Channel of viral DNA packaging motor for real time kinetic analysis of peptide oxidation states

Publication date: May 2017
Source:Biomaterials, Volume 126
Author(s): Shaoying Wang, Zhi Zhou, Zhengyi Zhao, Hui Zhang, Farzin Haque, Peixuan Guo
Nanopore technology has become a powerful tool in single molecule sensing, and protein nanopores appear to be more advantageous than synthetic counterparts with regards to channel amenability, structure homogeneity, and production reproducibility. However, the diameter of most of the well-studied protein nanopores is too small to allow the passage of protein or peptides that are typically in multiple nanometers scale. The portal channel from bacteriophage SPP1 has a large channel size that allows the translocation of peptides with higher ordered structures. Utilizing single channel conductance assay and optical single molecule imaging, we observed translocation of peptides and quantitatively analyzed the dynamics of peptide oligomeric states in real-time at single molecule level. The oxidative and the reduced states of peptides were clearly differentiated based on their characteristic electronic signatures. A similar Gibbs free energy (ΔG⁰) was obtained when different concentrations of substrates were applied, suggesting that the use of SPP1 nanopore for real-time quantification of peptide oligomeric states is feasible. With the intrinsic nature of size and conjugation amenability, the SPP1 nanopore has the potential for development into a tool for the quantification of peptide and protein structures in real time.



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Pathology-targeted cell delivery via injectable micro-scaffold capsule mediated by endogenous TGase

Publication date: May 2017
Source:Biomaterials, Volume 126
Author(s): Chunxiao Qi, Yaqian Li, Patrick Badger, Hongsheng Yu, Zhifeng You, Xiaojun Yan, Wei Liu, Yan Shi, Tie Xia, Jiahong Dong, Chenyu Huang, Yanan Du
Targeted cell delivery to lesion sites via minimally invasive approach remains an unmet need in regenerative medicine to endow satisfactory therapeutic efficacy and minimized side-effects. Here, we rationally designed a pathology-targeted cell delivery strategy leveraging injectable micro-scaffolds as cell-loading capsule and endogenous tissue transglutaminase (TGase) at lesion site as adhesive. Up-regulated TGase post-liver injury catalyzed chemical bonding between the glutamine and lysine residues on liver surface and micro-scaffolds both ex vivo and in vivo, facilitating sufficient adhesion on the pathological liver. Upon intraperitoneal injection, Mesenchymal Stem Cell-loaded capsules, exhibiting cell protection from shear-induced damage and post-transplantation anoikis, adhered to the CCl4-treated liver with a hundred-fold improvement in targeting efficiency (70.72%) compared to free-cell injection, which dramatically improved mice survival (33.3% vs. 0% for free-cell therapy) even with low-dosage treatment. This unique and widely-applicable cell delivery mechanism and strategy hold great promise for transforming cell therapy for refractory diseases.



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In situ heart valve tissue engineering using a bioresorbable elastomeric implant – From material design to 12 months follow-up in sheep

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): Jolanda Kluin, Hanna Talacua, Anthal I.P.M. Smits, Maximilian Y. Emmert, Marieke C.P. Brugmans, Emanuela S. Fioretta, Petra E. Dijkman, Serge H.M. Söntjens, Renée Duijvelshoff, Sylvia Dekker, Marloes W.J.T. Janssen-van den Broek, Valentina Lintas, Aryan Vink, Simon P. Hoerstrup, Henk M. Janssen, Patricia Y.W. Dankers, Frank P.T. Baaijens, Carlijn V.C. Bouten
The creation of a living heart valve is a much-wanted alternative for current valve prostheses that suffer from limited durability and thromboembolic complications. Current strategies to create such valves, however, require the use of cells for in vitro culture, or decellularized human- or animal-derived donor tissue for in situ engineering. Here, we propose and demonstrate proof-of-concept of in situ heart valve tissue engineering using a synthetic approach, in which a cell-free, slow degrading elastomeric valvular implant is populated by endogenous cells to form new valvular tissue inside the heart. We designed a fibrous valvular scaffold, fabricated from a novel supramolecular elastomer, that enables endogenous cells to enter and produce matrix. Orthotopic implantations as pulmonary valve in sheep demonstrated sustained functionality up to 12 months, while the implant was gradually replaced by a layered collagen and elastic matrix in pace with cell-driven polymer resorption. Our results offer new perspectives for endogenous heart valve replacement starting from a readily-available synthetic graft that is compatible with surgical and transcatheter implantation procedures.

Graphical abstract

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Orthogonal near-infrared upconversion co-regulated site-specific O2 delivery and photodynamic therapy for hypoxia tumor by using red blood cell microcarriers

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): Peiyuan Wang, Xiaomin Li, Chi Yao, Wenxing Wang, Mengyao Zhao, Ahmed Mohamed El-Toni, Fan Zhang
Pre-existing hypoxia in tumors can result in an inadequate oxygen supply during photodynamic therapy (PDT), which in turn hampers photodynamic efficacy. To overcome this problem, we developed an orthogonal near-infrared upconversion controlled red blood cell (RBC) microcarriers to selectively deliver O2 in hypoxia area. Moreover, this RBC microcarriers are able to overcome a series of complex biological barriers which include transporting across the inflamed endothelium, evading mononuclear phagocyte system, reducing reticuloendothelial system uptake. Based on these abilities, RBC microcarriers have efficient tumors accumulation and are capable of delivery a large amount of O2 for PDT under near-infrared (NIR) irradiation to realize effective solid tumor eradication.

Graphical abstract

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Timing of nicotine lozenge administration to minimize trigger induced craving and withdrawal symptoms

Publication date: August 2017
Source:Addictive Behaviors, Volume 71
Author(s): Michael Kotlyar, Bruce R Lindgren, John P Vuchetich, Chap Le, Anne M Mills, Elizabeth Amiot, Dorothy K. Hatsukami
IntroductionSmokers are often advised to use nicotine lozenge when craving or withdrawal symptoms occur. This may be too late to prevent lapses. This study assessed if nicotine lozenge use prior to a common smoking trigger can minimize trigger induced increases in craving and withdrawal symptoms.MethodsEighty-four smokers completed two laboratory sessions in random order. At one session, nicotine lozenge was given immediately after a stressor (to approximate current recommended use – i.e., after craving and withdrawal symptoms occur); at the other session subjects were randomized to receive nicotine lozenge at time points ranging from immediately to 30min prior to the stressor. Withdrawal symptoms and urge to smoke were measured using the Minnesota Nicotine Withdrawal Scale and the Questionnaire of Smoking Urges (QSU).ResultsRelative to receiving lozenge after the stressor, a smaller increase in pre-stressor to post-stressor withdrawal symptom scores occurred when lozenge was used immediately (p=0.03) and 10min prior (p=0.044) to the stressor. Results were similar for factors 1 and 2 of the QSU when lozenge was used immediately prior to the stressor (p<0.03) and for factor 1 of the QSU when lozenge was used 10min prior to the stressor (p=0.028). Absolute levels of post-stressor withdrawal symptom and urge to smoke severity were lower when lozenge was given prior to versus after a stressor.ConclusionsAdministering the nicotine lozenge prior to a smoking trigger can decrease trigger induced craving and withdrawal symptoms. Future studies are needed to determine if such use would increase cessation rates.Clinicaltrials.gov # NCT01522963



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Characterizing Attention with Predictive Network Models

Publication date: Available online 23 February 2017
Source:Trends in Cognitive Sciences
Author(s): M.D. Rosenberg, E.S. Finn, D. Scheinost, R.T. Constable, M.M. Chun
Recent work shows that models based on functional connectivity in large-scale brain networks can predict individuals' attentional abilities. While being some of the first generalizable neuromarkers of cognitive function, these models also inform our basic understanding of attention, providing empirical evidence that: (i) attention is a network property of brain computation; (ii) the functional architecture that underlies attention can be measured while people are not engaged in any explicit task; and (iii) this architecture supports a general attentional ability that is common to several laboratory-based tasks and is impaired in attention deficit hyperactivity disorder (ADHD). Looking ahead, connectivity-based predictive models of attention and other cognitive abilities and behaviors may potentially improve the assessment, diagnosis, and treatment of clinical dysfunction.



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Multi-spectral and thermodynamic analysis of the interaction mechanism between Cu 2+ and α-amylase and impact on sludge hydrolysis

Abstract

An increasing amount of heavy metals (e.g., Cu²⁺) is being discharged into sewage treatment plants and is accumulating in sludge, which is toxic to the enzyme in sludge or soil when the sludge is used as fertilizer, resulting in unfavorable effect on the biological treatment of sludge and the circulation and conversion of materials in soil. In this research, effect of Cu²⁺ on sludge hydrolysis by α-amylase is studied from the respect of concentration and components of soluble organic matter in sludge, using three-dimensional fluorescence spectra. Results show that Cu²⁺ exposure not only inhibits the hydrolysis of sludge due to the denaturation of α-amylase but also affects the components of soluble organic matter in sludge. In order to illuminate the interaction mechanism between Cu²⁺ and α-amylase (a model of hydrolase in sludge), multi-spectra and isothermal titration microcalorimetry techniques are applied. Results show that the secondary structure of α-amylase is changed as that the α-helical content increases and the structure loosens. The microenvironment of amino acid residue in α-amylase is changed that the hydrophobicity decreases and the polarity increases with Cu²⁺ exposure. Isothermal titration calorimetry results show that Van der Waals force and hydrogen bond exist in the interaction between Cu²⁺ and α-amylase. Results from this research would favor the development of advanced process for the biological treatment of sludge containing heavy metals.

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NO and H 2 O 2 contribute to SO 2 toxicity via Ca 2+ signaling in Vicia faba guard cells

Abstract

NO and H₂O₂ have been implicated as important signals in biotic and abiotic stress responses of plants to the environment. Previously, we have shown that SO₂ exposure increased the levels of NO and H₂O₂ in plant cells. We hypothesize that, as signaling molecules, NO and H₂O₂ mediate SO₂-caused toxicity. In this paper, we show that SO₂ hydrates caused guard cell death in a concentration-dependent manner in the concentration range of 0.25 to 6 mmol L⁻¹, which was associated with elevation of intracellular NO, H₂O₂, and Ca²⁺ levels in Vicia faba guard cells. NO donor SNP enhanced SO₂ toxicity, while NO scavenger c-PTIO and NO synthesis inhibitors l-NAME and tungstate significantly prevented SO₂ toxicity. ROS scavenger ascorbic acid (AsA) and catalase (CAT), Ca²⁺ chelating agent EGTA, and Ca²⁺ channel inhibitor LaCl₃ also markedly blocked SO₂ toxicity. In addition, both c-PTIO and AsA could completely block SO₂-induced elevation of intracellular Ca²⁺ level. Moreover, c-PTIO efficiently blocked SO₂-induced H₂O₂ elevation, and AsA significantly blocked SO₂-induced NO elevation. These results indicate that extra NO and H₂O₂ are produced and accumulated in SO₂-treated guard cells, which further activate Ca²⁺ signaling to mediate SO₂ toxicity. Our findings suggest that both NO and H₂O₂ contribute to SO₂ toxicity via Ca²⁺ signaling.

http://ift.tt/2lhgvac

Media reporting, carbon information disclosure, and the cost of equity financing: evidence from China

Abstract

By using Shanghai and Shenzhen A-share listed companies in heavy polluting industry as research object from 2009 to 2014, this paper examines the relationship between media reporting, carbon information disclosure, and the cost of equity financing. The results show that media reporting can improve the quality of carbon information disclosure, and carbon information disclosure level is negatively associated with the cost of equity financing. This study also finds that financial carbon information disclosure and non-financial carbon information disclosure have significant negative relationship with the cost of equity financing respectively. Moreover, this paper shows that media reporting can strengthen the relationship between carbon information disclosure and the cost of equity financing.

http://ift.tt/2lNnV8l

Erratum to: Genetic and biochemical characterization of rhizobacterial strains and their potential use in combination with chelants for assisted phytoremediation

http://ift.tt/2lh6vhv

Uninhibited biosynthesis and release of phytosiderophores in the presence of heavy metal (HM) favors HM remediation

Abstract

Production of phytosiderophore (PS) has been causally related to iron-deficiency tolerance in cereals. However, PS can also chelate heavy metal and thus may represent a viable phytoextraction strategy on contaminated soils. Two separate experiments were conducted to assess the affect of heavy metal on phytosiderophore biosynthesis and their release in the rhizosphere of wheat. Root exudates were collected from 10-day-old wheat seedlings raised on Fe-deficient nutrient solution in the presence of 2.5, 5.0, and 10 mM concentration of different heavy metals (Cd, Pb, and Ni) for 3-day period, for the phytosiderophore and the heavy metal analysis. Plant uptake of respective heavy metal was positively correlated with the heavy metal concentration of the nutrient solution. Phytosiderophore release was positively influenced in the presence of the heavy metal. Increasing concentration of Cd, Pb, and Ni showed positive correlation with the PS release until 5 mM concentration followed by a decline at 10 mM. However, a higher induction of PS release was measured in wheat seedlings treated with Cd and Pb than Ni. Further, transcript expression analysis of nicotianamine synthase (NAS) and nicotianamine amino transferase (NAAT), involved in phytosiderophore biosynthesis, was done in roots of 10-day-old Fe-deficient wheat subjected to 2.5, 5.0, and 10 mM of Cd, Pb, and Ni. Both NAS and NAAT were expressed not only under Fe deficiency but also in the presence of Cd, Pb, and Ni. Sequencing of partial cDNA of NAS revealed a nucleotide length of 998 bp, while multiple sequence alignment of NAS with HvNAS revealed 92% sequence similarity. This study irrevocably shows that phytosiderophore biosynthesis and release are not impaired in the presence of heavy metal and that phytosiderophore mediates the uptake of toxic heavy metal.

http://ift.tt/2lN719O

Comparison of soil heavy metal pollution caused by e-waste recycling activities and traditional industrial operations

Abstract

The traditional industrial operations are well recognized as an important source of heavy metal pollution, while that caused by the e-waste recycling activities, which have sprouted in some developing countries, is often overlooked. This study was carried out to compare the status of soil heavy metal pollution caused by the traditional industrial operations and the e-waste recycling activities in the Pearl River Delta, and assess whether greater attention should be paid to control the pollution arising from e-waste recycling activities. Both the total contents and the chemical fractionation of major heavy metals (As, Cr, Cd, Ni, Pb, Cu, and Zn) in 50 surface soil samples collected from the e-waste recycling areas and 20 soil samples from the traditional industrial zones were determined. The results show that the soils in the e-waste recycling areas were mainly polluted by Cu, Zn, As, and Cd, while Cu, Zn, As, Cd, and Pb were the major heavy metals in the soils from the traditional industrial zones. Statistical analyses consistently show that Cu, Cd, Pb, and Zn in the surface soils from both types of sites were contributed mostly by human activities, while As, Cr, and Ni in the soils were dominated by natural background. No clear distinction was found on the pollution characteristic of heavy metals in the surface soils between the e-waste recycling areas and traditional industrial zones. The potential ecological risk posed by heavy metals in the surface soils from both types of sites, which was dominated by that from Cd, ranged from low to moderate. Given the much shorter development history of e-waste recycling and its largely unregulated nature, significant efforts should be made to crack down on illegal e-waste recycling and strengthen pollution control for related activities.

http://ift.tt/2lhi4oR

Ecotoxicity assessment of particulate matter emitted from heavy-duty diesel-powered vehicles: influence of leaching conditions

Abstract

Concerns regarding the environmental impact of diesel exhaust particulate matter (DPM) have increased in recent years. Following emission to the atmosphere, these fine materials can sorb many contaminants at their surface, which can subsequently be released, for instance, due to physicochemical environmental changes. The desorption of contaminants from particulate matter will increase the environmental pollution and can promote ecotoxicological effects. In this context, the objective of this study was to assess the aquatic ecotoxicity profile of extracts of DPM obtained at two different pH values. Thus, after collecting particulate matter from the diesel exhaust of heavy engines, extracts were obtained with pure water (at pH 2.00 and 5.00) and with a mixture of three organic solvents (dichloromethane, n-hexane, and acetone). To assess the environmental impact of DPM, the exhaust extracts were used in a battery of aquatic bioassays including key organisms of the food chain: bacteria (Aliivibrio fischeri), algae (Scenedesmus subspicatus), daphnids (Daphnia magna), and fishes (Danio rerio). The aqueous leachate at natural pH (2.0) and solvent extracts were extremely ecotoxic, while the aqueous leachate at pH = 5.0 showed the lowest ecotoxicity. The global ranking of sensitivity for the biotests tested was daphnids > algae > bacteria > fishes. Thus, the use of this bioassay battery could improve our understanding of the impact of DPM on aquatic environments, which is dependent on the pH of the leaching process.

http://ift.tt/2lN40q8

Genotype-dependent alleviation effects of exogenous GSH on salinity stress in cotton is related to improvement in chlorophyll content, photosynthetic performance, and leaf/root ultrastructure

Abstract

Soil salinity is a major abiotic stress that is constraining crop growth and productivity. Greenhouse hydroponic experiments were performed using salt-sensitive (cv. Zhongmian 41) and tolerant (Zhong 9806) cotton seedlings to evaluate how different genotypes responded to salinity stress in the presence of exogenous GSH (reduced glutathione). Cotton plants grown in 150 mM NaCl showed severe reduction in plant height, root length, and shoot and root fresh/dry weight. Salinity also caused reduction in photosynthesis and chlorophyll content, but increase in malondialdehyde (MDA) content. However, the reduction was more in Zhongmian 41 compared to Zhong 9806. Importantly, Sodium concentration was increased in the two genotypes and the induction was more in Zhongmian 41. Calcium and magnesium concentration was decreased in Zhongmian 41; however, in Zhong 9806 there were no significant differences relative to control. Addition of 50 mg L⁻¹ GSH in150 mM NaCl solution (Na + GSH) significantly alleviated salinity stress. Compared with salinity treatment alone (NaCl), Na + GSH increased fresh and dry weight of the root, stem, and leaf, photosynthesis, and chlorophyll content. Obvious ultrastructural alterations were observed in the saline-treated leaf- and root-tip cells. Exogenous GSH greatly ameliorated the salinity-induced damage on the leaf/root ultrastructure, especially in Zhongmian 41.These results advocate a positive role for GSH in alleviation of salinity, which is related to significant improvement in chlorophyll content, photosynthetic performance, and leaf/root ultrastructure.

http://ift.tt/2lh6slP

External field-assisted laser ablation in liquid: an efficient strategy for nanocrystal synthesis and nanostructure assembly

Publication date: Available online 24 February 2017
Source:Progress in Materials Science
Author(s): J. Xiao, P. Liu, C.X. Wang, G.W. Yang
Laser ablation in liquid (LAL) has received considerable attention over the last decade, and is gradually becoming an irreplaceable technique to synthesize nanocrystals and fabricate functional nanostructures because it can offer effective solutions to some challenges in the field of nanotechnology. The goal of this review is to offer a comprehensive summary of recent developments of LAL in nanocrystal synthesis and nanostructure fabrication. First, we will introduce the fundamental processes of microsecond, nanosecond, and femtosecond LAL, and how the active species act differently in plasma, cavitation bubbles, and droplets in the different LAL processes. Second, a variety of LAL-based techniques for nanomaterials synthesis and processing are presented, such as electric-, magnetic-, and temperature-field LAL, as well as electrochemically assisted LAL, pulsed laser deposition in liquid, and laser writing of nanopatterns in liquid. Third, new progress in LAL-generated nanomaterials is described. Fourth, we emphasize five applications of LAL-generated nanomaterials that have emerged recently in the fields of optics, magnetism, environment, energy, and biomedicine. Finally, we consider the core advantages of LAL, the limitations of LAL and corresponding solutions, and the future directions in this promising research area.



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Role of topical dehydroepiandrosterone in ameliorating isotretinoin-induced Meibomian gland dysfunction in adult male albino rat

Publication date: May 2017
Source:Annals of Anatomy - Anatomischer Anzeiger, Volume 211
Author(s): Marwa A.A. Ibrahim, Walaa M. Elwan
Isotretinoin broad effectiveness is limited by its detrimental effect on the Meibomian glands. Androgens have been reported to regulate the Meibomian gland function. Dehydroepiandrosterone (DHEA) is an androgen precursor considered as an efficient and physiological anti-ageing skin agent. This study aimed to investigate the role of the topical DHEA in ameliorating Meibomian gland dysfunction caused by isotretinoin employing different histological and immunohistochemical techniques. Twenty-four adult male albino rats were divided into four equal groups; control group, DHEA-treated group (1% twice daily for 3 months), isotretinoin-treated group (0.5mg/kg/day for 3 months), and both isotretinoin and DHEA-treated group. Meibomian gland specimens were processed for light microscopy. Immunohistochemical study was carried out using antibodies for proliferating cell nuclear antigen (PCNA), androgen receptor (AR) and estrogen receptor-alpha (ER-α). Sections from the isotretinoin-treated group revealed a reduction in the number and size of acini. Thickening and keratinization of the epithelial lining of the ducts were observed. Multiple degenerated acini and casts of acinar cells in the ducts of Meibomian glands were detected. Some dilated congested blood vessels and mononuclear cells were occasionally seen. A significant decrease in PAS reaction and a significant increase in collagen fiber content were detected. Immunohistochemical study revealed a significant increase in immunoexpression of PCNA in basal ductal cells coupled with decreased expression in basal acinar cells. Both AR and ER-α immunoexpression was significantly decreased. Minimal alterations were observed upon concomitant treatment with isotretinoin and DHEA as compared to the control group. Topical DHEA could prove to be beneficial in ameliorating isotretinoin-induced Meibomian gland dysfunction most probably through its androgenic effect.



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[Spectrum of pathogens in postoperative complications of visceral surgery : The problem of multidrug resistance].

Related Articles

[Spectrum of pathogens in postoperative complications of visceral surgery : The problem of multidrug resistance].

Chirurg. 2017 Feb 22;:

Authors: Kramer A, Pochhammer J, Walger P, Seifert U, Ruhnke M, Harnoss JC

Abstract
In general surgery the etiology of surgical site infections has not significantly changed over the last 30 years. Gram-positive bacteria, e.g. coagulase negative staphylococci (CNS), Staphylococcus aureus and Enterococcus spp. as well as Gram-negative bacteria, e.g. Escherichia coli, Enterobacter spp., Klebsiella spp. and Pseudomonas aeruginosa, are the most common findings. Although in general surgery 10% of the S. aureus causing postoperative wound infections were methicillin resistant (MRSA), no cases of multidrug-resistant Gram-negative (MRGN) bacteria were reported. Yeasts (particularly Candida spp.) are rarely the pathogen causing surgical site infections (≤3%) and concomitant risk factors are typical (e.g. diabetes, chemotherapy, immunosuppression and malnutrition). Viruses are rarely the cause of surgical site infections. Transmission can occur by HBV, HCV or HIV positive surgical staff or in organ transplantations and postoperative reactivation of persistent infections is possible (especially for HBV, HCV, CMV, EBV and HIV). The principles for prevention of surgical site infections are dealt with as consequences of preoperative colonization by MRSA, methicillin-sensitive S. aureus (MSSA) and MRGN and reviewed with respect to screening, perioperative antibiotic prophylaxis and decolonization. In nosocomial peritonitis, the selection of antibiotics should consider previous antibiotic treatment. A single intra-abdominal detection of Candida spp. usually does not require antimycotic treatment in postoperatively stable and immunocompetent patients but is recommended in severe community-acquired or nosocomial peritonitis. Viral infections can be avoided by screening of organ donors and serological surveillance of surgery personnel.

PMID: 28229205 [PubMed - as supplied by publisher]

http://ift.tt/2kTS7zC

Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis.

Related Articles

Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis.

Sci Transl Med. 2017 Feb 22;9(378):

Authors: Nakatsuji T, Chen TH, Narala S, Chun KA, Two AM, Yun T, Shafiq F, Kotol PF, Bouslimani A, Melnik AV, Latif H, Kim JN, Lockhart A, Artis K, David G, Taylor P, Streib J, Dorrestein PC, Grier A, Gill SR, Zengler K, Hata TR, Leung DY, Gallo RL

Abstract
The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing Staphylococcus aureus, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against S. aureus was performed on isolates of coagulase-negative Staphylococcus (CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by S. aureus The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including Staphylococcus epidermidis and Staphylococcus hominis These AMPs were strain-specific, highly potent, selectively killed S. aureus, and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by S. aureus These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease.

PMID: 28228596 [PubMed - in process]

http://ift.tt/2kU6jsa

Increased levels of anti-phosphatidylcholine and anti-phosphatidylethanolamine antibodies in pediatric patients with cerebral infarction

Publication date: Available online 24 February 2017
Source:Brain and Development
Author(s): Seigo Korematsu, Hiroshi Yamada, Hiroaki Miyahara, Kenji Ihara
Cerebral infarction in children is rare and often occurs secondary to moyamoya disease, hereditary coagulopathies, vasculitis, antiphospholipid antibody syndrome, heart disease, mitochondrial disease. However, in some cases, the causes of cerebral infarction is unknown.In this study, we detected increased levels of serum anti-phosphatidylcholine and anti-phosphatidylethanolamine IgG antibodies in three pediatric patients with cerebral infarction whose primary disorders are unknown by routine examination. For the five disease control patients of cerebral infarction due to other primary disorders, there was no such increase in these antibodies levels.Phosphatidylcholine and phosphatidylethanolamine are major components of the phospholipids of vascular endothelial cells, while cardiolipin is a minor component. Anti-phosphatidylcholine and anti-phosphatidylethanolamine antibodies, as well as anti-cardiolipin antibody, might also be risk factors with cerebral infarction.



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Training Radiology Residents to be Stewards in Healthcare Value

Publication date: Available online 24 February 2017
Source:Academic Radiology
Author(s): Matthew D. Alvin, Karen M. Horton, Pamela T. Johnson
Medical imaging procedures have become a national target in the campaign to reduce wasteful practices. At a minimum, radiology residency programs must integrate high-value curricula and train residents to practice in accordance with value-based principles and new healthcare policy. A greater portion of radiology resident education needs to be devoted to appropriateness education and consultancy training. Ideally, radiology training programs will instill in residents the importance of embracing the movement and leading the change.



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Transitional Leadership

Publication date: Available online 24 February 2017
Source:Academic Radiology
Author(s): Alexander Norbash
Rationale and ObjectivesTo suggest a methodical approach for refining transitional management abilities, including empowerment of a growing leader, leading in an unfamiliar organization or leading in an organization that is changing.Materials and MethodsManagement approaches based on the body of work dealing with leadership studies and transitions and dealing with leadership during times of transition and change management were consolidated and categorized.ResultsTransitional leaders can benefit from effective leadership training including defining and prospectively accruing necessary experiences and skills; strengthening information gathering skills; effectively self-assessing; valuing and implementing mentoring; formulating strategy; and communicating.ConclusionsA categorical approach to transitional leadership may be implemented through a systems-based and methodical approach to gaining the definable, and distinct sets of skills and abilities necessary for transitional leadership success.



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CT for Acute Nontraumatic Abdominal Pain—Is Oral Contrast Really Required?

Publication date: Available online 23 February 2017
Source:Academic Radiology
Author(s): Rivka Kessner, Sophie Barnes, Pinchas Halpern, Vadim Makrin, Arye Blachar
Rationale and ObjectivesThis study aims to compare the diagnostic performance of abdominal computed tomography (CT) performed with and without oral contrast in patients presenting to the emergency department (ED) with acute nontraumatic abdominal pain.Materials and MethodsBetween December 2013 and December 2014, 348 adult patients presenting to the ED of a large tertiary medical center with nontraumatic abdominal pain were evaluated. Exclusion criteria for the study were history of inflammatory bowel disease, recent abdominal operation and suspected renal colic, abdominal aortic aneurysm rupture, or intestinal obstruction. All patients underwent intravenous contrast-enhanced abdominal CT on a Philips Brilliance 64-slice scanner using a routine abdomen protocol. The study group included 174 patients who underwent abdominal CT scanning without oral contrast, recruited using convenience sampling. A control group of 174 patients was matched to the cohort groups' gender and age and underwent abdominal CT with oral contrast material during the same time period. The patients' medical records were reviewed for various clinical findings and for the final clinical diagnosis. The CT exams were initially reviewed by a senior attending radiologist to determine the exams' technical adequacy and to decide whether an additional scan with oral contrast was required. Two senior radiologists, blinded to the clinical diagnosis, later performed consensus reading to determine the contribution of oral contrast administration to the radiologists' diagnostic confidence and its influence on diagnosing various radiological findings.ResultsEach group consisted of 82 men and 92 women. The average age of the two groups was 48 years. The main clinical diagnoses of the pathological examinations were appendicitis (17.5%), diverticulitis (10.9%), and colitis (5.2%). A normal CT examination was found in 34.8% of the patients. There was no significant difference between the groups regarding most of the clinical parameters that were examined. None of the examinations of all of the 174 study group patients was found to be technically inadequate, and therefore no patient had to undergo additional scanning to establish a diagnosis. The consensus reading of the senior radiologists determined that the lack of oral contrast was insignificant in 96.6% of the cases and that contrast material might have been useful in only 6 of 174 study group patients (3.4%). The radiologists found oral contrast to be helpful only in 8 of 174 control group patients (4.6%). There was no significant difference between the clinical and radiological diagnoses in both groups (study group, P = 0.261; control group, P = 0.075).ConclusionsOur study shows that oral contrast is noncontributory to radiological diagnosis in most patients presenting to the ED with acute nontraumatic abdominal pain. These patients can therefore undergo abdominal CT scanning without oral contrast, with no effect on radiological diagnostic performance.



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Increasing Adherence with Topical Agents for Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is an intensely pruritic dermatosis that develops most commonly during early infancy and childhood and may follow a chronic, relapsing course into adulthood. As a chronic disease, AD requires treatment over an extended period of time, and is therefore difficult to treat. The main difficulty stems from poor adherence to treatment by patients for reasons such as frustration with medication efficacy, inconvenience, and fear of side effects. Methods that improve adherence include creating therapeutic plans with patient preferences in mind, early follow-up visit, increasing patient education through workshops, and discussing with patients and their caretakers their fears about treatment methods. AD can be exceedingly detrimental to a patient's quality of life. Simple measures to improve adherence may improve patients' treatment outcomes and quality of life.

http://ift.tt/2lzooKT

Calcipotriol Plus Betamethasone Dipropionate Aerosol Foam in Patients with Moderate-to-Severe Psoriasis: Sub-Group Analysis of the PSO-ABLE Study

Abstract

Background

Fixed-combination calcipotriol 50 μg/g plus betamethasone 0.5 mg/g (Cal/BD) aerosol foam is a new topical treatment for psoriasis. Although moderate-to-severe psoriasis is typically treated with systemic/biologic therapies, a topical treatment that is efficacious in these patients may be a significant cost-saving alternative to systemic therapy.

Objective

The objective of this study was to assess the response to Cal/BD foam and gel in patients with moderate-to-severe psoriasis enrolled in the phase III, 12-week PSO-ABLE study.

Methods

Patients eligible for this analysis had moderate-to-severe psoriasis, defined by the 'Rule of Tens': body surface area ≥10% or Psoriasis Area and Severity Index (PASI) [excluding head; modified PASI (mPASI)] >10 or Dermatology Life-Quality Index >10. Endpoints included: proportion of patients achieving mPASI75 or mPASI90; change in body surface area; proportion of patients clear/almost clear with a ≥2 grade improvement (i.e., treatment success); change in Dermatology Life-Quality Index.

Results

Seventy-seven Cal/BD foam patients and 82 gel patients had moderate-to-severe psoriasis. A greater proportion achieved mPASI75 and mPASI90 with Cal/BD foam than gel at weeks 4, 8, and 12 (57.1 vs. 35.4%; p = 0.006 and 15.6 vs. 12.2% at week 12, respectively); overall reduction in mPASI from baseline to week 12 was 64% with the foam vs. 51% with the gel. Overall reduction in body surface area at week 12 was 50% with the foam and 39% with the gel. Treatment success rates were higher with the Cal/BD foam than the gel at weeks 1, 2, 4, 8 (p = 0.0089), and 12, and a greater proportion of foam patients achieved a Dermatology Life-Quality Index score of 0/1 at weeks 4 (p = 0.004), 8, and 12 (p = 0.001).

Conclusion

Cal/BD foam can be considered as a treatment option in some patients with moderate-to-severe psoriasis who are potential candidates for systemic therapy.

Clinicaltrials.gov identifier

NCT02132936.

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Interferon alpha impairs insulin production in human beta cells via endoplasmic reticulum stress

Publication date: Available online 24 February 2017
Source:Journal of Autoimmunity
Author(s): Angela Lombardi, Yaron Tomer
Despite substantial advances in the research exploring the pathogenesis of Type 1 Diabetes (T1D), the pathophysiological mechanisms involved remain unknown. We hypothesized in this study that interferon alpha (IFNα) participates in the early stages of T1D development by triggering endoplasmic reticulum (ER) stress. To verify our hypothesis, human islets and human EndoC-βH1 cells were exposed to IFNα and tested for ER stress markers, glucose stimulated insulin secretion (GSIS) and insulin content. IFNα treatment induced upregulation of ER stress markers including Binding immunoglobulin Protein, phospho-eukaryotic translation initiation factor 2α, spliced- X-box binding protein-1, C/EBP homologous protein and activating transcription factor 4. Intriguingly, IFNα treatment did not impair GSIS but significantly decreased insulin production in both human islets and EndoC-βH1 cells. Furthermore, IFNα decreased the expression of both proinsulin convertase 1 and proinsulin convertase 2, suggesting an altered functional state of the beta cells characterized by a slower proinsulin-insulin conversion. Pretreatment of both human islets and EndoC-βH1 cells with chemical chaperones 4-phenylbutyric acid and tauroursodeoxycholic acid completely prevented IFNα effects, indicating an ER stress-mediated impairment of insulin production. We demonstrated for the first time that IFNα elicits ER stress in human beta cells providing a novel mechanistic role for this virus-induced cytokine in the development of T1D. Compounds targeting molecular processes altered in ER-stressed beta cells could represent a potential therapeutic strategy to prevent IFNα-induced beta cell dysfunction in the early onset of T1D.

Graphical abstract

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Mitochondrial DNA oxidation induces imbalanced activity of NLRP3/NLRP6 inflammasomes by activation of caspase-8 and BRCC36 in dry eye

Publication date: Available online 24 February 2017
Source:Journal of Autoimmunity
Author(s): Wei Chi, Xia Hua, Xin Chen, Fang Bian, Xiaoyong Yuan, Lili Zhang, Xiaoran Wang, Ding Chen, Ruzhi Deng, Zhijie Li, Yizhi Liu, Cintia S. de Paiva, Stephen C. Pflugfelder, De-Quan Li
The concept of innate immunity has been expanded to recognize environmental pathogens other than microbial components. However, whether and how the innate immunity is initiated by epithelium in response to environmental physical challenges such as low humidity and high osmolarity in an autoimmune disease, dry eye, is still largely unknown. Using two experimental dry eye models, primary human corneal epithelial cultures exposed to hyperosmolarity and mouse ocular surface facing desiccating stress, we uncovered novel innate immunity pathway by ocular surface epithelium, where oxidized mitochondrial DNA induces imbalanced activation of NLRP3/NLRP6 inflammasomes via stimulation of caspase-8 and BRCC36 in response to environmental stress. Activated NLRP3 with suppressed NLRP6 stimulates caspase-1 activation that leads to IL-1β and IL-18 maturation and secretion. NLRP3-independent caspase-8 noncanonically activates caspase-1 via reciprocal regulation of NLRP3/NLRP6-mediated inflammasomes. Reactive oxygen species-induced mitochondrial DNA oxidative damage and BRCC36 deubiquitinating activity provide a missing link and mechanism by which innate immunity responds to environmental stress via caspase-8-involved NLRP3/NLRP6 inflammasomes.



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Long term follow-up on prepectoral ADM-assisted breast reconstruction: evidences after 4 years

Abstract

Prepectoral implant-based breast reconstruction is on the rise because of the advantages related to preservation of the pectoralis major muscle. Indeed, this reconstructive procedure improves the aesthetic outcomes and the postoperative recovery time, avoiding the risk of breast animation and deformity. On the other hand, the subcutaneous implant positioning has higher risk of capsular contracture and for this reason, the subpectoral breast reconstruction has been preferred for many years; but the introduction of a pre-shaped acellular dermal matrix (ADM) which allows a complete implant coverage led to the onset of the new prepectoral technique, solving the problem of a stiff periprosthetic capsule formation. In fact, the use of ADMs in breast reconstruction has been shown to decrease the capsular contracture formation. Nevertheless, no long-term outcomes have been reported with the use of a pre-shaped ADM for prepectoral breast reconstruction. The authors present the first ten patients who had a prepectoral ADM-assisted breast reconstruction showing no evidences of capsular contracture after a median follow-up of 4 years.

Level of Evidence: Level V, therapeutic study.

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Successful treatment of postburn flexion contracture in fingers of early childhood with dynamic splint therapy after operation: long-term follow-up

Abstract

Background

Infants or early childhood individuals are prone to be burned on the palm and fingers, since they tend to extend their hands to the heat source. Wounds with more than 3-week-prolonged ulcers frequently result in flexion contracture. Despite successful surgery, the outcome might be unsatisfactory because of postoperative contracture. This study aims to investigate the effectiveness of our dynamic splint therapy following operation of postburn flexion contracture of fingers in infants or early childhood.

Methods

Ten patients with postburn flexion contractures were enrolled in this study. After epithelialization of wounds had been completed, surgery was planned. Contracture was released by scar incision, and full-thickness skin was grafted. Postoperatively, the finger joints were fixed at the extended position with the Kirschner wires for 3 weeks. After the fixation was released, Capener-type dynamic splints were worn for 2 years. The functional outcome was assessed by measurement of total active motion (TAM). The aesthetic outcome was assessed using Vancouver scar scale (VSS).

Results

The mean postoperative follow-up period was 49.6 months (range 31–81 months). In all cases, contractures were released, and all skin grafts were completely taken. None developed late contracture. The mean postoperative TAM of the fingers (259.6 ± 2.54) was significantly higher than the preoperative one (148.0 ± 51.5). The mean postoperative VSS (1.40 ± 1.14) was significantly lower than the preoperative one (5.53 ± 0.50).

Conclusions

Our treatment protocol provided the excellent functional result and improved the aesthetic appearance.

Level of Evidence: Level IV, therapeutic study.

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Development of a highly sensitive radon-222 amplifier (HiSRA) for low-level atmospheric measurements

Publication date: May 2017
Source:Journal of Environmental Radioactivity, Volume 171
Author(s): Sylvain Topin, Patrick Richon, Vincent Thomas, Claire Gréau, Julie Pujos, Julien Moulin, Alexandre Hovesepian, Ludovic Deliere
Radon (²²²Rn), a radioactive gas with a half-life of 3.82 days, is continuously emanated from soil, rocks, and water by the radioactive decay of ²²⁶Ra. Radon-222 is released from the ground into the atmosphere, where it is transported mainly by turbulent diffusion or convection. For precise measurement of radon-222 atoms in the atmosphere, the detectors typically used present a small volume or surface area and are therefore not very sensitive, especially for online measurements and short sample intervals (<1 h). This article deals with the development of a Highly Sensitive Radon Amplifier (HiSRA) consisting in an enrichment system placed prior to a classic radon-222 analyzer. This system uses permeation membranes that make it possible to treat large quantities of air online (30 m³ h⁻¹). The radon-222 concentration is increased instantaneously by at least a factor of 30 across the HiSRA system. Therefore, in this study, when coupling to an ionization chamber (AlphaGUARDTM) at the outlet of the HiSRA system, the detection limit of the overall system is multiplied by factor of 30 and induces a new LD for a radon 222 gas analyzer lower than 1 Bq m⁻³ for an integrating time of 10 min and 0.1 Bq m⁻³ for 1 h. We constructed one radon amplifier prototype that provided the preliminary results for amplification efficiency and the initial measurements presented herein.



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Intracerebroventricular injection of beta-amyloid in mice is associated with long-term cognitive impairment in the modified hole-board test

Publication date: 1 May 2017
Source:Behavioural Brain Research, Volume 324
Author(s): Sebastian Schmid, Bettina Jungwirth, Verena Gehlert, Manfred Blobner, Gerhard Schneider, Stephan Kratzer, Kristine Kellermann, Gerhard Rammes
BackgroundThe intracerebroventricular injection of beta-amyloid (Aβ) in mice allows the investigation of acute effects on cognitive function and cellular pathology. The aim of this investigation was to further characterize the time course of Aβ-induced cognitive and behavioural changes and to detect potential molecular mechanisms.MethodsCannulas were implanted in the lateral cerebral ventricle. 14days after surgery the mice were injected with Aβ1-42 or phosphate buffered saline (PBS). Starting 2, 4 or 8 (PBS only 4) days after injection we evaluated cognitive and behavioural performance using the modified hole board test (mHBT). We determined tumour-necrosis factor alpha (TNF alpha) and caspase 3 by western blotting, on days 10, 12 and 16. Data were analysed using general linear modelling, Kruskall-Wallis and Mann-Whitney-U test.ResultsAβ induced a decline in cognitive performance represented as an increased total number of wrong choices during the testing period from day 2–15 (p<0.05). Behavioural parameters were comparable between mice treated with Aβ and PBS. There was no difference regarding TNF alpha levels between the groups. Compared to day 16 Caspase 3 levels were increased on day 10 (p=0.004).ConclusionsApplication of Aβ in the lateral ventricle of mice is associated with cognitive impairment of declarative memory in the mHBT. There is no interference caused by altered behaviour. Therefore, it represents a valid model for acute Aβ-mediated neurotoxic effects. Although the exact mechanisms remain unclear, changes in levels of Caspase 3 suggest apoptosis as an important factor for the development of cognitive dysfunction.



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The ameliorating effect of 1-palmitoyl-2-linoleoyl-3-acetylglycerol on scopolamine-induced memory impairment via acetylcholinesterase inhibition and LTP activation

Publication date: 1 May 2017
Source:Behavioural Brain Research, Volume 324
Author(s): Se Jin Jeon, Boseong Kim, Hye Jin Park, Jiabao Zhang, Yubeen Kwon, Dong Hyun Kim, Jong Hoon Ryu
In the present study, we investigated whether 1-palmitoyl-2-linoleoyl-3-acetylglycerol (PLAG), a component of antlers of Cervus nippon Temminck, would have memory-ameliorating properties against cholinergic blockade-induced memory impairment in mice. In the passive avoidance task to investigate the effects of PLAG on long-term memory, PLAG (10mg/kg, p.o.) administration ameliorated scopolamine-induced memory impairment. PLAG also reversed the impairments of working memory in the Y-maze task and spatial memory as shown in the Morris water maze. To identify the mechanism of the memory-ameliorating effect of PLAG, acetylcholinesterase (AChE) inhibition assay and the Western blot analysis were conducted. In the AChE inhibition assay, PLAG inhibited the AChE activity in mice and PLAG increased the expression levels of phosphorylated CaMKII, ERK, and CREB in the hippocampus. Additionally, long-term potentiation (LTP) of synaptic strength occurred by PLAG treatment in the hippocampal cultures. Overall, the present study suggests that PLAG reversed memory deficits in an animal model and that it affects biochemical pathways related to learning and memory.



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Injections of the of the α1-adrenoceptor antagonist prazosin into the median raphe nucleus increase food intake and Fos expression in orexin neurons of free-feeding rats

Publication date: 1 May 2017
Source:Behavioural Brain Research, Volume 324
Author(s): Eduardo Simão da Silva, Rafael Appel Flores, Anderson Savaris Ribas, Ana Paula Taschetto, Moacir Serralvo Faria, Leandro Bueno Lima, Martin Metzger, José Donato, Marta Aparecida Paschoalini
Previously, we showed that the blockade of α1-adrenoreceptors in the median raphe nucleus (MnR) increased food intake in free-feeding rats, indicating that adrenergic mechanisms in the MnR participate in the regulation of food intake. However, the impact of such a pharmacological manipulation on other neural circuits related to food intake remains unknown. In the current study, we sought to identify forebrain regions which are responsive to α1-adrenergic receptor blockade and presumably involved in the modulation of the feeding response. For this purpose, we examined the induction of c-Fos immunoreactivity in forebrain structures following injections of the α1-adrenoceptor antagonist prazosin into the MnR of free-feeding rats. To determine the chemical identity of hypothalamic c-Fos-positive cells, we then conducted double-label immunohistochemistry for Fos/orexin (OX) or Fos/melanin-concentrating hormone (MCH). Finally, we combined anterograde tracing from the MnR with immunohistochemical detection of orexin. Prazosin injections into the MnR significantly increased food intake. The ingestive response was accompanied by an increase in Fos expression in the basolateral amygdala (BLA) and lateral hypothalamic area (LHA). In the LHA, Fos expression occurred in neurons expressing OX, but not MCH. Combined anterograde tracing experiments revealed that LHA OX neurons are prominently targeted by MnR axons. These findings suggest that intra-MnR injection of prazosin, via activation of orexinergic neurons in the LHA and non-orexinergic neurons in the BLA, evoked a motivational response toward food intake.



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Acute and long-term effects of adolescent methylphenidate on decision-making and dopamine receptor mRNA expression in the orbitofrontal cortex

Publication date: 1 May 2017
Source:Behavioural Brain Research, Volume 324
Author(s): Leslie R. Amodeo, Eliza Jacobs-Brichford, Matthew S. McMurray, Jamie D. Roitman
Though commonly used as a treatment for ADHD, the psychostimulant methylphenidate (MPH) is also misused and abused in adolescence in both clinical and general populations. Although MPH acts via pathways activated by other drugs of abuse, the short- and long-term effects of MPH on reward processing in learning and decision-making are not clearly understood. We examined the effect of adolescent MPH treatment on a battery of reward-directed behaviors both in adolescence during its administration and in adulthood after its discontinuation. We further measured whether MPH had lasting effects on dopamine receptor mRNA expression in orbitofrontal cortex (OFC) that may correspond with behavior. Long-Evans rats were injected with MPH (0, 1, 2.5, or 5mg/kg IP) twice daily from middle to late adolescence (PD38-57). During adolescence, the high dose of MPH reduced preference for large rewards in a Reward Magnitude Discrimination task, but did not affect preference for smaller-sooner rewards in a Delay Discounting task. In adulthood, after discontinuation of MPH, animals previously treated with the moderate dose of MPH showed improved acquisition, but not reversal, in a Reversal Learning task. MPH exposure did not increase preference for large-risky rewards in a Risk task in adulthood. We then quantified mRNA expression of D1, D2, and D3 receptors in the OFC using qPCR. MPH increased mRNA expression of dopamine D3 receptor subtype, but not D1 or D2. Overall, these results indicate that MPH has both immediate and lasting effects on reward-dependent learning and decisions, as well as dopaminergic function in rodents.



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Affective valence of neurons in the vicinity of the rat amygdala: Single unit activity in response to a conditioned behavior and vocal sound playback

Publication date: 1 May 2017
Source:Behavioural Brain Research, Volume 324
Author(s): Hiroko Kagawa, Yoshimasa Seki, Kazuo Okanoya
We recorded single unit activity within and around the rat amygdala while rats were engaged in an operant task (which included both reward and aversive trials) and during playback of ultrasonic vocalizations (USVs) to determine if there existed neurons which responded to two different types of either positive contexts (i.e., water reward and positively associated 50kHz vocalizations) or negative contexts (i.e., white noise and negatively associated 22kHz vocalizations). Ultimately, we wanted to determine if these two contexts (operant condition task and vocal sounds) could be represented as either positive or negative in a single neuron. Neural activity in 90% of cells was modulated in response to one or more of those events. A small number of those cells showed neural responses to both the aversive operant trials and 22kHz USVs, but did not show responses to reward operant trials or 50kHz USVs, suggesting the activity of these neurons encodes for similar negative emotion in response to these two contexts. Some cells showed responses to either the reward trials or 50kHz USVs, but no cells showed responses to both, suggesting that these cells do not show a common response to events associated with positive emotion. This might mean that 50kHz vocal sounds and the operant rewards were segregated into two different categories within the neural representation at the level of the amygdala, even though it appeared that both events were associated with positive emotions in rats.



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Cognitive performance of male and female C57BL/6J mice after repetitive concussive brain injuries

Publication date: 1 May 2017
Source:Behavioural Brain Research, Volume 324
Author(s): Alexander G. Velosky, Laura B. Tucker, Amanda H. Fu, Jiong Liu, Joseph T. McCabe
In contact sports, repetitive concussive brain injury (rCBI) is the prevalent form of head injury seen in athletes. The need for effective treatment is urgent as rCBI has been associated with a host of cognitive, behavioral and neurological complaints. There has been a growing trend in the use of female animals in pre-clinical research, but few studies have investigated possible sex differences following rCBI. The goal of the current study was to determine any differences between male and female C57BL/6J mice on assessments of learning and memory after repetitive concussive injury. Following rCBI by impact to the scalp, male mice exhibited longer righting reflexes during acute recovery. In both sexes, there were no evident histopathological changes observed in the underlying cerebral cortex or hippocampus. Reactive astrogliosis was elevated in the corpus callosum and optic tract, and astrogliosis was slightly less in the optic tract of female mice. rCBI mice exhibited impairment during the learning phase of the Morris water maze (MWM), but female mice, in comparison to male mice, were observed to have superior spatial memory during standard MWM probe trials. Female mice were overall more active, evidenced by greater distances traveled in the y-maze and greater swim speeds in the MWM. The results of this study demonstrate sex differences in cognitive performance following rCBI and support previous research suggesting the neuroprotective role of sex in brain injury.



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The effects of CRF and urocortins on the preference for social novelty of mice

Publication date: 1 May 2017
Source:Behavioural Brain Research, Volume 324
Author(s): Zsolt Bagosi, András Czébely-Lénárt, Gergely Karasz, Krisztina Csabafi, Miklós Jászberényi, Gyula Telegdy
The aim of the present study was to determine the role of corticotropin-releasing factor (CRF), the urocortins (UCN 1, UCN 2 and UCN 3) and their receptors (CRF1 and CRF2) in the preference for social novelty of mice. Male CFLP mice were administered intracerebroventricularly (ICV) with CRF, UCN 1, UCN 2 or UCN 3 and/or antalarmin or astressin 2B, selective antagonists of CRF1 receptor and CRF2 receptor, respectively. The mice were investigated in a Crawley social interaction test arena consisting of three chambers: an unknown female was set in the first chamber and a known female, with which the male was familiarized previously for 24h, was set in the third chamber. First the tested male was habituated with the middle chamber for 5min and then allowed to explore the remaining chambers for 5min, during which the number of entries and the time of interaction were measured. CRF decreased significantly the number of entries and the time of interaction with the unknown female, but not the known female. UCN 1 decreased significantly the number of entries into the chamber of the unknown female, but not the known female, without changing the time of interaction. All decreasing effects were reversed by antalarmin, but not astressin 2B. UCN 2 and UCN 3 didn't influence significantly any of the parameters. The present study suggests that CRF and UCN 1 decrease the preference for social novelty by activating CRF1 receptor, while UCN 2 and UCN 3, activating selectively CRF2 receptor, do not participate to male-female interaction.



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Divergent effects of brain interleukin-1ß in mediating fever, lethargy, anorexia and conditioned fear memory

Publication date: 1 May 2017
Source:Behavioural Brain Research, Volume 324
Author(s): Tamzyn L. Baartman, Tanya Swanepoel, Ruth M. Barrientos, Helen P. Laburn, Duncan Mitchell, Lois M. Harden
The influence of brain interleukin-1 (IL-1ß) on memory processes includes both detrimental and beneficial effects. To further explore the dynamics of brain IL-1ß in mediating learning and memory during acute sickness, we injected species-homologous rat IL-1ß (100ng/5μl) or vehicle (0.1% bovine serum albumin, 5μl) directly into the cisterna magna (i.c.m.) of male Sprague-Dawley rats. We measured, in parallel, body temperature, food intake, body mass, cage activity, as well as learning and memory using contextual fear conditioning. To investigate the effects of IL-1ß on learning and memory processes we used: (1) a retrograde experiment that involved injecting rats i.c.m. with IL-1ß immediately after training in the novel context, and (2) an anterograde experiment that involved injecting rats i.c.m. with IL-1ß two hours before training in the novel context. In addition, hypothalamic and hippocampal concentrations of IL-1β were measured at several time points following injection. Administration of IL-1ß induced fever, lethargy and anorexia for∼two-to-three days and increased the concentration of IL-1ß in the hippocampus and hypothalamus for at least eight hours. Training in the context immediately before IL-1ß administration (retrograde experiment), did not impair contextual and auditory fear memory. However, when training in the context occurred concurrently with elevated hippocampal IL-1ß levels, two hours after IL-1ß administration (anterograde experiment), contextual, but not auditory, fear memory was impaired. Our results show that there are instances where memory consolidation can occur concurrently with elevated levels of IL-1ß in the hippocampus, fever, anorexia and lethargy during acute short-term sickness.



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Rapid induction of dopamine sensitization in the nucleus accumbens shell induced by a single injection of cocaine

Publication date: 1 May 2017
Source:Behavioural Brain Research, Volume 324
Author(s): Bryan F. Singer, Myranda A. Bryan, Pavlo Popov, Terry E. Robinson, Brandon J. Aragona
Repeated intermittent exposure to cocaine results in the neurochemical sensitization of dopamine (DA) transmission within the nucleus accumbens (NAc). Indeed, the excitability of DA neurons in the ventral tegmental area (VTA) is enhanced within hours of initial psychostimulant exposure. However, it is not known if this is accompanied by a comparably rapid change in the ability of cocaine to increase extracellular DA concentrations in the ventral striatum. To address this question we used fast-scan cyclic voltammetry (FSCV) in awake-behaving rats to measure DA responses in the NAc shell following an initial intravenous cocaine injection, and then again 2-h later. Both injections quickly elevated DA levels in the NAc shell, but the second cocaine infusion produced a greater effect than the first, indicating sensitization. This suggests that a single injection of cocaine induces sensitization-related plasticity very rapidly within the mesolimbic DA system.



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Effectiveness of a Perioperative Transthoracic Ultrasound Training Program for Students and Residents

Publication date: Available online 24 February 2017
Source:Journal of Surgical Education
Author(s): Juliet June Ray, Jonathan P. Meizoso, Valerie Hart, Davis Horkan, Vicente Behrens, Krishnamurti A. Rao, Charles A. Karcutskie, Joshua Lenchus, Carl I. Schulman, Roman Dudaryk
ObjectiveFocused ultrasound (US) is being incorporated across all levels of medical education. Although many comprehensive US courses exist, their scope is broad, requiring expert instructors, access to simulation, and extensive time commitment by the learner. We aim to compare learning across levels of training and specialties using a goal-directed, web-based course without live skills training.DesignA prospective observational study of students and residents from medicine, surgery, and anesthesiology. Analysis compared pretests and posttests assessing 3 competencies. Individual mean score improvement (MSI) was compared by paired-sample t-tests and MSI among cohorts by analysis of variance, with significance set at p ≤ 0.05. McNemar test compared those who agreed or strongly agreed with survey items with those who did not before and after intervention.SettingJackson Memorial Hospital, Miami, FL residency training programs in Medicine, Surgery, and Anesthesiology.ResultsA total of 180 trainees participated. A significant MSI was noted in each of 3 competencies in all 3 cohorts. Students' (S) MSI was significantly higher than residents' (R) and interns' (I) in US "knobology" and window recognition [S = 2.28 ± 1.29/5 vs R = 1.63 ± 1.21/5 (p = 0.014); vs I = 1.59 ± 1.12/5 (p = 0.032)]; students' total score MSI was significantly higher than residents [7.60 ± 3.43/20 vs 5.78 ± 3.08/20 (p < 0.008)]. All cohorts reported improved comfort in using transthoracic US and improved ability to recognize indications for use. More than 81% of all participants reported improved confidence in performing transthoracic US; more than 91% reported interest in additional training; and more than 88% believed course length was appropriate.ConclusionsLearners across levels of medical training and specialties can benefit from a brief, goal-directed, web-based training with early incorporation producing maximal yield.



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An Informed Consent Program Enhances Surgery Resident Education

Publication date: Available online 24 February 2017
Source:Journal of Surgical Education
Author(s): Sarah E. Koller, Ryan F. Moore, Michael B. Goldberg, Jeanette Zhang, Daohai Yu, Charles B. Conklin, Richard E. Milner, Amy J. Goldberg
ObjectiveFirst-year residents often obtain informed consent from patients. However, they typically receive no formal training in this area before residency. We wished to determine whether an educational program would improve residents' comfort with this process.DesignOur institution created an informed consent educational program, which included a didactic component, a role-play about informed consent, and a simulation exercise using standardized patients. Residents completed surveys before and after the intervention, and responses to survey questions were compared using the signed-rank test.SettingThis study took place at Temple University Hospital, a tertiary care institution in Philadelphia, PA.ParticipantsFirst-year surgery and emergency medicine residents at Temple University Hospital in 2014 participated in this study. Thirty-two residents completed the preintervention survey and 27 residents completed the educational program and postintervention survey.ResultsOnly 37.5% had ever received formal training in informed consent before residency. After participating in the educational program, residents were significantly more confident that they could correctly describe the process of informed consent, properly fill out a procedure consent form, and properly obtain informed consent from a patient. Their comfort level in obtaining informed consent significantly increased. They found the educational program to be very effective in improving their knowledge and comfort level in obtaining informed consent. In all, 100% (N = 27) of residents said they would recommend the use of the program with other first-year residents.ConclusionsResidents became more confident in their ability to obtain informed consent after participating in an educational program that included didactic, role-play, and patient simulation elements.



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Uptake of screening for type 2 diabetes risk in general dental practice; an exploratory study

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Dental implants: Potential relationship with cancer

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Game-changing restorative solutions

http://ift.tt/2mrRSba

Healthcare research: VR and AR

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Consolidated digital expertise

http://ift.tt/2mrLWPs

Patient safety: Cardiac devices

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Sugar consumption and changes in dental caries from childhood to adolescence

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Anticoagulants: Lack of research

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For the love of a dental chair

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Advertising: Longstanding dislike

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Top interdental brush company opens new UK HQ

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Antimicrobial resistance: Setting the record straight

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Association of endodontic lesions with coronary artery disease

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Electronic cigarettes: Necrotic ulcer

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The experience of dentists who gained enhanced skills in endodontics within a novel pilot training programme

http://ift.tt/2ms23fX

Drug interactions: Time to put our pens down

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DCPs and research in general dental practice

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Erratum: Updates on idarucizumab

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A new range of biocidal cleaners

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Dental students work with inner city kids

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The cationic liposomal adjuvants CAF01 and CAF09 formulated with the major outer membrane protein elicit robust protection in mice against a Chlamydia muridarum respiratory challenge

Publication date: Available online 24 February 2017
Source:Vaccine
Author(s): Sukumar Pal, Delia F. Tifrea, Frank Follmann, Peter Andersen, Luis M. de la Maza
Two cationic liposomal adjuvants CAF01 and CAF09 were formulated with the native or the recombinant Chlamydia muridarum major outer membrane protein (nMOMP and rMOMP). BALB/c mice were immunized with the four vaccine formulations using the subcutaneous followed by the intranasal (i.n.) routes. As positive controls mice were inoculated i.n. with live C. muridarum and negative controls received i.n. minimal essential medium (MEM). Four weeks after the last immunization mice were challenged i.n. with 10⁴ inclusion forming units (IFU) of C. muridarum. Following the challenge the mice were weighed daily. At 10days post-challenge the mice were euthanized, their lungs weighed and the number of C. muridarum IFU determined. Serum collected the day before the challenge showed that all four groups of mice immunized with CAF01, or CAF09 and MOMP had significant C. muridarum-specific antibody titers. As determined by a T-cell lymphoproliferative assay, these four groups of mice also mounted robust cell mediated immune responses with high production of IFN-γ and IL17 and low levels of IL-4. Following the challenge the four groups of mice lost significantly less body weight than the MEM-immunized group. Lungs of mice vaccinated with CAF01, or CAF09, and nMOMP were significantly lighter than those from mice immunized using rMOMP. The number of IFU recovered from the lungs of mice vaccinated with CAF01, or CAF09, and nMOMP was similar to the number of IFU recovered from mice immunized with live EB. Mice that received rMOMP had significantly higher numbers of IFU than other groups. In conclusion, CAF01 and CAF09 elicited very robust protective humoral and cellular immune responses and were equally effective at adjuntavizing the C. muridarum MOMP. Mice vaccinated with nMOMP were significantly better protected than those immunized with rMOMP, indicative of the importance of the structural conformation of this antigen in protection.



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Four-year persistence of type-specific immunity after quadrivalent human papillomavirus vaccination in HIV-infected children: Effect of a fourth dose of vaccine

Publication date: Available online 24 February 2017
Source:Vaccine
Author(s): Myron J. Levin, Sharon Huang, Anna-Barbara Moscicki, Lin-Ye Song, Jennifer S. Read, William A. Meyer, Alfred J. Saah, Kelly Richardson, Adriana Weinberg
ObjectiveAlthough HIV-infected children are recommended to receive quadrivalent human papillomavirus vaccine (QHPV) there is limited information on their response to QHPV. This study in HIV-infected children, evaluated the magnitude and duration of immune responses to QHPV. This report describes type-specific serum antibody responses over a 4-to-5year period after either 3 or 4 doses of QHPV.Design/methodsHIV-infected children, ages 7-to-11years, received 3 doses of QHPV (n=96) or placebo (n=30). At 72weeks QHPV recipients received a fourth dose (n=84), while placebo recipients began the 3-dose QHPV schedule (n=27). HPV serotype-specific antibody was determined, by competitive Luminex immunoassay (cLIA) and IgG Luminex immunoassay, at 2, 3.5, and 4-to-5years after the last dose of QHPV in each treatment arm.ResultsAt 4-to-5years after the last dose of QHPV, antibody titers were significantly higher in 4-dose than in 3-dose group. However, the proportion of vaccinees with a seroresponse in the cLIA assay was not different between the two groups (86–93% for HPV types 6, 11, and 16, and 64% for HPV type 18). These results were very similar to the seroresponse rate in these HIV-infected children at 1month after completing vaccination.ConclusionsChildren with well-controlled HIV infection who receive 3 doses of the QHPV vaccine maintain seropositivity and antibody levels that are generally similar to children of the same age who are not HIV-infected. Antibody titer correlated strongly with low log HIV RNA, low CD8%, and high CD4%. Additionally, a fourth dose of vaccine in HIV-infected children produces a marked rise in antibody characteristic of an anamnestic response and persistence of high antibody levels.Study identification: IMPAACT P1085 (V501-021). CLINICALTRIALS.GOV identifier: NCT01206556.



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Vaccines: Shaping global health

Publication date: Available online 23 February 2017
Source:Vaccine
Author(s): Sonia Pagliusi, Ching-Chia Ting, Fernando Lobos
The Developing Countries Vaccine Manufacturers' Network (DCVMN) gathered leaders in immunization programs, vaccine manufacturing, representatives of the Argentinean Health Authorities and Pan American Health Organization, among other global health stakeholders, for its 17th Annual General Meeting in Buenos Aires, to reflect on how vaccines are shaping global health. Polio eradication and elimination of measles and rubella from the Americas is a result of successful collaboration, made possible by timely supply of affordable vaccines. After decades of intense competition for high-value markets, collaboration with developing countries has become critical, and involvement of multiple manufacturers as well as public- and private-sector investments are essential, for developing new vaccines against emerging infectious diseases. The recent Zika virus outbreak and the accelerated Ebola vaccine development exemplify the need for international partnerships to combat infectious diseases. A new player, Coalition for Epidemic Preparedness Innovations (CEPI) has made its entrance in the global health community, aiming to stimulate research preparedness against emerging infections. Face-to-face panel discussions facilitated the dialogue around challenges, such as risks of viability to vaccine development and regulatory convergence, to improve access to sustainable vaccine supply. It was discussed that joint efforts to optimizing regulatory pathways in developing countries, reducing registration time by up to 50%, are required. Outbreaks of emerging infections and the global Polio eradication and containment challenges are reminders of the importance of vaccines' access, and of the importance of new public-private partnerships.



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Origins and trends in ethane and propane in the United Kingdom from 1993 to 2012

Publication date: May 2017
Source:Atmospheric Environment, Volume 156
Author(s): R.G. Derwent, R.A. Field, P. Dumitrean, T.P. Murrells, S.P. Telling
Continuous, high frequency in situ observations of ethane and propane began in the United Kingdom in 1993 and have continued through to the present day at a range of kerbside, urban background and rural locations. Whilst other monitored C2 – C8 hydrocarbons have shown dramatic declines in concentrations by close to or over an order of magnitude, ethane and propane levels have remained at or close to their 1993 values. Urban ethane sources appear to be dominated by natural gas leakage. Background levels of ethane associated with long range transport are rising. However, natural gas leakage is not the sole source of urban propane. Oil and gas operations lead to elevated propane levels in urban centres when important refinery operations are located nearby. Weekend versus weekday average diurnal curves for ethane and propane at an urban background site in London show the importance of natural gas leakage for both ethane and propane, and road traffic sources for propane. The road traffic source of propane was tentatively identified as arising from petrol-engined motor vehicle refuelling and showed a strong downwards trend at the long-running urban background and rural sites. The natural gas leakage source of ethane and propane in the observations exhibits an upwards trend whereas that in the UK emission inventory trends downwards. Also, inventory emissions for natural gas leakage appeared to be significantly underestimated compared with the observations. In addition, the observed ethane to propane ratio found here for natural gas leakage strongly disagreed with the inventory ratio.



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Turbulent dispersion of pollutants in urban-type canopies under stable stratification conditions

Publication date: May 2017
Source:Atmospheric Environment, Volume 156
Author(s): Zhi Shen, Guixiang Cui, Zhaoshun Zhang
Large eddy simulation is performed for the dispersion of a passive scalar in the turbulent boundary layer over an urban-like roughness surface under neutral and stable stratification. Square arrays of cubical obstacles are used to model the urban canopy with a ground level point source located in front of the obstacle. We design cases for varying building intervals to investigate the relationship between flow patterns and dispersion processes for different plan area densities λp. It has been found (Shen et al. 2015) that flow patterns in a three-dimensional urban canopy can be classified into five basic regimes in neutral stratification: isolated roughness, external wake interference, internal wake interference, skimming flow and streets network. This classification still holds in the presence of moderately stable stratification. In area with large λp, the material released from the point source tends to be trapped by the leeward recirculation and is well-mixed inside the canopy. The mean concentration level within roughness canopies is high due to the reduced advection velocity. In area with small λp, the great part of the material is entrained into the horseshoe vortex wrapping around the obstacle and carried downwind. The material is concentrated in the lower region of the canopy with a relatively higher temporal fluctuation. In the presence of stable stratification, the spread of the plume is reduced and the temporal fluctuation is suppressed as well. For area of large λp, the advective part of the scalar flux is responsible for carrying the material at ground level aloft into the urban canopy layer.



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Forecasting 7BE concentrations in surface air using time series analysis

Publication date: April 2017
Source:Atmospheric Environment, Volume 155
Author(s): María del Carmen Bas, Josefina Ortiz, Luisa Ballesteros, Sebastián Martorell
⁷Be is a cosmogenic radionuclide widely used as an atmospheric tracer, whose evaluation and forecasting can provide valuable information on changes in the atmospheric behavior. In this study, measurements of ⁷Be concentrations were made each month during the period 2007–2015 from samples of atmospheric aerosols filtered from the air. The aim was to propose a Seasonal Autoregressive Integrated Moving Average (SARIMA) model to develop an explanatory and predictive model of ⁷Be air concentrations. The Root Mean Square Error (RMSE) and the Adapted Mean Absolute Percentage Error (AMAPE) were selected to measure forecasting accuracy in identifying the best historical data time window to explain ⁷Be concentrations. A measure based on the variance of forecast errors was calculated to determine the impact of the model uncertainty on forecasts. We concluded that the SARIMA method is a powerful explanatory and predictive technique for explaining ⁷Be air concentrations in a longterm series of at least eight years of historical data to forecast ⁷Be concentration trends up to one year in advance.



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A simple model to assess odour hours for regulatory purposes

Publication date: April 2017
Source:Atmospheric Environment, Volume 155
Author(s): Dietmar Oettl, Enrico Ferrero
A novel methodology for estimating odour hours in the frame of licencing procedures is presented. In contrast to the widely used constant-factor-4 model, which is the prescribed method in Germany, a model based on computing concentration variances is proposed. It is derived upon the advection-diffusion equation for the concentration variance, but is strongly simplified by neglecting the transport and diffusion terms. In this way, the method becomes extremely efficient with regard to computation times. Furthermore, the model is independent on the type of dispersion model used to calculate average concentrations, which are necessary for subsequently computing concentration variances. In a second step, simulated concentration variances are used in combination with a slightly modified two-parameter Weibull probability density function to get the 90^th percentile of the cumulative frequency distribution of odour-concentration fluctuations, which is required for computing a so-called odour hour. The model is operated in post-processing mode and can, thus, easily be implemented in existing dispersion models. It's validity has been tested against two tracer tests carried out in Germany and the U.S.



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Atmospheric emissivity with clear sky computed by E-Trans/HITRAN

Publication date: April 2017
Source:Atmospheric Environment, Volume 155
Author(s): Víctor M. Mendoza, Elba E. Villanueva, René Garduño, Oscar Sánchez-Meneses
The vertical profiles of temperature and pressure from the International Standard Atmosphere, together with the mixing ratio profiles of the main greenhouse effect gases (GG), namely water vapour, CO2, CH4, N2O and stratospheric O3, are used to determine the downward emissivity of long wave radiation by cloudless atmosphere, by means of the spectral calculator E-Trans with the HITRAN (high-resolution transmission) database. We make a review of emissivity parameterizations, reported by several authors, in terms of the surface vapour pressure and surface air temperature. We compute vertically weighted averages of temperature and pressure, also parameterize the CH4, N2O and O3 mixing ratio profiles, in order to adapt these variables as required by the E-Trans/HITRAN. Our results of emissivity for the corresponding vapour pressures agree well with those obtained by the reviewed authors. With this method, the emissivity can be computed at a regional scale and towards the future global warming, according to the IPCC temperature projections that will also increase the atmospheric humidity, from the emission scenarios of GG.



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Palmatine inhibits TRIF-dependent NF-κB pathway against inflammation induced by LPS in goat endometrial epithelial cells

Publication date: April 2017
Source:International Immunopharmacology, Volume 45
Author(s): Baoqi Yan, Dongsheng Wang, Shuwei Dong, Zhangrui Cheng, Lidong Na, Mengqi Sang, Hongzao Yang, Zhiqiang Yang, Shidong Zhang, Zuoting Yan
Palmatine, a natural pharmaceutical drug, possesses many biological activities. But its clinical application is rarely reported in the veterinary medicine. The aim of this study was to investigate the anti-inflammatory effects of palmatine on lipopolysaccharide (LPS)-induced inflammation in goat endometrial epithelial cells (gEECs), and the possible molecular mechanisms. Palmatine cell toxicity was determined by MTT assay, and the production of inflammatory cytokine in the cultured medium was measured with ELISA, qRT-PCR and Western blotting. Our results showed that palmatine treatment inhibited the release of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, nitric oxide (NO), matrix metalloproteinase (MMP)-9 and MMP-2. Furthermore, palmatine enhanced the secretion of prostaglandins E2 (PGE2) and IL-10. Palmatine significantly down-regulated the expression of Toll-like receptor 4 (TLR4), cluster of differentiation 14 (CD14), Toll/interleukin 1 receptor (TIR)-domain-containing adaptor protein inducing interferon-β (TICAM, TRIF) and nuclear factor-κB (NF-κB) in LPS stimulated gEECs, but did not alter the production of MyD88. In conclusion, palmatine inhibits TRIF-dependent NF-κB pathway to reduce LPS-induced inflammatory responses in goat endometrial epithelial cells.



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Novel benzophenone-3 derivatives with promising potential as UV filters: Relationship between structure, photoprotective potential and phototoxicity

Publication date: 1 April 2017
Source:European Journal of Pharmaceutical Sciences, Volume 101
Author(s): María Teresa Páez González, Fernando Fumagalli, Carolina Gomes Benevenuto, Flavio da Silva Emery, Lorena Rigo Gaspar
Benzophenone-3 (BP-3) is a UV filter with absorption at the UVB and UVA wavelengths which has not been extensively studied in experiments involving its absorbing effects and toxicity. We synthetized four BP-3 derivatives and characterized their photoprotective potential by UV absorption and photodegradation, their phototoxicity potential by 3T3 Neutral Red Uptake (3T3 NRU PT) and their photoreactivity by the reactive oxygen species (ROS) assay. The UV absorption, photodegradation, phototoxicity and photoreactivity of the four BP-3 derivatives (BP-3 carbonate, BP-3 carbazole, BP-3 phenylamine and BP-3 methoxy-phenylamine) were evaluated and compared to those of BP-3. Results showed that all derivatives were photostable, except BP-3 carbonate, which did not absorb in the UVA range. BP-3 phenylamine and BP-3 methoxy-phenylamine were considered non-phototoxic and weakly photoreactive in the ROS assay, while the carbazole derivative was considered phototoxic and non-photoreactive due to its rigid structure. The UV spectra of BP-3 carbonate, BP-3 phenylamine and BP-3 methoxy-phenylamine showed the influence of hydrogen bonding on their UV absorption. Based on these results, we concluded that BP-3 phenylamine and BP-3 methoxy-phenylamine could be promising UVA filters.

Graphical abstract

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Is the ecological belt zonation of the Swiss Alps relevant for moth diversity and turnover?

Publication date: April 2017
Source:Acta Oecologica, Volume 80
Author(s): Jan Beck, Cecil M. Rüdlinger, Christy M. McCain
Mountain ecosystems are traditionally envisioned as elevational belts of homogenous vegetation, separated by intervening ecotones. Recent research has cast doubt on such predictable layering at least in animal communities. We test the link of two a priori defined ecological belt zonations to noctuid moth distributions in the Swiss Alps. Predictions, in particular, were a coincidence of proposed ecotones with increased range endpoint frequencies and with increased species turnover or species richness between equidistant elevational bands. Using >320,000 distributional records for >500 noctuid species, we found no support for these three predictions despite several contrasting analytical approaches. Concurrent with recently published vertebrate data, we conclude that simple ecological belt zonations are unrelated to the moth communities found along mountain slopes. Rather, species are distributed idiosyncratically following their specific niche requirements. Additional rigorous evidence, particularly comparing insect clades spanning a spectrum of host-plant relationships, may be required to support the relevance of the ecological belt concept in structuring mountain ecosystems beyond tree and plant communities.



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Interactions between synaptic homeostatic mechanisms: an attempt to reconcile BCM theory, synaptic scaling, and changing excitation/inhibition balance

Publication date: April 2017
Source:Current Opinion in Neurobiology, Volume 43
Author(s): Tara Keck, Mark Hübener, Tobias Bonhoeffer
Homeostatic plasticity is proposed to be mediated by synaptic changes, such as synaptic scaling and shifts in the excitation/inhibition balance. These mechanisms are thought to be separate from the Bienenstock, Cooper, Munro (BCM) learning rule, where the threshold for the induction of long-term potentiation and long-term depression slides in response to changes in activity levels. Yet, both sets of mechanisms produce a homeostatic response of a relative increase (or decrease) in strength of excitatory synapses in response to overall activity-level changes. Here we review recent studies, with a focus on in vivo experiments, to re-examine the overlap and differences between these two mechanisms and we suggest how they may interact to facilitate firing-rate homeostasis, while maintaining functional properties of neurons.



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MAGUKs: multifaceted synaptic organizers

Publication date: April 2017
Source:Current Opinion in Neurobiology, Volume 43
Author(s): Sehoon Won, Jon M Levy, Roger A Nicoll, Katherine W Roche
The PSD-95 family of proteins, known as MAGUKs, have long been recognized to be central building blocks of the PSD. They are categorized as scaffolding proteins, which link surface-expressed receptors to the intracellular signaling molecules. Although the four members of the PSD-95 family (PSD-95, PSD-93, SAP102, and SAP97) have many shared roles in regulating synaptic function, recent studies have begun to delineate specific binding partners and roles in plasticity. In the current review, we will highlight the conserved and unique roles of these proteins.



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Pseudo-progressing to an unmet need

Publication date: Available online 24 February 2017
Source:Seminars in Oncology
Author(s): Tito Fojo




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Data on the radioprotective effect of emodin in vivo and vitro via inhibition of apoptosis and modulation of p53

Publication date: April 2017
Source:Data in Brief, Volume 11
Author(s): Jing Wang, Yue Zhang, Qiuzhen Zhu, Yulan Liu, Hao Cheng, Yuefan Zhang, Tiejun Li
This paper contains the experiment data on the emodin, mice and cell survival rate, mice intestinal tissue H&E and TUNEL staining, the expression of p53 protein in mice small intestine, cell apoptosis, the expression of protein and RNA in vitro included. Data was worked out through MTT assay, Flow cytometry, Western blot, Real-time PCR and Staining.



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Dataset on metabolomics profile of acute leukemia blood obtained by the NMR methods

Publication date: Available online 24 February 2017
Source:Data in Brief
Author(s): Alexander Bogaychuk, Andrey Zyubin, Anastasiya Lavrova, Galina Kupriyanova, Svetlana Babak, Mariya Dambieva, Maksim Demin, Anastasiya Borisova, Nikita Opryshko
This article contains NMR (nuclear magnetic resonance) experimental data, obtained by the NMR Varian 400MHz spectrometer (USA) which can be used for the metabolites identification in human blood. Data include analyzed NMR spectra of plasma proteins extracted from human blood of 24 patients (0–5 years old) with the confirmed acute leukemia diagnosis. Data can provide information about metabolites and their concentration in blood.



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Higher Dihydrotestosterone Is Associated with the Incidence of Lung Cancer in Older Men

Abstract

Advancing age is associated with increased cancer incidence, but the role of sex hormones as risk predictors for common cancers in older men remains uncertain. This study was performed to assess associations of testosterone (T), dihydrotestosterone (DHT) and estradiol (E2), with incident prostate, lung and colorectal cancer in community-dwelling older men. Plasma T, DHT and E2 were assayed using liquid chromatography-mass spectrometry between 2001 and 2004 in 3690 men. Cancer outcomes until 20 June 2013 were ascertained using data linkage. Analyses were performed using proportional hazards competing-risks models, and adjustments were made for potential confounding factors including smoking status. Results are expressed as subhazard ratios (SHR). There were 348, 107 and 137 cases of prostate, lung and colorectal cancers respectively during a median of 9.1-year follow-up. Mean T was comparable in current and non-smokers, whilst mean DHT was lower in ex- and current smokers compared to non-smokers. After adjusting for confounders including smoking, higher T or DHT was associated with an increased incidence of lung cancer (SHR = 1.30, 95% CI 1.06–1.60; p = 0.012 per 1 SD increase in T and SHR = 1.29, 95% CI 1.08–1.54; p = 0.004 for DHT). Sex hormones were not associated with prostate or colorectal cancer. In older men, higher T or DHT predict increased incidence of lung cancer over the next decade. Sex hormones are not associated with incident prostate or colorectal cancer. Further studies are warranted to determine if similar associations of sex hormones with lung cancer are present in other populations and to investigate potential underlying mechanisms.

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Omega-3 fatty acids as adjunctive treatment for bexarotene-induced hypertriglyceridaemia in patients with cutaneous T-cell lymphoma

Summary

Background

Bexarotene is an oral retinoid approved for treating cutaneous T-cell lymphoma (CTCL) in patients resistant to first-line systemic treatment. Hypertriglyceridaemia is an unavoidable adverse effect of bexarotene therapy, and requires monitoring because of the risk of developing pancreatitis. Therefore, prophylactic hypolipidaemic therapy, usually with a fibrate alone, is required for preventing bexarotene-induced hypertriglyceridaemia. Despite these measures, a large number of patients develop very severe hypertriglyceridaemia.

Aim

To assess the lipid metabolism changes before and after the use of a combination of omega-3 fatty acids (n-3 FA) plus fenofibrate compared with fenofibrate alone as a more effective lipid-lowering therapy in patients with CTCL treated with bexarotene.

Methods

From January 2005 to January 2013, we analysed all 25 patients with CTCL treated with bexarotene. The first 18 consecutively enrolled patients received fenofibrate alone as a lipid-lowering therapy, and the next 7 consecutively enrolled patients received a combination of fenofibrate and n-3 FA.

Results

Data for all 25 consecutive patients with CTCL treated with bexarotene were evaluated. Of these, 24 patients (96%) developed hypertriglyceridaemia despite the hypolipidaemic therapy, with this being very severe (> 11.2 mmol/L) in 20% of the cases. Of the 18 patients receiving fenofibrate alone, 5 (28%) developed very severe hypertriglyceridaemia, compared with none of the 7 patients treated with the n-3 FA combination.

Conclusions

Our results suggest that the n-3 FA combination may be more effective than fibrate alone for preventing bexarotene-induced hypertriglyceridaemia.

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Protective Effect of SFE-CO2 of Ligusticum chuanxiong Hort Against d-Galactose-Induced Injury in the Mouse Liver and Kidney

Rejuvenation Research , Vol. 0, No. 0.


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Evaluation of impact of an external breast shield (FlexiShield) in electronic brachytherapy for breast IORT: A phantom study

Publication date: Available online 23 February 2017
Source:Brachytherapy
Author(s): Yongbok Kim, Jason Wei-Yeong Huynh, Victor J. Gonzalez
PurposeTo investigate Axxent (iCAD, Inc., San Jose, CA) electronic brachytherapy balloon deformation and its dosimetric impact because of an external flexible shield (FlexiShield [FS]; iCAD, Inc.).Methods and MaterialsProstheses breast tissue phantom overlaid three spherical balloon applicators to simulate three clinical scenarios depending on minimum skin-to-balloon surface spacing (SS): balloon with SS of 2 cm, 1 cm, and balloon with 1 cm SS and touching the chest wall. Two sets of megavoltage CT (MVCT) scans were obtained with or without FS for 15 different sizes of balloons. For 45 pairs of MVCT scans, balloon deformation was measured in superior–inferior (dSI) dimension on coronal and sagittal planes and anterior–posterior (dAP) and lateral (dLAT) dimensions on the equatorial plane of balloon. SS was also compared. A treatment plan was made on each MVCT scan. Doses at four balloon surface points and skin were compared. Conformity index value was also compared to evaluate three-dimensional dose distribution. Clinically, 20 Gy was prescribed to the surface of balloon.ResultsBalloon deformation was observed with compression in SI and AP dimensions and expansion in lateral dimension. Average SI compression was 0.5 mm. Average dLat - dAP was 2.4 mm, which resulted in elevated point doses at AP dimension by 10.8% of prescribed dose and reduced point doses at lateral dimension by 4.6%. FS decreased SS by 1.8 mm, increasing skin dose by 1.2 Gy, on average. Conformity index value was decreased from 0.922 to 0.908, on average.ConclusionsThis phantom study demonstrates that use of skin shielding during breast intraoperative radiation therapy can cause balloon deformation and SS reduction, resulting in dosimetric changes that are disregarded in current practice.



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Prostate MRI for brachytherapists: Anatomy and technique

Publication date: Available online 23 February 2017
Source:Brachytherapy
Author(s): A.M. Venkatesan, R.J. Stafford, C. Duran, P.D. Soni, A. Berlin, P.W. McLaughlin
PurposeTo present an overview of mp MRI techniques necessary for high-resolution imaging of prostate.MethodsWe summarize examples from our clinical experience and concepts from the current literature that illustrate normal prostate anatomy on multiparametric MRI (mp MRI).ResultsOur experience regarding optimal mp MRI image acquisition is provided, as well as a summary of prostate and periprostatic anatomy and anatomical variants that pose challenges for BT.Conclusionsmp MRI provides unparalleled assessment of the prostate and periprostatic anatomy, making it the most appropriate imaging modality to facilitate prostate BT treatment planning, implantation, and followup. This work provides an introduction to prostate mp MR imaging, anatomy, and anatomical variants essential for successful integration mp MRI into prostate brachytherapy practice.



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Common Carotid Artery Diameter, Blood Flow Velocity and Wave Intensity Responses at Rest and during Exercise in Young Healthy Humans: A Reproducibility Study

Publication date: Available online 23 February 2017
Source:Ultrasound in Medicine & Biology
Author(s): Nicola Pomella, Eurico Nestor Wilhelm Neto Wilhelm, Christina Kolyva, José González-Alonso, Mark Rakobowchuk, Ashraf W. Khir
The aim of this study was to assess the reproducibility of non-invasive, ultrasound-derived wave intensity (WI) in humans at the common carotid artery. Common carotid artery diameter and blood velocity of 12 healthy young participants were recorded at rest and during mild cycling, to assess peak diameter, change in diameter, peak velocity, change in velocity, time derivatives, non-invasive wave speed and WI. Diameter, velocity and WI parameters were fairly reproducible. Diameter variables exhibited higher reproducibility than corresponding velocity variables (intra-class correlation coefficient [ICC] = 0.79 vs. 0.73) and lower dispersion (coefficient of variation [CV] = 5% vs. 9%). Wave speed had fair reproducibility (ICC = 0.6, CV = 16%). WI energy variables exhibited higher reproducibility than corresponding peaks (ICC = 0.78 vs. 0.74) and lower dispersion (CV = 16% vs. 18%). The majority of variables had higher ICCs and lower CVs during exercise. We conclude that non-invasive WI analysis is reliable both at rest and during exercise.



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Biochemical Basis for Increased Activity of Ebola Glycoprotein in the 2013–16 Epidemic

Publication date: Available online 23 February 2017
Source:Cell Host & Microbe
Author(s): May K. Wang, Sun-Young Lim, Soo Mi Lee, James M. Cunningham
Ebola virus (EBOV) infection is characterized by sporadic outbreaks caused by zoonotic transmission. Fixed changes in amino acid sequence, such as A82V in the EBOV glycoprotein (GP) that occurred early in the 2013–16 epidemic, are suspected to confer a selective advantage to the virus. We used biochemical assays of GP function to show that A82V, as well as a polymorphism in residue 544 identified in other outbreaks, enhances infection by decreasing the threshold for activation of membrane fusion activity triggered by the host factors cathepsin B and Niemann-Pick C1. Importantly, the increase in infectivity comes with the cost of decreased virus stability. Thus, emergence of a virus GP with altered properties that can affect transmission and virulence may have contributed to the severity and scope of the 2013–16 EBOV epidemic.

Graphical abstract

Teaser

A fixed A82V polymorphism in the EBOV glycoprotein that occurred early in the 2013–16 epidemic is suspected to confer a selective advantage. Wang et al. show that A82V and another polymorphism from other outbreaks confers increased EBOV infectivity and decreased host entry factor dependency, at the cost of decreased virus stability.


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