapies and assess for possible efficacy endpoints.Background.Neuroendocrine tumors (NETs) are rare malignancies of the gastrointestinal (GI) tract that are highly vascularized and overexpress vascular‐endothelial growth factor (VEGF). Sunitinib has demonstrated efficacy in the pancreatic subset of NET. This study explored the activity of another oral VEGF inhibitor, AMG 706 or motesanib, a multikinase inhibitor that targets receptor tyrosine kinases, including VEGFR1, VEGFR2, VEGFR3, KIT, RET, and PDGFR (IC50s = 2, 3, 6, 8, 59, and 84 nM, respectively).Methods.This was a single‐arm, first‐line, phase II study run through the Eastern Cooperative Oncology Group. Patients with low‐grade NET (as defined by central confirmation of Ki‐67 of 0%–2%) were administered a flat dose of 125 mg per day orally combined with octreotide long acting‐repeatable (LAR) for patients who had been on a stable dose. The primary objective was to determine the 4‐month progression‐free survival (PFS).Results.Forty‐four patients were evaluated per protocol. The 4‐month PFS was 78.5%. The partial response rate was 13.6% (6/44), stable disease was 54.5% (24/44), 9.1% (4/44) had progressive disease, and 10/44 were not evaluable for response. Common toxicities included fatigue, hypertension, nausea, and headache, and most were grade 1–2. Median PFS was 8.7 months, and overall survival was 27.5 months.Conclusion.Motesanib (AMG 706) demonstrated a 4‐month PFS that met the per‐protocol definition of efficacy. Fatigue and hypertension were the most common toxicities, and few grade 3–4 toxicities were encountered. The progression‐free survival of 8.7 months in all NETs merits further study. The Oncologist 2018

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Ramucirumab Plus Pembrolizumab in Patients with Previously Treated Advanced or Metastatic Biliary Tract Cancer: Nonrandomized, Open‐Label, Phase I Trial (JVDF)

AbstractLessons Learned. Ramucirumab plus pembrolizumab revealed no unexpected safety findings in patients with advanced or metastatic biliary tract cancer, which is consistent with reports of other tumor cohorts within this phase Ia/b trial.Ramucirumab plus pembrolizumab did not demonstrate an improvement in overall survival when compared with historical controls in biomarker unselected, heavily pretreated patients with advanced or metastatic biliary tract cancer.Patients with programmed death‐ligand 1 (PD‐L1)‐positive tumors had improved overall survival compared with patients with PD‐L1‐negative disease.Background.Few treatment options exist for patients with advanced biliary tract cancer (BTC) following progression on gemcitabine‐cisplatin. Preclinical evidence suggests that simultaneous blockade of vascular endothelial growth factor receptor 2 (VEGFR‐2) and programmed death 1 (PD‐1) or programmed death‐ligand 1 (PD‐L1) enhances antitumor effects. We assessed the safety and efficacy of ramucirumab, an IgG1 VEGFR‐2 antagonist, with pembrolizumab, an IgG4 PD‐1 antagonist, in biomarker‐unselected patients with previously treated advanced or metastatic BTC.Methods.Patients had previously treated advanced or metastatic adenocarcinoma of the gallbladder, intrahepatic and extrahepatic bile ducts, or ampulla of Vater. Ramucirumab 8 mg/kg was administered intravenously on days 1 and 8 with intravenous pembrolizumab 200 mg on day 1 every 3 weeks. The primary endpoint was safety and tolerability of the combination. Secondary endpoints included objective response rate (ORR), progression‐free survival (PFS), and overall survival (OS).Results.Twenty‐six patients were treated at 12 centers in five countries. Hypertension was the most common grade 3 treatment‐related adverse event (TRAE), occurring in five patients. One patient experienced a grade 4 TRAE (neutropenia), and no treatment‐related deaths occurred. Objective response rate was 4%. Median progression‐free survival and overall survival were 1.6 months and 6.4 months, respectively.Conclusion.Ramucirumab‐pembrolizumab showed limited clinical activity with infrequent grade 3–4 TRAEs in patients with biomarker‐unselected progressive BTC. The Oncologist 2018

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A Phase I Study of Ganetespib and Ziv‐Aflibercept in Patients with Advanced Carcinomas and Sarcomas

AbstractLessons Learned. The combination of the antiangiogenic agent ziv‐aflibercept and the heat shock protein 90 inhibitor ganetespib was associated with several serious and unexpected adverse events and was not tolerable on the dosing schedule tested.Studies such as these emphasize the importance of considering overlapping toxicities when designing novel treatment combination regimens.Background.Although inhibition of angiogenesis is an effective strategy for cancer treatment, acquired resistance to antiangiogenic therapy is common. Heat shock protein 90 (Hsp90) is a molecular chaperone that regulates various oncogenic signaling pathways involved in acquired resistance and has been shown to play a role in angiogenesis. Combining an antiangiogenic agent with an Hsp90 inhibitor has therefore been proposed as a strategy for preventing resistance and improving antitumor activity. We conducted a single‐arm phase I study evaluating the combination of ziv‐aflibercept, an antiangiogenic drug, with the Hsp90 inhibitor ganetespib.Methods.Adult patients were eligible if they had recurrent or metastatic gastrointestinal carcinomas, nonsquamous non‐small cell lung carcinomas, urothelial carcinomas, or sarcomas that had progressed after at least one line of standard therapy. Ziv‐aflibercept was administered intravenously on days 1 and 15, and ganetespib was administered intravenously on days 1, 8, and 15, of each 28‐day cycle.Results.Five patients were treated with the combination. Although three patients achieved stable disease, study treatment was associated with several serious and unexpected adverse events.Conclusion.The dose escalation phase of this study was not completed, but the limited data obtained suggest that this combination may be too toxic when administered on this dosing schedule. The Oncologist 2018

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In Memoriam: Jimmie C. Holland, M.D., and James F. Holland, M.D.

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Comparison of carboplatin versus cisplatin in the treatment of paediatric extracranial malignant germ cell tumours: A report of the Malignant Germ Cell International Consortium

Publication date: July 2018
Source:European Journal of Cancer, Volume 98
Author(s): A. Lindsay Frazier, Sara Stoneham, Carlos Rodriguez-Galindo, Ha Dang, Caihong Xia, Thomas A. Olson, Matthew J. Murray, James F. Amatruda, Furqan Shaikh, Farzana Pashankar, Deborah Billmire, Mark Krailo, Dan Stark, Mark F.H. Brougham, James C. Nicholson, Juliet P. Hale
PurposeTo compare the outcomes of paediatric and adolescent extracranial malignant germ cell tumour (GCT) patients treated with either carboplatin or cisplatin on clinical trials conducted by the Children's Oncology Group (COG) and the Children's Cancer and Leukaemia Group (CCLG).MethodsThe Malignant Germ Cell International Consortium (MaGIC) has created a database of the GCT clinical trials conducted since 1983 by COG (United States, Canada and Australia), which used cisplatin-based regimens, and by CCLG (United Kingdom), which used carboplatin-based regimens. Using the parametric cure model, this study compared the overall 4-year event-free survival (EFS), stratified by age, stage, site and the a-priori defined MaGIC 'risk' groups: standard risk ((SR) 1 (EFS >80%; age <11 years), SR2 (EFS >80%, age ≥ 11y) and poor risk (PR) (EFS ≤ 70%, age ≥ 11y).ResultsCisplatin-based therapy was used in 620 patients; carboplatin was used in 163 patients. In the overall multivariate cure model, the two regimens did not differ significantly (cisplatin: 4-year EFS 86%; 95% confidence interval (CI) 83–89% versus carboplatin 4-year EFS 86%; 95% CI 79–90%; p = 0.87). No significant differences were noted in stratified analyses by site, stage, age and MaGIC risk groups: SR1 (p = 0.20), SR2 (p = 0.55) or PR (p = 0.72) patients.ConclusionsIn these trials conducted contemporaneously, there is no significant difference in outcome observed overall, or any subset of patients, who were treated with regimens containing cisplatin versus carboplatin These results suggested sufficient equipoise to justify a randomised trial to evaluate the effectiveness of carboplatin versus cisplatin in the treatment of children, adolescents and young adults with standard risk GCT, which is currently underway.



https://ift.tt/2xxAuMJ

Weekly versus 3-weekly cabazitaxel for the treatment of castration-resistant prostate cancer: A randomised phase II trial (ConCab)

Publication date: July 2018
Source:European Journal of Cancer, Volume 97
Author(s): Jeffrey Yachnin, Bjørnar Gilje, Kristian Thon, Hemming Johansson, Yvonne Brandberg, Theocharis Panaretakis, Anders Ullén
AimPatients treated with cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC) may experience dose delays and reductions or terminate treatment because of toxicity. A lower and more frequent dose of cabazitaxel could improve dose intensity.Patients and methodsThis prospective, multi-center, phase II study randomly assigned 101 patients to Arm A, cabazitaxel Q3W, 25 mg/m² or Arm B, Q1W, 10 mg/m² 5 of 6 weeks. The primary end-point was dose intensity, and we hypothesised that the experimental arm (Arm B) would result in a 20% absolute increase in the relative cumulative dose by week 18. Secondary end-points were overall survival (OS), progression-free survival (PFS), pain progression, radiological and prostate-specific antigen (PSA) response rates, quality of life (Functional Assessment of Cancer Therapy Prostate) and tolerability.ResultsMedian doses of cabazitaxel were 276 mg (45–320) and 257 mg (20–330) in Arms A and B, respectively, at week 18 (p = 0.13). More patients in Arm B stopped treatment because of toxicity. Median PFS in Arms A and B were 6.0 and 6.4 months (hazard ratio [HR] 0.73, 95% confidence interval [CI]: 0.47–1.13, p = 0.156) and for OS, 14.6 and 15.6 months (HR 0.95, CI: 0.58–1.58, p = 0.85), respectively. PSA responses ≥50% were seen in 52% and 46% of patients in Arms A and B, respectively. A higher incidence of febrile neutropenia was observed in the standard arm (10 events versus 1, p < 0.008). A grade V febrile neutropenia occurred in Arm A. Low-grade haematuria was more prevalent with weekly cabazitaxel (15 events versus 5, p = 0.003). Three patients in Arm B experienced clinically significant inflammation of the ureters. A toxicity is not previously described for cabazitaxel.ConclusionWeekly cabazitaxel reduces the incidence of febrile neutropenia but does not increase the dose intensity compared with the standard therapy. Cabazitaxel has clinical meaningful efficacy in heavily pre-treated patients with mCRPC.



https://ift.tt/2LNpTjC

Real-time Doppler ultrasound to identify vessels and guide needle placement for gynecologic interstitial brachytherapy

Publication date: Available online 31 May 2018
Source:Brachytherapy
Author(s): Rajni Sethi, Yueh Chun Kuo, Babak Edraki, Dimitry Lerner, Daniel Paik, William Bice
PurposeDoppler ultrasound (US) gives real-time information regarding anatomy and blood vessel location to guide needle placement for gynecologic interstitial (IS) brachytherapy (BT). We retrospectively assessed Doppler US images for vessel quantity, size, and distribution in cervical cancer patients undergoing high-dose-rate BT at our institution.Methods and MaterialsEleven consecutive patients undergoing IS high-dose-rate BT implants for cervical cancer between 2015 and 2017 were included. Transrectal Doppler US was used for real-time image guidance. US images were retrospectively evaluated. Vessel quantity, size, and distribution at superior and inferior levels of the cervix were recorded. Correlation of vessel quantity with tumor size and International Federation of Gynecology and Obstetrics stage was evaluated.ResultsAverage vessel quantity was 4.2 in the inferior cervix and 3.8 in the superior cervix (range 1–11). Median vessel diameter was 2 mm in the inferior cervix and 2 mm in the superior cervix (range 1–6 mm). The most common location was posterolateral (3:00–5:00 and 7:00–9:00), outer third (78% of vessels inferiorly, 64% of vessels superiorly). Vessel quantity was correlated to initial tumor size superiorly (p = 0.04, paired t-test) but not inferiorly (p = 0.31, paired t-test). There was no correlation between vessel quantity and International Federation of Gynecology and Obstetrics stage (p > 0.05, analysis of variance). Doppler US was successfully used to guide needle placement away from visualized blood vessels with no incidents of hemorrhage in these patients.ConclusionsDoppler US is a useful tool to guide needle placement for IS BT for cervical cancer. Vessel quantity varied with increased vessel quantity seen higher in the cervix for larger tumors. Vessels were most commonly distributed in the outer third of the posterolateral cervix.



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Identification of Novel Thiazolo[5,4-d]pyrimidine Derivatives as human A1 and A2A Adenosine Receptor Antagonists/Inverse Agonists

Publication date: Available online 31 May 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Flavia Varano, Daniela Catarzi, Matteo Falsini, Fabrizio Vincenzi, Silvia Pasquini, Katia Varani, Vittoria Colotta
In this study a new set of thiazolo[5,4-d]pyrimidine derivatives was synthesized. These derivatives bear different substituents at positions 2 and 5 of the thiazolopyrimidine core while maintaining a free amino group at position-7. The new compounds were tested for their affinity and potency at human (h) A1, A2A, A2B and A3 adenosine receptors expressed in CHO cells. The results reveal that the higher affinity of these new set of thiazolopyrimidines is toward the hA1 and hA2A adenosine receptors subtypes and is tuned by the substitution pattern at both the 2 and 5 positions of the thiazolopyrimidine nucleus. Functional studies evidenced that the compounds behaved as dual A1/A2A antagonists/inverse agonists. Compound 3, bearing a 5-((2-methoxyphenyl) methylamino) group and a phenyl moiety at position 2, displayed the highest affinity (hA1 Ki = 10.2 nM; hA2A Ki = 4.72 nM) and behaved as a potent A1/A2A antagonist/inverse agonist (hA1 IC50 = 13.4 nM; hA2A IC50 = 5.34 nM).

Graphical abstract

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The tyrosinase inhibitory effects of isoxazolone derivatives with a (Z)-β -phenyl-α, β -unsaturated carbonyl scaffold

Publication date: Available online 31 May 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Su Jeong Kim, Jungho Yang, Sanggwon Lee, Chaeun Park, Dongwan Kang, Jinia Akter, Sultan Ullah, Yeon-Jeong Kim, Pusoon Chun, Hyung Ryong Moon
Thirteen (Z)-4-(substituted benzylidene)-3-phenylisoxazol-5(4H)-ones were designed to confirm the geometric effect of the double bond of the β -phenyl- α, β -unsaturated carbonyl scaffold on tyrosinase inhibitory activity. Compounds 1a – 1m, which all possessed the (Z)- β -phenyl- α, β -unsaturated carbonyl scaffold, were synthesized using a tandem reaction consisting of an isoxazolone ring formation and a Knoevenagel condensation, and three starting materials, ethyl benzoylacetate, hydroxylamine and benzaldehydes. Some of the compounds showed inhibitory activity against mushroom tyrosinase as potent as compounds containing the "(E)"- β -phenyl- α, β -unsaturated carbonyl scaffold. Compounds 1c and 1m showed greater inhibitory activity than kojic acid: IC50 = 32.08±2.25 μM for 1c; IC50 = 14.62±1.38 μM for 1m; and IC50 = 37.86±2.21 μM for kojic acid. A kinetic study indicated that 1m inhibited tyrosinase in a competitive manner and that it probably binds to the enzyme's active site. In silico docking simulation supported binding of 1m (- 7.6 kcal/mol) to the active site of tyrosinase with stronger affinity than kojic acid (- 5.7 kcal/mol). Similar results were obtained using cell-based assays, and in B16F10 cells, compound 1m dose-dependently inhibited tyrosinase activity and melanogenesis. These results indicate the anti-melanogenic effect of compound 1m is due to the inhibition of tyrosinase and (Z)-isomer of the β -phenyl- α, β -unsaturated carbonyl scaffold can, like its congener the (E)-isomer, act as an excellent scaffold for tyrosinase inhibition.

Graphical abstract

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Age-dependent regulation of excitatory synaptic transmission at hippocampal temporoammonic-CA1 synapses by leptin

Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Gemma McGregor, Leigh Clements, Adham Farah, Andrew J. Irving, Jenni Harvey
The hippocampus is a key target for the hormone leptin and leptin regulation of excitatory synaptic transmission at Schaffer-collateral–CA1 synapses during aging are well documented. However, little is known about the age-dependent actions of leptin at the temporoammonic (TA) input to CA1 neurons. Here we show that leptin induces a novel form of N-methyl-D-aspartate receptor–dependent long-term depression (LTD) at adult (12–24 weeks old) TA-CA1 synapses. Leptin-induced LTD requires activation of canonical Janus tyrosine kinase 2- signal transducer and activator of transcription signaling and removal of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors from synapses. Moreover, leptin-induced LTD is occluded by activity-dependent LTD at TA-CA1 synapses. By contrast, leptin has no effect on excitatory synaptic transmission at aged (12–14 months old) TA-CA1 synapses, and low-frequency stimulation also fails to induce LTD at this age. These findings demonstrate clear age-related alterations in the leptin sensitivity of TA-CA1 synapses and provide valuable information on how the leptin system alters with age. As leptin has been linked to Alzheimer's disease, these findings have important implications for understanding of age-related disorders such as Alzheimer's disease.



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Pediatric Residents’ Assessment of Atopic Dermatitis Severity for Risk Assessment of Early Peanut Introduction,

Publication date: Available online 31 May 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): James Shea, Monika Martusiewicz, Lucy A Bilaver, Ozge N Aktas, Jialing Jiang, Anthony J Mancini, Ruchi S Gupta




https://ift.tt/2L73HQg

Development of Food Protein-Induced Enterocolitis Syndrome (FPIES) to egg following Immunoglobulin E (IgE)-mediated egg allergy,

Publication date: Available online 31 May 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Hannah Duffey, Maureen Egan




https://ift.tt/2JheLx1

Pilot study of the CAPS (Clinical extent, Area, Pruritus, Sleep) measure for atopic dermatitis severity,,✯✯✯,✯✯✯✯

Publication date: Available online 31 May 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Aaron M Drucker, Natalie H Matthews, Jennie Muglia, Abrar A Qureshi
Eczema; Atopic dermatitis; Outcome measures; Severity; Symptoms; ItchAbbreviations: AD, atopic dermatitis; BSA, body surface area; CAPS, Clinical extent, Area, Pruritus, Sleep; DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; IGA, Investigator Global Assessment; POEM, Patient-Oriented Eczema Measure



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Geochemical, radiometric, and environmental approaches for the assessment of the intensity and chronology of metal contamination in the sediment cores from Oualidia lagoon (Morocco)

Abstract

The present study evaluates the distribution of metals over the last 100 years in the Oualidia lagoon by examining their concentrations in the sediment cores. The samples were analyzed by instrumental neutron activation analysis and inductively coupled plasma mass spectrometry. Activities of ²¹⁰Pb, ²²⁶Ra, and ¹³⁷Cs were determined by gamma-ray spectrometry for establishing the age-depth relationships throughout the sediment cores by applying conventional models. The results indicated that the study area is contaminated by As and Cd revealing a detectable anthropogenic input of occurring metals as a consequence of the continuous development of human activities around the lagoon since 1950. The enrichment factor calculated for each layer of the three cores revealed that the studied sediments present no enrichment by Pb, K, and Mn; minor enrichment by Zn, Cr, Co, Cu, V, and Ni; and a moderately to severe enrichment by As and Cd. The pollution load index values increase from the bottom to the top of cores, and ranged from 0.9 to 2.8, which indicates levels of pollutants ranging from background to relatively high concentrations in the investigated sediments.

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Investigating the effect of MgO and CeO 2 metal nanoparticle on the gasoline fuel properties: empirical modeling and process optimization by surface methodology

Abstract

The main purpose of this paper is to investigate how to optimize gasoline in order to reduce the emitted pollutants caused by combustion, while the torque and power of the engine reach the maximum capabilities. To optimize gasoline formulation, an ethanol and magnesium oxide (MgO) or cerium oxide (CeO₂) mixture was added to gasoline. This study explores the role of main variables such as type of metal nanoparticle additive, engine speed, and throttle on engine performance and exhaust gas emissions through the modeling and optimization methods. Experimental design conducted through the implementation of D-optimal design, taking into account the three main parameters. To review the efficiency of this novel fuel, it was tested by a four-stroke engine connected to a dynamometer and an analyzer, under different controlled environments: speeds of 1500, 2000, 2500, and 3000 rpm at both half and full throttle conditions. The analyzed data are the power and torque of the engine, the amount of emitted CO, CO₂, HC, and NO_x, the octane index, and the viscosity. The analyzed data were calculated and turned into models. Applying the models to data (the optimization process), close correlation between predicted and actual outcomes was found, highlighting the validity of the work. A secondary finding is that the CeO₂ mixture used at higher speeds and throttles produces less emissions, while lower speeds and throttles using the MgO mixture produce less emissions.

https://ift.tt/2swUCsB

Otolaryngology resident experience with supraclavicular, submental and other regional flaps in the United States

Despite the resurgence in regional flap use, otolaryngology resident regional flap experience has been incompletely studied. We sought to characterize United States (US) otolaryngology resident exposure to, and perceptions of, supraclavicular flaps (SCFs), submental flaps (SMFs), and other regional flaps.

https://ift.tt/2socB53

Successful conservative treatment of type 3 injury (ductal injury) developing after ERCP

Publication date: Available online 31 May 2018
Source:Arab Journal of Gastroenterology
Author(s): Rahman Şenocak, Ali Kağan Coşkun, Şahin Kaymak, Yusuf Serdar Sakin
Although endoscopic retrograde cholangio-pancreatography (ERCP) is considered a safe procedure, it is associated with complications such as pancreatitis, bleeding and perforation of the bile duct, pancreatic duct and duodenum. In recent years, successful conservative treatment in selected patients with complications have increased. We present a case with successful conservative treatment of rare injury (type 3) developing after ERCP.



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The linguistic constraint on contraction in children with SLI

Publication date: Available online 31 May 2018
Source:Journal of Communication Disorders
Author(s): Kelly Rombough, Rosalind Thornton




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Association of family structure with atopic dermatitis in United States children

The relationship between family structure and atopic dermatitis has not previously been elucidated., Children from family structures without two married, biological parents have increased odds of AD and poorer overall health outcomes., Children from family structures without two, married, biological parents may benefit from increased surveillance, closer follow-up and optimized treatment for incident AD.

https://ift.tt/2H9ApOz

Daily Oxymetazoline Cream Demonstrates High and Sustained Efficacy in Patients With Persistent Erythema of Rosacea Through 52 Weeks of Treatment

https://ift.tt/2J47CBb

Long-term adalimumab efficacy in patients with moderate-to-severe hidradenitis suppurativa/acne inversa: 3-year results of a phase 3 open-label extension study

Adalimumab is approved for moderate-to-severe hidradenitis suppurativa/acne inversa., A sustained response is seen through week 168 in 52.3% of patients treated with adalimumab 40 mg weekly, with no additional safety issues identified. Adalimumab can be considered for long term control of moderate-to-severe hidradenitis suppurativa.

https://ift.tt/2syXOnE

The readability of iPledge program patient education materials

https://ift.tt/2J43aC4

A cohort study of risk factors, clinical presentations and outcomes for dermatophyte, non-dermatophyte and mixed toenail infections

https://ift.tt/2H9sK2Q

Response to: Reply to:"Determination of the impact of melanoma surgical timing on survival using the National Cancer Database"

https://ift.tt/2kGf8DE

Changes in chronic rhinosinusitis symptoms differentially associate with improvement in general health-related quality of life

Chronic rhinosinusitis (CRS) is an inflammatory disease of the paranasal sinus mucosa.1 CRS is characterized by nasal as well as extra-nasal symptoms related to poor sleep, ear/facial discomfort and emotional disturbance.2 Due to these associated symptoms as well as other clinical manifestations—such as acute exacerbations of CRS and exacerbation of comorbid pulmonary disease—CRS causes a significant quality of life (QOL) detriment.3–5 The clinical manifestations of CRS are also associated with significant productivity losses.

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Food-induced Anaphylaxis in Infants and Children

Recent recommendations to introduce peanut products to infants for peanut allergy prevention requires a focused assessment of infant anaphylaxis.

https://ift.tt/2L8MUN2

Bedroom Exposure to Airborne Allergens in the Chicago Area Using a Patient-Operated Sampling Device

Background: In current practice, allergens in vacuum collected dust are used as surrogates for inhalable allergens. We developed an airsampling device that can be used by patients themselves for direct measurement of airborne allergen concentrations in their own homes.Objective: To demonstrate the use of this device to establish allergen concentration reference ranges in a target population. To evaluate relationships of patient-reported information to measured allergen concentrations.Methods: Patients from 5 allergist's practices in the Chicagoland region were provided with instructions, questionnaire, informed consent forms and samplers to run for 5 days in their bedrooms.

https://ift.tt/2JjVqLB

Are there different subtypes of eosinophilic esophagitis?

Currently, eosinophilic esophagitis (EoE) is defined by the combination of clinical symptoms and pathologic findings. Patients should have symptoms of esophageal dysmotility as well as a defined (albeit somewhat arbitrarily so) level of esophageal eosinophilia. Thus, using this definition, the diagnosis of EoE is purely a phenotype, possibly allowing for multiple different etiologies to funnel into this diagnosis. In this manner, EoE is similar to other conditions that we treat, such as asthma, in which treatment strategies are evolving in an era of precision medicine.

https://ift.tt/2Ldda8Z

Cadmium phytoavailability under greenhouse vegetable production system measured by diffusive gradients in thin films (DGT) and its implications for the soil threshold

Publication date: October 2018
Source:Environmental Pollution, Volume 241
Author(s): Kang Tian, Zhe Xing, Guoming Liu, Huifeng Wang, Mengmeng Jia, Wenyou Hu, Biao Huang
The diffusive gradients in thin films (DGT) technique is recognized to have advantages over traditional techniques. For example, the passive measurement generally follows the principle of metal uptake by plants, and its result incorporates the influences of soil properties, which may make DGT a good protocol for improving soil quality guidelines (SQGs). However, DGT has rarely been applied to assess Cd phytoavailability in soils under greenhouse vegetable production (GVP) systems. In this study, 29 turnips (Raphanussativus L.), 21 eggplants (Solanum melongena L.) and their corresponding soils were collected from GVP systems in Dongtai and Shouguang, eastern China. Simple linear regression and stepwise regression were performed using the soil Cd content and soil properties to predict the vegetable Cd content. Soil thresholds were derived based on both total and available Cd concentrations. The results showed that total Cd, DGT-measured Cd (DGT-Cd), soil-solution Cd (Soln-Cd) and CaCl2-extractable Cd (CaCl2-Cd) were all significantly correlated with vegetable Cd. DGT-Cd had the best correlation with turnip Cd. The total Cd threshold values ranged from 4.87 (pH 6.5) to 5.18 (pH 7.5) mg kg⁻¹ for turnips and 14.60 (pH 6.5) to 14.90 (pH 7.5) mg kg⁻¹ for eggplants. These Cd thresholds were higher than the current SQGs. The predicted of turnip Cd by DGT-Cd was not improved significantly by further considering the soil properties. The calculated soil threshold of DGT-Cd was 5.35 μg L⁻¹ for turnips. However, the predicted soil threshold of DGT-Cd for eggplant was improved by including SOM, with R² values from 0.53 to 0.70. The DGT-Cd threshold was calculated as 1.81 μg L⁻¹ for eggplant (30.0 g kg⁻¹ SOM). In conclusion, whether DGT measurements are independent of soil properties and preferable for the evaluation of Cd phytoavailability and the generation of soil thresholds remains to be clarified in future research.

Graphical abstract

Teaser

Phytoavailability and soil threshold values of Cd were established based on the DGT technique in collected soils under GVP systems.


https://ift.tt/2suWTVe

Graphitic carbon nitride-carbon nanofiber as oxygen catalyst in anion-exchange membrane water electrolyzer and rechargeable metal–air cells

Publication date: 5 December 2018
Source:Applied Catalysis B: Environmental, Volume 237
Author(s): Ji Eun Park, Mi-Ju Kim, Myung Su Lim, Sun Young Kang, Jong Kwan Kim, Seung-Hyeon Oh, Min Her, Yong-Hun Cho, Yung-Eun Sung
Graphitic carbon nitride-carbon nanofiber (g-CN-CNF) was synthesized as a bifunctional catalyst in an anion-exchange membrane water electrolyzer (AEMWE), and primary and rechargeable Zn–air cells. The g-CN-CNF catalyst shows high catalytic activity for oxygen reduction reaction and oxygen evolution reaction in half-cell, with low overpotentials and low Tafel slopes. The high activity is attributed to the synergistic effect of abundant active sites and the electrical conductivity following the pyrolysis of g-CN and CNF. As a result, AEMWE with the g-CN-CNF anode, the first application of a carbon-based catalyst, exhibits outstanding performance that is the highest record in the literature for AEMWE using a non-noble metal catalyst. In addition, the performance and durability of Zn-air cells with g-CN-CNF cathode outperform those fabricated with commercial platinum.

Graphical abstract

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Provenance and environmental risk of windblown materials from mine tailing ponds, Murcia, Spain

Publication date: October 2018
Source:Environmental Pollution, Volume 241
Author(s): Hossein Khademi, Ali Abbaspour, Silvia Martínez-Martínez, María Gabarrón, Vajihe Shahrokh, Angel Faz, Jose A. Acosta
Atmospheric particulates play a vital role in the transport of potentially toxic metals, being an important exposure pathways of people to toxic elements, which is faster and can occur in a much larger scale than water, soil and biota transport. Windblown materials in abandoned tailing ponds have not been well examined. The objectives of this investigation were: to study the major physical and geochemical properties of the materials eroded by wind inside the tailing ponds, and to understand the relative contribution of different sources to its heavy metals concentration. Study area is located in Cartagena-La Union mining district (SE Spain), where metallic mining of Fe, Pb and Zn has been developed for more than 2500 years. Wind-eroded particulates were monthly collected at 3 different heights (20, 50, and 80 cm) from the ground for a period of a full year using 4 dust collectors. Four tailing samples and 4 surface soil samples from the surrounding hills were also taken. Dust, soil, and tailing samples were examined for pH, particle size distribution, electrical conductivity, calcium carbonate content, Pb, Cu, Zn, Cd, Mn, Co, Ni, Ti and Zr concentrations. The results indicated that very coarse textured, slightly saline, and almost neutral wind-eroded deposits were generated with a very high temporal variability throughout the year. They also showed that the concentration of Cd, Mn, Pb and Zn, in the dust samples is extraordinarily high (18, 1254, 1831, and 5747 mg kg⁻¹ respectively), whereas Co, Ni, and Cu had concentrations into the range of background concentrations found in the Earth's crust (3.8, 12, and 60 mg kg⁻¹ respectively). Besides, the concentration of both categories of heavy metals in the dust samples was higher than that in tailing and less than that of the soils. The barren surfaces of tailing ponds and also the surface soils of the surrounding area seem to be the major contributors to the dust collected. Therefore, abandoned mines as well as their tailing ponds should be rehabilitated by proper technologies and then well stabilized and/or covered by appropriate plant vegetation to control the transfer, particularly by air, of environmentally hazardous materials to other areas.

Graphical abstract

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Dehiscencia de la lámina papirácea del etmoides

Publication date: Available online 30 May 2018
Source:Acta Otorrinolaringológica Española
Author(s): Gabriel Huguet Llull, Marta Mesalles Ruiz, Xavier González Compta




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miR-146a induces apoptosis in neuroblastoma cells by targeting BCL11A

Publication date: August 2018
Source:Medical Hypotheses, Volume 117
Author(s): Sheng-Hua Li, Jin-Pin Li, Lan Chen, Jing-Li Liu
Aberrant expression of miR-146a has been reported to be involved in the progression and metastasis of various types of human cancers; however, its potential role in human neuroblastoma is still poorly understood. The purpose of our study was to investigate the molecular mechanism and possible role of miR-146a in human neuroblastoma. In this study, targeted genes were predicted by bioinformatic analysis and confirmed by dual-Luciferase reporter assay. The expression level of miR-146a in the human neuroblastoma SK-N-SH cell line was detected by quantitative RT-PCR. We used flow cytometric analysis to determine apoptosis and necrosis of SK-N-SH cells after transfection with miR-146a inhibitor, miR-146a mimic, and negative controls. The expression level of target genes was detected by RT-PCR and Western blotting. We identified BCL11A as a target of miR-146a. Thus, miR-146a targets the 3′UTR of BCL11A and inhibits its mRNA and protein expression. Overexpression of miR-146a can inhibit the growth and promote the apoptosis of human neuroblastoma SK-N-SH cells through inhibiting the expression of BCL11A. Furthermore, we found that upregulation of BCL11A by miR-146a inhibitor can promote SK-N-SH cells growth and protect SK-N-SH cells against apoptosis. Our results showed that miR-146a is a potential tumor suppressor gene in human neuroblastoma via directly targeting BCL11A. These findings suggest that miR-146a might be a new candidate target for treatment of human neuroblastoma.



https://ift.tt/2J1BGx9

To move or to sense? Incorporating somatosensory representation into striatal functions

Publication date: October 2018
Source:Current Opinion in Neurobiology, Volume 52
Author(s): David Robbe
A long-standing hypothesis postulates that the striatum is essential for the concurrent selection of adaptive actions and repression of inappropriate alternatives. Here, classical and recent anatomical and physiological studies are reviewed to show that, in mammals, the striatum can detect discrete task-relevant sensory stimuli and continuously track somatosensory information associated with the generation of simple movements and more complex actions. Rather than contributing to the immediate selection of actions, the striatum may monitor the sensorimotor state of animals by integrating somatosensory information and motor-related signals on a moment-by-moment basis. Such function could be critical for the progressive acquisition or updating of adaptive actions and the emergence of an embodied sense of time.



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Extranodal involvement of diffuse large B-cell lymphoma in the head and neck: An indicator of good prognosis

In this study, we analyzed clinicopathological characteristics and survival outcomes according to extranodal involvement of diffuse large B-cell lymphoma (DLBCL) in the head and neck.

https://ift.tt/2xwLh9Y

Pediatric cochlear reimplantation: Decision-tree efficacy

Publication date: Available online 31 May 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): L. Distinguin, M. Blanchard, I. Rouillon, M. Parodi, N. Loundon
ObjectivesThe context leading to pediatric cochlear reimplantation (CreI) can be complex. The objectives of this study were to define initial CreI indications, analyze final diagnosis and draw up a decision-tree.MethodsA retrospective study included patients undergoing CreI between 2005 and 2015. Demographic characteristics, CreI circumstances and technical reports were collected. Circumstances indicating CreI were classified in 3 groups: performance decrement, suspected device failure, or medical. After CreI, final diagnoses were classified in 2 groups: confirmed failure (DFail) or medical (DMed).Results69 out of 734 cochlear implantation surgeries were for CreI (8%). Manufacturers' reports were available in 64 cases (93%). Two principal causes were found: trauma and infection. Initial indications were: performance decrement: 27%; device failure: 56%; and medical: 17%. Final diagnoses were: DFail: 72%; and DMed: 28%. Initial indication and final diagnosis were similar in 86% of cases. The majority of the 14% initial indication errors belonged to the "performance decrement" group. Traumatic causes correlated with risk of initial indication error (P=0.039).ConclusionApart from spontaneous device failure, the two causes of CreI were infection and trauma. Using the present decision algorithm, half of the complex cases were resolved after CreI.



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Tonsillectomy in children and in adults: changes in practice following the opening of a day-surgery unit with dedicated operating room

Publication date: Available online 30 May 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): S. Bartier, I. Gharzouli, N. Kiblut, H. Bendimered, L. Cloutier, D. Salvan
ObjectivesTo study the impact of the opening of a day-surgery unit on the practice of tonsillectomy in adults and children in the light of the experience of our department, and to compare complications between day-surgery and conventional admission.Material and methodsA retrospective review was conducted of all tonsillectomies performed since the opening of a dedicated day-surgery room, using the ENT and emergency department data-bases.ResultsBetween October 2013 and December 2014, 179 tonsillectomies were performed (51 in adults, 128 in children), including 108 day-surgeries. Between 2012 and 2014, the number of tonsillectomies increased by 12.7%, with an 18.27% increase in children and stable adult rate. Within 1 year, day-surgery became predominant for children (73.19%) and equaled conventional admission for adults (47.22%). For almost all patients without same-day discharge, the reasons were organizational or due to malorientation (comorbidity, or unsuitable home environment). Day-case tonsillectomy in children showed a 30-day complications rate comparable to those reported in the literature (8.3% postoperative hemorrhage), with a higher rate in adults (35.3%). Onset of complications was at a mean 6 days in adults and 9 days in children; only 2 patients developed complications between 6 and 24hours postoperatively.ConclusionThe present study showed that opening a day-surgery unit led to changes in practice, with most tonsillectomies now performed on an outpatient basis, without increased complications, and notably immediate complications. Outpatient tonsillectomy thus seems to be a solution of choice compared to conventional admission, in terms of cost saving and of patient comfort, without sacrificing safety. The dedicated operating room facilitates scheduling and thereby increasing turnover by reducing wait time.



https://ift.tt/2Haonob

Revisiting Correlation Between Pre Operative High Resolution Computed Tomography and Operative Findings in Attico Antral Disease

Abstract

(1) To correlate the findings of high resolution computed tomography (HRCT) scans with operative findings in chronic otitis media (attico antral disease). (2) To assess the role of HRCT in chronic otitis media (attico antral disease). This prospective observational study undertaken at a tertiary level teaching hospital included 50 patients of chronic otitis media (attico antral disease) who underwent pre-operative HRCT scanning and the findings were compared with the operative findings and correlation between the two was assessed with appropriate statistical methods. HRCT findings correlated well for the status of malleus and incus, facial nerve canal, lateral semicircular canal, and sinus plate but were less accurate for stapes and tegmen plate. As for disease extent and prediction of cholesteatoma the degree of correlation was site dependent being greater in mastoid air cell system and epitympanum and lesser in mesotympanum and hypotympanum. HRCT despite of its value in management of chronic otitis media has its drawbacks and limitations. CT's accuracy of prediction in some aspects of the disease varies with the site of pathology and this point must always be kept in mind by the operating surgeon. We suggest that each health care centre should establish their own correlative indices for HRCT temporal bone imaging in COM. HRCT cannot be entirely relied upon in management of chronic otitis media patients. However against the backdrop of improved radiological skills in interpreting temporal bone ct images, improved CT machines and importantly the growing concern over medicolegal issues, the role of pre operative CT scan in COM is much more than what was thought previously. Undoubtedly, it is a very useful 'aid' to management BUT a well-trained, experienced and alert surgeon is the key for an accurate diagnosis and successful management of chronic otitis media (attico-antral disease).

https://ift.tt/2snPXd3

Parotid Gland Tumours: Our Experience

Abstract

Salivary gland tumor comprises of approximately 3 to 10% of neoplasms of the head and neck region. Parotid gland is the most commonly involved salivary gland with an incidence of 62% followed by submandibular gland and other minor salivary gland tumors. However clinical course of benign and malignant tumors resemble each other in clinical findings, we require histopatholocal or cytological diagnosis for planning of management. To analyze parotid tumors retrospectively with following objectives. (1) Demographic distribution of parotid tumors. (2) To evaluate cytological and histopathological findings of parotid tumors. (3) Correlation of cytological and histopathological findings of parotid tumors. It was a retrospective observational study involving 31 patients who presented with parotid region swelling. Pre operative FNAC (fine needle aspiration cytology) and post operative histopathology were correlated. Surgical management depended on nature of disease. Correlation of FNAC and Histopathology: among 27 cases pre operative FNAC and post operative histopathology was same and in only 3 cases reports differed. One FNAC was inconclusive. In present study, Sensitivity of FNAC is 81.81%, Specificity is 94.73% and accuracy is 90%. FNAC is usually the first investigative modality, as it is a minimally invasive, cheap, OPD procedure that can differentiate benign from malignant tumors. Knowing preoperative pathological nature of disease can help in planning of surgical process.

https://ift.tt/2supiL7

Carcinogenesis as a Result of Multiple Inflammatory and Oxidative Hits: a Comprehensive Review from Tumor Microenvironment to Gut Microbiota

Publication date: July 2018
Source:Neoplasia, Volume 20, Issue 7
Author(s): Floriana Morgillo, Marcello Dallio, Carminia Maria Della Corte, Antonietta Gerarda Gravina, Giuseppe Viscardi, Carmelina Loguercio, Fortunato Ciardiello, Alessandro Federico




https://ift.tt/2kEeiHt

The effect of ICT on CO 2 emissions in emerging economies: does the level of income matters?

Abstract

In the modern era of globalization, the rapid increase in information and telecommunication technologies (ICTs) contributes in various sectors of an economy; however, the environmental consequences of ICTs cannot be ignored. Therefore, the study investigates the nexus between ICTs, economic growth, financial development, and environmental quality in emerging economies. The novel feature of the study is that the interaction term of ICT is introduced with economic growth and financial development. The empirical findings of the study are based on panel mean group (MG) and augmented mean group (AMG) estimation methods from 1990 to 2015. The following empirical results are established: first the ICTs significantly affect CO₂ emissions. Second, the moderating effect of ICT and financial development stimulate the level of CO₂ emissions. Third, economic growth contributes CO₂ emission; however, the interaction between ICT and GDP mitigates the level of pollution. Policy thresholds with the R&D in ICT sector are required to mitigate the level of CO₂ emission. Introduction of green ICTs projects in the financial sector is a better choice to improve the energy efficiency.

https://ift.tt/2kC7wSt

Study of ecological compensation in complex river networks based on a mathematical model

Abstract

Transboundary water pollution has resulted in increasing conflicts between upstream and downstream administrative districts. Ecological compensation is an efficient means of restricting pollutant discharge and achieving sustainable utilization of water resources. The tri-provincial region of Taihu Basin is a typical river networks area. Pollutant flux across provincial boundaries in the Taihu Basin is hard to determine due to complex hydrologic and hydrodynamic conditions. In this study, ecological compensation estimation for the tri-provincial area based on a mathematical model is investigated for better environmental management. River discharge and water quality are predicted with the one-dimensional mathematical model and validated with field measurements. Different ecological compensation criteria are identified considering the notable regional discrepancy in sewage treatment costs. Finally, the total compensation payment is estimated. Our study indicates that Shanghai should be the receiver of payment from both Jiangsu and Zhenjiang in 2013, with 305 million and 300 million CNY, respectively. Zhejiang also contributes more pollutants to Jiangsu, and the compensation to Jiangsu is estimated as 9.3 million CNY. The proposed ecological compensation method provides an efficient way for solving the transboundary conflicts in a complex river networks area and is instructive for future policy-making.

https://ift.tt/2sue2hI

Anaplastic carcinoma of the pancreas diagnosed by endoscopic ultrasound-guided fine-needle aspiration: a case report and review of the literature

Anaplastic carcinoma of the pancreas is a rare pancreatic neoplasm with a poor prognosis. It is classified as a variant of ductal adenocarcinoma, but the clinical features and treatment of it remain unknown be...

https://ift.tt/2suIbxd

Gallbladder metastasis of renal clear cell carcinoma 15 years after primary cancer excision: a case report

Renal cell carcinoma is well-known for its propensity to metastasize to unusual sites. However, metastasis to the gallbladder has been rarely reported in the literature.

https://ift.tt/2IZg1FM

A better indicator to measure the effects of meteorological factors on cardiovascular mortality: heat index

Abstract

Although many studies have examined the correlation between temperature and mortality from cardiovascular diseases (CVD), other meteorological factors, such as relative humidity, may modify the relationship. Yet the studies on this aspect are relatively few. We chose a heat index (HI, which is an index that combines air temperature and relative humidity) as an alternative indicator of temperature, and used a distributed lag nonlinear model (DLNM) to analyze the combined effects of temperature and relative humidity on CVD mortality among all of the Beijing residents and subsociodemographic groups by age, sex, and occupation. The heat index can better reflect the human-perceived temperature when relative humidity is combined with air temperature. The results show that females, elderly people, and outdoor workers have higher vulnerability levels in regard to a high heat index. The strongest effect of heat index was found among females, for which the highest mortality risk was about 2.4 (95% CI 1.8–3) times greater than the lowest mortality risk. In addition, we found that there is a significant interaction effect of temperature and relative humidity on CVD mortality. The impact of extreme high temperature may be exacerbated by increases in humidity. Based on these results, we draw the risk level map of CVD death under different temperatures and grades of relative humidity. These findings may aid governments in the development of more accurate heat alerts and the provision of measures to prevent or reduce temperature-related deaths.

https://ift.tt/2H7TWPv

Differential regulation of human monocytes and NK cells by antibody-opsonized tumors

Abstract

The monocyte network is important for therapeutic efficacy of antibody therapies against cancer. One mechanism which monocytes/macrophages use to kill cancer cells is phagocytosis. Using trastuzumab and human breast cancer cell lines as a model, we used flow cytometry to evaluate the importance of avidity, antigen density, Fcγ receptor (FcγR) expression, and FcγR polymorphisms in human monocyte phagocytosis. By increasing avidity for the tumor through the addition of pertuzumab to trastuzumab, there was a two-to-threefold increase in phagocytosis potency against the HCC1419 cell line compared to antibodies alone, while NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) failed to increase tumor cell death. Consistent with increasing the avidity through multiple antibodies, antigen density significantly enhanced phagocytosis with breast cancer cell lines that were HER2 gene-amplified compared to non-amplified tumor cells. Confirmation that high antigen density enhanced phagocytosis was obtained when HER2 was overexpressed in HER2 non-amplified cell lines. In contrast, NK cell ADCC failed to distinguish differences in tumor cell death when comparing gene-amplified and non-amplified breast cancer cell lines. The level of phagocytosis was influenced by FcγRIIa and FcγRIIIa expression. Most monocytes are FcγRIIIa⁻, and the induction of the receptor significantly enhances antibody-dependent phagocytosis. Although both receptors are involved, when blocked FcγRIIIa had a greater influence on phagocytosis. Furthermore, the polymorphism FcγRIIIa 158V significantly enhanced phagocytosis; whereas FcγRIIa 131H polymorphism appeared to improve phagocytosis but was not statistically significant. Targeting of monocytes for enhanced phagocytosis may improve the effectiveness of therapeutic antibodies to improve clinical outcomes.

https://ift.tt/2H7tu8S

Editorial Board

Publication date: July 2018
Source:Atmospheric Environment, Volume 185





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Effects of precipitation exclusion on N2O emissions in a savanna ecosystem in SW China

Publication date: August 2018
Source:Atmospheric Environment, Volume 187
Author(s): Jing Li, Yanqiang Jin, Yuntong Liu, Yiping Zhang, John Grace, Qinghai Song, Liqing Sha, Youxing Lin, Aiguo Chen, Peiguang Li, Xuehai Fei
Savanna ecosystems play a crucial role in global N2O emissions. However, our understanding of N2O emissions under limiting precipitation conditions is lacking. This study evaluates the effects of precipitation reduction on soil N2O fluxes from a woody savanna ecosystem in Yunnan Province, Southwest China. Precipitation exclusion shelters were installed above the tree canopy, and four total treatments were established as follows: a control (CK) and precipitation exclusions of 30% (PE3), 50% (PE5), and 70% (PE7). Two years (2015–2016) of N2O fluxes, soil temperature and soil water content data were collected. The N2O fluxes were generally low, ranging from 0.039 to 0.245 mg N m⁻² day⁻¹, and they were strongly linked to precipitation events. Additionally, the N2O fluxes during the rainy season were significantly greater than those during the dry season. The maximum N2O flux was observed in August, and the minimum flux occurred in December. Precipitation exclusion had a significant negative influence on the N2O fluxes. The N2O emissions of CK, PE3, PE5, and PE7 were 0.20, 0.17, 0.13, and 0.12 kg N ha⁻¹ yr⁻¹, respectively. With the exacerbation of precipitation exclusion, the decrease rate of precipitation exclusion on the N2O emissions increased over the entire year (eventually reaching 41.8% in PE7), but the decrease rate of precipitation exclusion on the soil N2O emission during the dry season was stronger than that during the rainy season. Additionally, the proportion of dry season N2O emissions to total annual emissions decreased (from 45% to 41%), and that of rainy season N2O emissions to total annual emissions increased (from 55% to 59%) over the year, whereas they exhibited a stable trend from PE5. The data show that the Yuanjiang savanna is a net source of N2O; precipitation reduction decreases the N2O emissions in the savanna regions, indicating that precipitation reduction can only slow the increase in the N2O concentration in the atmosphere and can therefore slow global warming. In addition, the N2O emissions during the dry season may play a significant role in total N2O emissions and be more sensitive to precipitation reduction than those during rainy season. These possibilities should be considered in future studies, especially in those ecosystems that experience substantial inter-annual climatic fluctuations.



https://ift.tt/2Jj1Nip

Review of sulfur dioxide to sulfate aerosol chemistry at Kīlauea Volcano, Hawai‘i

Publication date: July 2018
Source:Atmospheric Environment, Volume 185
Author(s): Andre K. Pattantyus, Steven Businger, Steven G. Howell
Sulfur dioxide emissions from the Kīlauea Volcano on the island of Hawai'i and the subsequent formation of sulfate aerosols have caused a public health hazard across the state of Hawai'i since the volcano began erupting continuously in 1983. The University of Hawai'i at Mānoa began to forecast the trajectory and dispersion of emissions in 2010 to help mitigate the hazards to public health. In this paper a comprehensive review of potential conversion reactions is presented with the goal of more accurately representing the sulfur dioxide chemistry in the dispersion model.Atmospheric sulfur dioxide chemistry and major process responsible for sulfate formation are well documented in urban and industrial settings. The atmosphere in the vicinity of Kīlauea Volcano on the island of Hawai'i differs from that in previous investigations by virtue of being far removed from both urban and industrial settings in a remote, tropical marine atmosphere. Additionally, the combination of the high rate of sulfur dioxide emissions and trace gases and metals from Kīlauea Volcano creates a unique circumstance that requires a new look at potential conversion pathways to determine the dominant reactions.The theoretical analysis suggests that the dominant reaction in clear air will be between sulfur dioxide and the hydroxyl radical (0.01–5% h⁻¹) and the dominant reaction in cloudy air involves hydrogen peroxide (3–50% s⁻¹). Moreover, given the high SO2 emissions from the Halema'uma'u Crater vent, the oxidation of sulfur dioxide by these reactants is limited by their rate of production.



https://ift.tt/2L87SM0

Adenopharyngoplasty vs Adenotonsillectomy in Children With Severe Obstructive Sleep Apnea

This randomized clinical trial compares the outcomes of adenotonsillectomy vs adenopharyngoplasty in children with severe obstructive sleep apnea.

https://ift.tt/2J2mCva

Association of Idiopathic Sudden Sensorineural Hearing Loss With Affective Disorders

This cohort study uses a Korean nationwide database to investigate whether idiopathic sudden sensorineural hearing loss is associated with the development of affective disorders such as anxiety, depression, and bipolar disorder.

https://ift.tt/2LMmVfe

The Unrecognized Dangers of Sudden Hearing Loss

The impact of an idiopathic sudden sensorineural hearing loss (ISSNHL) on a patient can be devastating. Practitioners who treat this malady are always worried about potential life-threatening issues, such as an intracranial complication or a tumor. However, practitioners need to be aware of other life-altering consequences of a sudden hearing loss. The study by Kim et al reveals that an often-overlooked sequela is the onset of affective disorders such as depression and anxiety.

https://ift.tt/2xr7KVI

B-cell activating factor and related genetic variants in lupus related atherosclerosis

Publication date: Available online 31 May 2018
Source:Journal of Autoimmunity
Author(s): Evangelos Theodorou, Adrianos Nezos, Eleni Antypa, Dimitrios Ioakeimidis, Michael Koutsilieris, Maria Tektonidou, Haralampos M. Moutsopoulos, Clio P. Mavragani
BackgroundSystemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with an increased atherosclerotic risk compared to healthy population, partially explained by traditional cardiovascular (CV) risk factors. Recent data suggest B-cell activating factor (BAFF) as an important contributor in the pathogenesis of both SLE and atherosclerosis. The aim of the current study is to explore whether serum BAFF levels along with variants of the BAFF gene increase lupus related atherosclerotic risk.Patients-Methods250 SLE patients underwent assessment of plaque formation and/or intimal media thickness (IMT) measurements in carotid and femoral arteries by ultrasound. Disease related features and CV traditional risk factors were also assessed. Serum BAFF levels were determined by commercially available ELISA and five single nucleotide polymorphisms (SNPs) of the BAFF gene (rs1224141, rs12583006, rs9514828, rs1041569 and the rs9514827) were evaluated by PCR-based assays in all patients and 200 healthy controls (HC) of similar age and sex distribution. SLE patients were further divided in high and low BAFF groups on the basis of the upper quartile level of the distribution (1358 pg/ml). Genotype and haplotype frequencies in SLE patients and HC were determined by SNPStats and SHEsis software.ResultsHigh-BAFF SLE group displayed increased rates of both plaque formation and arterial wall thickening (defined as IMT>0.90 mm) compared to patients with low BAFF levels (58.1% vs 43.6%, p:0.048 and 38.6% vs 23.2%, p-value: 0.024, respectively). The association remained significant after disease related features were taken into account (ORs [95%CI]: 2.2 [1.0–5.1] and 2.5 [1.1–5.5] for plaque formation and arterial wall thickening, respectively). Moreover, the presence of the AA genotype of the rs12583006 BAFF gene variant increased susceptibility for both lupus and lupus related plaque formation (ORs [95%CI]: 2.8 [1.1–7.1], and 4.4 [1.3–15.4] in the codominant model, respectively). Finally, the haplotype TTTAT was found to be protective for plaque formation among SLE patients (OR 0.3 [0.1–0.9]. No associations between BAFF gene variants with arterial wall thickening were detected.ConclusionsHigh BAFF serum levels in the upper 4th quartile as well as BAFF genetic variants seem to increase susceptibility for both lupus and lupus related subclinical atherosclerosis implying B-cell hyperactivity as a potential contributor in the pronounced lupus related atherosclerotic risk.



https://ift.tt/2JlwzHw

Engineered MBP-specific human Tregs ameliorate MOG-induced EAE through IL-2-triggered inhibition of effector T cells

Publication date: Available online 30 May 2018
Source:Journal of Autoimmunity
Author(s): Yong Chan Kim, Ai-Hong Zhang, Jeongheon Yoon, William E. Culp, Jason R. Lees, Kai W. Wucherpfennig, David W. Scott
Expanded polyclonal T regulatory cells (Tregs) offer great promise for the treatment of immune-mediated diseases. Inhibition by Tregs is under the control of the T-cell receptor (TCR). Therefore, we created Tregs with defined antigen specificity, using a recombinant T-cell receptor isolated from a myelin-basic protein specific T-cell clone of a multiple sclerosis (MS) patient (Ob2F3). We expressed this TCR using a retroviral expression vector in human Tregs from peripheral blood. We observed that transduced Tregs were activated in vitro in response to myelin basic protein (MBP) peptide on DR15 antigen-presenting cells (APC) and upregulated Treg markers, Foxp3, LAP and Helios. These engineered MBP-specific Tregs could suppress MBP-specific T effector cells, and were also able to suppress T cells with other specificities after Tregs had been activated through the TCR. Importantly, we showed that these engineered Tregs were able to function effectively in the presence of strong TLR-induced inflammatory signals, and that MBP-specific Tregs ameliorated EAE in myelin oligodendrocyte glycoprotein (MOG)-immunized DR15 transgenic mice. We further demonstrated in vitro that IL-2 produced by neighboring effector T cells activated MBP-specific Tregs, initiating contact-independent suppression to T effectors in local milieu. Mechanistic studies demonstrated that bystander suppression in vivo may involve transfer of soluble mediators, enhanced by cell contact between Tregs and effectors. Taken together, we show that engineered clonal MBP-specific Tregs are able to suppress autoimmune pathology in EAE. This approach may serve as a cellular therapy for MS patients with the common DR15 haplotype that is associated with disease susceptibility.



https://ift.tt/2L9KIVj

Effect of pyrolytic carbon interface thickness on conductivity and mechanical and wear properties of copper mesh modified carbon/carbon composite

Publication date: 15 September 2018
Source:Materials & Design, Volume 154
Author(s): Pei Wang, Hongbo Zhang, Jian Yin, Xiang Xiong, Chaoyong Deng, Xiaoguang Wu
Carbon fiber/copper fiber-reinforced carbon matrix composite, a kind of novel sliding contact strip material, was fabricated using a chemical vapor infiltration (CVI) technology, following by furan resin impregnation and carbonization processes. To improve the interface combination, pyrolytic carbon (PyC) with different layer thicknesses (0–18.86 μm) were formed on the copper and carbon fiber surfaces via controlling deposition time of the CVI. Microstructure, electrical conductivity, flexural strength and current-carrying friction performances were investigated. The results showed the dominant affecting factor on the material performances was the microstructure of matrix carbon. The electrical conductivity increased with increasing of the PyC layer thickness, which was an approximate linear collection. As compared to the one without the PyC interface, Cf/Cuf-C composites with PyC interface increased flexural strength and wear resistance by more than two times owing to the effective protection for carbon fibers and copper fibers. In addition, three physical models were used to describe wear mechanisms of Cf/Cuf-C composites with different PyC layer thicknesses.

Graphical abstract

https://ift.tt/2sq63SA

Localized stress recoveries in hierarchical aligned porous materials with the influence of surface effects or interphases

Publication date: 5 October 2018
Source:Materials & Design, Volume 155
Author(s): Guannan Wang, Quanquan Yang, Bo Yang
In order to study the micromechanical behavior of hierarchical aligned porous structures, an infinite plate with an arbitrarily shaped hole reinforced with a functionally graded hierarchical coating, is investigated. The coating is further composed of aligned porous materials with the considerations of surface effects or interphases/coatings. The solution is derived by following the Muskhelishvili approach at the higher structural level, while the locally exact homogenization theory model is employed to recover the microstructural stress distributions. It can be seen that even though certain magnitudes of stress concentrations already happen at the structural levels (depending on the shape of the hole), the local stress concentrations appear to be much larger. By changing the surface parameters of microstructures, the stress concentrations are varied within certain amounts. Moreover, the magnitudes of local stresses are significantly reduced with the existence of the coatings within the microstructures. Some conclusions are thus summarized: First, the mechanical behavior at higher structural level is not reliable in predicting the possible damages or cracks starting from the microstructures; second, both surface parameters and interphases/coatings in the microstructures play important roles in changing the stress concentrations in the local microstructures, which could be instructive in the design of hierarchical structures.

Graphical abstract

https://ift.tt/2skWW6A

Zirconium phosphate (ZrP)-based functional materials: Synthesis, properties and applications

Publication date: 5 October 2018
Source:Materials & Design, Volume 155
Author(s): Huaping Xiao, Shuhai Liu
Zirconium phosphate (ZrP) and its organic derivative, zirconium phosphonate, increasingly attract research interest due to their outstanding physical and chemical properties, both in their amorphous and in their crystalline phases. These include an extremely high ion-exchange capability, high aspect ratio, excellent thermal stability and good biocompatibility. These superior properties, along with their simple synthesization, functionalization and easily controlled morphology, make ZrP-based materials promising candidates for a wide range of applications. The excellent performance of ZrP-based materials used as catalysts, flame retardants, drug delivery agents, lubrication modifiers, electrolyte membranes in fuel cells, and anti-corrosive agents, has been widely reported. This review will provide an introduction to the structures, properties and related synthesization technologies of various types of ZrP-based materials, followed by a discussion of recent developments in their functional applications.

Graphical abstract

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In situ measurements of layer roughness during laser powder bed fusion additive manufacturing using low coherence scanning interferometry

Publication date: 15 September 2018
Source:Materials & Design, Volume 154
Author(s): Philip J. DePond, Gabe Guss, Sonny Ly, Nicholas P. Calta, Dave Deane, Saad Khairallah, Manyalibo J. Matthews
Layer-to-layer height measurements of additively manufactured 316L stainless steel using high speed spectral-domain optical coherence tomography (SD-OCT) are presented. Layers are built up using an open architecture laser powder bed fusion machine while height measurements are made in-line along the process laser path following each layer print. Printed cubes, with and without an internal 'overhang' channel, were built to investigate the effect of scanning parameters on surface structure. Layer-to-layer scan rotation strategy significantly impacts surface roughness between layers which in turn can influence porosity. Spatter particles, which have been correlated with numerous defect modalities, generate high points in the powder bed and can persist on a melted surface for many layers. Laser power significantly affects overhang morphology, as measured by SD-OCT. Large dross occurs in the high energy density regime, while balling and a capillary-driven coalescence of unstable melt pools perpendicular to the scanning direction occurs in the low energy density regime. High fidelity powder-scale simulations of deep powder layers were used to further elucidate the underlying physics revealed by SD-OCT measurements and high speed imaging, yielding insight to defect formation mechanisms which can lead to improved process parameters.

Graphical abstract

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Local lattice distortion in NiCoCr, FeCoNiCr and FeCoNiCrMn concentrated alloys investigated by synchrotron X-ray diffraction

Publication date: 5 October 2018
Source:Materials & Design, Volume 155
Author(s): Y. Tong, K. Jin, H. Bei, J.Y.P. Ko, D.C. Pagan, Y. Zhang, F.X. Zhang
Severe lattice distortion is presumptively considered as a core effect of high-entropy alloys, but quantitative measurements are still missing. Here, we demonstrate that the lattice distortion in high-entropy alloys can be quantitatively analyzed based on pair distribution function obtained from synchrotron X-ray diffraction. By applying this method to equiatomic NiCoCr, FeCoNiCr and FeCoNiCrMn concentrated alloys, we found that the local lattice distortion in the NiCoCr (0.23%) and FeCoNiCrMn (0.24%) alloys are comparable while negligible in the FeCoNiCr alloy (0.04%). The origin of local lattice distortion in the NiCoCr and FeCoNiCrMn concentrated alloys was discussed.

Graphical abstract

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Angle defines attachment: Switching the biological response to titanium interfaces by modifying the inclination angle during selective laser melting

Publication date: 15 September 2018
Source:Materials & Design, Volume 154
Author(s): Avik Sarker, Nhiem Tran, Aaqil Rifai, Joe Elambasseril, Milan Brandt, Richard Williams, Martin Leary, Kate Fox
Developing patient-specific biomedical implants for clinical application requires the integration of material science, manufacturing engineering, and biology. As selective laser melted (SLM) metallic additive manufactured implants become common, a key, but overlooked design parameter is its inclination angle. In this study, we have fabricated Ti6Al4V implants at three different inclination angles (0, 45 and 90 degrees) reporting the relationship between cell attachment, surface topography and surface chemistry at each angle. During the SLM process, we show that as the inclination angles increase, there is a corresponding increase in the number of partially melted particles adhering to the surface, greatly affecting the surface topography, morphology, roughness, chemistry, and wettability of the implant. In order to validate the approach, the effect of surface properties on cell fate was determined. In each case, the overall viability of Chinese hamster ovarian cells (CHO) was found to be statistically indistinguishable; however, the number of spindle cells and their dimension were found to increase significantly at higher inclination angles. This work demonstrates a novel approach for combining SLM technology in manufacturing metallic biomedical implants and provides a novel insight in case of switching cell‑titanium interface by modifying one process parameter, inclination angle, during rapid prototyping process.

Graphical abstract

https://ift.tt/2skWANi