Reply to “Need for updating safety recommendations on repetitive transcranial magnetic stimulation in stroke patients”

Publication date: Available online 3 June 2017
Source:Clinical Neurophysiology
Author(s): Ela B. Plow, Vishwanath Sankarasubramanian, Kelsey A. Potter-Baker, Yin-Liang Lin




http://ift.tt/2soOZM6

Need for updating safety recommendations on repetitive transcranial magnetic stimulation in stroke patients

Publication date: Available online 3 June 2017
Source:Clinical Neurophysiology
Author(s): Bertrand Glize, Dominique Guehl, Mélanie Cogné




http://ift.tt/2rPyfRa

Movat Pentachrom stain reveals unexpected high osteogenesis rate in aortic valves

Publication date: Available online 2 June 2017
Source:Acta Histochemica
Author(s): Claudia Dittfeld, Michael Haase, Maria Feilmeier, Anett Jannasch, Petra Büttner, Katrin Plötze, Thomas Waldow, Sems-Malte Tugtekin
Background and aim of the studyAortic valve (AV) stenosis is the most common valvular heart disease with an incidence of 3% for people ≥ 65years in the industrialized world with indication for a surgical or transcatheter valve replacement. Researchers suppose osteogenic processes as key mechanisms in calcific aortic valve stenosis. Recently, Torre et al. published impressive histological analyses and detected osseous and/or chondromatous metaplasia in 15.6% of 6685 native calcified aortic valves. Therefore one HE section per valve originated from the area with the greatest extent of calcification was analyzed. Aim of our experimental setup was to identify regions of neo-osteogenesis and to determine the rate of specimens with active mineralization in human aortic valve tissue by Movat Pentachrom staining of sections of lager tissue segments.MethodsOperational replaced aortic valves of 35 patients, 15 female and 20 male with an average age of 66.2 years were formalin fixed and decalcified using Osteosoft^®-solution. Tissue samples were cut and 2μm specimens were stained with Movat Pentachrom to visualize osteogenic regions. Instead of screening a large number of sections, tissue samples were cut up to five times with at least 100μm space each if no region of osseous and/or chondromatous metaplasia was visible.Results/ConclusionsUsing this setup, a region of osseous metaplasia was detected in 25 (71.4%) of 35 samples analyzed. In some cases, these regions were small sized and only visible due to the bright color of Movat Pentachrom stain. This leads to the suggestion that a higher rate of calcified aortic valve samples would be classified as cusps with areas of neo-osteogenesis after staining with Movat Pentachrom stain and by the systematic analysis of larger parts of the tissue blocks.



http://ift.tt/2rm0x4h

Particulate matter air pollution: individual choices for improving cardiometabolic well-being

Abstract

Exposure to small particulate matter (PM_2.5) has become the 5th highest ranking risk factor for death, responsible for 4.2 million deaths worldwide. PM pollution is also associated with cardiovascular disease and type 2 diabetes, and may contribute to deteriorate the already poor cardiometabolic outlook of the diabetic patient. Although most sources of outdoor air pollution are well beyond the control of individuals, there is still room for personal action. Health behaviors (smoking cessation, avoiding obesity, and increasing physical activity) may increase the poor life expectancy of individuals in the lowest income quartile of the Western population; moreover, a favorable lifestyle, (no current smoking, no obesity, physical activity at least once weekly, and a healthy diet pattern), may cut by nearly 50% the risk of coronary heart disease among people at high genetic risk. Things seem not immutable, as individual healthy choices do matter.

http://ift.tt/2ruLC64

Long lasting prophylaxis of iodine deficiency after a successful information campaign for iodized salt consumption

http://ift.tt/2rPy1cX

Free Diced Cartilage: A new application of diced cartilage grafts in primary and secondary Rhinoplasty.

Background: Irregularities or deformities of the nasal dorsum after hump reduction account for a significant number of revision rhinoplasties. We therefore developed a technique of meticulously dicing and exactly placing free diced cartilage grafts (fDC), harvested from septum, rib, or ear cartilage. The cartilage paste is used for smoothening, augmentation, or camouflaging of the nasal dorsum in primary or revision rhinoplasties. Methods: A retrospective analysis of multi-surgeon consecutive open approach rhinoplasties from January to December 2014 was conducted at a single center. We compared the outcome of three different techniques to augment or cover the nasal dorsum after an observation period of seven months: In Group I, 325 patients with fDC as the only onlay were included. In Group II, consisting of 73 patients, the dorsal onlay was either fascia alone, or in combination with fDC. 48 patients in Group III received a dorsal augmentation with the 'classical' diced cartilage in fascia (DCF) technique. Results: 446 patients with primary and secondary rhinoplasties in which one of the above-mentioned diced cartilage techniques was used were included in the study. We found revision rates for dorsal irregularities within the seven-month postoperative observation period of 5.2%, 8.2%, and 25% for Groups I-III, respectively. Conclusion: Our findings strongly support our clinical experience that the fDC technique presents an effective and easily reproducible method for camouflage and augmentation in aesthetic and reconstructive rhinosurgery. (C)2017American Society of Plastic Surgeons

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Dynamic Rheology for the Prediction of Surgical Outcomes in Autologous Fat Grafting.

Background: Due to the abundance and biocompatibility of fat, lipotransfer has become an attractive method for treating soft tissue deficits. However, it is limited by unpredictable graft survival and retention. Currently, little is known about the viscoelastic properties of fat after various injection methods. Here, we assess the effects of cannula diameter, length, and shape on the viscoelastic properties, structure, and retention of fat. Methods: Human lipoaspirate was harvested using suction-assisted liposuction and prepared for grafting. A syringe pump was used to inject fat at a controlled flow rate through cannulas of varying gauge, length, and shape. Processed samples were tested in triplicate on an oscillatory rheometer to measure their viscoelastic properties. Fat grafts from each group were placed into the scalps of immunocompromised mice. After 8 weeks, graft retention was measured using micro-CT and grafts were explanted for histological analysis. Results: Lipoaspirate injected through narrower, longer, and bent cannulas exhibited more shear thinning with diminished quality. The storage modulus (G') of fat processed with 18-gauge cannulas was significantly lower than when processed with 14-gauge or larger cannulas, which also corresponded with inferior in vivo histological structure. Similarly, the longer cannula group had a significantly lower G' than the shorter cannula, and was associated with decreased graft retention. Conclusions: Discrete modifications in the methods used for fat placement can have a significant impact on immediate graft integrity, and ultimately on graft survival and quality. Respecting these biomechanical influences during the placement phase of lipotransfer may allow surgeons to optimize outcomes. (C)2017American Society of Plastic Surgeons

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Five Operations that give the best results after brachial plexus injury.

Treatment of brachial plexus injuries has slowly improved over the last 45 years. Changes in strategy, techniques, microsurgical equipment and technology have expanded the surgical options to reconstruct these life altering, highly complex injuries. The surgical armamentarium includes neurolysis, nerve repair, nerve grafting, nerve transfers, tendon transfer, muscle transfer and other soft tissue and bony procedures. In this article we have selected five surgical procedures (Oberlin's procedure, Leechavengvongs' procedure, free functional muscle transfer, radial nerve tendon transfers and C5-C6 nerve grafting in obstetrical birth palsy) that have consistently given us good results in our patients who require surgical reconstruction. (C)2017American Society of Plastic Surgeons

http://ift.tt/2sAcnp7

Minor suture fusion in syndromic craniosynostosis.

Background: Infants with craniofacial dysostosis syndromes may present with midface abnormalities but without major (calvarial) suture synostosis and head shape anomalies. Delayed presentation of their calvarial phenotype is known as progressive postnatal craniosynostosis. Minor sutures/synchondroses are continuations of major sutures toward and within the skull base. We hypothesized that minor suture synostosis is present in infants with syndromic, progressive postnatal craniosynostosis, and is associated with major suture synostosis. Methods: A two-institution review of infants (

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Prepectoral Breast Reconstruction: A Safe Alternative To Submuscular Prosthetic Reconstruction Following Nipple Sparing Mastectomy.

Background: Nipple sparing mastectomy (NSM) with immediate prosthetic reconstruction is routinely performed due to excellent aesthetic results, and safe oncologic outcomes. Typically, subpectoral expanders are placed, but in select patients, this can lead to significant postoperative pain and animation deformity, due to pectoralis major muscle disinsertion and stretch. Prepectoral reconstruction is a technique that eliminates dissection of the pectoralis major, by placing the prosthesis completely above the muscle with complete acellular dermal matrix (ADM) coverage. Methods: A single surgeon's experience with immediate prosthetic reconstruction following NSM from 2012 - 2016 was reviewed. Patient demographics, adjuvant treatment, length and characteristics of the expansion, and incidence of complications during the tissue expander stage were compared, between partial submuscular/partial ADM (dual-plane) cohort and prepectoral cohort. Results: Fifty-one patients (84 breasts) underwent immediate prepectoral tissue expander placement, compared to 115 patients (186 breasts) undergoing immediate partial submuscular expander placement. The groups had similar comorbidities and postoperative radiation exposure. There was no significant difference in overall complication rate between the two groups (17.9% vs 18.8%, p = 0.49). Conclusions: Prepectoral breast reconstruction provides a safe and effective alternative to partial submuscular reconstruction, that yields comparable aesthetic results with less operative morbidity. In the authors' experience, the incidence of acute and chronic postoperative pain, and animation deformity, is significantly lower following prepectoral breast reconstruction. This technique is now considered for all patients who are safe oncologic candidates, and are undergoing NSM and prosthetic reconstruction. (C)2017American Society of Plastic Surgeons

http://ift.tt/2sAaLMl

Single-artery human ear graft procurement: a simplified approach.

Background. In the field of experimental facial vascularized composite tissue allotransplantation (VCA), a human auricular subunit model, pedicled on both superficial temporal (STA) and posterior auricular (PAA) arteries was described. Clinical cases of extensive auricular replantation however, suggested that a single artery could perfuse the entire flap. In our study, variants of this single pedicle approach have been studied, aiming to develop a more versatile replantation technique, in which the question of venous drainage has also been addressed. Methods. For arterial perfusion study, we harvested 11 auricular grafts, either on a single STA pedicle (n=3) or a double STA-PAA pedicle (n=8). We then proceeded to selective barium injections, in STA, PAA or both PAA-STA. Arteriograms were acquired with a Micro-CT scan and analyzed on 3D-reconstructed images. Venous drainage was investigated in eight hemi-faces, carefully dissected after latex injection. Results. Observations showed a homogenous perfusion of the whole auricle in all arterial graft variants. Venous drainage was highly variable, with either a dominant superficial temporal vein (37.5%), dominant posterior auricular vein (12.5%) or co-dominant trunks (50%). Conclusions. We demonstrated that auricular subunit VCA can be performed on a single artery, relying on the dynamic intra-auricular anastomoses between STA and PAA branches. Potentially, this vascular versatility is prone to simplify the subunit harvest and allows various strategies for pedicle selection. Venous drainage, however, remains inconstant and thus the major issue when considering auricular transplantation. (C)2017American Society of Plastic Surgeons

http://ift.tt/2rBLh3P

Quantitative profiling of 19 bile acids in rat plasma, liver, bile and different intestinal section contents to investigate bile acid homeostasis and the application of temporal variation of endogenous bile acids

Publication date: Available online 3 June 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Tingting Yang, Ting Shu, Guanlan Liu, Huifang Mei, Xiaoyu Zhu, Xin Huang, Luyong Zhang, Zhenzhou Jiang
Bile acid homeostasis is maintained by liver synthesis, bile duct secretion, microbial metabolism and intestinal reabsorption into the blood. When drug insults result in liver damage, the variances of bile acids (BAs) are related to the physiological status of the liver. Here, we established a method to simultaneously quantify 19 BAs in rat plasma, liver, bile and different intestinal section contents (duodenum, jejunum, ileum, cecum and colon) using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) to reveal the pattern of bile acid homeostasis in the enterohepatic circulation of bile acids in physiological situations. Dynamic changes in bile acid composition appeared throughout the enterohepatic circulation of the BAs; taurine- and glycine-conjugated BAs and free BAs had different dynamic homeostasis levels in the circulatory system. cholic acid (CA), beta-muricholic acid (beta-MCA), lithocholic acid (LCA), glycocholic acid (GCA) and taurocholic acid (TCA) greatly fluctuated in the bile acid pool under physiological conditions. Taurine- and glycine-conjugated bile acids constituted more than 90% in the bile and liver, whereas GCA and TCA accounted for more than half of the total bile acids and the secretion of bile mainly via conjugating with taurine. While over 80% of BAs in plasma were unconjugated bile acids, CA and HDCA were the most abundant elements. Unconjugated bile acids constituted more than 90% in the intestine, and CA, beta-MCA and HDCA were the top three bile acids in the duodenum, jejunum and ileum content, but LCA and HDCA were highest in the cecum and colon content. As the main secondary bile acid converted by microflora in the intestine, LCA was enriched in the cecum and DCA mostly in the colon. As endogenous substances, the concentrations of plasma BAs were closely related to time rhythm and diet. In conclusion, analyzing detailed BA profiles in the enterohepatic circulation of bile acids in a single run is possible using LC-MS/MS. Based on the physiological characteristics of the metabolic profiling of 19 BAs in the total bile acid pool and the time rhythm variation of the endogenous bile acids, this study provided a new valuable method and theoretical basis for the clinical research of bile acid homeostasis.



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Absolute venomics: Absolute quantification of intact venom proteins through elemental mass spectrometry

Publication date: Available online 2 June 2017
Source:Journal of Proteomics
Author(s): Francisco Calderón-Celis, Laura Cid-Barrio, Jorge Ruiz Encinar, Alfredo Sanz-Medel, Juan J. Calvete
We report the application of a hybrid element and molecular MS configuration for the parallel absolute quantification of μHPLC-separated intact sulfur-containing venom proteins, via ICP triple quadrupole MS and ³²S/³⁴S isotope dilution analysis, and identification by ESI-QToF-MS of the toxins of the medically important African black-necked spitting cobra, Naja nigricollis (Tanzania); New Guinea small-eyed snake, Micropechis ikaheka; and Papuan black snake, Pseudechis papuanus. The main advantage of this approach is that only one generic sulfur-containing standard is required to quantify each and all intact Cys- and/or Met-containing toxins of the venom proteome. The results of absolute quantification are in reasonably good agreement with previously reported relative quantification of the most abundant protein families. However, both datasets depart in the quantification of the minor ones, showing a tendency for this set of proteins to be underestimated in standard peptide-centric venomics approaches. The molecular identity, specific toxic activity, and concentration in the venom, are the pillars on which the toxicovenomics-aimed discovery of the most medically-relevant venom toxins, e.g. those that need to be neutralized by an effective therapeutic antivenom, should be based. The pioneering venom proteome-wide absolute quantification shown in this paper represents thus a significant advance towards this goal. The potential of ICP triple quadrupole MS in proteomics in general, and venomics in particular, is critically discussed.Biological significanceAnimal venoms provide excellent model systems for investigating interactions between predators and prey, and the molecular mechanisms that contribute to adaptive protein evolution. On the other hand, numerous cases of snake bites occur yearly by encounters of humans and snakes in their shared natural environment. Snakebite envenoming is a serious global public health issue that affects the most impoverished and geopolitically disadvantaged rural communities in many tropical and subtropical countries. Unveiling the temporal and spatial patterns of venom variability is of fundamental importance to understand the molecular basis of envenoming, a prerequisite for developing therapeutic strategies against snakebite envenoming. Research on venoms has been continuously enhanced by advances in technology. The combined application of next-generation transcriptomic and venomic workflows has demonstrated unparalleled capabilities for venom characterization in unprecedented detail. However, mass spectrometry is not inherently quantitative, and this analytical limitation has sparked the development of methods to determine absolute abundance of proteins in biological samples. Here we show the potential of a hybrid element and molecular MS configuration for the parallel ESI-QToF-MS and ICP-QQQ detection and absolute quantification of intact sulfur-containing venom proteins via ³²S/³⁴S isotope dilution analysis. This configuration has been applied to quantify the toxins of the medically important African snake Naja nigricollis (Tanzania), and the Papuan species Micropechis ikaheka and Pseudechis papuanus.

Graphical abstract

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Hydrocarbon-induced changes in proteins and fatty acids profiles of Raoultella ornithinolytica M03

Publication date: Available online 2 June 2017
Source:Journal of Proteomics
Author(s): A. Zdarta, J. Tracz, M. Łuczak, U. Guzik, E. Kaczorek
Microorganisms can support environmental restoration by biodegradation of hydrocarbons but the mechanism of this process has been not described in detail yet. We present the effect of benzene derivatives on Raoultella ornithinolytica M03 cell composition. Comparison of the cell response after short-term and long-term stress revealed significant differences in surface properties, fatty acid composition and proteins profile. R. ornithinolytica M03 after long-term stress was characterized by lower cell surface hydrophobicity and much higher inner membrane permeability. Also decrease in the content of branched and unsaturated fatty acids was observed. Cells after short- and long-term stress were characterized by analyses of changes related to thirty-nine proteins participating in various metabolic pathways. The presence of benzene derivatives resulted in modifications in the abundance of proteins involved in determination of cell shape and ability to ion transport, lipid biosynthesis, amino-acid biosynthesis, tRNA ligases, chaperone and TCA cycleproteins, gluconeogenesis, transcription and nucleotide synthesis. Uptake and transport associated proteins, cell properties and membrane stability were also found to differ in the cells after short- and long-term stress suggesting the use of different mechanisms for transport and biodegradation of benzene derivatives and modification of cell response depending on the length of exposure to the stressor.Biological significanceThis is the first comprehensive study whose results may contribute to a better understanding of the changes occurring during short- and long-term contact with benzene derivatives. R. ornithinolytica M03 after long-term stress was characterized by lower cell surface hydrophobicity and much higher inner membrane permeability. Also decrease in the content of branched and unsaturated fatty acids was observed. Cells after short- and long-term stress were characterized by analyses of changes related to thirty-nine proteins participating in various metabolic pathways. The presence of benzene derivatives resulted in modifications in the abundance of proteins involved in determination of cell shape and ability to ion transport, lipid biosynthesis, amino-acid biosynthesis, tRNA ligases, chaperone and TCA cycleproteins, gluconeogenesis, transcription and nucleotide synthesis. Uptake and transport associated proteins, cell properties and membrane stability were also found to differ in the cells after short- and long-term stress suggesting the use of different mechanisms for transport and biodegradation of benzene derivatives and modification of cell response depending on the length of exposure to the stressor. The provided results seem to constitute an important aspect of remediation techniques, and the present article shall be of great interest to the Journal's readership.

Graphical abstract

http://ift.tt/2rPaLMa

Particulate matter air pollution: individual choices for improving cardiometabolic well-being

Abstract

Exposure to small particulate matter (PM_2.5) has become the 5th highest ranking risk factor for death, responsible for 4.2 million deaths worldwide. PM pollution is also associated with cardiovascular disease and type 2 diabetes, and may contribute to deteriorate the already poor cardiometabolic outlook of the diabetic patient. Although most sources of outdoor air pollution are well beyond the control of individuals, there is still room for personal action. Health behaviors (smoking cessation, avoiding obesity, and increasing physical activity) may increase the poor life expectancy of individuals in the lowest income quartile of the Western population; moreover, a favorable lifestyle, (no current smoking, no obesity, physical activity at least once weekly, and a healthy diet pattern), may cut by nearly 50% the risk of coronary heart disease among people at high genetic risk. Things seem not immutable, as individual healthy choices do matter.

http://ift.tt/2ruLC64

Multiple laser pulses in conjunction with an optical clearing agent to improve the curative effect of cutaneous vascular lesions

Abstract

Port-wine stains (PWSs) usually respond poorly to pulsed dye laser treatment because of the shallow penetration and light absorption of melanin in the epidermis. Multiple laser pulses (MLPs) Nd:YAG laser in conjunction with an optical clearing agent can help to reduce the total laser energy required for blood coagulation. The quantitative optical clearing effect (OCE) of glycerol was investigated by using a tissue-like phantom. Thereafter, an in vitro capillary tube experimental system and an in vivo hamster dorsal skin chamber experiment for the laser treatment of PWSs were established to visually obtain the quantitative relationship between the OCE and the blood coagulation properties under the irradiation of 1064 nm MLPs. Diffuse reflection coefficient decreases by 36.69% and transmission coefficient increases by 38.73% at 1064 nm, after applying 0.5 mL anhydrous glycerol for 10 min on the surface of the tissue-like phantom. The number of laser pulses required for blood coagulation decreases by 25% after the application of 0.5 mL anhydrous glycerol for 4 min, thrombosis appears after 10 min, and the 0.0854 clotting area completely blocks the capillary tubes in 6 pulses. For 10 min, the incident energy can be reduced by 35.09 and 29.82%. When the 0.3-mm vessel's buried depths are 1 and 0.5 mm, the pulse number can be reduced from 11 to 8 and from 6 to 4, respectively. Adding anhydrous glycerol directly on the hamster dorsal skin is an effective way to reduce the number of laser pulses from 4∼5 to 2∼3 for similar capillary tube diameter. Therefore, the MLPs of 1064 nm Nd:YAG demonstrates a substantial curative effect for large capillary tubes. In conjunction with glycerol, this approach may treat deeply buried cutaneous capillary tubes and prevent the unwanted thermal damage of normal dermal tissue.

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pH-responsive unimolecular micelle-gold nanoparticles-drug nanohybrid system for cancer theranostics

Publication date: Available online 3 June 2017
Source:Acta Biomaterialia
Author(s): Wenjing Lin, Na Yao, Long Qian, Xiaofang Zhang, Quan Chen, Jufang Wang, Lijuan Zhang
The development of an in situ formed pH-responsive theranostic nanocomposite for anticancer drug delivery and computed tomography (CT) imaging was reported. β-cyclodextrin-{poly(lactide)-poly(2-(dimethylamino) ethyl methacrylate)-poly[oligo(2-ethyl-2-oxazoline)methacrylate]}21 [β-CD-(PLA-PDMAEMA-PEtOxMA)21] unimolecular micelles served as a template for the in situ formation of gold nanoparticles (GNPs) and the subsequent encapsulation of doxorubicin (DOX). The formation of unimolecular micelles, microstructures and the distributions of GNPs and DOX were investigated through the combination of experiments and dissipative particle dynamics (DPD) simulations. β-CD-(PLA-PDMAEMA-PEtOxMA)21 formed spherical unimolecular micelles in aqueous solution within a certain range of polymer concentrations. GNPs preferentially distributed in the PDMAEMA area. The maximum wavelength (λmax) and the size of GNPs increased with increasing concentration of HAuCl4. DOX preferentially distributed in the PDMAEMA mesosphere, but penetrated the inner PLA core with increasing DOX concentration. DOX-loaded micelles with 41-61% entrapment efficiency showed fast release (88% after 102 h) under acidic tumor conditions. Both in vitro and in vivo experiments revealed superior anticancer efficacy and effective CT imaging properties for β-CD-(PLA-PDMAEMA-PEtOxMA)21/Au/DOX. We conclude that the reported unimolecular micelles represent a class of versatile smart nanocarriers for theranostic application.Statement of SignificanceDeveloping polymeric nanoplatforms as integrated theranostic vehicles for improving cancer diagnostics and therapy is an emerging field of much importance. This article aims to develop an in situ formed pH-responsive theranostic nanocomposite for anticancer drug delivery and computed tomography (CT) imaging. Specific emphases is on structure-properties relationship. There is a sea of literature on polymeric drug nanocarriers, and a couple of polymer-stablized gold nanoparticles (GNPs) systems for cancer diagnosis are also known. However, to our knowledge, there has been no report on polymeric unimolecualr micelles capable of dual loading of GNPs without external reducing agents and anticancer drugs for cancer diagnosis and treatment. To this end, the target of the current work was to develop an in situ formed nanocarrier, which actively dual wrapped CT contrast agent GNPs and hydrophobic anticancer drug doxorubicin (DOX), achieving high CT imaging and antitumor efficacy under in vitro and in vivo acid tumor condition. Meanwhile, by taking advantage of dissipative particle dynamics (DPD) simulation, we further obtained the formation process and mechanism of unimolecular micelles, and detailed distributions and microstructures of GNPs and DOX on unimolecular micelles. Taken together, our results here provide insight and guidance for the design of more effective nanocarriers for cancer theranostic application.

Graphical abstract

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Highly efficient delivery of potent anticancer iminoquinone derivative by multilayer hydrogel cubes

Publication date: Available online 3 June 2017
Source:Acta Biomaterialia
Author(s): Bing Xue, Wei Wang, Jiang-Jiang Qin, Bhavitavya Nijampatnam, Srinivasan Murugesan, Veronika Kozlovskaya, Ruiwen Zhang, Sadanandan E. Velu, Eugenia Kharlampieva
We report a novel delivery platform for a highly potent anticancer drug, 7-(benzylamino)-3,4-dihydro-pyrrolo[4,3,2-de]quinolin-8(1H)-one (BA-TPQ), using pH- and redox-sensitive poly(methacrylic acid) (PMAA) hydrogel cubes of micrometer size as the encapsulating matrix. The hydrogels are obtained upon cross-linking PMAA with cystamine in PMAA/poly(N-vinylpyrrolidone) multilayers assembled within mesoporous sacrificial templates. The BA-TPQ-loaded hydrogels maintain their cubical shape and pH-sensitivity after lyophilization, which is advantageous for long-term storage. Conversely, the particles degrade in vitro in the presence of glutathione (5 mM) providing 80% drug release within 24 h. Encapsulating BA-TPQ into hydrogels significantly increases its transport via Caco-2 cell monolayers used as a model for oral delivery where the apparent permeability of BA-TPQ-hydrogel cubes was ∼2-fold higher than that of BA-TPQ. BA-TPQ-hydrogel cubes exhibit better anticancer activity against HepG2 (IC50=0.52 µg/mL) and Huh7 (IC50=0.29 µg/mL) hepatoma cells with a 40% decrease in the IC50 compared to the non-encapsulated drug. Remarkably, non-malignant liver cells have a lower sensitivity to BA-TPQ-hydrogel cubes with 2-fold increased IC50 values compared to those of cancer cells. In addition, encapsulating BA-TPQ in the hydrogels amplifies the potency of the drug via down-regulation of MDM2 oncogenic protein and upregulation of p53 (a tumor suppressor) and p21 (cell proliferation suppressor) expression in HepG2 liver cancer cells. Moreover, enhanced inhibition of MDM2 protein expression by BA-TPQ-hydrogel cubes is independent of p53-status in Huh7 cells. This drug delivery platform of non-spherical shape provides a facile method for encapsulation of hydrophobic drugs and can facilitate the enhanced efficacy of BA-TPQ for liver cancer therapy.Statement of SignificanceMany potent anticancer drugs are hydrophobic and lack tumor selectivity, which limits their application in cancer therapy. Although cubical hydrogels of poly(methacrylic acid) exhibit excellent biocompatibility and versatility, they have not been investigated for hydrophobic drug delivery due to poor mechanical stability and incompatibility between hydrophobic drugs and a hydrophilic hydrogel network. In this study, we provide a facile method to prepare a multilayer hydrogel-based platform with controlled nanostructure, cubical shape and redox-responsiveness for delivery of highly potent anticancer therapeutics, hydrophobic BA-TPQ. The BA-TPQ-hydrogel cubes have exceptional structural stability upon lyophilization which is advantageous for a long-term storage. The greatly enhanced trans-epithelial permeability and amplified anti-tumor activity of BA-TPQ are achieved by encapsulation in these hydrogel cubes. Furthermore, the anticancer BA-TPQ-hydrogel platform retains the selective activity of BA-TPQ to hepatocellular carcinoma cells. Overall, the produced BA-TPQ-hydrogel cubes demonstrate a high potential for clinical liver cancer therapy.

Graphical abstract

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pH-responsive self-healing injectable hydrogel based on N-carboxyethyl chitosan for hepatocellular carcinoma therapy

Publication date: Available online 2 June 2017
Source:Acta Biomaterialia
Author(s): Jin Qu, Xin Zhao, Peter X. Ma, Baolin Guo
Injectable hydrogels with pH-responsiveness and self-healing ability have great potential for anti-cancer drug delivery. Herein, we developed a series of polysaccharide-based self-healing hydrogels with pH-sensitivity as drug delivery vehicles for hepatocellular carcinoma therapy. The hydrogels were prepared by using N-carboxyethyl chitosan (CEC) synthesized via Michael reaction in aqueous solution and dibenzaldehyde-terminated poly(ethylene glycol) (PEGDA). Doxorubicin (Dox), as a model of water-soluble small molecule anti-cancer drug was encapsulated into the hydrogel in situ. Self-healing behavior of the hydrogels was investigated at microscopic and macroscopic levels, and the hydrogels showed rapid self-healing performance without any external stimulus owing to the dynamic covalent Schiff-base linkage between amine groups from CEC and benzaldehyde groups from PEGDA. The chemical structures, rheological property, in vitro gel degradation, morphology, gelation time and in vitro Dox release behavior from the hydrogels were characterized. Injectability was verified by in vitro injection and in vivo subcutaneous injection in a rat. pH-responsive behavior was verified by in vitro Dox release from hydrogels in PBS solutions with different pH values. Furthermore, the activity of Dox released from hydrogel matrix was evaluated by employing human hepatocellular liver carcinoma (HepG2). Cytotoxicity test of the hydrogels using L929 cells confirmed their good cytocompatibility. Together, these pH-responsive self-healing injectable hydrogels are excellent candidates as drug delivery vehicles for liver cancer treatment.Statement of SignificancepH-responsive drug delivery system could release drug efficiently in targeted acid environment and minimalize the amount of drug release in normal physiological environment. pH-sensitive injectable hydrogels as smart anti-cancer drug delivery carriers show great potential application for cancer therapy. The hydrogels with self-healing property could prolong their lifetime during implantation and provide the advantage of minimally invasive surgery and high drug-loading ratio. This work reported the design of a series of pH-responsive self-healing injectable hydrogels based on N-carboxyethyl chitosan synthesized in aqueous solution and dibenzaldehyde-terminated poly(ethylene glycol) via a green approach, and demonstrated their potential as intelligent delivery vehicle of doxorubicin for hepatocellular carcinoma therapy via the pH-responsive nature of dynamic Schiff base.

Graphical abstract

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Interleukin-13 conjugated quantum dots for identification of glioma initiating cells and their extracellular vesicles

Publication date: Available online 3 June 2017
Source:Acta Biomaterialia
Author(s): A.B. Madhankumar, Oliver Mrowczynski, Suhag Patel, Cody Weston, Brad Zacharia, Michael Glantz, Christopher Siedlecki, Lichong Xu, James R. Connor
Cadmium selenide (CdSe) based quantum dots modified with polyethylene glycol and chemically linked to interleukin-13 (IL13) were prepared with the aim of identifying the high affinity receptor (IL13Rα2) which is expressed in glioma stem cells and exosomes secreted by these cancer stem cells. IL13 conjugated quantum dots (IL13QD) were thoroughly characterized for their physicochemical properties including particle size and surface morphology. Furthermore, the specific binding of the IL13QD to glioma cells and to glioma stem cells (GSC) was verified using a competitive binding study. The exosomes were isolated from the GSC conditioned medium and the expression of IL13Rα2 in the GSC and exosomes was verified. The binding property of IL13QD to the tumor associated exosomes was initially confirmed by transmission electron microscopy. The force of attraction between the quantum dots and U251 glioma cells and the exosomes was investigated by atomic force microscopy, which indicated a higher force of binding interaction between the IL13QD and IL13Rα2 expressing glioma cells and exosomes secreted by glioma stem cells. Flow cytometry of the IL13QD and exosomes from the culture media and cerebrospinal fluid (CSF) of patients with glioma tumors indicated a distinctly populated complex pattern different from that of non-targeted quantum dots and bovine serum albumin (BSA) conjugated quantum dots confirming specific binding potential of the IL13QD to the tumor associated exosomes. The results of this study demonstrate that IL13QD can serve as an ex vivo marker for glioma stem cells and exosomes that can inform diagnosis and prognosis of patients harboring malignant disease.Statement of significanceFunctionalized quantum dots are flexible semiconductor nanomaterials which have an immense application in biomedical research. In particular, when they are functionalized with biomolecules like proteins or antibodies, they have the specialized ability to detect the expression of receptors and antigens in cells and tissues. In this study we designed a cytokine (interleukin-13) functionalized quantum dot to detect a cancer associated receptor expressed in cancer stem cells and the extracellular vesicles (exosomes) secreted by the cancer cells themselves. The binding pattern of these cytokine modified quantum dots to the cancer stem cells and exosomes alters the physical properties of the complex in the fixed and suspended form. This altered binding pattern can be monitored by a variety of techniques, including transmission electron microscopy, atomic force microscopy and flow cytometry, and subsequent characterization of this quantum dot binding profile provides useful data that can be utilized as a fingerprint to detect cancer disease progression. This type of functionalized quantum dot fingerprint is especially useful for invasive cancers including brain and other metastatic cancers and may allow for earlier detection of disease progression or recurrence, thus saving the lives of patients suffering from this devastating disease.

Graphical abstract

http://ift.tt/2rlItr0

Comparison of dimensional accuracy of conventionally and digitally manufactured intracoronal restorations

Publication date: Available online 2 June 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Reza Eftekhar Ashtiani, Leila Nasiri Khanlar, Minoo Mahshid, Alireza Moshaverinia
Statement of problemAdvances have been made in digital dentistry for the fabrication of dental prostheses, but evidence regarding the efficacy of digital techniques for the fabrication of intracoronal restorations is lacking.PurposeThe purpose of this in vitro study was to compare the dimensional accuracy of intracoronal restorations fabricated with digital and conventional techniques.Material and methodsA sound mandibular molar tooth received a standard onlay preparation, and onlays were fabricated with 1 of 3 fabrication techniques. In group CC, the onlays were made after conventional impression and conventional fabrication of a resin pattern. In group CP, the onlays were made after conventional impression and 3-dimensional (3D) printing of the pattern. In group IP, the onlays were made after intraoral scanning, and 3D printing produced the resin pattern. Ten specimens in each group (N=30) were evaluated. Glass-ceramic restorations were fabricated using the press technique. The replica technique was used to assess the marginal fit. Each replica was assessed at 8 points. One-way ANOVA was used to compare the marginal discrepancy among the 3 groups. The Tukey honest significant differences test was applied for pairwise comparisons of the groups (α=.05).ResultsNo significant differences were noted in the marginal discrepancy at the gingival margin among the 3 groups (P=.342), but significant differences were noted among the 3 groups in the pulpal (P=.025) and lingual (P=.031) areas. Comparison of the absolute discrepancy among the 3 groups revealed that only groups CC and CP were significantly different (P=.020) from each other.ConclusionsWithin the limitations of this in vitro study, the conventional method yielded more accuracy than the 3D printing method, and no differences were found between the methods which used the 3D printer (groups CP and IP).



http://ift.tt/2s3rzyC

Retrieval as a Fast Route to Memory Consolidation

Publication date: Available online 2 June 2017
Source:Trends in Cognitive Sciences
Author(s): James W. Antony, Catarina S. Ferreira, Kenneth A. Norman, Maria Wimber
Retrieval-mediated learning is a powerful way to make memories last, but its neurocognitive mechanisms remain unclear. We propose that retrieval acts as a rapid consolidation event, supporting the creation of adaptive hippocampal–neocortical representations via the 'online' reactivation of associative information. We describe parallels between online retrieval and offline consolidation and offer testable predictions for future research.



http://ift.tt/2qQuxSe

Intraoperative 1-Hour Electrical Nerve Stimulation Enhances Outcomes of Nerve–Muscle-Endplate Band Grafting Technique for Muscle Reinnervation

J reconstr Microsurg
DOI: 10.1055/s-0037-1602824

Background Increasing evidence suggests that 1-hour electrical nerve stimulation during surgery improves nerve regeneration and functional recovery. However, it remains unknown if this approach has beneficial effects on the outcomes of our recently developed nerve–muscle-endplate band grafting-native motor zone (NMEG-NMZ) technique for muscle reinnervation. Methods In this study, NMEG-NMZ transplantation was performed in a rat model. The right sternomastoid muscle was experimentally denervated and immediately reinnervated by implanting a NMEG harvested from the ipsilateral sternohyoid (SH) muscle into the NMZ of the target muscle. Before implantation of the NMEG, the SH nerve branch innervating the NMEG was subjected to intraoperative 1-hour continuous electrical stimulation (20 Hz). Three months after surgery, the degree of functional recovery was evaluated with muscle force measurement and the extent of nerve regeneration and endplate reinnervation was examined using histological and immunohistochemical methods. Results A combination of NMEG-NMZ with electrical nerve stimulation resulted in a greater degree of functional recovery than the NMEG-NMZ alone. The mean muscle force of the treated muscles was 90% of the contralateral control. The muscle mass was recovered up to 90% of the control. The mean number and percentage of area of the regenerated axons in the treated muscles was computed to be 81 and 84% of the control muscles, respectively. On average, 83% of the denervated endplates in the treated muscles were reinnervated by regenerated axons. Conclusion Intraoperative brief nerve stimulation promotes nerve regeneration, endplate reinnervation, and functional recovery of the muscles reinnervated with NMEG-NMZ technique.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Enhancement of sorption capacity of cocoa shell biomass modified with non-thermal plasma for removal of both cationic and anionic dyes from aqueous solution

Abstract

Removal of cationic dye, Azur II, and anionic dye, Reactive Red 2 (RR-2) from aqueous solutions, has been successfully achieved by using a modified agricultural biomaterial waste: cocoa shell husk (Theobroma cacao) treated by gliding arc plasma (CPHP). The biomass in its natural form CPHN and modified form CPHP was characterized by infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and point of zero charge (pH_pzc). Experimental variables such as initial pH, contact time, and temperature were optimized for adsorptive characteristics of CPHN and CPHP. The results show that the removal of the Azur II dye was favorable in the basic pH region (pH 10) while the Reactive Red 2 dye was favorable in the acidic pH region (pH 2). The minimum equilibrium time for Azur II and RR-2 dye was obtained after 40 and 240 min, respectively. The adsorption kinetics and isotherm data obtained were best described by a pseudo-second-order kinetic rate model and a combination of Langmuir-Freundlich isotherm models. This work indicates that the plasma-treated raw materials are good alternative multi-purpose sorbents for the removal of many coexisting pollutants from aqueous solutions.

http://ift.tt/2sokPsh

Assessing energy efficiencies, economy, and global warming potential (GWP) effects of major crop production systems in Iran: a case study in East Azerbaijan province

Abstract

Efficient use of energy in farming systems is one of the most important implications for decreasing greenhouse gas (GHG) emissions and mitigating global warming (GW). This paper describes the energy use patterns, analyze the economics, and report global warming potential effects of major crop production systems in East Azerbaijan province, Iran. For this purpose, 110 farmers whose main activity was major crop production in the region, including wheat, barley, carrot, tomato, onion, potato, alfalfa, corn silage, canola, and saffron, were surveyed. Some other data was obtained from the Ministry of Agriculture Jihad of Iran. Results showed that, in terms of total energy input, onion (87,556 Mj ha⁻¹) and potato (80,869 Mj ha⁻¹) production systems were more energy-intensive than other crops. Among the studied crops, the highest values of net return (6563.8 $ ha⁻¹) and benefit/cost ratio (1.95) were related to carrot and corn silage production systems, respectively. Studies have also shown that onion and saffron production systems emit the highest (5332.6 kg CO2eq ha⁻¹) and lowest (646.24 kg CO₂eq ha⁻¹) CO₂ eq. emission, respectively. When it was averaged across crops, diesel fuel accounted for the greatest GHG contribution with 43% of the total, followed by electric power (28%) and nitrogen fertilizer (21%). In the present study, eco-efficiency was calculated as a ratio of the gross production value and global warming potential effect for the studied crops. Out of all the studied crops, the highest values of eco-efficiency were calculated to be 8.65 $ kg CO₂eq⁻¹ for the saffron production system followed by the carrot (3.65 $ kg CO₂eq⁻¹) production. Generally, from the aspect of energy balance and use efficiency, the alfalfa production system was the best; however, from an economical point of view, the carrot production system was better than the other crops.

http://ift.tt/2rP5zI0

Pseudocontingencies and Choice Behavior in Probabilistic Environments With Context-Dependent Outcomes.

Author: Meiser, Thorsten; Rummel, Jan; Fleig, Hanna

DOI: 10.1037/xlm0000432

Publication Date: POST AUTHOR CORRECTIONS, 1 June 2017

http://ift.tt/2qJRoj5

In sickness and in health: The many roles of the minichromosome maintenance proteins

Publication date: Available online 1 June 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Henrique Neves, Hang Fai Kwok
Cell division is a tightly-regulated process that involves the contribution of a large number of proteins. Before they are able to undergo mitosis, cells must first synthesize new DNA, effectively duplicating their genome. This occurs during what is called the S-phase and requires a fine control in order to avoid replication errors.The synthesis of new DNA takes place in origin sites, specific locations in the genome where the double strands of DNA are unwound and separated, allowing for the binding of proteins and complexes that will build new strands of the genomic material, using the existent ones as molds, in what is referred to as semi-conservative process.While the overall flow of the DNA synthesis process has been elucidated, its regulation and the exact role of its contributors are not yet entirely understood. It is believed that the Minichromosome Maintenance (MCM) proteins occupy a central role in DNA synthesis. While the functions of each protein in this family vary, they are believed to have helicase and proofreading activity.Given their contribution to a central aspect in the conservation of life, further studies have been launched to understand how the MCM proteins may affect or be affected by pathologies involving cell division, namely neoplasia.In this review, we aim to give an overview on the members of the MCM family, what their functions are in a healthy environment and how they are altered in a variety of pathologies.



http://ift.tt/2rP70WW

Light-emitting diode modulates carbohydrate metabolism by pancreatic duct regeneration

Abstract

Pancreatic lesions can produce metabolic disorders. Light-emitting diode (LED) has been used as a safe and effective phototherapy for cell proliferation and regeneration. We investigate the effects of phototherapy using LED irradiation on the pancreas after the injection of streptozotocin (STZ) to induce experimental diabetes and evaluate that the β cells can regenerate in the pancreas in an in vivo model and observe its implications on the control of carbohydrate metabolism. Twenty Wistar rats were randomized into three groups: non-diabetic control, diabetic control, and diabetic treated with LED. Except for the non-diabetic control group, all were induced to diabetes type I by streptozotocin injection. Treated groups were irradiated by LED: λ = 805 nm; 40 mW, 22 s; spot diameter 5 mm, spot area 0.196 cm², 0.88 J that it was applied on pancreas projection area for 5 consecutive days and monitored for 30 days. Diabetic group treated with LED showed regeneration of islets and ducts (p = 0.001) on the pancreas. Intraperitoneal insulin tolerance test showed differences between the diabetic control and diabetic treated groups (p = 0.03). In diabetic control group, the hepatic glycogen content was 296% lower when compared with diabetic treated with LED. Furthermore, in the diabetic control group, the glycogen content of the gastrocnemius muscle was 706% smaller when compared with diabetic treated with LED. This study shows that LED was able to modify morphological and metabolic features and also altered carbohydrate metabolism on irradiated pancreas in experimental model of diabetes.

http://ift.tt/2rP0rn9

Immunization of Tg-APPswe/PSEN1dE9 mice with Aβ3-10-KLH vaccine prevents synaptic deficits of Alzheimer’s disease

Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): Yuan Meng, Li Ding, HuiYi Zhang, WenChao Yin, Yi Yan, YunPeng Cao
The amyloid cascade hypothesis is widely accepted by researchers as the mechanism of Alzheimer's disease. Active immunization to eliminate Aβ depositions has been used in preclinical and clinical studies. Aβ3-10-KLH is a vaccine of the Aβ3-10 peptide combined with keyhole limpet hemocyanin (KLH). We immunized 2.5-month-old Tg-APPswe/PSEN1dE9 mice with Aβ3-10-KLH peptide and Aβ1-42 peptide to eliminate Aβ deposits in the brains of these transgenic mice. The results of immunohistochemical staining and transmission electron microscopy detection indicated that our new vaccine was more advantageous in protecting synaptic function and structure than the Aβ1-42 peptide. Aβ3-10-KLH peptide is an effective vaccine in the treatment of Alzheimer's disease.



http://ift.tt/2rPdncF

Präoperative Evaluation erwachsener Patienten vor elektiven, nicht herz-thoraxchirurgischen Eingriffen1*

Anästhesiol Intensivmed Notfallmed Schmerzther
DOI: 10.1055/s-0043-111784

Die präoperative Anamnese und körperliche Untersuchung sind anerkannter Standard bei der Risikoevaluation von Patienten vor elektiven chirurgischen Eingriffen. Ob und unter welchen Umständen technische Voruntersuchungen dazu beitragen können, das perioperative Risiko zu reduzieren, ist bislang nur unzureichend untersucht. Auch besteht unter Anästhesisten, Chirurgen und Internisten vielfach Unsicherheit im perioperativen Umgang mit der Dauermedikation. Die deutschen wissenschaftlichen Fachgesellschaften für Anästhesiologie und Intensivmedizin (DGAI), Chirurgie (DGCH) und Innere Medizin (DGIM) haben daher eine gemeinsame Empfehlung zur präoperativen Evaluation erwachsener Patienten vor elektiven, nicht herz-thoraxchirurgischen Eingriffen erarbeitet und erstmals im Jahr 2010 publiziert. Die vorliegende Fassung ist eine Überarbeitung der Stellungnahme von 2010 unter Einbeziehung der seither publizierten Literatur sowie von aktuellen Leitlinien internationaler Fachgesellschaften. Zunächst werden die allgemeinen Prinzipien der präoperativen Evaluation dargestellt (Teil A). Das Vorgehen bei Patienten mit bekannten oder vermuteten kardiovaskulären Vorerkrankungen wird gesondert betrachtet (Teil B: „Erweiterte kardiale Diagnostik"). Abschließend wird der perioperative Umgang mit der Dauermedikation diskutiert (Teil C). Die vorgestellten Konzepte stellen fachübergreifende Empfehlungen dar, die ein strukturiertes und gemeinsames Vorgehen ermöglichen sollen. Ihr Ziel ist es, durch transparente und verbindliche Absprachen eine hohe Patientenorientierung unter Vermeidung unnötiger Voruntersuchungen zu gewährleisten, präoperative Untersuchungsabläufe zu verkürzen sowie letztlich Kosten zu reduzieren. Die gemeinsamen Empfehlungen von DGAI, DGCH und DGIM spiegeln den gegenwärtigen Kenntnisstand, aber auch die Meinungen von Experten wider, da nicht für jede Fragestellung wissenschaftliche Evidenz besteht. Daher werden eine regelmäßige Überprüfung und Aktualisierung der Empfehlungen erfolgen, sobald gesicherte neue Erkenntnisse vorliegen.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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BRAF Mutations as Predictive Biomarker for Response to Anti-EGFR Monoclonal Antibodies

Recently, the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) recommended that patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer could be treated with anti-EGFR monoclonal antibodies (mAbs) cetuximab and panitumumab only in absence of Rat-Sarcoma (RAS) mutations. In addition to the previously established biomarker Kirsten rat sarcoma viral oncogene homolog (KRAS) exon 2, cumulative evidence also shows that patients whose tumors harbor KRAS exons 3 or 4 and neuroblastoma rat-sarcoma viral oncogene homolog (NRAS) exons 2, 3, and 4 mutations are found unlikely to benefit from anti-EGFR treatment.

In line with the resistance of RAS mutated (mt) tumors, treatment response in BRAFmt tumors may also be altered given their important role in the EGFR signaling pathway. However, BRAF is not recommended as predictive biomarker yet because the evidence for the impact of BRAF mutations on treatment outcome is considered insufficient.

This article summarizes the evidence for the impact of BRAF mutations on treatment outcome of anti-EGFR mAbs. Based on a review of literature, eight meta-analyses were included that consistently show that patients with BRAF mutations have a lack of treatment benefit of anti-EGFR mAbs. After discussing the quality and quantity of available evidence, we conclude that evidence is stronger than suggested by ESMO and ASCO. Additionally, we highlight that the quality of evidence for BRAF is even higher than for extended RAS as a biomarker. We therefore advise ESMO and ASCO to reconsider BRAF status as a predictive biomarker for response. The Oncologist 2017;22:1–9

Implications for Practice.

In metastatic colorectal cancer (mCRC), therapy with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab and panitumumab is indicated in absence of RAS mutations. Cumulative evidence shows that patients with BRAF mutations, who comprise 10% of the mCRC population, do not benefit from anti-EGFR-antibody treatment. Although guidelines state that evidence for BRAF as a predictive marker is insufficient, we highlight that the quality and quantity of evidence is higher than suggested. We therefore encourage the use of BRAF as a predictive marker in order to exclude patients from therapy for whom limited treatment benefit is expected.

http://ift.tt/2qKc4Yq

Oncology Drug Approvals: Evaluating Endpoints and Evidence in an Era of Breakthrough Therapies

http://ift.tt/2s3n4Ec

Inflammatory Arthritis: A Newly Recognized Adverse Event of Immune Checkpoint Blockade

http://ift.tt/2qJB9CY

Regarding "Oncology Drug Approvals: Evaluating Endpoints and Evidence in an Era of Breakthrough Therapies"

http://ift.tt/2s3xvr9

Thoracic Outlet Syndrome after the Nuss Procedure for Pectus Excavatum―Is It a Rare Complication?

The present study aims to elucidate the frequency of thoracic outlet syndrome after the Nuss procedure for pectus excavatum and the conditions in which thoracic outlet syndrome is likely to develop.

http://ift.tt/2qJChX6

Reliability and validity of Mamma Balance®: Novel software to assess the symmetry of the nipple-areola-complex position

It is important to achieve as much symmetry in the breasts as possible during breast reconstruction. The nipple-areola complex (NAC) position is an important component of a breast appearance, and it critically affects the aesthetic outcome of surgery. Mamma Balance® (MB) (Medic Engineering K.K, ver. 1.0.3) can automatically calculate and assess the degree of the NAC position's symmetry with one continuous variable. The purpose of this study was to evaluate the reliability and validity of this software to assess the NAC's symmetry.

http://ift.tt/2s3cwF8

An objective assessment of Botulinum toxin type A injection in the treatment of post facial palsy synkinesis and hyperkinesis using the Synkinesis Assessment Questionnaire (SAQ)

The aim of this study is to provide reliable and valid evidence that Botulinum toxin (BTX-A) is a successful treatment for facial synkinesis in facial palsy using the synkinesis assessment questionnaire tool (SAQ). 51 patients completed questionnaires pre and post BTX-A treatment over 103 cycles of treatment. Each patient was individually assessed and then treated according to their presenting symptoms with a dosage in each injection site of between 0.5 to 5 U of BTX-A. A two-tailed, paired samples t-test was used to compare the scores for each question before and after treatment.

http://ift.tt/2qJYvrO

Impact of adjuvant anti-estrogen therapies (tamoxifen and aromatase inhibitors) on perioperative outcomes of breast reconstruction

Hormone (anti-estrogen) therapy (HT) plays a major role in hormone receptor-positive breast cancer management. The latest guidelines propose to extend adjuvant treatment duration from 5 to 10 years. The link between HT and thromboembolic or microvascular complications during breast reconstruction has been investigated. However, while estrogens play a crucial role in skin healing, no study has assessed the impact of tamoxifen or aromatase inhibitors on other postoperative complications, including wound healing complications.

http://ift.tt/2s306gm

Refining the Extended Circumflex Scapular Flap for Neck Burn Reconstruction: A 30-Year Experience

Neck burn sequelae remain a major challenge for the reconstructive surgeon. To achieve satisfactory functional and aesthetic results, the anterior neck aesthetic unit must be covered as a single unit. In cases where free flaps are required, harvesting a flap of sufficient size can cause major donor site morbidity. In 1994, we published our favorable 6-year experience reconstructing neck burn sequelae with an Extended Circumflex Scapular Flap (ECSF). We have since made several modifications to the technique that improve long-term functional and aesthetic results.

http://ift.tt/2s3tKC3

Donor Site Morbidity in DIEP Free Flap Breast Reconstructions: A Comparison of Unilateral, Bilateral, and Bipedicled Surgical Procedure Types

The use of abdominal tissue in post-mastectomy autologous breast reconstruction is a popular choice among reconstructive surgeons. This is the first study to evaluate donor complications comparing unilateral, bilateral and bipedicled DIEP breast reconstructions.

http://ift.tt/2qKantO

The Indian Nose: An anthropometric analysis

Anthropometric measurements of nose are of great importance in planning aesthetic nasal surgery. Abundant literature is available on anthropometric analysis of Caucasians and Orientals, without similar references on Indian nose and its regional differences. Thus, we conducted a descriptive cross sectional epidemiological study of one thousand volunteers, with equal number of subjects derived from five geographic groups namely North; Central; West; South; and Himalayan region to determine differences in nasal morphology of Indian population and amongst its various regions.

http://ift.tt/2s2XnDO

Incidence and Risk Factors for Venous Thromboembolism in Bilateral Breast Reduction Surgery: An Analysis of the National Surgical Quality Improvement Program

Risk of venous thromboembolism (VTE) in patients undergoing bilateral breast reduction surgery remains unknown. Aim of this study was to determine VTE incidence and risk factors in this patient cohort.

http://ift.tt/2qK7b1o

Historical and future emission of hazardous air pollutants (HAPs) from gas-fired combustion in Beijing, China

Abstract

The consumption of natural gas in Beijing has increased in the past decade due to energy structure adjustments and air pollution abatement. In this study, an integrated emission inventory of hazardous air pollutants (HAPs) emitted from gas-fired combustion in Beijing was developed for the period from 2000 to 2014 using a technology-based approach. Future emission trends were projected through 2030 based on current energy-related and emission control policies. We found that emissions of primary HAPs exhibited an increasing trend with the rapid increase in natural gas consumption. Our estimates indicated that the total emissions of NO_X , particulate matter (PM)₁₀, PM_2.5, CO, VOCs, SO₂, black carbon, Pb, Cd, Hg, As, Cr, Cu, Ni, Zn, polychlorinated dibenzo-p-dioxins and dibenzofurans, and benzo[a]pyrene from gas-fired combustion in Beijing were approximately 22,422 t, 1042 t, 781 t, 19,097 t, 653 t, 82 t, 19 t, 0.6 kg, 0.1 kg, 43 kg, 52 kg, 0.3 kg, 0.03 kg, 4.3 kg, 0.6 kg, 216 μg, and 242 g, respectively, in 2014. To mitigate the associated air pollution and health risks caused by gas-fired combustion, stricter emission standards must be established. Additionally, combustion optimization and flue gas purification system could be used for lowering NO_X emissions from gas-fired combustion, and gas-fired facilities should be continuously monitored based on emission limits.

Graphical abstract

Spatial distribution and typical live photos of gas-fired boiler in Beijing

http://ift.tt/2rOtW8G

The pesticide chlordecone is trapped in the tortuous mesoporosity of allophane clays

Abstract

Some volcanic soils like andosols contain short-range order nanoclays (allophane) which build aggregates with a tortuous and fractal microstructure. The aim of the work was to study the influence of the microstructure and mesoporosity of the allophane aggregates on the pesticide chlordecone retention in soils. Our study shows that the allophane microstructure favors pollutants accumulation and sequestration in soils. We put forth the importance of the mesoporous microstructure of the allophane aggregates for pollutant trapping in andosols. We show that the soil contamination increases with the allophane content but also with the mesopore volume, the tortuosity, and the size of the fractal aggregate. Moreover, the pore structure of the allophane aggregates at nanoscale favors the pesticide retention. The fractal and tortuous aggregates of nanoparticles play the role of nanolabyrinths. It is suggested that chlordecone storage in allophanic soils could be the result of the low transport properties (permeability and diffusion) in the allophane aggregates. The poor accessibility to the pesticide trapped in the mesopore of allophane aggregates could explain the lower pollutant release in the environment.

http://ift.tt/2rtQPuV

Resource recovery of food waste through continuous thermophilic in-vessel composting

Abstract

In the Kingdom of Saudi Arabia (KSA) and Gulf region, a very small amount of municipal solid waste (MSW) is treated for compost production. The produced compost through traditional methods of compost piles and trenches does not coincide with the international standards of compost quality. Therefore, in this study, a continuous thermophilic composting (CTC) method is introduced as a novel and efficient technique for treating food waste into a quality compost in a short period of time. The quality of the compost was examined by degradation rates of organic matter (OM), changes in total carbon (TC), ash contents, pH, dynamics in ammonium nitrogen (NH₄-N) and nitrate nitrogen (NO₃-N), and nitrification index (NI). The results showed that thermophilic treatment at 60 °C increased the pH of the substrate and promoted degradation and mineralization process. After 30 days of composting, the degree of OM degradation was increased by 43.26 and 19.66%, NH₄-N by 65.22 and 25.23%, and NO₃-N by 44.76 and 40.05% as compared to runs treated at 25 and 40 °C, respectively. The stability of the compost was attained after 30 to 45 days with quality better than the compost that was stabilized after 60 days of the experiment under mesophilic treatment (25 °C). The final compost also showed stability at room temperature, confirming the rapid degradation and maturation of food waste after thermophilic treatment. Moreover, the quality of produced compost is in line with the compost quality standard of United States (US), California, Germany, and Austria. Hence, CTC can be implemented as a novel method for rapid decomposition of food waste into a stable organic fertilizer in the given hot climatic conditions of KSA and other Gulf countries with a total net saving of around US $70.72 million per year.

http://ift.tt/2qLbaPf

Heat and mass transfer characteristics of carbon nanotube nanofluids: A review

Publication date: December 2017
Source:Renewable and Sustainable Energy Reviews, Volume 80
Author(s): Muhammad Noor Afiq Witri Muhammad Yazid, Nor Azwadi Che Sidik, Wira Jazair Yahya
The pursuit of superior working fluids for heat and mass transfer systems in the industry is on the rise, inspired by not only to maximize revenue but also to accommodate heat dissipation or chemical separation under extreme conditions. The addition of a small amount of nanoparticle, a product called nanofluid, has been initiated over the last decade. In particular, researchers have employed carbon nanotubes (CNTs) into conventional fluids as their preferred nanoparticles due to the merits of having a remarkable thermal conductivity compared to other nanoparticles. Here, we present a comprehensive and up to date review of this incredible fluid being applied in various heat transfer (convective and boiling) and mass transfer systems such as heat exchangers and separators. Other critical parameters associated with the practicality of the CNT nanofluids such as pumping power and efficiency are also discussed. We surveyed a remarkable range of results of some of the heat and mass transfer studies that strongly depend on the inherent CNT nanofluid characteristics and operating conditions such as CNT treatment, size, concentration, Reynolds number, and so on. A major conclusion that can be drawn from this review is the significantly higher heat transfer coefficient at lower pressure drop or pumping power of the CNT nanofluid compared to other nanofluids, which implied better thermal performance of the heat transfer system. Besides that, the concentration of CNT is the influential factor to achieve optimum boiling heat transfer while the mass transfer performance of the CNT nanofluid is moderately good against other nanofluids. Additionally, CNT treatment using covalent functionalization is crucial for the overall stability and performance of the CNT nanofluid. However, several issues that inhibit their widespread use such as possible corrosion-erosion in systems, lack of risk assessments, and high cost of CNT nanofluid must be thoroughly addressed in future studies.



http://ift.tt/2sznkHw

Determination of trace metals in TSP and PM2.5 materials collected in the Metropolitan Area of Monterrey, Mexico: A characterization study by XPS, ICP-AES and SEM-EDS

Publication date: 1 November 2017
Source:Atmospheric Research, Volume 196
Author(s): Lucy T. González, F.E. Longoria Rodríguez, M. Sánchez-Domínguez, Aleyda Cavazos, C. Leyva-Porras, L.G. Silva-Vidaurri, Karim Acuña Askar, B.I. Kharissov, J.F. Villarreal Chiu, J.M. Alfaro Barbosa
The concentration levels of trace metals of toxicological importance were evaluated in the total suspended particles (TSP) and particulate matter smaller than 2.5μm (PM2.5) collected in the Metropolitan Area of Monterrey (MAM) in Mexico. Samples were characterized by inductively coupled plasma atomic emission spectroscopy (ICP-AES), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy with an energy-dispersive spectroscopy system (SEM-EDS). In addition, the data were statistically treated by the methodology of Pearson Correlation (PC) and Principal Components Analysis (PCA) to identify the possible emitting sources. Surface analysis of the particulate matter (PM) by XPS revealed that the most abundant elements were Ca, Al, Na, Zn, Cu and Mg. The deconvolution of the Ca2p, Zn2p and Cu2p signals showed that the main contributors were CaCO3, ZnO and Cu/Cu2O, respectively. The bulk analysis of the PM by ICP-AES showed Fe, Cu and Zn as the most abundant elements. Fe-rich particles presented two different morphologies: the prismatic particles were associated with a natural origin, while the spherical particles with anthropogenic sources. The Zn and Cu were predominantly observed in the sampling stations with high vehicular traffic, and the emitting sources were associated with the burning of fuels from automobiles and the wear of the tires and brakes. The highest concentration of Pb was detected in the sampling station located near the industrial zones, and its cause was associated with the ceramic and glass industries, the burning of fuel oil in power plants and the production of lead-based batteries for automobiles.



http://ift.tt/2rB1hD8

Distribution of organic and inorganic substances in the sediments of the “Great Bačka Canal”, a European environmental hotspot

Publication date: 1 December 2017
Source:Science of The Total Environment, Volumes 601–602
Author(s): Dejan Krčmar, Miloš Dubovina, Nenad Grba, Vesna Pešić, Malcolm Watson, Jelena Tričković, Božo Dalmacija
The Great Bačka Canal in Serbia is one of the most polluted waterways in Europe. Surface sediments from the canal were subject to systematic annual monitoring between 2007 and 2014 at 33 representative sampling sites. Eight heavy metals (Ni, Zn, Cd, Cr, Cu, Pb, As and Hg), mineral oils, 16 EPA PAHs and selected pesticides and polychlorinated biphenyls (PCB) were monitored.This study aims to evaluate the quality of the sediments and determine the potential ecological risks in order to establish pollutants of interest. The spatial and temporal influence of different and intense sources of pollution are investigated.The analysis includes multivariate statistical methods (factor analysis of principal component analysis (PCA/FA)) in order to assess the extent and origin (anthropogenic or natural, geogenic sources) of the contaminants detected in the sediment samples and the risks the present to the environment.Various sources, predominantly the food industry, were found to be responsible for most of the contamination by Cd, Cu, Cr and Zn, the mineral oils and PAHs (dibenzo[a,h]anthracene and benzo[a]pyrene contributed 86.0% of the total between 2007 and 2014). In contrast, the As was convincingly of geogenic origin, and the Hg, Pb and Ni present exhibit dual origins. Cd and Cu significantly raise the levels of potential ecological risk at all sampling locations, demonstrating the long-term effects of bioaccumulation and biomagnification.Significantly, the results of this work indicate that Cu, As and dibenzo[a,h]anthracene should be added to the EU watch list of emerging contaminants. This is supported by significant national and similar environmental data from countries in the region.

Graphical abstract

http://ift.tt/2szcwcH

Performance of Raphidocelis subcapitata exposed to heavy metal mixtures

Publication date: 1 December 2017
Source:Science of The Total Environment, Volumes 601–602
Author(s): Nora Expósito, Vikas Kumar, Jordi Sierra, Marta Schuhmacher, Gemma Giménez Papiol
Microalgae growth inhibition assays are candidates for referent ecotoxicological assays, and are a fundamental part in the strategy to reduce the use of fish and other animal models in aquatic toxicology. In the present work, the performance of Raphidocelis subcapitata exposed to heavy metals following standardized growth inhibition assays has been assessed in three different scenarios: 1) dilutions of single heavy metals, 2) artificial mixture of heavy metals at similar levels than those found in natural rivers and, 3) natural samples containing known mixtures of contaminants (heavy metals). Chemical speciation of heavy metals has been estimated with Eh-pH diagram and Visual MINTEQ software; heavy metal and free heavy metal ion concentrations were used as input data, together with microalgae growth inhibition, for Dr. Fit software. The final goal was to assess the suitability of the ecotoxicological test based on the growth inhibition of microalgae cultures, and the mathematic models based on these results, for regulatory and decision-making purposes.The toxicity of a given heavy metal is not only determined by its chemical speciation; other chemical and biological interaction play an important role in the final toxicity. Raphidocelis subcapitata 48h-h-EC50 for tested heavy metals (especially Cu and Zn) were in agreement with previous studies, when ion metal bioavailability was assumed to be 100%. Nevertheless, the calculated growth inhibition was not in agreement with the obtained inhibition when exposed to the artificial mixture of heavy metals or the natural sample. Interactions between heavy metal ions and the compounds of the culture media and/or the natural sample determine heavy metal bioavailability, and eventually their toxicity.More research is needed for facing the challenge posed by pollutant mixtures as they are present in natural environments, and make microalgae-based assays suitable for pollution management and regulatory purposes.

Graphical abstract

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In-situ growth of ZIF-8 on layered double hydroxide: Effect of Zn/Al molar ratios on their structural, morphological and adsorption properties

Publication date: 1 November 2017
Source:Journal of Colloid and Interface Science, Volume 505
Author(s): Yingli Yang, Xinlong Yan, Xiaoyan Hu, Rui Feng, Min Zhou
In-situ growth of Zeolite imidazolate frameworks (ZIFs) on layered double hydroxides (LDHs) to form porous composites is a promising and challenging strategy to develop materials for separation application. Herein, the Zn-Al LDH with different Zn/Al molar ratios was prepared and used as matrix for the growth of ZIF-8 on its surface. The resulting composites were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), N2 physisorption, thermogravimetric (TG), scanning electron microscope (SEM) and elemental analysis followed by testing for As^V removal from aqueous solution. Results showed that ZIF-8 could form on the surface of LDH with different Zn/Al molar ratios. At low Zn/Al molar ratios, the morphology and surface area of the ZIF/LDH composites and the content of ZIF-8 in the composites were little affected by the Zn/Al molar ratio. With increasing Zn/Al molar ratio, ZIF-8/LDH exhibited a lower surface area, which resulted from reduced content of ZIF-8 caused by impurities generated in the LDH matrix. All ZIF-8/LDH samples showed high As^V adsorption capacity, which was significantly higher than that of pure LDH or ZIF-8.

Graphical abstract

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Zinc-doping enhanced cadmium sulfide electrochemiluminescence behavior based on Au-Cu alloy nanocrystals quenching for insulin detection

Publication date: 15 November 2017
Source:Biosensors and Bioelectronics, Volume 97
Author(s): Wenjuan Zhu, Chao Wang, Xiaojian Li, Malik Saddam Khan, Xu Sun, Hongmin Ma, Dawei Fan, Qin Wei
Novel and sensitive sandwich-type electrochemiluminescence (ECL) immunosensor was fabricated for insulin detection. Au-ZnCd14S combined nitrogen doping mesoporous carbons (Au-ZnCd14S/NH2-NMCs) acted as sensing platform and Au-Cu alloy nanocrystals were employed as labels to quench the ECL of Au-ZnCd14S/NH2-NMCs. Zinc-doping promoted the ECL behavior of CdS nanocrystals, with the best ECL emission obtained when the molar ratio of Zn/Cd was 1:14. Simultaneously, the modification of gold nanoparticles (Au NPs) and combination with NH2-NMC further enhanced the ECL emission of ZnCd14S due to its excellent conductivity and large specific surface area, which is desirable for the immunosensor construction. Au-Cu alloy nanocrystals were employed in the ECL system of ZnCd14S/K2S2O8 triggering ECL quenching effects. The ECL spectra of ZnCd14S, acting as the energy donor, exhibited well overlaps with the absorption band of Au-Cu alloy nanocrystals which acted as the energy acceptor, leading to an effective ECL resonance energy transfer (ECL-RET). On the basis of the ECL quenching effects, a sensitive ECL immunosensor for insulin detection was successfully constructed with a linear response range of insulin concentration from 0.1pg/mL to 30ng/mL and the limit of detection was calculated to be 0.03pg/mL (S/N = 3).



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Meal time behavior difficulties but not nutritional deficiencies correlate with sensory processing in children with autism spectrum disorder

Publication date: July 2017
Source:Research in Developmental Disabilities, Volume 66
Author(s): Yael Shmaya, Sigal Eilat-Adar, Yael Leitner, Shimon Reif, Lidia V. Gabis
BackgroundFood aversion and nutritional difficulties are common in children with autism spectrum disorder.AimTo compare meal time behavior of children with autism to their typically developing siblings and to typical controls and to examine if sensory profiles can predict meal time behavior or nutritional deficiencies in the autism group.



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Evaluating relationships among clinical working memory assessment and inattentive and hyperactive/impulsive behaviors in a community sample of children

Publication date: July 2017
Source:Research in Developmental Disabilities, Volume 66
Author(s): Alison M. Colbert, Jin Bo
ObjectiveThis study examined relationships between inattentive and hyperactive/impulsive behaviors and working memory (WM) functioning, and the utility of WM in categorical diagnosis of ADHD versus considering ADHD symptoms on a continuum.MethodThe study included 50 male children (6–12 years). Inattentive and hyperactive/impulsive behaviors were measured by the Conners-3P parent report, and WM was assessed by the WISC-IV WM subtests and Working Memory Index (WMI).ResultsWISC-IV Arithmetic and Digit Span Backward were most consistently related to inattentive behaviors, and no WM measure was consistently related to ADHD hyperactive/impulsive behaviors. Arithmetic and Digit Span Backward also accounted for significant variance in inattentive behaviors and ADHD inattention symptoms, respectively. Neither the WMI nor the Arithmetic subtest correctly classified individuals diagnosed with ADHD.ConclusionMeasurement of inattentive behaviors on a continuum best characterized relationships between symptoms of ADHD and WM functioning; WM functioning did not have utility in categorical understanding of ADHD.



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Gait analysis of young male patients diagnosed with primary bladder neck obstruction

Publication date: Available online 2 June 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Matteo Zago, Tommaso Ciro Camerota, Stefano Pisu, Daniela Ciprandi, Chiarella Sforza
Primary bladder neck obstruction (PBNO) represents an inappropriate or inadequate relaxation of the bladder neck during micturition. Based on the observation of an increased rate of postural imbalances in male patients with PBNO, we hypothesized a possible role of an unbalanced biomechanics of the pelvis on urethral sphincters activity. Our aim was to identify kinematic imbalances, usually disregarded in PBNO patients, and which could eventually be involved in the etiopathogenesis of the disease.Seven male adult patients (39.6±7.1 years) were recruited; in all patients, PBNO was suspected at bladder diary and uroflowmetry, and was endoscopically confirmed with urethroscopy. Participants gait was recorded with a motion capture system (BTS Spa, Italy) to obtain three-dimensional joint angles and gait parameters. Multivariate statistics based on a Principal Component model allowed to assess the similarity of patients' gait patterns with respect to control subjects.The main finding is that patients with PBNO showed significant discordance in the observations at the ankle and pelvis level. Additionally, 6/7 patients demonstrated altered trunk positions compared to normal curves. We suggest that the identified postural imbalances could represent the cause for an anomalous activation of pelvic floor muscles (hypertonia). The consequent urinary sphincters hypercontraction may be responsible for the development of voiding dysfunction in male patients with no significant morphological alterations.Results reinforced the hypothesis of an etiopathogenetic role of postural imbalances on primary bladder neck obstruction in male patients.



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Spectroscopic and molecular characterization of humic substances ( HS) from soils and sediments in a watershed: comparative study of HS chemical fractions and the origins

Abstract

Optical properties and molecular composition of humic substances (HS) can provide valuable information on the sources and the history of the associated biogeochemical processes. In this study, many well-known spectral and molecular characteristics were examined in eight different HS samples, which were extracted from soils and sediments located in a forested watershed, via two advanced tools including fluorescence excitation emission matrix-parallel factor analysis (EEM-PARAFAC) and high-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Two humic-like (C1 and C2) and one protein-like (C3) components were identified from EEM-PARAFAC. Irrespective of the origins, humic acid (HA) fractions were distinguished from fulvic acid (FA) fractions by the HS characteristics of specific UV absorbance (SUVA), the number of formulas, maximum fluorescence intensities of C1 and C2, condensed aromatics, tannins, and CHON, CHOS, and CHONS classes. In contrast, only five HS indices, including C3 intensity, H%, modified aromatic index (AI_mod), the percentages of carbohydrates, and unsaturated hydrocarbons, were found to be significant factors in discriminating between the two HS origins (i.e., soils and sediments). The ordination of the Bray-Curtis dissimilarity matrix further confirmed that the HS chemical fraction (i.e., HA or FA) was the more important factor to determine the measured HS characteristics than the HS origin. Our results provided an in-depth insight into the chemical and structural heterogeneity of bulk HS, which could be even beyond the differences observed along the two HS origins. This study also delivers a cautious message that the two operationally defined HS chemical fractions should be carefully considered in tracking the origins of different HS samples.

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Acute toxic effect of sewage effluent on the early life phase of an estuarine crab Scylla serrata

Abstract

The biological quality of secondary treated sewage effluent was evaluated using a toolbox approach, which combined a larval developmental bioassay and measurement of fecal indicator organisms. The zoea developmental toxicity of Scylla serrata from stage I to stage II was determined by exposing to a range of secondary treated sewage concentrations. Results indicated that the relative progress of zoea stage I to zoea stage II negatively correlated with increasing sewage concentrations. Data was analyzed statistically to determine lethal, median lethal, sublethal, low observed effect, and no observed effect concentrations. Water samples collected along the Buckingham canal discharge zone were also analyzed for its toxicity to the larval development. Fecal indicator organisms chosen to determine the water quality were E. coli, enterococci, C. perfrigens, and F+ coliphages. Concentrations of these fecal markers were determined in the raw influent, primary treated effluent, secondary treated effluent, and in four discharge zone sites. Data showed that this biological toolbox is helpful for providing baseline information on the effectiveness of the wastewater treatment and environmental health of the discharge zone.

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A Puzzle of Life: Crafting Ribosomal Subunits

Publication date: Available online 1 June 2017
Source:Trends in Biochemical Sciences
Author(s): Dieter Kressler, Ed Hurt, Jochen Baßler
The biogenesis of eukaryotic ribosomes is a complicated process during which the transcription, modification, folding, and processing of the rRNA is coupled with the ordered assembly of ∼80 ribosomal proteins (r-proteins). Ribosome synthesis is catalyzed and coordinated by more than 200 biogenesis factors as the preribosomal subunits acquire maturity on their path from the nucleolus to the cytoplasm. Several biogenesis factors also interconnect the progression of ribosome assembly with quality control of important domains, ensuring that only functional subunits engage in translation. With the recent visualization of several assembly intermediates by cryoelectron microscopy (cryo-EM), a structural view of ribosome assembly begins to emerge. In this review we integrate these first structural insights into an updated overview of the consecutive ribosome assembly steps.



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Monitoring Protein Folding Through High Pressure NMR Spectroscopy

Publication date: Available online 2 June 2017
Source:Progress in Nuclear Magnetic Resonance Spectroscopy
Author(s): Julien Roche, Catherine A. Royer, Christian Roumestand
High-pressure is a well-known perturbation method used to destabilize globular proteins. It is perfectly reversible, which is essential for a proper thermodynamic characterization of a protein equilibrium. In contrast to other perturbation methods such as heat or chemical denaturant that destabilize protein structures uniformly, pressure exerts local effects on regions or domains of a protein containing internal cavities. When combined with NMR spectroscopy, hydrostatic pressure offers the possibility to monitor at a residue level the structural transitions occurring upon unfolding and to determine the kinetic properties of the process. High-pressure NMR experiments can now be routinely performed, owing to the recent development of commercially available high-pressure sample cells. This review summarizes recent advances and some future directions of high-pressure NMR techniques for the characterization at atomic resolution of the energy landscape of protein folding.

Graphical abstract

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Saccharomyces cerevisiae-derived virus-like particle parvovirus B19 vaccine elicits binding and neutralizing antibodies in a mouse model for sickle cell disease

Publication date: 22 June 2017
Source:Vaccine, Volume 35, Issue 29
Author(s): Rhiannon R. Penkert, Neal S. Young, Sherri L. Surman, Robert E. Sealy, Jason Rosch, Philip R. Dormitzer, Ethan C. Settembre, Sumana Chandramouli, Susan Wong, Jane S. Hankins, Julia L. Hurwitz
Parvovirus B19 infections are typically mild in healthy individuals, but can be life threatening in individuals with sickle cell disease (SCD). A Saccharomyces cerevisiae-derived B19 VLP vaccine, now in pre-clinical development, is immunogenic in wild type mice when administered with the adjuvant MF59. Because SCD alters the immune response, we evaluated the efficacy of this vaccine in a mouse model for SCD. Vaccinated mice with SCD demonstrated similar binding and neutralizing antibody responses to those of heterozygous littermate controls following a prime-boost-boost regimen. Due to the lack of a mouse parvovirus B19 challenge model, we employed a natural mouse pathogen, Sendai virus, to evaluate SCD respiratory tract responses to infection. Normal mucosal and systemic antibody responses were observed in these mice. Results demonstrate that mice with SCD can respond to a VLP vaccine and to a respiratory virus challenge, encouraging rapid development of the B19 vaccine for patients with SCD.



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Semantic network analysis of vaccine sentiment in online social media

Publication date: 22 June 2017
Source:Vaccine, Volume 35, Issue 29
Author(s): Gloria J. Kang, Sinclair R. Ewing-Nelson, Lauren Mackey, James T. Schlitt, Achla Marathe, Kaja M. Abbas, Samarth Swarup
ObjectiveTo examine current vaccine sentiment on social media by constructing and analyzing semantic networks of vaccine information from highly shared websites of Twitter users in the United States; and to assist public health communication of vaccines.BackgroundVaccine hesitancy continues to contribute to suboptimal vaccination coverage in the United States, posing significant risk of disease outbreaks, yet remains poorly understood.MethodsWe constructed semantic networks of vaccine information from internet articles shared by Twitter users in the United States. We analyzed resulting network topology, compared semantic differences, and identified the most salient concepts within networks expressing positive, negative, and neutral vaccine sentiment.ResultsThe semantic network of positive vaccine sentiment demonstrated greater cohesiveness in discourse compared to the larger, less-connected network of negative vaccine sentiment. The positive sentiment network centered around parents and focused on communicating health risks and benefits, highlighting medical concepts such as measles, autism, HPV vaccine, vaccine-autism link, meningococcal disease, and MMR vaccine. In contrast, the negative network centered around children and focused on organizational bodies such as CDC, vaccine industry, doctors, mainstream media, pharmaceutical companies, and United States. The prevalence of negative vaccine sentiment was demonstrated through diverse messaging, framed around skepticism and distrust of government organizations that communicate scientific evidence supporting positive vaccine benefits.ConclusionSemantic network analysis of vaccine sentiment in online social media can enhance understanding of the scope and variability of current attitudes and beliefs toward vaccines. Our study synthesizes quantitative and qualitative evidence from an interdisciplinary approach to better understand complex drivers of vaccine hesitancy for public health communication, to improve vaccine confidence and vaccination coverage in the United States.



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Immune response to pneumococcal conjugate vaccine in patients with systemic vasculitis receiving standard of care therapy

Publication date: 22 June 2017
Source:Vaccine, Volume 35, Issue 29
Author(s): Per Nived, Johanna Nagel, Tore Saxne, Pierre Geborek, Göran Jönsson, Lillemor Skattum, Meliha C. Kapetanovic
AimTo study the effect of standard of care therapy on antibody response and functionality following immunization with 13-valent pneumococcal conjugate vaccine (PCV13) in patients with primary systemic vasculitis compared to healthy controls.Methods49 patients with vasculitis and 49 controls received a single dose (0.5ml) PCV13 intramuscularly. Ongoing treatments: azathioprine (AZA; n=11), cyclophosphamide (CYC; n=6), methotrexate (MTX; n=9), rituximab (n=3); anti-TNF (n=2), mycophenolate mofetil (n=2), prednisolone alone (n=15) and no active treatment (n=2). Specific antibody concentrations for serotypes 6B and 23F were determined using ELISA and opsonophagocytic activity (OPA) assay (23F) was performed, on serum samples taken immediately before and 4–6weeks after vaccination. Proportion of individuals with putative protective antibody concentration (≥1.0µg/mL) and positive antibody response (≥2-fold increase from prevaccination concentration) for both serotypes were calculated and groups were compared.ResultsAt baseline, 6 patients (12%) and 12 controls (24%) had protective antibody levels for both serotypes. After vaccination, antibodies increased for both serotypes in patients and controls (p<0.001), 32 patients (65%) and 35 controls (71%) reached protective level for 6B, and 32 patients (65%) and 37 controls (76%) for 23F. Compared to controls, patients had lower prevaccination geometric mean concentration (23F, p=0.01) and a numerical trend towards lower prevaccination level (6B) and postvaccination levels (both serotypes). Patients with prednisolone alone had lower prevaccination OPA (p<0.01) compared to controls. OPA increased after vaccination in both patients and controls (p<0.001), but improvement was better in controls (p=0.001). AZA, CYC or MTX, but not prednisolone alone, tended towards a lower proportion of patients reaching protective antibody levels (p=0.06), compared to controls.ConclusionsPneumococcal conjugate vaccine was safe and immunogenic in patients with established vasculitis. Treatment with DMARDs, mostly AZA, CYC and MTX but not systemic prednisolone may impair antibody response.Trial registration. ClinicalTrials.gov Identifier: NCT02240888. Registered 4 September, 2014



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Burden of vaccine-preventable pneumococcal disease in hospitalized adults: A Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) network study

Publication date: 22 June 2017
Source:Vaccine, Volume 35, Issue 29
Author(s): Jason J. LeBlanc, May ElSherif, Lingyun Ye, Donna MacKinnon-Cameron, Li Li, Ardith Ambrose, Todd F. Hatchette, Amanda L. Lang, Hayley Gillis, Irene Martin, Melissa K. Andrew, Guy Boivin, William Bowie, Karen Green, Jennie Johnstone, Mark Loeb, Anne McCarthy, Allison McGeer, Sanela Moraca, Makeda Semret, Grant Stiver, Sylvie Trottier, Louis Valiquette, Duncan Webster, Shelly A. McNeil
BackgroundPneumococcal community acquired pneumonia (CAPSpn) and invasive pneumococcal disease (IPD) cause significant morbidity and mortality worldwide. Although childhood immunization programs have reduced the overall burden of pneumococcal disease, there is insufficient data in Canada to inform immunization policy in immunocompetent adults. This study aimed to describe clinical outcomes of pneumococcal disease in hospitalized Canadian adults, and determine the proportion of cases caused by vaccine-preventable serotypes.MethodsActive surveillance for CAPSpn and IPD in hospitalized adults was performed in hospitals across five Canadian provinces from December 2010 to 2013. CAPSpn were identified using sputum culture, blood culture, a commercial pan-pneumococcal urine antigen detection (UAD), or a serotype-specific UAD. The serotype distribution was characterized using Quellung reaction, and PCR-based serotyping on cultured isolates, or using a 13-valent pneumococcal conjugate vaccine (PCV13) serotype-specific UAD assay.Results and conclusionsIn total, 4769 all-cause CAP cases and 81 cases of IPD (non-CAP) were identified. Of the 4769 all-cause CAP cases, a laboratory test for S. pneumoniae was performed in 3851, identifying 14.3% as CAPSpn. Of CAP cases among whom all four diagnostic test were performed, S. pneumoniae was identified in 23.2% (144/621). CAPSpn cases increased with age and the disease burden of illness was evident in terms of requirement for mechanical ventilation, intensive care unit admission, and 30-day mortality. Of serotypeable CAPSpn or IPD results, predominance for serotypes 3, 7F, 19A, and 22F was observed. The proportion of hospitalized CAP cases caused by a PCV13-type S. pneumoniae ranged between 7.0% and 14.8% among cases with at least one test for S. pneumoniae performed or in whom all four diagnostic tests were performed, respectively. Overall, vaccine-preventable pneumococcal CAP and IPD were shown to be significant causes of morbidity and mortality in hospitalized Canadian adults in the three years following infant PCV13 immunization programs in Canada.



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Maternal Tdap vaccination and risk of infant morbidity

Publication date: 22 June 2017
Source:Vaccine, Volume 35, Issue 29
Author(s): Malini DeSilva, Gabriela Vazquez-Benitez, James D. Nordin, Heather S. Lipkind, Nicola P. Klein, T. Craig Cheetham, Allison L. Naleway, Simon J. Hambidge, Grace M. Lee, Michael L. Jackson, Natalie L. McCarthy, Elyse O. Kharbanda
IntroductionAn increased risk of diagnosed chorioamnionitis in women vaccinated with Tdap during pregnancy was previously detected at two Vaccine Safety Datalink (VSD) sites. The clinical significance of this finding related to infant outcomes remains uncertain.MethodsRetrospective cohort study of singleton live births born to women who were continuously insured from 6months prior to their last menstrual period through 6weeks postpartum, with ≥1 outpatient visit during pregnancy from January 1, 2010 to November 15, 2013 at seven integrated United States health care systems part of the VSD. We re-evaluated the association between maternal Tdap and chorioamnionitis and evaluated whether specific infant morbidities differ among infants born to mothers who did and did not receive Tdap during pregnancy. We focused on 2 Tdap exposure windows: the recommended 27–36weeks gestation or anytime during pregnancy. We identified inpatient diagnostic codes for transient tachypnea of the newborn (TTN), neonatal sepsis, neonatal pneumonia, respiratory distress syndrome (RDS), and newborn convulsions associated with an infant's first hospitalization. A generalized linear model with Poisson distribution and log-link was used to estimate propensity score adjusted rate ratios (ARR) with 95% confidence intervals (CI).ResultsThe analyses included 197,564 pregnancies. Chorioamnionitis was recorded in 6.4% of women who received Tdap vaccination any time during pregnancy and 5.2% of women who did not (ARR [95% CI]: 1.23 [1.17, 1.28]). Compared with unvaccinated women, there were no significant increased risks (ARR [95% CI]) for TTN (1.04 [0.98, 1.11]), neonatal sepsis (1.06 [0.91, 1.23]), neonatal pneumonia (0.94 [0.72, 1.22]), RDS (0.91 [0.66, 1.26]), or newborn convulsions (1.16 [0.87, 1.53]) in infants born to Tdap-vaccinated women.Conclusions and RelevanceDespite an observed association between maternal Tdap vaccination and maternal chorioamnionitis, we did not find increased risk for clinically significant infant outcomes associated with maternal chorioamnionitis.



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Editorial Board/Aims and Scope

Publication date: 22 June 2017
Source:Vaccine, Volume 35, Issue 29





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Immunization requirements of the top 200 universities: Implications for vaccine-hesitant families

Publication date: 22 June 2017
Source:Vaccine, Volume 35, Issue 29
Author(s): Allison Noesekabel, Ada M. Fenick
BackgroundThe majority of pediatricians encounter vaccine hesitancy in their practices. As part of a broad discussion about vaccination, school requirements arise as a topic yet providers may lack information about the effects of immunization on university matriculation.MethodsWe surveyed the top-ranked 200 universities regarding required immunizations, medical, religious, and philosophical exemptions, and noncompliance policies. We examined the legal requirements for involved jurisdictions.ResultsOf 129 responding universities (64%), 94% had ≥1 pre-matriculation immunization requirement (PIR), with a mean of 3.53 (95%CI 3.17–3.89) requirements. In unadjusted analyses, funding, region, jurisdictional requirements, undergraduate size, and tuition were significant predictors of the number of PIRs. In multivariate modeling, jurisdictional requirements outperformed all other university demographics, but excluding these, Northeast and South region and smaller undergraduate size persisted. The most common PIR was measles (93%). 67% of involved jurisdictions have laws mandating ≥1 university PIR, and 45% of universities surpassed their jurisdiction's law. With respect to medical, religious, and philosophical exemptions, 24%, 40%, and 60% of universities with PIRs had the highest hardship category, and 2%, 2%, and 46% disallowed these outright. Frequent responses to student noncompliance were: hold on classes (89%), additional registration fees (13%), and hold on housing (11%).ConclusionsRequirements for pre-matriculation immunizations in top universities are common and exemptions are difficult to obtain. Conversations between providers and vaccine-hesitant families may be enriched by discussion of these future effects of their decision on immunization.



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