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Τετάρτη 21 Μαρτίου 2018

Hematological and histopathological effects of silver nanoparticles in rainbow trout ( Oncorhynchus mykiss )—how about increase of salinity?

Abstract

Hematological and histopathological toxicities of silver nanoparticles (Ag-NPs) to rainbow trout were assessed in three water salinities: 0.4 ppt (low salinity), 6 ± 0.3 ppt (moderate salinity), and 12 ± 0.2 ppt (high salinity). The concentrations of Ag-NPs in the low salinity were 0.032, 0.1, 0.32, and 1 ppm, and in the moderate and high salinities were 3.2, 10, 32, and 100 ppm. The results indicated a concentration-dependently increased (thrombocyte, monocyte, and large lymphocyte) and decreased (neutrophil and small lymphocyte) white blood cell count in the Ag-NP treatments in the low salinity than the other ones in the moderate and high salinities. Red blood cell volume significantly increased in all of the experimental groups exposed to higher Ag-NP concentrations, especially those in the low salinity. In the moderate and high salinities, blood plasma total protein decreased in 10 and 32 ppm Ag-NP treatments, but albumin increased in the groups in the low salinity. Blood plasma ions (Cl, Na+, K+, Ca2+, and Mg2+) showed high changes in the higher Ag-NP treatments. In all treatments, gill histological analysis demonstrated a time- and Ag-NP concentration-dependent extent of abnormalities, with the highest epithelial lifting in 1 ppm Ag-NPs in the low salinity and also the highest necrosis and aneurism in the 32 ppm treatments in other salinities. Lower Ag-NP concentrations in the low salinity led to fibrosis, villus fusion, inflammation, vacuolization, and microvillus hyperplasia in the gut, yet villi lifting and necrosis in 0.32 and 1 ppm of Ag-NPs were the main anomalies. In addition to the mentioned alterations, villi abolitions predominantly occurred in 32 ppm Ag-NP concentrations in the moderate and high salinities. Overall, despite exposing to lower Ag-NP concentrations, the fish kept in the low salinity demonstrated more vulnerability to Ag-NPs than those in the other salinities.



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Alterations of antioxidant indexes and inflammatory cytokine expression aggravated hepatocellular apoptosis through mitochondrial and death receptor-dependent pathways in Gallus gallus exposed to arsenic and copper

Abstract

In this study, we sought to investigate the effects of sub-chronic exposure of arsenic (As) and copper (Cu) on oxidative stress, inflammatory response, and mitochondria and death receptor apoptosis pathways in chicken liver. Seventy-two 1-day-old male Hy-line chickens were treated with basal diet, 30 mg/kg arsenic trioxide (As2O3), or/and 300 mg/kg copper sulfate (CuSO4) for 4, 8, and 12 weeks. Study revealed that exposure to As or/and Cu undermined the antioxidant function and increased lipid peroxidation. Worse yet, liver cell swollen, vacuolar degeneration, and inflammatory cell infiltration were accompanied by an increase of the nuclear factor-κB (NF-κB) and its downstream inflammation-related genes after exposure to As or/and Cu. Furthermore, mitochondria swollen and chromatin condensation were found in As and Cu groups, and hepatocyte nuclear membrane rupture and markedly increased (P < 0.01) apoptosis index were observed in As combined with Cu group. Meanwhile, the transcription and protein expression levels of Bcl-2-associated X protein (Bax), p53, cytochrome c (Cyt c), and caspase-3, 8, 9 were upregulated and B cell lymphoma-2 (Bcl-2) was downregulated in As, Cu, and As + Cu groups in the liver tissues (P < 0.05, P < 0.01). Our results indicated that exposure to As or/and Cu could lead to oxidative stress, inflammatory response, and tissue damage and aggravate hepatocellular apoptosis through mitochondrial and death receptor-dependent pathways in chicken liver. And As and Cu showed a possible synergistic relationship in liver damage.



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Detection of 2-aminoethylphosphonic acid in suspended particles in an ultraoligotrophic lake: a two-dimensional nuclear magnetic resonance (2D-NMR) study

Abstract

Particulate organic phosphorus (P) compounds were examined in ultraoligotrophic Lake Saiko, Japan. A cartridge filter was used to collect sufficient amount of suspended particles for analysis by a two-dimensional NMR (1H-31P heteronuclear multiple bond correlation). 2-Aminoethylphosphonic acid (2-AEP), a phosphonate, was detected in suspended particles in Lake Saiko. The identity of the phosphonate was confirmed by comparison with a commercially available compound. Because 2-AEP is bioavailable, microorganisms can store and use this compound under extremely P-limited conditions. This is the first study to detect 2-AEP in an ultra-oligotrophic environment.



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CD34 and BerEP4 Are Helpful to Distinguish Basaloid Tricholemmoma From Basal Cell Carcinoma

Abstract: Tricholemmoma, a benign follicular neoplasm with outer root sheath differentiation, typically comprises clear or pale cells, and when multiple is pathognomic of Cowden's syndrome. The tumor is probably underrecognized and in basaloid examples can be difficult to distinguish from basal cell carcinoma (BCC). We studied 55 tricholemmomas (including 15 basaloid cases) and compared immunohistochemical profile with nodular BCC from our archives. Basaloid and non–basaloid tricholemmomas had similar staining characteristics. BerEP4 was focally positive (range 10%–20%) in only 3/39 (7.7%) tricholemmomas compared with widespread positivity in BCC (90.8%, 139 of 151 cases with ≥50% tumor area stained). CD34 was expressed, usually focally (median 20%, range 10%–90%), in 52/53 (98.1%) tricholemmomas and was negative in all 21 BCCs stained. EMA staining lacked sensitivity or specificity in differentiating tricholemmoma from BCC. Five or more Merkel cells were found in 7/17 (40.1%) tricholemmomas and 1/23 (4.3%) nodular BCCs studied. In summary, immunohistochemistry is helpful in distinction between tricholemmoma, including difficult basaloid examples (BerEP4 negative or focal, CD34 positive) compared with BCC (BerEP4 widespread in most cases, CD34 negative). The presence of 5 or more Merkel cells is a relatively specific but not a particularly sensitive discriminator. Correspondence: Nicholas Turnbull, BHB, MBChB, FRACP, ICDP-UEMS, Dermatology Department, North Shore Hospital, 124 Shakespeare Road, Takapuna, Auckland 0620 (e-mail: drnickturnbull@hotmail.com). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Cholesterol Clefts in Basal Cell Carcinoma: An Under-Recognized Association

Abstract: Cholesterol clefts have rarely been described in cutaneous tumors other than lipid-rich tumors. However, they seem to be a relatively common phenomenon in basal cell carcinoma (BCC). This study was undertaken to determine the frequency of cholesterol cleft deposition in BCCs, and to identify associated histopathologic and clinical features. Twenty-eight of 249 BCC cases reviewed showed features of cholesterol cleft. Mean disease duration in those with cholesterol cleft was significantly longer than in those without cholesterol cleft (5.58 vs. 3.29 years, respectively; P = 0.013). Sex and age distributions, and average tumor longest diameter (11.6 vs. 9.41 mm) were no different for those with or without cholesterol clefts. The most common anatomical location was the nose in both those with and without cholesterol clefts. BCCs without cholesterol clefts more frequently involved the periauricular and perioral areas, and areas other than the head and neck, such as the trunk and lower extremities (P = 0.087). Histopathologic features of necrosis (26/28, 92.86%), keratinization (19/28, 67.86%), and pigment deposition (18/28, 64.29%) were found to be associated with cholesterol clefts. Cholesterol clefts were intratumorally located in 27/28 cases (96.43%), and stromally located in 2 cases (7.14%); intravascularly located cholesterol clefts were observed in no case. In conclusion, this study shows that cholesterol clefts are relatively common in BCC, and suggests that cholesterol crystal deposition could be associated with longer disease duration and microtrauma. Correspondence: Hee Joo Kim, MD, PhD, Assistant Professor, Department of Dermatology, Gil Medical Center, Gachon University School of Medicine, 21, Namdong-daero 774beon-gil, Namdong-gu, Incheon 21565, South Korea (e-mail: hjbp0610@gmail.com). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Painful Piezogenic Pedal Papules in a Female Babysitter: A Case-Based Review

No abstract available

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Xanthomatous Cells in Cutaneous Graft-Versus-Host Disease Biopsies: A Clue for the Diagnosis of Hepatic Graft-Versus-Host Disease

Abstract: Graft-versus-host disease (GVHD) is one of the most common and serious complications of hematopoietic stem-cell transplantation that mainly affects the skin, gastrointestinal tract, and liver. Hepatic GVHD is associated with high morbidity and mortality, and its diagnosis can be especially challenging because of nonspecific clinical signs and symptoms. It must be suspected in patients with elevated liver enzymes and cholestasis, especially in those with a history of preceding skin rash and diarrhea. We describe 3 patients with cutaneous and hepatic GVHD that presented with severe hypercholesterolemia and hypertriglyceridemia, and no xanthomatous macular lesions, in which cutaneous biopsies revealed the presence of xanthomatous dermal histiocytes. We propose that the presence of these xanthomatous cells in skin biopsies from patients with cutaneous GVHD could be a dermatopathological clue for the diagnosis of hepatic GVHD. Correspondence: Denise Gamé, MD, Department of Dermatology, Hospital Germans Trias i Pujol, Carretera de Canyet s/n 08916, Badalona, Barcelona, Spain (e-mail: denisegame@gmail.com). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Small Vessel Vasculitis in Herpes Zoster—Discussion of Current Aspects of Varicella Zoster Virus Vasculopathy

Abstract: Varicella zoster virus (VZV) vasculopathy was initially described as herpes zoster ophthalmicus with contralateral hemiplegia in 1896. VZV is able to infect endothelial cells directly, leading to a thickened intima and vascular remodeling due to inflammation. Therefore, a spectrum of vasculopathies is induced, ranging from a discrete capillaritis-to-granulomatous vasculitis and obliterative angiitis. Cutaneous vasculitic changes sui generis with leukocytoclasia, cell debris, vascular damage, and endothelial swelling are very rare feature of herpetic infections in skin biopsies. We report an immunocompetent patient who presented with a rare form of cutaneous VZV infection of the upper leg characterized by vasculitic changes of the small vessels without typical herpetic epidermal features or neural involvement. Intriguingly, the vasculitis appeared prior to the characteristic vesicular rush without any pain symptoms. Because VZV can cause vasculopathic damage mainly within the central nervous system in immunocompetent and immunosuppressed patients, we recommend continuous clinical controls to recognize central symptoms that are related to VZV vasculopathy or giant cell arteriitis. Correspondence: Cornelia S. L. Müller, MD, Department of Dermatology, The Saarland University Hospital, Kirrberger Str., 66421 Homburg/Saar, Germany (e-mail: cornelia.mueller@uks.eu). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Ecchymotic Nodule on the Scalp: Challenge

No abstract available

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Diffuse Papular Rash in a Young Woman: Challenge

No abstract available

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Small Subset of Adenoid Cystic Carcinoma of the Skin Is Associated With Alterations of the MYBL1 Gene Similar to Their Extracutaneous Counterparts

Abstract: Adenoid cystic carcinoma (ACC) of the skin is a rare malignant neoplasm histologically identical to homonymous tumors in other organs. Cutaneous ACC has been found to harbor MYB gene activations, either through MYB chromosomal abnormalities or by generation of the MYB–NFIB fusion. In salivary gland ACC, in addition to the MYB gene, alterations in MYBL1, the gene closely related to MYB, have been reported. We studied 10 cases of cutaneous ACC (6 women, 4 men; and age range 51–83 years) for alterations in the MYB, NFIB, and MYBL1 genes, using FISH and PCR. MYB break-apart and NFIB break-apart tests were positive in 4 and 5 cases, respectively. MYB–NFIB fusions were found in 4 cases. The break of MYBL1 was found in 2 cases, and in one of them, the NFIB break-apart probe was positive, strongly indicating a MYBL1–NFIB fusion. In 2 cases, the MYB break-apart test was positive, whereas no MYB–NFIB was detected, strongly suggesting another fusion partner. It is concluded that MYBL1 alterations are detected in primary cutaneous ACC but are apparently less common compared with MYB and NFIB alterations. Correspondence: Dmitry V. Kazakov, MD, PhD, Sikl's Department of Pathology, Charles University Medical Faculty Hospital, Alej Svobody 80, 304 60 Pilsen, Czech Republic (e-mail: kazakov@medima.cz). Supported in part by a Charles University project (SVV 260 391/2017). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Cosmetics, Vol. 5, Pages 25: Development and Stability Evaluation of Liquid Crystal-Based Formulations Containing Glycolic Plant Extracts and Nano-Actives

Cosmetics, Vol. 5, Pages 25: Development and Stability Evaluation of Liquid Crystal-Based Formulations Containing Glycolic Plant Extracts and Nano-Actives

Cosmetics doi: 10.3390/cosmetics5020025

Authors: Andreza Rodrigues Ueoka Carla Pedriali Moraes

Emulsions are of great use in cosmetic formulations due to their stability. The aim of this work was to develop and assess organoleptic, physicochemical, and microscopic properties of four auto-emulsifiable oil-in-water formulations. Such formulations were developed containing 4.0% cetearyl alcohol, dicetyl phosphate, and ceteth-10 phosphate (Formulation A), nano-actives obtained from safflower, coconut, and clove oils (Formulation B); a mixture of glycolic extracts from Centella asiatica leaves, Aesculus hippocastanum seeds, and Hamamelis virginiana leaves (Formulation C); association between the nano-actives and glycolic extracts described above (Formulation D). The formulations were trialed for 90 days under the normal stability test. The developed formulations were considered all stable and homogeneous, with liquid crystals possibly being formed. Organoleptic parameters and pH of Formulations A and B remained unchanged, but the color of Formulations C and D changed due to the natural color of the glycolic extracts used. It can be concluded that the formation of liquid crystals increased the stability of the formulations, and future tests should be carried out in order to assess the rheological properties and hydration potential of the developed formulations.



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Artifacts in Shear Wave Elastography Images of Thyroid Nodules

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Publication date: Available online 21 March 2018
Source:Ultrasound in Medicine & Biology
Author(s): Manjiri Dighe, Daniel S. Hippe, Jeff Thiel
The purpose of the study described here was to evaluate the presence and types of artifacts seen in color elastograms in thyroid elastography using shear wave elastography. This Health Insurance Portability and Accountability Act of 1996 (HIPAA)-compliant study was approved by the ethics committee of our institution, and all patients provided written informed consent. One hundred seventy-eight patients (40 men and 138 women; mean age, 49 y; range, 19–84 y) were enrolled for a total of 241 thyroid nodules. After a short ultrasound (US) examination, SWE images were acquired at multiple levels in the nodule in transverse and longitudinal orientations. A total of 1297 images were obtained from 241 nodules for an average of 5.4 ±  2.7 (mean ± standard deviation) images per nodule. A retrospective review of all images was performed by one reviewer experienced in thyroid elastography. Two hundred eighty images (21.6%) were rated as good quality, and 112 (8.6%) were rated as moderate quality without artifacts. A total of 905 (69.8%) images had some artifact present, though most of these images (73.4%) were still interpretable. Two hundred forty-one images (18.6% of all images) were considered uninterpretable because of artifact. The most common types of artifacts were due to operator error (44.6% of all images), primarily compression (36.5% of all images). Other artifacts seen were due to anatomy (presence of carotid pulsation or adjacent to thyroid or location in isthmus, 11% of all images), nodule characteristics (cystic and calcified nodules or large nodules with lack of penetration, 17% of all images) and other artifacts that could not be explained by the prior mentioned causes (13% of all images). Our study indicates that artifacts are common in elastography images. Operator error was the most common type of artifact we saw. This should be easily correctable by adequate knowledge and recognition with subsequent correction of the artifacts.



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Effects of Low-Intensity Pulsed Ultrasound for Preventing Joint Stiffness in Immobilized Knee Model in Rats

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Publication date: Available online 21 March 2018
Source:Ultrasound in Medicine & Biology
Author(s): Nobuyuki Itaya, Yutake Yabe, Yoshihiro Hagiwara, Kenji Kanazawa, Masashi Koide, Takuya Sekiguchi, Shinichirou Yoshida, Yasuhito Sogi, Toshihisa Yano, Masahiro Tsuchiya, Yoshihumi Saijo, Eiji Itoi
The purpose of this study was to examine the effect of low-intensity pulsed ultrasound (LIPUS) in preventing joint stiffness. Unilateral knee joints were immobilized in two groups of rats (n = 6/period/group). Under general anesthesia, the immobilized knee joints were exposed to LIPUS for 20 min/d, 5 d/wk, using an existing LIPUS device (LIPUS group, 1.5-MHz frequency, 1.0-kHz repetition cycle, 200-µs burst width and 30-mW/cm2 power output) until endpoints (2, 4 or 6 wk). In the control group, general anesthesia alone was administered in the same manner as in the other group. The variables compared between the groups included joint angles; histologic, histomorphometric and immunohistochemical analyses; quantitative reverse transcription polymerase chain reactions; and tissue elasticity. LIPUS had a preventive effect on joint stiffness, resulting in decreased adhesion, fibrosis and inflammation and hypoxic response after joint immobilization.



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Evaluation of the pig-tailed macaque (Macaca nemestrina) as a model of human Staphylococcus aureus nasal carriage.

Related Articles

Evaluation of the pig-tailed macaque (Macaca nemestrina) as a model of human Staphylococcus aureus nasal carriage.

Infect Immun. 2018 Mar 19;:

Authors: Cole AL, Sweeney YC, Lasseter AG, Gray JM, Beavis AC, Chong CF, Hajheidari SV, Beyene A, Patton DL, Cole AM

Abstract
Staphylococcus aureus (SA) nasal carriage is a common condition effecting both healthy and immunocompromised populations, and provides a reservoir for dissemination of potentially infectious strains by casual contact. Factors regulating the onset and duration of nasal SA colonization are mostly unknown, and a human-relevant animal model is needed. Here, we screened 17 pig-tailed macaques (Macaca nemestrina) for SA carriage, and 14 of 17 animals tested positive in the nose at one or both screening sessions (8 weeks apart), while the other three animals were negative in the nose but positive in the pharynx at least once. Similar to humans, SA colonization was densest in the nose and treatment of the nostrils with mupirocin ointment effectively cleared the nostrils and 6 extra-nasal body sites. Experimental nasal SA colonization was established with 104 CFU/nostril, and both autologous and non-autologous strains survived over 40 days without any apparent adverse effects. A human nasal SA isolate (D579/ST398) was carried in 4 of 6 animals for over three weeks. Nostrils that did eradicate experimentally applied SA exhibited neutrophilic innate immunity marked by elevated nasal IL-1β, IL-8, MCP-1, and a 10-fold decreased IL-1RA:IL-1β ratio within 7 days post-inoculation, analogous to the human condition. Taken together, pig-tailed macaques represent a physiological model of human SA nasal carriage that may be utilized for testing natural colonization and decolonization mechanisms as well as novel classes of anti-SA therapeutics.

PMID: 29555678 [PubMed - as supplied by publisher]



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Oligonucleotide aptamers against tyrosine kinase receptors: Prospect for anticancer applications

Publication date: Available online 21 March 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Simona Camorani, Elvira Crescenzi, Monica Fedele, Laura Cerchia
Transmembrane receptor tyrosine kinases (RTKs) play crucial roles in cancer cell proliferation, survival, migration and differentiation. Area of intense research is searching for effective anticancer therapies targeting these receptors and, to date, several monoclonal antibodies and small-molecule tyrosine kinase inhibitors have entered the clinic. However, some of these drugs show limited efficacy and give rise to acquired resistance. Emerging highly selective compounds for anticancer therapy are oligonucleotide aptamers that interact with their targets by recognizing a specific three-dimensional structure. Because of their nucleic acid nature, the rational design of advanced strategies to manipulate aptamers for both diagnostic and therapeutic applications is greatly simplified over antibodies.In this manuscript, we will provide a comprehensive overview of oligonucleotide aptamers as next generation strategies to efficiently target RTKs in human cancers.

Graphical abstract

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Graphical Abstracts



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Commentary: Recalling Memory by Brain Stimulation



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Commentary: Toward a Personalized Medicine in Wake-Up Stroke?



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Every Cloud Has a Silver Lining: Proneurogenic Effects of Aβ Oligomers and HMGB-1 via Activation of the RAGE-NF-ΚB Axis



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Innate Immune Surveillance in the Central Nervous System Following Legionella pneumophila Infection



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Role of Epigenetics and Oxidative Stress in Gliomagenesis



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Targeted Blockade of TARP-γ8-Associated AMPA Receptors: Anticonvulsant Activity with the Selective Antagonist LY3130481 (CERC-611)



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Low Dose of Anisodine Hydrobromide Induced Neuroprotective Effects in Chronic Cerebral Hypoperfusion Rats



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The Combined Effects of ω-3 Fatty Acids and Nano-Curcumin Supplementation on Intercellular Adhesion Molecule-1 (ICAM-1) Gene Expression and Serum Levels in Migraine Patients



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Systemic Administration of Antipsychotic Asenapine Pre or Postnatal does not Induce Anxiety-like Behaviors in Mice



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Conference Report: 10th Clinical Trials on Alzheimer's Disease (CTAD), Boston MA, USA, November 1-4, 2017



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Acknowledgements to Reviewers



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Micro-computed tomography-based anatomical study of the branch canals in mandibular anterior teeth in a Chinese population

Abstract

Objectives

To analyze the incidence and distribution of branch canals in mandibular anterior teeth.

Materials and methods

Three hundred mandibular anterior teeth, comprising 100 central incisors, 100 lateral incisors, and 100 canines, were scanned using a micro-computed tomography (micro-CT) system. Three-dimensional (3-D) visualization reconstruction of the root canal system and its branch canals was performed on each specimen. Data regarding the number of branch canals, the distance from the anatomical apex to the branch canal, and the orientation of each branch orifice were collected and analyzed.

Results

One hundred and fifty-three primary branch canals and 35 secondary branch canals were detected in the specimens overall. The incidence of branch canals in mandibular anterior teeth was 34%, with the highest incidence (50%) exhibited in mandibular canines, followed by lateral incisors (29%). Of the 153 primary branch canals found in the mandibular anterior tooth samples investigated, 82.35% appeared within 3 mm of the apical region, while 71.90% were labial and lingual canals.

Conclusions

There was regularity in the distribution and orientation of branch canals in mandibular anterior teeth.

Clinical relevance

This knowledge may be employed as a guide in clinical endodontic therapy.



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CD105 maintains the thermogenic program of beige adipocytes by regulating Smad2 signaling

Publication date: Available online 22 March 2018
Source:Molecular and Cellular Endocrinology
Author(s): Ryoko Higa, Toshikatsu Hanada, Hitoshi Teranishi, Daisuke Miki, Kazuyuki Seo, Kazumasa Hada, Hiroshi Shiraishi, Hiromitsu Mimata, Reiko Hanada, Kenji Kangawa, Toshiya Murai, Kazuwa Nakao
Beige adipocytes are thermogenic adipocytes with developmental and anatomical properties distinct from those of classical brown adipocytes. Recent studies have revealed several key molecular regulators of beige adipocyte development. CD105, also called endoglin, is a membrane protein composed of TGF-β receptor complex. It regulates TGF-β-family signal transduction and vascular formation in vivo. We report here that CD105 maintains the thermogenic gene program of beige adipocytes by regulating Smad2 signaling. Cd105−/− adipocyte precursors showed augmented Smad2 activation and decreased expression of thermogenic genes such as Ucp1 and Prdm16—which encodes a transcriptional regulatory protein for thermogenesis—after adipogenic differentiation. Smad2 signaling augmentation by the constitutively active form of Smad2 decreased the expression of thermogenic genes in beige adipocytes. Loss of thermogenic activity in Cd105−/− beige adipocytes was rescued by Prdm16 expression. These data reveal a novel function of CD105 in beige adipocytes: maintaining their thermogenic program by regulating Smad2 signaling.

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Oral exposure of deltamethrin and/or lipopolysaccharide (LPS) induced activation of the pulmonary immune system in Swiss albino mice

Abstract

The deltamethrin, a synthetic pyrethroid, is used worldwide and has been linked with several type of acute toxicity. However, effect of low level of deltamethrin alone or in combination with the microbial antigen on pulmonary system is not understood. Lipopolysaccharide (LPS) was used as antigen which is a key inflammatory component of gram-negative bacteria, which induces a distinctive pattern of cytokine release that regulates inflammation. The aim was to determine whether chronic exposure to a low level of deltamethrin alone or in combination with LPS impair the lung response in adult male Swiss albino mice. The mice were orally exposed to different doses of deltamethrin (0.1, 0.05, 0.005, 0.001 mg/kg bwt) and then immunized with LPS at the 60th day. None of the treatment groups contained residues of deltamethrin above the limits of quantification. Deltamethrin combined with LPS challenge caused significant lymphocytosis and neutropenia in group 1 (0.1 mg/kg) mice (P < 0.05). The highest dose of deltamethrin exposure (0.1 mg/kg bwt) alone altered the total cell count significantly in blood and total leukocyte count (TLC) and macrophage count in bronchoalveolar lavage fluid. Microscopic pulmonary damage was evaluated by H&E staining and EM which indicated that two higher doses of deltamethrin, i.e., 0.1 and 0.05 mg/kg bwt, distinctly increased inflammatory cell infiltration and caused alveolar septa thickening and leukocyte infiltration into the alveolar septum (septal cell infiltration) in the lungs. Deltamethrin exposure alone and/or with endotoxin revealed different degrees of immunopositive reaction for Toll-like receptor 4 (TLR4) and pro-inflammatory cytokine-like tumor necrosis factor-alpha (TNFα) in different parts of the lungs. The expression of TLR4 and TNFα in the lung tissue was more pronounced in two higher dose groups. Thus, chronic low-level deltamethrin exposure may impair the main pro-inflammatory response in the lungs which is more pronounced in combination with LPS. Further research is required in direction of the mechanism of action of deltamethrin on the immune cell lineage and their differentiation.



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Determination of the proton RBE in the rat spinal cord: Is there an increase towards the end of the spread-out Bragg peak?

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Publication date: Available online 21 March 2018
Source:Radiotherapy and Oncology
Author(s): Maria Saager, Peter Peschke, Stephan Brons, Jürgen Debus, Christian P. Karger
Background and purposeTo determine the relative biological effectiveness (RBE) of protons in the rat spinal cord as a function of linear energy transfer (LET) and dose.Materials and methodsThe rat cervical spinal cord was irradiated with single or two equal fractions (split doses) of protons at four positions (LET 1.4–5.5 keV/µm) along a 6 cm spread-out Bragg peak (SOBP). From dose-response analysis, TD50- (dose at 50% effect probability) and RBE-values were derived using the endpoint of radiation-induced myelopathy.ResultsAlong the SOBP, the TD50-values decreased from 21.7 ± 0.3 Gy to 19.5 ± 0.5 Gy for single and from 32.3 ± 0.3 Gy to 27.9 ± 0.5 Gy for split doses. The corresponding RBE-values increased from 1.13 ± 0.04 to 1.26 ± 0.05 (single doses) and from 1.06 ± 0.02 to 1.23 ± 0.03 (split doses).ConclusionsFor the relative high fractional doses, the experimental RBE at the distal edge of the proton SOBP is moderately increased. The conventionally applied RBE of 1.1 appears to be valid for the mid-SOBP region, but the higher values occurring more distally could be of clinical significance, especially if critical structures are located in this area. Further in vivo studies at lower fractional doses are urgently required.



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Remediation techniques for heavy metal-contaminated soils: Principles and applicability

Publication date: 15 August 2018
Source:Science of The Total Environment, Volume 633
Author(s): Lianwen Liu, Wei Li, Weiping Song, Mingxin Guo
Globally there are over 20millionha of land contaminated by the heavy metal(loid)s As, Cd, Cr, Hg, Pb, Co, Cu, Ni, Zn, and Se, with the present soil concentrations higher than the geo-baseline or regulatory levels. In-situ and ex-situ remediation techniques have been developed to rectify the heavy metal-contaminated sites, including surface capping, encapsulation, landfilling, soil flushing, soil washing, electrokinetic extraction, stabilization, solidification, vitrification, phytoremediation, and bioremediation. These remediation techniques employ containment, extraction/removal, and immobilization mechanisms to reduce the contamination effects through physical, chemical, biological, electrical, and thermal remedy processes. These techniques demonstrate specific advantages, disadvantages, and applicability. In general, in-situ soil remediation is more cost-effective than ex-situ treatment, and contaminant removal/extraction is more favorable than immobilization and containment. Among the available soil remediation techniques, electrokinetic extraction, chemical stabilization, and phytoremediation are at the development stage, while the others have been practiced at full, field scales. Comprehensive assessment indicates that chemical stabilization serves as a temporary soil remediation technique, phytoremediation needs improvement in efficiency, surface capping and landfilling are applicable to small, serious-contamination sites, while solidification and vitrification are the last remediation option. The cost and duration of soil remediation are technique-dependent and site-specific, up to $500ton−1 soil (or $1500m−3 soil or $100m−2 land) and 15years. Treatability studies are crucial to selecting feasible techniques for a soil remediation project, with considerations of the type and degree of contamination, remediation goals, site characteristics, cost effectiveness, implementation time, and public acceptability.

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Detection and quantitation of irisin in human cerebrospinal fluid by tandem mass spectrometry

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Publication date: Available online 21 March 2018
Source:Peptides
Author(s): Qingwei Ruan, Limin Zhang, Jian Ruan, Xixue Zhang, Jie Chen, Cheng Ma, Zhuowei Yu
The myokine irisin can cross the blood brain barrier and act as a neurokine to protect brain function during endurance exercise. However, the mechanism of transport from the blood to cerebrospinal fluid is unknown. Irisin has been detected in rodent and human brain and human cerebrospinal fluid by using commercial antibodies and enzyme linked immunosorbent assay kits. However, as human FNDC5 has an atypical translation start codon, some studies have questioned the specificity of commercial antibodies. Recently, human irisin was identified and quantitated in plasma by using mass spectrometry. We investigated whether there was irisin in human cerebrospinal fluid and an irisin concentration gradient between in human cerebrospinal fluid and paired plasma. An irisin peptide was identified and quantitated by using mass spectrometry with control peptides enriched with heavy stable isotopes as internal standards. Quantitative mass spectrometry identified the presence of irisin in human cerebrospinal fluid. The internal irisin peptides were modified to the deamidated asparagine form after deglycosylation. The unmodified internal irisin peptides were not found in CSF and irisin concentration was approximately 0.26–1.86 ng/ml in men over 80 years of age with various diseases. However, the parallel reaction monitoring (PRM) elution profiles of both modified and unmodified internal irisin peptides were not found in paired plasma samples. These data unequivocally demonstrated the presence of the glycosylated form of irisin in human cerebrospinal fluid. There were significant individual differences in men over 80 years of age with diseases. However, irisin was not detected in plasma samples by using mass spectrometry.



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Unraveling the Structure and Mechanism of the MST(ery) Enzymes

Publication date: Available online 21 March 2018
Source:Trends in Biochemical Sciences
Author(s): Catherine L. Shelton, Audrey L. Lamb
The menaquinone, siderophore, and tryptophan (MST) enzymes transform chorismate to generate precursor molecules for the biosynthetic pathways defined in their name. Kinetic data, both steady-state and transient-state, and X-ray crystal structures indicate that these enzymes are highly conserved both in mechanism and in structure. Because these enzymes are found in pathogens but not in humans, there is considerable interest in these enzymes as drug design targets. While great progress has been made in defining enzyme structure and mechanism, inhibitor design has lagged behind. This review provides a detailed description of the evidence that begins to unravel the mystery of how the MST enzymes work, and how that information has been used in inhibitor design.



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Resource requirements and reduction in cardiac mortality from deep inspiration breath hold (DIBH) radiotherapy for left sided breast cancer patients: A prospective service development analysis

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Publication date: Available online 21 March 2018
Source:Practical Radiation Oncology
Author(s): Sanjoy Chatterjee, Santam Chakraborty, Arunsingh Moses, Chandran Nallathambi, Anurupa Mahata, Samar Mandal, Rimpa Basu Achari, Indranil Mallick, Raj Kumar Shrimali, Tapesh Bhattacharyya, Sanjit Agrawal, Joydeep Ghosh, Rosina Ahmed
IntroductionUse of Deep Inspiration Breath Hold (DIBH) radiotherapy may reduce long-term cardiac mortality. The resource and time commitments associated with DIBH are impediments to its widespread adoption. We report the dosimetric benefits, workforce requirements and potential reduction in cardiac mortality when DIBH is used for left-sided breast cancers.MethodsData regarding the time consumed for planning and treating 50 patients with left-sided breast cancer with DIBH and 20 patients treated with free breathing (FB) radiotherapy were compiled prospectively for all personnel (regarding person-hours, PH). A second plan was generated for all DIBH patients in the FB planning scan, which was then compared to the DIBH plan. Mortality reduction due to use of DIBH was calculated using the years of life lost (YLLs) due to Ischemic Heart Disease (IHD) for Indians and the postulated reduction in risk of major cardiac events due to reduced cardiac dose.ResultsThe median reduction in mean heart dose (MHD) between the DIBH and FB plans was 166.7cGy (IQR: 62.7–257.4cGy). An extra 6.76 PH was required when implementing DIBH as compared to FB treatments. Approximately 3.57 PH were necessary per Gy of reduction in mean heart dose. The excess YLLs due to IHD if DIBH was not done in was 0.95 per 100 patients, which translates into a saving of 12.8hours of life saved per PH of work required for implementing DIBH. DIBH was cost effective with cost for implementation of DIBH for all left sided breast cancers at 2.3 times the annual per-capita GDP.ConclusionAlthough routine implementation of DIBH requires significant resource commitments, it seems to be worthwhile regarding the projected reductions in cardiac mortality.



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The Impact of Tumor Cell Metabolism on T Cell-Mediated Immune Responses and Immuno-Metabolic Biomarkers in Cancer

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Publication date: Available online 21 March 2018
Source:Seminars in Cancer Biology
Author(s): Grégory Noël, Mireille Langouo Fontsa, Karen Willard-Gallo
The role of adaptive immunity is increasingly recognized as an important element both in the process of tumorigenesis and in the patient's response to treatment. While this understanding has led to new therapeutic strategies that potentiate the activities of tumor infiltrating lymphocytes, only a minority of patients attain durable responses. Metabolic activities in the tumor microenvironment, including hypoxia and acidity, can adversely affect immune responses, making the identification of metabolic biomarkers critically important for understanding and employing immunotherapies.



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Oral processing behaviours that promote children's energy intake are associated with parent-reported appetitive traits: Results from the GUSTO cohort

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Publication date: 1 July 2018
Source:Appetite, Volume 126
Author(s): Anna Fogel, Lisa R. Fries, Keri McCrickerd, Ai Ting Goh, Phaik Ling Quah, Mei Jun Chan, Jia Ying Toh, Yap-Seng Chong, Kok Hian Tan, Fabian Yap, Lynette P. Shek, Michael J. Meaney, Birit F.P. Broekman, Yung Seng Lee, Keith M. Godfrey, Mary Foong Fong Chong, Ciarán G. Forde
Oral processing behaviours associated with faster eating rates have been consistently linked to increased energy intakes, but little is known about their links to children's appetitive traits. This study used the Child Eating Behaviour Questionnaire (CEBQ) to explore cross-sectional and prospective associations between parent-reported appetitive traits and observed oral processing behaviours. Participants were 195 children from the Growing Up in Singapore Towards healthy Outcomes cohort, who participated in a video-recorded ad libitum lunch at 4.5 (Time 1) and 6 years (Time 2). Their mothers completed the CEBQ around the same time points. Children's bites, chews and swallows were coded, and used to calculate their eating rate, bite size, chews per bite, chew rate, oral exposure time and oral exposure per bite. At Time 1, children with higher scores in slowness in eating had lower eating and chew rates. At Time 2, higher scores for food enjoyment and lower for satiety responsiveness, slowness in eating, and food fussiness were linked with higher eating rates and greater energy intakes (r > 0.16, p < 0.05). Post-hoc analyses revealed that these associations were moderated by BMI and only present among children with higher BMI. Faster eating rates mediated the associations between greater food enjoyment, lower slowness in eating, lower food fussiness and higher intakes of energy. Children with higher slowness in eating scores had lower increases in eating rates over time, and children with higher BMI who had greater food enjoyment and food responsiveness scores had greater increases in eating rates over time. The findings suggest that oral processing behaviours linked with increased obesity risk may be underpinned by appetitive traits and may be one of the behavioural pathways through which these appetitive traits influence energy intakes.



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Carmen Gerlach

Publication date: Available online 21 March 2018
Source:Trends in Immunology





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Meeting the needs of breast cancer: a nucleolin’s perspective

Publication date: Available online 21 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Ana C. Gregório, Manuela Lacerda, Paulo Figueiredo, Sérgio Simões, Sérgio Dias, João Nuno Moreira
A major challenge in the management of breast cancer disease has been the development of metastases. Finding new molecular targets and the design of targeted therapeutic approaches to improve the overall survival and quality of life of these patients is, therefore, of great importance. Nucleolin, which is overexpressed in cancer cells and tumor-associated blood vessels, have been implicated in various processes supporting tumorigenesis and angiogenesis. Additionally, its overexpression has been demonstrated in a variety of human neoplasias as an unfavorable prognostic factor, associated with a high risk of relapse and low overall survival. Hence, nucleolin has emerged as a relevant target for therapeutic intervention in cancer malignancy, including breast cancer. This review focus on the contribution of nucleolin for cancer disease and on the development of therapeutic strategies targeting this protein. In this respect, it also provides a critical analysis about the potential and pitfalls of nanomedicine for cancer therapy.



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SEXUAL DIMORPHISM IN SELENIUM METABOLISM AND SELENOPROTEINS

Publication date: Available online 21 March 2018
Source:Free Radical Biology and Medicine
Author(s): Lucia A. Seale, Ashley N. Ogawa-Wong, Marla J. Berry
Sexual dimorphism, the condition in which males and females in a species differ beyond the morphology of sex organs, delineates critical aspects of the biology of higher eukaryotes, including selenium metabolism. While sex differences in selenium biology have been described by several laboratories, delineation of the effects of sex in selenium function and regulation of selenoprotein expression is still in its infancy. This review encompasses the available information on sex-dependent parameters of selenium metabolism, as well as the effects of selenium on sex hormones. Gaps in the current knowledge of selenium and sex are identified and discussed.

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Wheat amylase/trypsin inhibitors exacerbate intestinal and airway allergic immune responses in humanized mice

Publication date: Available online 21 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Iris Bellinghausen, Benno Weigmann, Victor Zevallos, Joachim Maxeiner, Sonja Reißig, Ari Waisman, Detlef Schuppan, Joachim Saloga
BackgroundAmylase-trypsin inhibitors (ATIs) in wheat and related cereals are potent activators of myeloid innate immune cells via engagement of TLR4. Furthermore, ATIs have been shown to serve as adjuvants in experimental intestinal inflammatory diseases.ObjectiveThe aim of this study was to analyze whether ATIs are also modifiers of allergic inflammation.MethodsTherefore, CD4+ T cells from grass or birch pollen sensitized donors were stimulated with autologous allergen-pulsed dendritic cells in the presence or absence of ATIs or the control storage protein zein from corn. To analyze allergen-induced gut and lung inflammation, immunodeficient mice were engrafted with PBMC from these allergic donors plus the respective allergen, and fed with selected diets. Three weeks later, inflammation was induced by rectal or intranasal allergen challenge and monitored by mini-endoscopy or airway hyperreactivity (AHR), respectively.ResultsAllergen-specific T cell proliferation and cytokine production was significantly exacerbated by ATIs and not by zein. In vivo, allergen-specific human IgE was strongly elevated in sera of mice receiving an ATI-containing diet compared to mice that were fed gluten- and thus ATI-free. Importantly, allergen-induced IgE-dependent colitis and AHR were also enhanced in ATI-fed mice. Gut inflammation was further increased in mice receiving an additional ATI injection and even detectable in the absence of the aeroallergen, while zein had no such effect. Injection of anti-human TLR4 mAbs or the anti-human IgE mAb omalizumab completely abolished ATI-induced allergic inflammation.ConclusionThese results underline that wheat ATIs are important nutritional activators and adjuvants of allergy which might be exploited for nutritional therapeutic strategies.Clinical ImplicationsAllergen-induced IgE-mediated inflammation of the intestine and the lung is exacerbated by ATIs which might be important for future therapies.

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Anti-inflammatory activity of mulberrofuran K isolated from the bark of Morus bombycis

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Publication date: May 2018
Source:International Immunopharmacology, Volume 58
Author(s): Sun-Yup Shim, Sang Hyun Sung, Mina Lee
Morus bombycis Koidzumi, commonly known as silkworm mulberry, is a plant belonging to family Moraceae. It has been used in Asian countries as a traditional medicine for treating hypertension, diabetes, and inflammatory disorders. In this study, we isolated eleven compounds from the cortex of M. bombycis and evaluated their inhibitory effects on nitric oxide (NO) production as an indicator of their anti-inflammatory activities using lipopolysaccharide (LPS)-stimulated murine macrophages. Compound 4 showed the most potent inhibitory activity on NO production. It was identified as mulberrofuran K (MFK). Anti-inflammatory activity of MFK was then carried out using LPS-stimulated RAW264.7 cells. MFK suppressed the production of NO, reactive oxygen species (ROS), and proinflammatory cytokines (interleukin (IL)-1β, IL-6 and tumor necrosis factor alpha (TNF-α)) in a concentration-dependent manner. Western blot analysis revealed that MFK treatment inhibited expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). MFK also inhibited transcriptional activation of nuclear factor-κB (NF-κB) and extracellular-regulated kinases (ERK) 1/2 in LPS-stimulated murine macrophages. These results suggest that MFK, an anti-inflammatory constituents of M. bombycis cortex, has potential as a therapeutic candidates for preventing and treating inflammatory diseases.



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Editorial Board

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Publication date: April 2018
Source:International Immunopharmacology, Volume 57





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Andrographolide suppresses TRIF-dependent signaling of toll-like receptors by targeting TBK1

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Publication date: April 2018
Source:International Immunopharmacology, Volume 57
Author(s): Ah-Yeon Kim, Hyun-Jin Shim, Hyeon-Myeong Shin, Yoo Jung Lee, Hyeonjeong Nam, Su Yeon Kim, Hyung-Sun Youn
Toll-like receptors (TLRs) play a crucial role in danger recognition and induction of innate immune response against bacterial and viral infections. The TLR adaptor molecule, toll-interleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF), facilitates TLR3 and TLR4 signaling, leading to the activation of the transcription factor, NF-κB and interferon regulatory factor 3 (IRF3). Andrographolide, the active component of Andrographis paniculata, exerts anti-inflammatory effects; however, the principal molecular mechanisms remain unclear. The objective of this study was to investigate the role of andrographolide in TLR signaling pathways. Andrographolide suppressed NF-κB activation as well as COX-2 expression induced by TLR3 or TLR4 agonists. Andrographolide also suppressed the activation of IRF3 and the expression of interferon inducible protein-10 (IP-10) induced by TLR3 or TLR4 agonists. Andrographolide attenuated ligand-independent activation of IRF3 following overexpression of TRIF, TBK1, or IRF3. Furthermore, andrographolide inhibited TBK1 kinase activity in vitro. These results indicate that andrographolide modulates the TRIF-dependent pathway of TLRs by targeting TBK1 and represents a potential new anti-inflammatory candidate.



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Corrigendum to “Rapid infusions of human normal immunoglobulin 50g/l are safe and well tolerated in immunodeficiencies and immune thrombocytopenia” [Int. Immunopharmacol. 44 (2017) 38–42]

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Publication date: April 2018
Source:International Immunopharmacology, Volume 57
Author(s): Giuseppe Spadaro, Alessandra Vultaggio, Alberto Bosi, Dietmar Reichert, Jan Janssen, Donatella Lamacchia, Liliana Nappi, Antonio Pecoraro, Cinzia Milito, Andrea Ferraro, Andrea Matucci, Francesca Bacchiarri, Valentina Carrai, Azra Hibbeler, Elisabet Speckman, Chiara Guarnieri, Serena Bongiovanni, Isabella Quinti




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Disposable electrochemical detection of breast cancer tumour marker CA 15-3 using poly(Toluidine Blue) as imprinted polymer receptor

Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): J.A. Ribeiro, C.M. Pereira, A.F. Silva, M. Goreti F. Sales
In this work, electrically-conducting poly(Toludine Blue) was employed for the first time as synthetic receptor film, prepared by Molecular Imprinting strategies and using electrochemical methods, for the specific screening of breast cancer biomarker Carbohydrate Antigen 15-3 (CA 15-3).The protein imprinted poly(Toluidine Blue) film was grown in a pre-formed Toluidine Blue (TB) tailed SAM at the AuSPE surface, which greatly enhanced the stability against degradation of the Molecular Imprinted Polymer (MIP) film at the electrode surface.The MIP receptor film recognition ability towards the protein was investigated by fitting data to Freundlich isotherm. The binding affinity (KF) obtained for the MIP system was significantly higher (~ 12-fold) to that obtained for the NIP system, demonstrating the success of the approach in creating imprinted materials that specifically respond to CA 15-3 protein.The incubation of the MIP modified electrode with increasing concentration of protein (from 0.10 U mL−1 to 1000 U mL−1) resulted in a decrease of the ferro/ferricyanide redox current. The device displayed linear response from 0.10 U mL−1 to 100 U mL−1 and LODs below 0.10 U mL−1 were obtained from calibration curves built in neutral buffer and diluted artificial serum, using DPV technique, enabling the detection of the protein biomarker at clinically relevant levels. The developed MIP biosensor was applied to the determination of CA 15-3 in spiked serum samples with satisfactory results.The developed device provides a new strategy for sensitive, rapid, simple and cost-effective screening of CA 15-3 biomarker. Importantly, the overall approach seems suitable for point-of-care (PoC) use in clinical context.



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Single-molecule porphyrin-metal ion interaction and sensing application

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Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Keke Wei, Fujun Yao, Xiao-Feng Kang
It remains a significant challenge to study the interactions between metal ions and porphyrin molecules at single ion level. Here, we constructed a nanopore-based sensing for label-free and real-time analysis of the interaction between Cu2+ and 5,10,15,20-tetrakis(4-sulfonatophenyl)-porphyrin (TPPS). The results demonstrate that emerging electronic signatures of the Cu2+-TPPS complex that is completely different form the original free TPPS were observed in the α-hemolysin (α-HL) nanopore. Based on the distinctive electronic signal patterns between TPPS and Cu2+-TPPS complex, the unique nanopore sensor can achieve a highly sensitive detection of Cu2+ in aqueous media. The frequency of signature events showed a linear response toward the concentration of Cu2+ in the range of 0.03 µM – 1.0 μM, with a detection limit of 16 nM (S/N = 3). The sensing system also exhibited high selectivity against other metal ions, and the feasibility of this approach for practical applications was demonstrated with the determination of Cu2+ in running water.



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Performance comparison between multienzymes loaded single and dual electrodes for the simultaneous electrochemical detection of adenosine and metabolites in cancerous cells

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Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Khalil K. Hussain, Mahmood H. Akhtar, Moo-Hyun Kim, Dong-Keun Jung, Yoon-Bo Shim
The analytical performance of the multi enzymes loaded single electrode sensor (SES) and dual electrode sensor (DES) was compared for the detection of adenosine and metabolites. The SES was fabricated by covalent binding of tri-enzymes, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and xanthine oxidase (XO) along with hydrazine (Hyd) onto a functionalized conducting polymer [2,2:5,2-terthiophene-3-(p-benzoic acid)] (pTTBA). The enzyme reaction electrode in DES was fabricated by covalent binding of ADA and PNP onto pTTBA coated on Au nanoparticles. The detection electrode in DES was constructed by covalent binding of XO and Hyd onto pTTBA coated on porous Au. Due to the higher amount (3.5 folds) of the immobilized enzymes and Hyd onto the DES than SES, and the lower Michaelis constant (Km) value for DES (28.7 µM) compared to SES (36.1 µM), the sensitivity was significantly enhanced for the DES (8.2 folds). The dynamic range obtained using DES was from 0.5 nM to 120.0 µM with a detection limit of 1.43 nM ± 0.02, 0.76 nM ± 0.02, and 0.48 nM ± 0.01, for adenosine (AD), inosine (IN), and hypoxanthine (Hypo) respectively. Further, the DES was coupled with an electrochemical potential modulated microchannel for the separation and simultaneous detection of AD, IN, and Hypo in an extracellular matrix of cancerous (A549) and non-cancerous (Vero) cells. The sensor probe confirms a higher basal level of extracellular AD and its metabolites in cancer cells compared to normal cells. In addition, the effect of dipyridamole on released adenosine in A549 cells was investigated.



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A novel electrochemical sensor based on silver/halloysite nanotube/molybdenum disulfide nanocomposite for efficient nitrite sensing

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Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Masoud Ghanei-Motlagh, Mohammad Ali Taher
In the present study, the silver/halloysite nanotube/molybdenum disulfide (Ag/HNT/MoS2) nanocomposite was successfully synthesized. For this purpose, the lumen of HNTs was firstly modified by silver to generate Ag nanorods via chemical process and then the MoS2 layers deposited on the Ag/HNT nanocomposite by hydrothermal method. The characterization of Ag/HNT/MoS2 nanocomposite were investigated by field emission scanning electron microscopy (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), X-ray photoelectron spectra (XPS), energy dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD) analyses. The nanocomposite modified carbon paste electrode (CPE) was applied for the electrocatalytic detection of nitrite in aqueous solutions. It was demonstrated that the treatment of HNTs with Ag and MoS2 materials enhanced the catalytic performance of modified CPE. At optimal experimental conditions, the designed sensor displayed remarkable sensing ability toward nitrite oxidation, offering a good linearity from 2 to 425 µM. The limit of detection (LOD) of the proposed strategy was estimated to be 0.7 µM based S/N = 3. The good reproducibility, acceptable stability, fast response time and anti-interference performance of the proposed assay suggests that the modified CPE has great potential working as a nitrite electrochemical sensor for environmental applications.



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Hybrid integration of scalable mechanical and magnetophoretic focusing for magnetic flow cytometry

Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Mathias Reisbeck, Lukas Richter, Michael Johannes Helou, Stephan Arlinghaus, Birgit Anton, Ignas van Dommelen, Mario Nitzsche, Michael Baßler, Barbara Kappes, Oliver Friedrich, Oliver Hayden
Time-of-flight (TOF) magnetic sensing of rolling immunomagnetically-labeled cells offers great potential for single cell function analysis at the bedside in even optically opaque media, such as whole blood. However, due to the spatial resolution of the sensor and the low flow rate regime required to observe the behavior of rolling cells, the concentration range of such a workflow is limited. Potential clinical applications, such as testing of leukocyte function, require a cytometer which can cover a cell concentration range of several orders of magnitude. This is a challenging task for an integrated dilution-free workflow, as for high cell concentrations coincidences need to be avoided, while for low cell concentrations sufficient statistics should be provided in a reasonable time-to-result. Here, we extend the spatial bandwidth of a magnetoresistive sensor with an adaptive and integratable workflow concept combining mechanical and magnetophoretic guiding of magnetically labeled targets for in-situ enrichment over a dynamic concentration range of 3 orders of magnitude. We achieve hybrid integration of the enrichment strategy in a cartridge mold and a giant-magnetoresistance (GMR) sensor in a functionalized Quad Flat No-Lead (QFN) package, which allows for miniaturization of the Si footprint for potential low-cost bedside testing. The enrichment results demonstrate that TOF magnetic flow cytometry with adaptive particle focusing can match the clinical requirements for a point-of-care (POC) cytometer and can potentially be of interest for other sheath-less methodologies requiring workflow integration.



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A robust, magnetic, and self-accelerated electrochemiluminescent nanosensor for ultrasensitive detection of copper ion

Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Yan-Mei Lei, Bai-Qi Xiao, Wen-Bin Liang, Ya-Qin Chai, Ruo Yuan, Ying Zhuo
It is well known that the conventional electrochemiluminescence (ECL) biosensor rely on the heterogeneous assay formats that involves the immobilization of biorecognition probe on the electrode surface before signal collection, which inevitably cause the efficiency of bio-recognition reactions to be limited owing to the existence of local steric hindrance. Herein, a robust, magnetic, and self-accelerated ECL nanosensor based on the multifunctionalized cobalt ferrite magnetite nanoparticles (CoFe2O4 MNPs) was firstly designed for copper ion (Cu2+) detection in quasi-homogeneous system. The prepared nanosensor has its unique advantages compared to the iron oxide (Fe3O4) MNPs-based nanosensor for which magnetic nanoparticle just provide the reaction interface and magnetic enrichment. Specifically, the prepared CoFe2O4 MNPs-based biosensing platform could bridge the gap between aqueous phase and solid materials in homogeneous solution, achieving the expansion of reaction area and the reduction of local steric hindrance with high biorecognition efficiency. Furthermore, compared with the common magnetite nanosensors, the prepared CoFe2O4 MNPs achieved a set of magnetic collection, biorecognition probes immobilization, rapid separation and signal amplification in an ECL measurement system because it could act as a new co-reaction accelerator in ECL ternary (PTC-NH2 + S2O82- + CoFe2O4) system, achieving a self-accelerated biosensing platform with significant enhancement of the detection sensitivity. As expected, the prepared CoFe2O4 MNPs-based ECL nanosensors were successfully applied for ultrasensitive detection of Cu2+via click reaction with a linear range from 10−13 M to 1.0 × 10−7 M, which exhibited high sensitivity, excellent selectivity and good reproducibility.

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Silver decahedral nanoparticles empowered SPR imaging-SELEX for high throughput screening of aptamers with real-time assessment

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Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Wenchao Jia, Hui Li, Thomas Wilkop, Xiaohui Liu, Xiaodong Yu, Quan Cheng, Danke Xu, Hong-Yuan Chen
A highly efficient method for aptamer screening with real-time monitoring of the SELEX process was described by silver decahedra nanoparticles (Ag10-NPs) enhanced surface plasmon resonance imaging (SPRI). A microarray chip was developed by immobilization of target protein (Lactoferrin (Lac)) and control proteins (α-lactalbumin (α), β-lactoglobulin (β), casein, and bovine serum albumin (BSA)) on the biochip surface. Ag10-NPs were conjugated with an ssDNA library (lib) (Ag10-NPs-library) that consisted of a central 40 nt randomized sequence and a 20 nt fixed primer sequence. Introduction of the Ag10-NPs-library to the SPRI flow channels drastically increased the sensitivity of SPRI signal for real-time monitoring of SELEX. The work allows rapid screening of potential targets, and yields nine aptamers with high affinity (nanomolar range) for Lac after only six-rounds of selection. The aptamer Lac 13-26 was then further tested by SPRI, and the results demonstrated that the aptamer had the capacity to be ultra-sensitive for specific detection of Lac. The novel SPRI-SELEX method demonstrated here showed many advantages of real-time evaluation, high throughput, and high efficiency.



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Porous graphite: A facile synthesis from ferrous gluconate and excellent performance as anode electrocatalyst of microbial fuel cell

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Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Juan Xiong, Meihua Hu, Xiaoping Li, Hongying Li, Xin Li, Xiang Liu, Guozhong Cao, Weishan Li
A porous graphite (PG) is proposed as anode electrocatalyst of microbial fuel cell (MFC), which is synthesized by thermally decomposing ferrous gluconate followed by leaching iron. The physical characterizations from scanning electron microscopy, Brunauer-Emmett-Teller, X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy, indicate that the resulting PG is mesopore-rich and exhibits high graphitization with oxygen-containing functional groups. When evaluated on a naked carbon felt (NCF) anode, the resulting PG provides the MFC based on Escherichia coli with excellent power output. The MFC using the carbon felt anode loaded with 3.0 mg cm−2 PG delivers a maximum power density of 2.6 W m−2, compared to the 0.2 W m−2 for the MFCs using NCF anode. This excellent performance is attributed to the electronically conductive graphite and porous structure of the resulting PG. The former provides the anode with high activity towards redox reactions of c-type cytochromes in bacteria, the latter stimulates bacteria to produce their flagella that help bacteria to firmly bond each other.



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Molecularly imprinted sensor based on Russian Matryoshka structured molecules for enhanced specific identification and double amplification in ultra-trace Tb3+ determination

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Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Jianping Li, Bin Yang, Hongcheng Pan, Guobao Xu
The selective and sensitive detection of rare earth elements is thought to be difficult because the concentration of those elements in the sample is commonly at a low level and they normally have severe mutual interference which is caused by homologous chemical properties. In this study, a novel molecularly imprinted polymer (MIP) sensor was fabricated for highly sensitive and selective determination of ultra-trace Tb3+. The Tb3+-ethylenediaminetetraacetic acid complex (Tb-EDTA) as the template molecule was incorporated into mono-6-mercapto-β-cyclodextrin (mono-6-SH-β-CD) to form a Russian Matryoshka (RM)-structured molecule (CD/Tb-EDTA). Titanium isopropoxide was utilized in vapor sol–gel polymerization to construct MIP membrane. Moreover, the selectivity of the RM MIP sensor was remarkably enhanced by the "triple-selectivity" recognition of EDTA-to-Tb3+, β-CD-to-(Tb-EDTA), and 3D cavity-to-(CD/Tb-EDTA), while the sensitivity of the MIP sensor was significantly improved by ECL signal enhancement based on double amplification, in other words, the electrochemiluminescence resonance energy transfer (ECL-RET) between the ECL donor of CD/Tb-EDTA and the ECL acceptor of Ru(bpy)32+, and the ECL enhancement by the co-reactant of CD/Tb-EDTA on Ru(bpy)3Cl2. When the imprinted cavities were occupied by Tb-EDTA during rebinding, the host-guest inclusion structured complex was formed and the ECL intensities produced by the Ru(bpy)3Cl2 ECL system increased with increasing concentration of Tb-EDTA. The proposed sensor was used for quantitative analysis of Tb3+ with concentrations ranging from 8.00 × 10–13 mol/L to 4.00 × 10–9 mol/L and successfully applied to detect Tb3+ in seawater samples. The detection limit of the sensor was found to be 3.90 × 10–13 mol/L (DL = 3δb/K), which is lower than previously reported values. Thus, the fabricated sensor is feasible for practical applications.



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Portable electrochemical sensor based on 4-aminobenzoic acid-functionalized herringbone carbon nanotubes for the determination of ascorbic acid and uric acid in human fluids

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Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): A. Abellán-Llobregat, C. González-Gaitán, L. Vidal, A. Canals, E. Morallón
A new portable electrochemical sensor based on 4-aminobenzoic acid-modified herringbone carbon nanotubes (hCNTs-4ABA/Au-IDA) has been developed for the simultaneous determination of ascorbic acid (AA) and uric acid (UA) in physiological fluids. AA and UA were quantified by chronoamperometry at 0.1 and 0.32 V, respectively, in phosphate buffer solution (PBS 0.25 M, pH 7.0). Significant results were obtained for the separate quantification of AA and UA, with a limit of detection (LOD) of 0.65 μM for both analytes, and sensitivities of (9.0 ± 0.4) A g−1 mM−1 and (8.8 ± 0.3) A g−1 mM−1 for AA and UA, respectively. Repeatability was studied at 50 μM for AA and UA, providing relative standard deviations (RSD) lower than 9%. Additions of glucose, dopamine and epinephrine did not interfere with the AA and UA determination. Furthermore, UA did not interfere with AA determination at 0.1 V, although AA additions increased the current recorded at 0.32 V. The method has been successfully applied to human urine, perspiration and serum samples, without significant matrix effects, which allows for the use of an external calibration and the analysis of all the matrices investigated.



http://ift.tt/2puHfIF

One-step selective screening of bioactive molecules in living cells using sulfur-doped microporous carbon

Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Mohammed Y. Emran, Mohamed A. Shenashen, Hiromi Morita, Sherif A. El-Safty
A metal-free electrode using heteroatom-doped microporous carbon was fabricated for the ultrasensitive monitoring of mono-bioactive molecules and the selective signaling of dopamine (DA) secreted by living cells. The constructed electrode based on sulfur-doped microporous carbon (S-MC) shows a high surface area, a spherical construction, numerous carbon chain defects, and microporous structures, which are the key factors of the interactive signaling transducer, fast response, and active interfacial surfaces. The intrinsic features of S-MC with different %S-doping (S-MC-1, and S-MC-2) through the sp2-carbon chain create abundant catalytic active sites, facilitate molecular diffusion through the microporous structure, promote strong binding with the targeted molecules, and induce interactions at electrolyte–electrode interfaces. The S-MC-1 provides selective signaling in a tertiary mixture of DA, ascorbic acid (AA), and uric acid (UA) with a high sensitivity and a wide linear range of 0.01–5, 10–4000, and 1–2000 µM, respectively. The detection limits were set at 3 nM, 1.26 µM, and 0.23 µM for DA, AA, and UA respectively. The S-MC-1 demonstrated a selective screening of DA released from PC12 cells under a K+ ion- stimulator with high sensitivity and promoted high biocompatibility, low cytotoxicity, high stability, and reliable reproducibility (%RSD ranged from 1 to 2.7). Our findings indicated that the S-MC-1 can be utilized as an in-vitro model for simultaneously monitoring extracellular-DA secreted from living cells and sensing mono-bioactive molecules in biological samples.



http://ift.tt/2uaAD6U

Sensitive electrogenerated chemiluminescence biosensors for protein kinase activity analysis based on bimetallic catalysis signal amplification and recognition of Au and Pt loaded metal-organic frameworks nanocomposites

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Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Zhiyong Yan, Feng Wang, Pingye Deng, Yu Wang, Kai Cai, Yanhui Chen, Zonghua Wang, Yang Liu
In this work, a novel and sensitive electrogenerated chemiluminescence (ECL) biosensor for protein kinase A (PKA) activity analysis and relevant inhibitor screening was proposed based on bimetallic catalysis signal amplification and recognition of Au and Pt nanoparticles loaded metal-organic frameworks (Au&Pt@UiO-66) nanocomposite. After being phosphorylated by PKA in the presence of ATP, Au&Pt@UiO-66 probes were specifically chelated to the modified electrode by forming Zr-O-P bonds between the surface defects of UiO-66 and the phosphorylated kemptide. Due to the high synergistic catalysis of Au&Pt@UiO-66 nanocomposites to the luminol-H2O2 reaction, the ECL signal of luminol was greatly enhanced. Moreover, UiO-66 afford numerous Zr defect sites for high efficient phosphate group recognition, and can also prevent the nanoparticles from aggregating during catalytic reactions. Thus, the excellent performance of the ECL biosensor with high sensitivity and superior stability was obtained. Under the optimized conditions, the detection limit for PKA activity was 0.009 UmL−1 (S/N = 3). Meanwhile, the ECL biosensor was successfully applied in inhibitor screening and cell lysates PKA activity analysis, showing great promise in kinase related research.



http://ift.tt/2pu8oLQ

Facile crosslinking of polythiophenes by polyethylenimine via ester aminolysis for selective Cu(II) detection in water

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Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Xuewei Wang, Chi Zhang, Yajie Zhang, Jian Sun, Leilei Cao, Jinkai Ji, Fude Feng
Functionalization of π-conjugated polymers is dispensable for solubilization of the rigid and hydrophobic backbones in water. However, polymer aggregation is always present and leads to issues with complication and reproducibility in spectral properties. Herein, we reported a simple and robust method to make a series of conjugated polymer nanostructures by a crosslinking strategy. In favor of multivalency effect, polythionenes with various chain lengths were functionalized with branched polyethylenimine (PEI) via ester aminolysis reaction under mild conditions. Photophysical studies revealed the conjugated backbones could be well stabilized and dispersed in water. By taking advantage of intermolecular recognition interaction between copper ions and cationic PEI, we applied crosslinked polythiophenes as a nano probe at very low concentration (0.01 mg/mL) to fluorescently detect copper ions with high sensitivity up to 10 nM and selectivity over other metal ions in aqueous solutions, without occurrence of detectable aggregates. The overall performance of our nano probes outperforms reported water-soluble polymers-based probes, particularly in probe availability and manipulation as well as selective copper detection capability.



http://ift.tt/2u88ZHJ

Electrochemical coupled immunosensing platform based on graphene oxide/gold nanocomposite for sensitive detection of Cronobacter sakazakii in powdered infant formula

Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Shruti Shukla, Yuvaraj Haldorai, Vivek K. Bajpai, Arunkumar Rengaraj, Seung Kyu Hwang, Xinjie Song, Myunghee Kim, Yun Suk Huh, Young-Kyu Han
A sensitive electrochemical immunosensing platform for the detection of Cronobacter sakazakii was developed using a graphene oxide/gold (GO/Au) composite. Transmission electron microscopy showed that the Au nanoparticles, with an average size of < 30 nm, were well dispersed on the GO surface. For the detection of C. sakazakii, a polyclonal anti-C. sakazakii antibody (IgG) was covalently immobilized to the Au nanoparticles on the surface of the GO/Au composite coated glassy carbon electrode (GCE). The electrochemical sensing performance of immunofunctionalized GCE was characterized by cyclic voltammetry and differential pulse voltammetry. Under optimized conditions, in pure culture there was a linear relationship between electrical signal and C. sakazakii levels over the range 2.0 × 102–2.0 × 107 cfu/mL (R2 = 0.999), with a detection limit of 2.0 × 101 cfu/mL. The total analytical time was 15 min per sample. The C. sakazakii electrochemical immunosensing assay was able to successfully detect 2.0 × 101 cfu/mL of C. sakazakii in artificially contaminated powdered infant formula without any enrichment or pre-enrichment steps. Furthermore, the recovery rates of the C. sakazakii electrochemical immunosensing assay following spiking of powdered infant formula with different concentrations of C. sakazakii (cfu/mL) were 82.58% at 2.0 × 101 cfu/mL, 84.86% at 2.0 × 102 cfu/mL, and 95.40% at 2.0 × 103 cfu/mL. The C. sakazakii electrochemical immunosensing assay had good selectivity, reproducibility, and reactivity compared with other Cronobacter spp. and/or pathogens belonging to other genera, indicating its significant potential in the clinical diagnosis of C. sakazakii.

Graphical abstract

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http://ift.tt/2prdpVy

A novel “modularized” optical sensor for pH monitoring in biological matrixes

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Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Xun Liu, Shang-Qing Zhang, Xing Wei, Ting Yang, Ming-Li Chen, Jian-Hua Wang
A novel core-shell structure optical pH sensor is developed with upconversion nanoparticles (UCNPs) serving as the core and silica as the shell, followed by grafting bovineserumalbumin (BSA) as another shell via glutaraldehyde cross-linking. The obtained core-shell-shell structure is shortly termed as UCNPs@SiO2@BSA, and its surface provides a platform for loading various pH sensitive dyes, which are alike "modules" to make it feasible for measuring pHs within different pH ranges by simply regulating the type of dyes. Generally, a single pH sensitive dye is adopted to respond within a certain pH range. This study employs bromothymol blue (BTB) and rhodamine B (RhB) to facilitate their responses to pH variations within two ranges, i.e., pH 5.99–8.09 and pH 4.98–6.40, respectively, with detection by ratio-fluorescence protocol. The core-shell-shell structure offers superior sensitivity, which is tens of times more sensitive than those achieved by ratio-fluorescence approaches based on various nanostructures, and favorable stability is achieved in high ionic strength medium. In addition, this sensor exhibits superior photostability under continuous excitation at 980 nm. Thanks to the near infrared excitation in the core-shell-shell structure, it effectively avoids the self-fluorescence from biological samples and thus facilitates accurate sensing of pH in various biological sample matrixes.



http://ift.tt/2DJ5reJ

Fully 3D printed integrated reactor array for point-of-care molecular diagnostics

Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Karteek Kadimisetty, Jinzhao Song, Aoife M. Doto, Young Hwang, Jing Peng, Michael G. Mauk, Frederic D. Bushman, Robert Gross, Joseph N. Jarvis, Changchun Liu
Molecular diagnostics that involve nucleic acid amplification tests (NAATs) are crucial for prevention and treatment of infectious diseases. In this study, we developed a simple, inexpensive, disposable, fully 3D printed microfluidic reactor array that is capable of carrying out extraction, concentration and isothermal amplification of nucleic acids in variety of body fluids. The method allows rapid molecular diagnostic tests for infectious diseases at point of care. A simple leak-proof polymerization strategy was developed to integrate flow-through nucleic acid isolation membranes into microfluidic devices, yielding a multifunctional diagnostic platform. Static coating technology was adopted to improve the biocompatibility of our 3D printed device. We demonstrated the suitability of our device for both end-point colorimetric qualitative detection and real-time fluorescence quantitative detection. We applied our diagnostic device to detection of Plasmodium falciparum in plasma samples and Neisseria meningitides in cerebrospinal fluid (CSF) samples by loop-mediated, isothermal amplification (LAMP) within 50 min. The detection limits were 100 fg for P. falciparum and 50 colony-forming unit (CFU) for N. meningitidis per reaction, which are comparable to that of benchtop instruments. This rapid and inexpensive 3D printed device has great potential for point-of-care molecular diagnosis of infectious disease in resource-limited settings.

Graphical abstract

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http://ift.tt/2prdoks

Biofunctionalization of PAMAM-montmorillonite decorated poly (Ɛ-caprolactone)-chitosan electrospun nanofibers for cell adhesion and electrochemical cytosensing

Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Fatma Ozturk Kirbay, Esra Evrim Yalcinkaya, Gozde Atik, Gizem Evren, Betul Unal, Dilek Odaci Demirkol, Suna Timur
The construction and biofunctionalization of the poly (Ɛ-caprolactone) (PCL)-chitosan (CHIT) nanofibrous mats, which included Polyamidoamine (PAMAM) dendrimer modified montmorillonite (Mt), for the cell adhesion and electrochemical cytosensing were accomplished in this report. After the intercalation of the PAMAM generation zero dendrimer into the Mt, PAMAM-Mt decorated PCL-CHIT electrospun nanofibers were formed. The addition of PAMAM caused the decrease of contact angle of PCL-CHIT nanofibers. The covalent immobilization of a tripeptide namely Arginylglycylaspartate (RGD) on both the PCL-CHIT/Mt and PCL-CHIT/PAMAM-Mt surface was carried out. U87-MG and HaCaT (negative control) cell lines were incubated on the PCL-CHIT/Mt/RGD and PCL-CHIT/PAMAM-Mt/RGD. The proliferation studies and imaging of the cells were carried out on these fibers. Finally, electrochemical measurements were performed after each modification step by differential pulse/cyclic voltammetry and electrochemical impedance spectroscopy. U87-MG cells were grown better than HaCaT cells on the PCL-CHIT/PAMAM-Mt/RGD surfaces. To the best of our knowledge, there is no study that developed electrochemical cytosensor using electrospun nanofibers as a cell adhesion platform.

Graphical abstract

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http://ift.tt/2DIwDu0

A facile synthesis of 3D NiFe2O4 nanospheres anchored on a novel ionic liquid modified reduced graphene oxide for electrochemical sensing of ledipasvir: Application to human pharmacokinetic study

Publication date: 30 June 2018
Source:Biosensors and Bioelectronics, Volume 109
Author(s): Mohamed M. El-Wekil, Ashraf M. Mahmoud, Saad A. Alkahtani, Adel A. Marzouk, Ramadan Ali
Novel and sensitive electrochemical sensor was fabricated for the assay of anti-HCV ledipasvir (LEDV) in different matrices. The designed sensor was based on 3D spinel ferromagnetic NiFe2O4 nanospheres and reduced graphene oxide (RGO) supported by morpholinium acid sulphate (MHS), as an ionic liquid (RGO/NSNiFe2O4/MHS). This sensor design was assigned to synergistically tailor the unique properties of nanostructured ferrites, RGO, and ionic liquid to maximize the sensor response. Electrode modification prevented aggregation of NiFe2O4, increasing electroactive surface area and allowed remarkable electro-catalytic oxidation of LEDV with an enhanced oxidation response. Differential pulse voltammetry was used for detection LEDV in complex matrices whereas; cyclic voltammetry and other techniques were employed to characterize the developed sensor properties. All experimental factors regarding sensor fabrication and chemical sensing properties were carefully studied and optimized. Under the optimum conditions, the designated sensor displayed a wide linear range (0.4–350 ng mL-1) with LOD of 0.133 ng mL-1. Additionally, the proposed sensor demonstrated good selectivity, stability and reproducibility, enabling the quantitative detection of LEDV in Harvoni® tablets, human plasma and in a pharmacokinetic study. Our findings suggest that the developed sensor is a potential prototype material for fabrication of high-performance electrochemical sensors.

Graphical abstract

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http://ift.tt/2psXF4q

Authentication of an Italian PDO hazelnut (“Nocciola Romana”) by NIR spectroscopy

Abstract

Common hazelnuts are widely present in human diet all over the world, and their beneficial effects on the health have been extensively investigated and demonstrated. Different in-depth researches have highlighted that the harvesting area can define small variations in the chemical composition of the fruits, affecting their quality. As a consequence, it has become relevant to develop methodologies which would allow authenticating and tracing hazelnuts. In the light of this, the present work aims to develop a non-destructive method for the authentication of a specific high-quality Italian hazelnut, "Nocciola Romana," registered with a protected designation of origin (PDO). Thus, different samples of this fruit have been analyzed by near-infrared (NIR) spectroscopy and then classification models have been built, in order to distinguish between the PDO fruits and the hazelnuts not coming from the designated region. In particular, two different classification approaches have been tested, a discriminant one, partial least squares-discriminant analysis, and a class-modeling one, soft independent modeling of class analogies. Both methods led to very high prediction capability in external validation on a test set (classification accuracy in one case, and sensitivity and specificity in the other, all higher than 92%), suggesting that the proposed methodologies are suitable for a rapid and non-destructive authentication of the product.



http://ift.tt/2HUyCxB

Zinc oxide nanoparticles induce HIF-1α protein stabilization through increased reactive oxygen species generation from electron transfer chain complex III of mitochondria

Publication date: Available online 20 March 2018
Source:Journal of Dermatological Science
Author(s): Yoon-Hee Park, Hyun Cheol Bae, Jaehyung Kim, Sang Hoon Jeong, Sung Ik Yang, Sang Wook Son




http://ift.tt/2GeN72m

Vision Screening in Children Ages 6 Months to 5 Years: A Systematic Review for the U.S. Preventive Services Task Force [Internet].

To systematically review the evidence on screening for and treatment of amblyopia, its risk factors, and refractive error in children ages 6 months to 5 years.

http://ift.tt/2IIC0wL

Schistosomes, Liver Flukes and Helicobacter pylori.

This volume Evaluates the carcinogenic risk to humans posed by infection with three schistosoma trematodes, three liver flukes, and the bacterium Helicobacter pylori. These biological agents were selected for evaluation on the basis of evidence suggesting a causal association between infection and the development of human cancers.

http://ift.tt/2pxIRAm

A randomised controlled trial to evaluate the impact of a human rights based approach to dementia care in inpatient ward and care home settings.

The findings of this study did not support the hypothesis that increasing staff knowledge and attitudes towards human rights improves the quality of life of people with dementia.

http://ift.tt/2IIBDST

Attention Deficit Hyperactivity Disorder: Diagnosis and Treatment in Children and Adolescents [Internet].

Attention deficit hyperactivity disorder (ADHD) is a common pediatric neurobehavioral disorder often treated in the primary care setting. This systematic review updates and extends two previous Agency for Healthcare Research and Quality (AHRQ) systematic evidence reviews and focuses on the comparative effectiveness of methods to establish the diagnosis of ADHD, updates the comparative effectiveness of pharmacologic and nonpharmacologic treatments, and evaluates different monitoring strategies in the primary care setting for individuals from birth through 17 years of age.

http://ift.tt/2pxIplE

The Effectiveness of Health Coaching [Internet].

Chronic medical conditions such as diabetes, cardiovascular disease (CVD), and hypertension are highly prevalent among VA healthcare system users. Among VA patients, 72% have one or more chronic medical conditions (compared with 40% to 50% of other U.S. adults), and more than half have at least 2 chronic conditions. The management of chronic medical conditions is a time-consuming process for primary care physicians. One study found that it would take 828 hours per year to provide the required care for the top 10 chronic diseases. Thus, patients are increasingly being asked to take an active role in the self-management of their chronic medical conditions. Yet many patients leave a physician encounter confused about what to do to manage their own health due to conflicting and contradictory information.

http://ift.tt/2IGhfSD

The Effect of Different Ways of Organising Municipal Rehabilitation Services with Respect to Persons with Neurological Conditions [Internet].

Today, there are differences between municipalities in how they organise their habilitation and rehabilitation services. We have systematically reviewed research about the effects of different ways of organising municipal habilitation and rehabilitation services to persons with neurological conditions. The research documentation is based on ten RCT's. The documentation includes mainly studies with small sample sizes and some of the studies are not relevant with respect to current medical practice. Within neurology, we have only found relevant documentation on the diagnosis stroke.

http://ift.tt/2pwA9m3

Mechanical Thrombectomy for Acute Ischemic Stroke [Internet].

Each year around 10,000 patients are treated for severe acute stroke at Norwegian hospitals. Whereas many patients die, survivors often suffer from considerable loss of function. Mechanical thrombectomy is a treatment option for large vessel ischemic stroke. Thrombectomy consists in physically removing the obstructing clot (thrombe) using specific for-purpose designed devices. The method is used when standard treatment (thrombolysis) has failed to dissolve the thrombe, or is contraindicated. In Norway, thrombectomy is performed at specific intervention centres. However, time is a crucial factor, as the intervention is recommended maximum 6 hours following the stroke. Thus implementation of this method at the national level, i.e. being available to all citizens, will meet important challenges due to the particular population distribution, topography and weather conditions in large parts of our country.

http://ift.tt/2IIBpv1

Effects of Group Interventions for Children Who Experience Family Disruption [Internet].

Children and youth who experience divorce or family break up will generally have an increased risk of emotional and behavioral adjustment problems. Consequently, prevention programs in the form of group intervention have been developed to prevent negative psychosocial consequences in both the short and long term.

http://ift.tt/2G293Kv

Systematic Reviews on Preventing Pressure Ulcers: A Systematic Review [Internet].

Norwegian studies imply that between 7 and 15 per cent of inpatients develop pressure ulcers. They develop more often in specific groups of patients, like patients with spinal cord injury, hip fracture and patients in intensive care.

http://ift.tt/2IHxs9Z

Co-organization of General Practitioners with Other Primary Health Care Services: A Systematic Review [Internet].

In this systematic review we have summarized results from 28 controlled US studies that compared co-organized clinics with clinics where primary health care resources were not co-organized.

http://ift.tt/2G0sWSk

Cognitive Therapies for Smoking Cessation: A Systematic Review [Internet].

Around six million people die every year due to diseases caused by smoking, most commonly cancer, cardiovascular disease and chronic obstructive pulmonary disease. Nicotine replacement therapy, medication and counselling are common methods used to help people quit smoking.

http://ift.tt/2IDCNzc

The Effects of Concurrent Prescription of Benzodiazepines for People Undergoing Opioid Maintenance Treatment: Systematic Review [Internet].

Opioid maintenance treatment uses long acting opiates to reduce an opioid dependent person's urge to take illicit opioid substances. Opioid dependent persons are likely to experience elevated levels of anxiety and sleep disturbance. Therefore, patients undergoing opioid maintenance treatment often use medications containing benzodiazepines, both prescribed by a doctor and from the illegal market, to alleviate these problems. Concurrent use of benzodiazepines during opioid maintenance treatment raise a concern.

http://ift.tt/2G0hHZY

Alternative Opioid Agonists in the Treatment of Opioid Dependence: A Systematic Review [Internet].

In this review, we have looked at treatment with slow release oral morphine and levomethadone. These treatments are compared to the three medications used in Norway: buprenorphine with naloxone, buprenorphine, or methadone.

http://ift.tt/2IDCqoi

Systematic Reviews on Preventing Catheter-Associated Urinary Tract Infection [Internet].

The number of patients in hospitals and rehabilitation institutions at any time is large, and a considerable number of them need to use a urinary catheter. Catheter-associated urinary tract infection may affect a large number of persons. The survey of prevalence of May 2015 from the Norwegian Institute of Public Health reported that 1.2 percent of patients in hospitals suffered from a urinary tract infection. We have systematically reviewed research on effect of interventions to prevent catheter-associated urinary tract infection.

http://ift.tt/2ptaZF5

Effect of Thrombolytic Treatment 3 to 4.5 Hours After Onset of Stroke [Internet].

The Norwegian Knowledge Centre for the Health Services (now part of the Norwegian Institute of Public Health) was commissioned to update the evidence on the effect of intravenous thrombolytic treatment administered 3 to 4.5 hours after stroke. There was already a Cochrane systematic review by Wardlaw et al. from 2014. We searched for systematic reviews published after Wardlaw's review, but found none that fulfilled the inclusion criteria. Then we searched for randomised controlled trials published later than the search date for the Cochrane review, but we found no relevant trials. We have, therefore, conveyed the findings from Wardlaw and supplemented with data from an individual patient data meta-analysis. We have also graded our confidence in the estimates of effect using the GRADE tool (Grading of Recommendations Assessment, Development and Evaluation). The outcomes are assessed 3-6 months after the stroke and are compared with placebo.

http://ift.tt/2IIu4vG

Can We Finally Dispense With Ketamine's Many Myths?

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Publication date: Available online 21 March 2018
Source:The Journal of Emergency Medicine
Author(s): Joshua Hurwitz




http://ift.tt/2GbbQEv

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Effect of shear rate on the residual shear strength of pre-sheared clays | Open Access
Farzad Habibbeygi & Hamid Nikraz | Silvana Irene Torri Reviewing Editor
1453989 | DOI: 10.1080/23312041.2018.1453989This is the author accepted version which has not been proofed or edited


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Zinc in an ultraoligotrophic lake food web

Abstract

Zinc (Zn) bioaccumulation and trophic transfer were analyzed in the food web of Lake Nahuel Huapi, a deep, unpolluted ultraoligotrophic system in North Patagonia. Benthic macroinvertebrates, plankton, and native and introduced fish were collected at three sites. The effect of pyroclastic inputs on Zn levels in lacustrine food webs was assessed by studying the impact of the eruption of Puyehue-Cordón Caulle volcanic complex (PCCVC) in 2011, by performing three sampling campaigns immediately before and after the PCCVC eruption, and after 2 years of recovery of the ecosystem. Zinc trophodynamics in L. Nahuel Huapi food web was assessed using nitrogen stable isotopes (δ15N). There was no significant increase of Zn concentrations ([Zn]) in L. Nahuel Huapi biota after the PCCVC eruption, despite the evidence of [Zn] increase in lake water that could be associated with volcanic ash leaching. The organisms studied exhibited [Zn] above the threshold level considered for dietary deficiency, regulating Zn adequately even under a catastrophic situations like PCCVC 2011 eruption. Zinc concentrations exhibited a biodilution pattern in the lake's food web. To the best of our knowledge, present research is the first report of Zn biodilution in lacustrine systems, and the first to study Zn transfer in a freshwater food web including both pelagic and benthic compartments.



http://ift.tt/2pyB1XB

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