Publication date: Available online 4 November 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Fábio Muradás Girardi, Laura Mezzomo da Silva, Cecilia Dias Flores
IntroductionA discussion in literature about a standardized decision support tool for the management of thyroid nodules remains.ObjectiveThe purpose of this study was to create a statistical prediction model for thyroid nodules management.MethodsTwo hundred and four benign and 57 malignant thyroid nodules were selected for a retrospective study. The variables age, gender and ultrasonographic features were examined using univariate and multivariate models. A statistical formula was used to calculate the risk of cancer of each case.ResultsIn multivariate analysis, irregular shape, absence of halo, lower mean age, homogeneous echotexture, microcalcifications and solid content were associated with cancer. After applying the formula, 20 cases (7.6%) with a calculated risk for malignancy ≤3.0% were found, all of them benign. Setting the calculated risk in ≥80%, 21 (8.0%) cases were selected, and in 85.7% of them cancer was confirmed in histopathology. Internal accuracy of the prediction formula was 92.5%.ConclusionsThe prediction formula reached high accuracy and may be an alternative to other decision support tools for thyroid nodule management.
http://ift.tt/2hcfL9M
Σάββατο 4 Νοεμβρίου 2017
A predictive model to distinguish malignant and benign thyroid nodules based on age, gender and ultrasonographic features
Difficulty Concentrating in Generalized Anxiety Disorder: An Evaluation of Incremental Utility and Relationship to Worry
Source:Journal of Anxiety Disorders
Author(s): Lauren S. Hallion, Shari A. Steinman, Susan N. Kusmierski
Difficulty concentrating is one of the most common diagnostic criteria across DSM-5 categories, especially within the emotional (mood- and anxiety-related) disorders. A substantial literature has characterized cognitive functioning in emotional disorders using objective (behavioral) computerized cognitive tasks. However, diagnoses are typically formed on the basis of subjective (self-reported; clinician-rated) assessments of symptoms, and little is known about difficulty concentrating as a symptom. These questions are particularly important for generalized anxiety disorder (GAD), which has long been the subject of nosological debates, and for which several theoretical models that suggest a central role for cognitive impairments (including difficulty concentrating) in the maintenance of psychopathology have been proposed. The present study evaluated the incremental utility of difficulty concentrating and its relationship to worry and other symptoms in 175 GAD-diagnosed adults. Clinician-assessed difficulty concentrating incrementally predicted clinician-rated GAD, anxiety, and depression severity even after other GAD symptoms were controlled. Consistent with theoretical models of GAD that propose a direct relationship between worry and cognitive impairment, difficulty concentrating mediated the relationship between trait worry and clinical severity. These findings suggest that difficulty concentrating has value as a diagnostic criterion and is a potential mechanism by which worry increases distress and impairment.
http://ift.tt/2zehlyR
Metastatic non-small cell lung carcinoma a mimic of primary breast carcinoma—case series and literature review
Abstract
Metastatic tumors to the breast are rare but constitute a major diagnostic dilemma. Of these, non-mammary carcinomatous metastases to the breast are particularly challenging and, without a clinical history, may be extremely difficult to distinguish from primary breast carcinoma (PBC). We specifically studied metastatic tumors of pulmonary origin, as the lung is one of the major primary sites for carcinomatous metastasis to breast. Sixteen metastatic lung tumors to the breast were identified in our archives between 1996 and 2017 including 12 non-small cell lung carcinomas (NSCLC), one large-cell neuroendocrine, one atypical carcinoid, and two small-cell carcinomas. Adenocarcinoma was the most frequent amongst the NSCLCs (11/14). We retrieved the clinical information of these cases and reviewed the pathological characteristics to provide practical tools for pathologists to aid in their identification. Even in the absence of a clinical history of lung cancer, metastatic pulmonary adenocarcinoma to the breast should be considered in at least one of the following scenarios: (1) single or multiple well-circumscribed lesions of the breast that lack an in situ component and that are accompanied by distant metastases but negative axillary lymph nodes, (2) breast tumors that are triple negative yet not high-grade, or (3) breast tumors presenting as stage 4 disease and/or having an unusually aggressive clinical course on standard breast therapy. Accurate and timely diagnosis of these tumors is mandatory because of treatment and prognostic implications.
http://ift.tt/2AihkYx
Luminescent hybrid materials based on nanodiamonds
Publication date: Available online 4 November 2017
Source:Carbon
Author(s): Dongxue Zhang, Qi Zhao, Jinhao Zang, Ying-Jie Lu, Lin Dong, Chong-Xin Shan
Luminescent hybrid materials were prepared by covalently functionalizing nanodiamonds (NDs) with rare earth (RE) complexes. Pyromellitic acid (PMA), as the organic sensitizer, was grafted onto amino-terminated NDs to chelate lanthanide ions (Eu3+ and Tb3+). The emission colors of the hybrid composite of ND-PMA-EuxTby can be tuned from red to orange, yellow and green by adjusting the molar ratio of Eu3+ to Tb3+. Moreover, the luminescence of the hybrid composites exhibits remarkable photostability under ultraviolet irradiation for 60 h. As a proof-of-concept experiment, the as-synthesized ND-PMA-Eu and ND-PMA-Tb were employed as the phosphors for red and green light-emitting-diode (LED) devices with ultraviolet (UV) chips. Therefore, the nanodiamond-based luminescent hybrid material may find potential application in optical device.
Graphical abstract
http://ift.tt/2j3wtsp
Ratiometric Fluorescence Detection of Hydroxyl Radical Using Cyanine-Based Binary NanoGUMBOS
Publication date: Available online 4 November 2017
Source:Sensors and Actuators B: Chemical
Author(s): Mingyan Cong, Noureen Siraj, Nimisha Bhattarai, Paulina E. Kolic, Kevin S. McCarter, Pratap K. Chhotaray, Isiah M. Warner
Overproduction of reactive oxygen species (ROS) results in oxidative stress, which is closely associated with pathogenesis of many diseases. Visualized detection of ROS in situ enables deeper insight into the mechanisms that underlie such pathological and physiological processes. Among reactive species, selective detection of hydroxyl radical is the most challenging, due to high aggression and short life time of this specie. In this regard, we have developed a sensitive and selective ratiometric fluorescence nanoprobe for detection of hydroxyl radical. This probe is based on use of GUMBOS (a Group of Uniform Materials Based on Organic Salts) that are derived from 1,1′-diethyl-2,2′-cyanine iodide and 1,1′-diethyl-2,2′-carbocyanine iodide. Each GUMBOS exhibit different reactivity towards reactive species. Without any chemical linkage, these two GUMBOS were combined into a single nanomaterial to produce a ratiometric fluorescent sensing profile through Förster resonance energy transfer. This cyanine-based ratiometric nanoprobe exhibited high selectivity for the hydroxyl radical in comparison to other ROS, including superoxide anion, singlet oxygen, hydrogen peroxide, and peroxynitrite. Furthermore, detection of hydroxyl radical was successfully demonstrated by use of these binary nanoGUMBOS in vitro using hormone-independent human breast adenocarcinoma cells (MDA-MB-231).
http://ift.tt/2j0QqQF
In the cage
Source:Materials Today
Author(s): David Bradley
http://ift.tt/2zdDBJg
Researchers unlock the secrets of dragonfly wings
Source:Materials Today
Author(s): Cordelia Sealy
http://ift.tt/2hd1Sbi
Methanol means power
Source:Materials Today
Author(s): David Bradley
http://ift.tt/2ze7JUN
Throw it a curve and 2D becomes 3D
Source:Materials Today
Author(s): David Bradley
http://ift.tt/2hbR7pJ
2D materials make the grade for faster electronics
Source:Materials Today
Author(s): Cordelia Sealy
http://ift.tt/2zeKk5Q
Engineering vascularized and innervated bone biomaterials for improved skeletal tissue regeneration
Publication date: Available online 4 November 2017
Source:Materials Today
Author(s): Alessandra Marrella, Tae Yong Lee, Dong Hoon Lee, Sobha Karuthedom, Denata Syla, Aditya Chawla, Ali Khademhosseini, Hae Lin Jang
Blood vessels and nerve fibers are distributed throughout the entirety of skeletal tissue, and play important roles during bone development and fracture healing by supplying oxygen, nutrients, and cells. However, despite the successful development of bone mimetic materials that can replace damaged bone from a structural point of view, most of the available bone biomaterials often do not induce sufficient formation of blood vessels and nerves. In part, this is due to the difficulty of integrating and regulating multiple tissue types within artificial materials, which causes a gap between native skeletal tissues. Therefore, understanding the anatomy and underlying interaction mechanisms of blood vessels and nerve fibers in skeletal tissue is important to develop biomaterials that can recapitulate its complex microenvironment. In this perspective, we highlight the structure and osteogenic functions of the vascular and nervous systems in bone, in a coupled manner. In addition, we discuss important design criteria for engineering vascularized, innervated, and neurovascularized bone implant materials, as well as recent advances in the development of such biomaterials. We expect that bone implant materials with neurovascularized networks can more accurately mimic native skeletal tissue and improve the regeneration of bone tissue.
Graphical abstract
http://ift.tt/2hdiv70
Conductive polymer fibers support new applications
Source:Materials Today
Author(s): Cordelia Sealy
http://ift.tt/2hd1PfC
Insect wings inspire antibacterial coatings
Source:Materials Today
Author(s): Cordelia Sealy
http://ift.tt/2zeKiuK
Early developmental trajectories of preterm infants
Source:Research in Developmental Disabilities
Author(s): Maya Yaari, David Mankuta, Ayelet Harel- Gadassi, Edwa Friedlander, Benjamin Bar-Oz, Smadar Eventov-Friedman, Nimrod Maniv, David Zucker, Nurit Yirmiya
Background and objectivesPreterm infants are at risk for neuro-developmental impairments and atypical developmental trajectories. The aims of this study were to delineate early developmental trajectories of preterm and full-term infants.MethodsThe cognitive, language, and motor development of 149 infants – 19 extremely preterm (EPT), 34 very preterm (VPT), 57 moderately preterm (MPT), and 39 full-term (FT) – was evaluated using Mullen Scales at 1, 4, 8, 12, and 18 months. Mixed models were applied to examine group differences. Gender, maternal education, and neurobehavior were included as predictors of developmental trajectories.ResultsThe EPT and VPT infants achieved significantly lower scores than the FT infants in all domains, with a significantly increasing gap over time. The MPT infants' trajectories were more favorable than those of the EPT and VPT infants yet lower than the FT infants on the Visual Reception, Gross, and Fine Motor subscales. Male gender and lower maternal education were associated with lower scores that declined over time. Abnormal neonatal neurobehavior was associated lower Mullen scores and with less stability in scores over time.ConclusionsThe EPT and VPT infants were found to have disadvantages across all domains. The MPT infants revealed more favorable developmental trajectories yet displayed vulnerability compared to the FT infants. Gender, maternal education, and neonatal neurobehavior are important in predicting the developmental outcomes of preterm infants.
http://ift.tt/2zzHB7i
School bullying from a sociocultural perspective
Source:Aggression and Violent Behavior
Author(s): Rachel E. Maunder, Sarah Crafter
School bullying is an important concern. Whilst there is growing knowledge about the nature, extent and effects of school bullying, areas of complexity in research findings remain. In this paper we develop our thinking on school bullying using a sociocultural theoretical framework. We review existing literature around three main themes: 1) The conceptualisation and interpretation of bullying; 2) The relational aspects of bullying 3) Bullying as part of someone's life trajectory. For each theme, empirical findings are discussed to highlight key issues, and arguments presented from relevant sociocultural theories to provide insight in each case. During the paper, we show how varying strands of research into bullying can be integrated, and how areas of complexity can be explained. Adopting a sociocultural view of school bullying presents implications for both research and practice. Bullying is contextual, and attention should be given to the situated relationships and multiple settings surrounding the behaviour.
http://ift.tt/2zxvkQY
Fibroblast responses and antibacterial activity of Cu and Zn co-doped TiO2 for percutaneous implants
Publication date: 15 March 2018
Source:Applied Surface Science, Volume 434
Author(s): Lan Zhang, Jiaqi Guo, Ting Yan, Yong Han
In order to enhance skin integration and antibacterial activity of Ti percutaneous implants, microporous TiO2 coatings co-doped with different doses of Cu2+ and Zn2+ were directly fabricated on Ti via micro-arc oxidation (MAO). The structures of coatings were investigated; the behaviors of fibroblasts (L-929) as well as the response of Staphylococcus aureus (S. aureus) were evaluated. During the MAO process, a large number of micro-arc discharges forming on Ti performed as penetrating channels; O2−, Ca2+, Zn2+, Cu2+ and PO43− delivered via the channels, giving rise to the formation of doped TiO2. Surface characteristics including phase component, topography, surface roughness and wettability were almost the same for different coatings, whereas, the amount of Cu doped in TiO2 decreased with the increased Zn amount. Compared with Cu single-doped TiO2 (0.77Wt% Cu), the co-doped with appropriate amounts of Cu and Zn, for example, 0.55Wt% Cu and 2.53Wt% Zn, further improved proliferation of L-929, facilitated fibroblasts to switch to fibrotic phenotype, and enhanced synthesis of collagen I as well as the extracellular collagen secretion; the antibacterial properties including contact-killing and release-killing were also enhanced. By analyzing the relationship of Cu/Zn amount in TiO2 and the behaviors of L-929 and S. aureus, it can be deduced that when the doped Zn is in a low dose (<1.79Wt%), the behaviors of L-929 and S. aureus are sensitive to the reduced amount of Cu2+, whereas, Zn2+ plays a key role in accelerating fibroblast functions and reducing S. aureus when its dose obviously increases from 2.63 to 6.47Wt%.
Graphical abstract
http://ift.tt/2zwTA5R
Bacterial, archaeal, and fungal community responses to acid mine drainage-laden pollution in a rice paddy soil ecosystem
Publication date: March 2018
Source:Science of The Total Environment, Volumes 616–617
Author(s): Han Wang, Yufei Zeng, Chuling Guo, Yanping Bao, Guining Lu, John R. Reinfelder, Zhi Dang
Lacking sufficient clean water, the paddy soils along the Hengshi River have suffered from long-term acid mine drainage (AMD) contamination. The impacted cropland is too heavily contaminated to grow food safely. The microbial communities inhabiting the environment play pivotal roles in the crop growth, health, and ecological services. In this study, the bacterial, archaeal, and fungal communities in the impacted paddy soil were examined using high-throughput Illumina MiSeq sequencing. The results showed that AMD irrigation considerably enriched the bacterial phylum Acidobacteria and the archaeal phylum Crenarchaeota, while the fungal community was more stable. The abundances of Acidobacteria and Crenarchaeota were significantly positively correlated with the AMD-related environmental factors of pH and heavy metals (Cu, Pb, and Zn). In the most contaminated samples, communities were dominated by the bacteria Candidatus Solibacter and Candidatus Koribacter from the Acidobacteria family. Functional gene profile analysis demonstrated that the energy metabolic processes of the microbial communities, especially C/N related pathways, have adjusted and are well-adapted to tolerating AMD contamination. The present study described the structural and functional differentiation of microbial communities in the rice paddy soil under AMD irrigation. The results are useful for the development of bioremediation strategies using native microbes in the cleanup and biorestoration of AMD-contaminated agriculture soil.
Graphical abstract
http://ift.tt/2zx80D3
Re-designing a viable ELTs depolymerization in circular economy: Pyrolysis prototype demonstration at TRL 7, with energy optimization and carbonaceous materials production
Publication date: 10 February 2018
Source:Journal of Cleaner Production, Volume 174
Author(s): N. Antoniou, A. Zabaniotou
The present study aims to demonstrate challenge-based innovations of ELTs depolymerization, show evidence of promising developments and improve pyrolysis performance towards its economic viability. A pyrolysis prototype, with a ELTs mass flow rate of 20 kg h−1 was designed, constructed, and demonstrated. Up to 100 kg h−1 of steel-free tyre granulates were pyrolyzed for up to 100 h continuous operation. The tests were carried out at 550 °C, under atmospheric pressure and residence time ∼12 min with good reliability and reproducibility. All three pyrolysis products showed good fuel characteristics. The LHV of the obtained producer gas estimated to 23.5 MJ Nm−3 and 26% of the prototype energy requirements were provided by using the producer gas as fuel. Pyro-oil showed high carbon content (86.04 wt%), GCV of 44.2 MJ kg−1 and H/C ratio (1.74). Despite its higher sulphur content, pyro-oil is comparable to diesel fuel in all other characteristics. Chars exhibited high percentage of fixed carbon (>80 wt %) and a high GCV = 30.3 MJ kg−1. S, Zn and Si were detected in chars, at low concentration. Based on surface and structural characteristics, chars were considered comparable to carbon blacks of N400-N500 series. Upgrading of char to activated carbon by physical and chemical activation, increased N2 surface area to 589 m2 g−1 and 402 m2 g−1, respectively. The study contributes significantly to increase knowledge on the viability of pyrolysis, providing to the recycling sector an opportunity for the deployment of take-off systems, within a Circular Economy. End of Life Tyres (ELTs) pyrolysis can be viable, if all produced streams are valorized.
Graphical abstract
http://ift.tt/2zx43Ox
A novel DTI-QA tool: Automated metric extraction exploiting the sphericity of an agar filled phantom
Source:Magnetic Resonance Imaging, Volume 46
Author(s): Sofia Chavez, Joseph Viviano, Mojdeh Zamyadi, Peter B. Kingsley, Peter Kochunov, Stephen Strother, Aristotle Voineskos
PurposeTo develop a quality assurance (QA) tool (acquisition guidelines and automated processing) for diffusion tensor imaging (DTI) data using a common agar-based phantom used for fMRI QA. The goal is to produce a comprehensive set of automated, sensitive and robust QA metrics.MethodsA readily available agar phantom was scanned with and without parallel imaging reconstruction. Other scanning parameters were matched to the human scans. A central slab made up of either a thick slice or an average of a few slices, was extracted and all processing was performed on that image. The proposed QA relies on the creation of two ROIs for processing: (i) a preset central circular region of interest (ccROI) and (ii) a signal mask for all images in the dataset. The ccROI enables computation of average signal for SNR calculations as well as average FA values. The production of the signal masks enables automated measurements of eddy current and B0 inhomogeneity induced distortions by exploiting the sphericity of the phantom. Also, the signal masks allow automated background localization to assess levels of Nyquist ghosting.ResultsThe proposed DTI-QA was shown to produce eleven metrics which are robust yet sensitive to image quality changes within site and differences across sites. It can be performed in a reasonable amount of scan time (~15min) and the code for automated processing has been made publicly available.ConclusionsA novel DTI-QA tool has been proposed. It has been applied successfully on data from several scanners/platforms. The novelty lies in the exploitation of the sphericity of the phantom for distortion measurements. Other novel contributions are: the computation of an SNR value per gradient direction for the diffusion weighted images (DWIs) and an SNR value per non-DWI, an automated background detection for the Nyquist ghosting measurement and an error metric reflecting the contribution of EPI instability to the eddy current induced shape changes observed for DWIs.
http://ift.tt/2h5V63G
Magnetic Resonance Imaging with RF Encoding on Curved Natural Slices
Source:Magnetic Resonance Imaging
Author(s): Gordon E. Sarty, Logi Vidarrson
While the idea of using spatial encoding fields (SEM) for image formation has been proven, conventional wisdom still holds that a magnetic resonance imaging (MRI) system begins with a highly uniform magnetic field. In particular, radio frequency (RF) encoding MRIs designed and tested to date have largely used uniform magnetic fields. Here we demonstrate magnetic resonance imaging in a magnetic field with a built-in gradient that gives non-planar slices – curved surfaces – when the nuclear spins are excited with narrow band RF pulses. Image encoding on these naturally occurring non-planar slices was accomplished with RF encoding using a non-linear spatially varying B1 phase gradient. The imaging methods were demonstrated on a small prototype MRI instrument. The MRI has no switched magnetic field gradients – it is "gradient-free". A low field gradient-free MRI with low mass permanent magnets and simple, low power, RF encoding hardware is ideal for deployment on the International Space Station for the study of astronaut muscle and bone mass loss. Gradient-free natural slice encoding MRI designs would also be portable enough for application in remote terrestrial locations, in emergency rooms and in operating rooms where they can be used with minimally invasive and robotic surgery.
http://ift.tt/2ixVoAn
Utility of Shoulder Imaging in the Outpatient Setting: A Pilot Study
Source:Current Problems in Diagnostic Radiology
Author(s): Elisabeth R. Garwood, Gregory S Mittl, Michael J. Alaia, James Babb, Soterios Gyftopoulos
http://ift.tt/2zdU7Jh
Risk Factors for Late Screening Mammography
Source:Current Problems in Diagnostic Radiology
Author(s): John Davis, Juliana Liang, Matthew B. Petterson, Albert T. Roh, Navya Chundu, Paul Kang, Samantha L. Matz, Mary J. Connell, Daniel G. Gridley
BackgroundBreast cancer has the highest incidence of cancers in women in the United States. Previous research has shown that screening mammography contributes to reduced breast cancer mortality. This study aimed to clarify why late screening might occur in an at-risk population.Materials and MethodsThis study was a prospective cross-sectional study including 758 patients presenting to our radiology department for routine screening mammography who completed a 30-question survey regarding personal characteristics and mammography history. Univariate and multivariate logistic regression were performed to determine whether survey responses correlated with late screening.ResultsOf the 758 patients, 184 (24%) were noncompliant with screening mammography guidelines. Risk factors for late screening included younger age (p = 0.001), white race/ethnicity (p = 0.03), self-reported lack of financial means or health insurance (p = 0.005), lack of satisfaction with a previous mammogram experience (p = 0.001), inadequate mammography education by a physician (p = 0.001), and lack of awareness/comprehension of screening mammography guidelines (p = 0.002).ConclusionMany factors contribute to late screening mammography. Although some are outside physician control, others can be influenced: patient education regarding screening mammography guidelines, and patient satisfaction with the mammography experience. This study highlights the importance of communication with and education of patients.
http://ift.tt/2hgD2Y5
Human plasma C3 is essential for the development of memory B, but not T, lymphocytes
Primary or secondary plasma C3 deficiency due to mutations in C3 or in complement Factor I impairs memory B, but not T, cell differentiation, but does not preclude intracellular C3 fragment expression in lymphocytes.
http://ift.tt/2yvUGyo
An opportunistic route to success: towards a change of paradigm to fully exploit the potential of Cell-Penetrating Peptides
Publication date: Available online 4 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Estel Collado Camps, Roland Brock
About 25 years ago it was demonstrated that certain peptides possess the ability to cross the plasma membrane. This led to the development of cell-penetrating peptides (CPPs) as vectors to mediate the cellular entry of (macro-)molecules that do not show cell entry by themselves. Nonetheless, in spite of an early bloom of promising pre-clinical studies, not a single CPP-based drug has been approved, yet. It is a paradigm in CPP research that the peptides are taken up by virtually all cells. In exploratory research and early preclinical development, this assumption guides the choice of the therapeutic target. However, while this indiscriminatory uptake may be the case for tissue culture experiments, in an organism this is clearly not the case. Biodistribution analyses demonstrate that CPPs only target a very limited number of cells and many tissues are hardly reached at all. Here, we review biodistribution analyses of CPPs and CPP-based drug delivery systems. Based on this analysis we propose a paradigm change towards a more opportunistic approach in CPP research. The application of CPPs should focus on those pathophysiologies for which the relevant target cells have been shown to be targeted in vivo.
Graphical abstract
http://ift.tt/2yxiAJQ
Design, synthesis and biological mechanisms research on 1,2,3-triazole derivatives of Jiyuan Oridonin A
Publication date: Available online 4 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Yu Ke, Wang Wang, Long-Fei Zhao, Jian-Jia Liang, Ying Liu, Xiao Zhang, Kai Feng, Hong-Min Liu
Two series of derivatives with 1,2,3-triazole as heterocyclic moiety of Jiyuan Oridonin A, a new ent-kaurene diterpenoid which was isolated from genus Isodon rubescens, were synthesized and biologically evaluated. All the derivatives possessed good anti-proliferative activities. Among them, compound 8g was found to significantly induce cell apoptosis and cell cycle arrest in MGC-803 via a series of signals activated by the increased intracellular ROS levels.
Graphical abstract
http://ift.tt/2ywywfr
Exploiting a water network to achieve enthalpy-driven, bromodomain-selective BET inhibitors
Publication date: Available online 4 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): William R. Shadrick, Peter J. Slavish, Sergio C. Chai, Brett Waddell, Michele Connelly, Jonathan A. Low, Cynthia Tallant, Brandon M. Young, Nagakumar Bharatham, Stefan Knapp, Vincent A. Boyd, Marie Morfouace, Martine F. Roussel, Taosheng Chen, Richard E. Lee, R. Kiplin Guy, Anang A. Shelat, Philip M. Potter
Within the last decade, the Bromodomain and Extra-Terminal domain family (BET) of proteins have emerged as promising drug targets in diverse clinical indications including oncology, auto-immune disease, heart failure, and male contraception. The BET family consists of four isoforms (BRD2, BRD3, BRD4, and BRDT/BRDT6) which are distinguished by the presence of two tandem bromodomains (BD1 and BD2) that independently recognize acetylated-lysine (KAc) residues and appear to have distinct biological roles. BET BD1 and BD2 bromodomains differ at five positions near the substrate binding pocket: the variation in the ZA channel induces different water networks nearby. We designed a set of congeneric 2- and 3-heteroaryl substituted tetrahydroquinolines (THQ) to differentially engage bound waters in the ZA channel with the goal of achieving bromodomain selectivity. SJ830599 (9) showed modest, but consistent, selectivity for BRD2-BD2. Using isothermal titration calorimetry, we showed that the binding of all THQ analogs in our study to either of the two bromodomains was enthalpy driven. Remarkably, the binding of 9 to BRD2-BD2 was marked by negative entropy and was entirely driven by enthalpy, consistent with significant restriction of conformational flexibility and/or engagement with bound waters. Co-crystallography studies confirmed that 9 did indeed stabilize a water-mediated hydrogen bond network. Finally, we report that 9 retained cytotoxicity against several pediatric cancer cell lines with EC50 values comparable to BET inhibitor (BETi) clinical candidates.
Graphical abstract
http://ift.tt/2yvSJly
Design, synthesis, and biological evaluation of thieno[2,3-d]pyrimidine derivatives as novel dual c-Met and VEGFR-2 kinase inhibitors
Publication date: Available online 4 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Jieming Li, Weijie Gu, Xinzhou Bi, Huilan Li, Chen Liao, Chunxia Liu, Wenlong Huang, Hai Qian
Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report a series of potent dual c-Met and VEGFR-2 inhibitors bearing thieno[2,3-d]pyrimidine scaffold. The cell proliferation assay in vitro demonstrated that most target compounds had inhibition potency both on c-Met and VEGFR-2 with IC50 values in nanomolar range, especially compound 12j and 12m. Based on the further enzyme assay in vitro, compound 12j was considered as the most potent one, the IC50 values of which were 25 nM and 48 nM for c-Met and VEGFR-2, respectively. Following that, we docked the compound 12j with the proteins c-Met and VEGFR-2, and interpreted the SAR of these analogues. All the results indicate that 12j is a dual inhibitors of c-Met and VEGFR-2 that holds promising potential.
Graphical abstract
http://ift.tt/2yvPsCL
Nose-to-brain peptide delivery – the potential of nanotechnology
Publication date: Available online 4 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Eleni Samaridou, María José Alonso
Nose-to-Brain (N-to-B) delivery offers to protein and peptide drugs the possibility to reach the brain in a non-invasive way. This article is a comprehensive review of the state-of-the-art of this emerging peptide delivery route, as well as of the challenges associated to it. Emphasis is given on the potential of nanosized drug delivery carriers to enhance the direct N-to-B transport of protein or peptide drugs. In particular, polymer- and lipid- based nanocarriers are comparatively analyzed in terms of the influence of their physicochemical characteristics and composition on their in vivo fate and efficacy. The use of biorecognitive ligands and permeation enhancers in order to enhance their brain targeting efficiency is also discussed. The article concludes highlighting the early stage of this research field and its still unveiled potential. The final message is that more explicatory PK/PD studies are required in order to achieve the translation from preclinical to the clinical development phase.
Graphical abstract
http://ift.tt/2yvfR3U
Design, synthesis and evaluation of 3-arylidene azetidin-2-ones as potential antifungal agents against Alternaria solani Sorauer
Publication date: Available online 4 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Wang Delong, Wu Yongling, Wang Lanying, Feng Juntao, Zhang Xing
A new concise and facile method was explored to synthesize a collection of new 3-arylidene azetidin-2-ones, which could be regarded as the derivatives of the hybrid scaffold of bioactive natural cinnamamide and heterocycle azetidi-2-one. The structures of the synthesized compounds were characterized by 1H-, 13C NMR, and MS; and their antifungal activity were evaluated against Alternaria solani Sorauer. These antifungal data were subjected to a quantitative structure–activity relationship (QSAR) analysis using Codessa software on the basis of the results from B3LYP/6-31G(d,p) quantum calculations. The best regressive model revealed that potentially more active compounds should have low dipole moments and QC-min (minimal net atomic charge for a C atom), and high QO-max (maximal net atomic charge for an O atom) and QN-min (minimal net atomic charge for an N atom). The most potent compound 7k could lead to intracellular accumulation of reactive oxygen species, dissipation of mitochondrial transmembrane potential, and an autophagy-like cell death process in A. solani Sorauer. Taken together, these results laid the foundation for further design of improved crop-protection agents based on this hybrid scaffold.
Graphical abstract
http://ift.tt/2yuFZf3
Synthesis and biological evaluation of isobutyrophenone analogs as potential inhibitors of class-II fructose-1,6-bisphosphate aldolase
Publication date: Available online 4 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Ding Li, Tuong Thi Mai Luong, Wen-Jia Dan, Yanliang Ren, Hoang Xuan Nien, An-Ling Zhang, Jin-Ming Gao
Several recently identified antifungal compounds share the backbone structure of acetophenones. The aim of the present study was to develop new isobutyrophenone analogs as new antifungal agents. A series of new 2,4-dihydroxy-5-methyl isobutyrophenone derivatives were prepared and characterized by 1H, 13C NMR and MS spectroscopic data. These products were evaluated for in vitro antifungal activities against seven plant fungal pathogens by the mycelial growth inhibitory rate assay. Compounds 3, 4a, 5a, 5b, 5e, 5f and 5g showed a broad-spectrum high antifungal activity. On the other hand, for the first time, these compounds were also assayed as potential inhibitors against Class II fructose-1,6-bisphosphate aldolase (Fba) from the rice blast fungus, Magnaporthe grisea. Compounds 5e and 5g were found to exhibit the inhibition constants (Ki) for 15.12 and 14.27 μM, respectively, as the strongest competitive inhibitors against Fba activity. The possible binding-modes of compounds 5e and 5g were further analyzed by molecular docking algorithms. The results strongly suggested that compound 5g could be a promising lead for the discovery of new fungicides via targeting Class II Fba.
Graphical abstract
http://ift.tt/2yvfBSu
Identification of cytotoxic, glutathione-reactive moieties inducing accumulation of reactive oxygen species via glutathione depletion
Publication date: Available online 4 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Julian Wilke, Tatsuro Kawamura, Nobumoto Watanabe, Hiroyuki Osada, Slava Ziegler, Herbert Waldmann
Reactive oxygen species (ROS) play an essential role in the survival and progression of cancer. Moderate oxidative stress drives proliferation, whereas high levels of ROS induce cytotoxicity. Compared to cancer cells, healthy cells often exhibit lower levels of oxidative stress. Elevation of cellular ROS levels by small molecules could therefore induce cancer-specific cytotoxicity. We have employed high-throughput phenotypic screening to identify inducers of ROS accumulation. We found 4,5-dihalo-2-methylpyridazin-3-one (DHMP) and 2,3,4,5(6)-tetrachloro-6(5)-methylpyridine (TCMP) moieties to strongly deplete GSH, to cause ROS accumulation and to induce cell death.. Small molecules containing these fragments will most likely share the same properties and should therefore be carefully considered in the development of bioactive molecules.
Graphical abstract
http://ift.tt/2yvGMwr
Peptide Therapeutics for the Treatment of Gastrointestinal Disorders
Publication date: Available online 4 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Angelika Fretzen
Graphical abstract
http://ift.tt/2yvFsJQ
Features and influencing factors of nitrogen and phosphorus diffusive fluxes at the sediment-water interface of Erhai Lake
Abstract
Nitrogen and phosphorus diffusion at the sediment-water interface is vital to the water quality of lakes. In this paper, N and P diffusive fluxes at the sediment-water interface in Erhai Lake were studied using the sediment-pore water diffusive flux method. Characteristics of temporal and spatial variation of N and P diffusive fluxes were analyzed. Effects of the physicochemical properties of sediments and overlying water were discussed. Results showed that (1) the total N and P diffusive fluxes at the sediment-water interface of Erhai Lake are relatively low. The diffusive flux of ammonia nitrogen is 8.97~74.84 mgd−1 m−2, higher in the middle of the lake, followed by the northern and southern regions successively. The P diffusive flux is −0.007~0.050 mgd−1 m−2, higher in northern region of the lake, followed by middle and southern regions successively. The annual N diffusive flux has two peaks, and the higher peak is in September. The annual P diffusive flux shows a "V-shaped" variation, reaching the valley in July. N and P diffusive fluxes decrease with an increase of sediment depth. Overall, N and P diffusive fluxes at the sediment-water interface in Erhai Lake show different temporal and spatial variation. (2) Aquatic plants promote N and P diffusion at the sediment-water interface in Erhai Lake. The pH, DO, and SD of the overlying water are important influencing factors for the P diffusive flux. P diffusive flux is inversely proportional to the total phosphorous (TP) concentration of the overlying water. The physicochemical environment of overlying water slightly influences the N diffusive flux. The activity of sediments and the organic content are two main influencing factors of N diffusive flux, while P content and morphology of sediments are the main influencing factors of P diffusive flux. Iron and manganese ions are important elements that influence N and P diffusive fluxes at the sediment-water interface. (3) The P diffusive flux at the sediment-water interface in Erhai Lake is mainly affected by the physical and chemical properties of water, whereas the N diffusive flux is mainly influenced by the mineralization of organic matter in sediments. The P diffusive flux at the sediment-water interface is sensitive to the overlying water quality. Sediment transformation from "source" to "sink" was observed in 1 year. On the contrary, N diffusive flux is less sensitive to lake water quality. Endogenetic pollutant control in Erhai Lake should focus on P control.
http://ift.tt/2yvHmKq
Histological liver chances in Swiss mice caused by tannery effluent
Abstract
Although tannery effluents are known for being highly toxic to organisms, reports about the effects of the intake of these xenobiotics on experimental mammal models are recent. Studies about the damages the chronic intake of these effluents can cause in the liver of outbred mice remain an unexplored field. Thus, the aim of the present study is to assess (histological) the hepatic condition of Swiss mice (outbred strain) chronically exposed to the intake of different raw tannery effluent concentrations diluted in water for 150 days. Accordingly, the mice (males and females) were divided in the following groups: control group—animals treated with drinking water, only; and groups 5 and 10%—treated with raw tannery effluent diluted in water. After exposure, the animals were subjected to euthanasia for liver fragment sample collection and histological analysis, respectively. Moderate hydropic degeneration was observed in the centrilobular regions of the liver of mice exposed to 5 and 10% tannery effluent, as well as greater amounts of hepatocytes presenting karyomegaly and necrotic hepatocytes, and a smaller amount of Kuffer cells in the liver of mice exposed to the xenobiotic. Finally, animals exposed to 10% tannery effluent showed mild hyperplasia of the bile ducts in the portal areas and fibroblast proliferation around the bile ducts, thus suggesting a fibrous process. Except for the frequency of hepatocytes presenting karyomegaly (lower in females), the herein observed hepatic changes were similar in male and female Swiss mice. Accordingly, the present data support the hypothesis that the chronic intake of tannery effluent by outbred mice (Swiss) causes damages in the liver, a fact that broadens the knowledge about the toxic potential of this pollutant, which goes beyond that of C57Bl/6J male mice (inbred strain).
http://ift.tt/2lRKBpC
Extreme Violence and the Invisibility of Women Who Murder: The Intersectionality of Gender, Race, Ethnicity, Sexual Orientation, and Gender Identity Equals Silence
Violence and Gender , Vol. 0, No. 0.
http://ift.tt/2lT7wRk
Nitrogen deposition reduces the cover of biocrust-forming lichens and soil pigment content in a semiarid Mediterranean shrubland
Abstract
Biocrusts are key drivers of the structure and functioning of drylands and are very sensitive to disturbance, including atmospheric nitrogen (N) deposition. We studied the impacts of simulated N deposition on biocrust community composition and soil photosynthetic and photoprotective pigment content after five years of N application in a European semiarid Mediterranean shrubland. The experiment consisted in six experimental blocks with four plots, each receiving 0, 10, 20, or 50 kg NH4NO3-N ha−1 year−1 + 6–7 kg N ha−1 year−1 background. After 5 years of N application, total lichen cover decreased up to 50% compared to control conditions and these changes were only clearly evident when evaluated from a temporal perspective (i.e. as the percentage of change from the first survey in 2008 to the last survey in 2012). In contrast, moss cover did not change in response to N, suggesting that biocrust community alterations operate via species- and functional group-specific effects. Interestingly, between-year variations in biocrust cover tracked variations in autumnal precipitation, showing that these communities are more dynamic than previously thought. Biocrust species alterations in response to N were, however, often secondary when compared to the role of ecologically relevant drivers such as soil pH and shrub cover, which greatly determined the composition and inter-annual dynamics of the biocrust community. Similarly, cyanobacterial abundance and soil pigment concentration were greatly determined by biotic and abiotic interactions, soil pH for pigments, and organic matter content and shrub cover for cyanobacteria. Biocrusts, and particularly the lichen component, are highly sensitive to N deposition and their responses to pollutant N can be best understood when evaluated from a temporal and multivariate perspective, including impacts mediated by interactions with biotic and abiotic drivers.
http://ift.tt/2zeF2oq
Silver bioaccumulation in chironomid larvae as a potential source for upper trophic levels: a study case from northern Patagonia
Abstract
Silver (Ag) is a pollutant of high concern in aquatic ecosystems, considered among the most toxic metallic ions. In lacustrine environments, contaminated sediments are a source of Ag for the food web. Chironomidae (Insecta: Diptera) are the most abundant, diverse, and representative insect groups in aquatic ecosystems. Chironomid larvae are closely associated to benthic substrates and link primary producers and secondary consumers. Given their trophic position and their life habits, these larvae can be considered the entry point for the transference of Ag, from the benthic deposit to the higher trophic levels of the food web. Previous studies in lakes from Nahuel Huapi National Park (Northern Patagonia) showed Ag enrichment over background levels (0.04–0.1 μg g−1 dry weight) both in biota (bivalves and fish liver) and sediments from sites near human settlements. The aim of this study was to analyze the role of chironomids in the transference of Ag from the benthic reservoir of Lake Moreno Oeste to the food web. The concentration of Ag in chironomid larvae tissue ranged from 0.1 to 1.5 μg g−1 dry weight, reaching a bioaccumulation factor up to 17 over substrates and depending on the associated substrate type, feeding habitats, larval stage, and season. The main Ag transfer to higher trophic levels by chironomids occurs in the littoral zone, mostly from larvae inhabiting submerged vegetation (Myriophyllum quitense) and sediment from vegetated zones. This study presents novel evidence of the doorway role played by chironomid larvae in Ag pathways from the sediments into food webs of freshwater ecosystems.
http://ift.tt/2y2PWME
Debates in allergy, regarding the symposium on: “Position Statements and Therapeutic Guidelines”
Publication date: Available online 3 November 2017
Source:Allergologia et Immunopathologia
Author(s): P. Rodríguez del Río, A. Cisteró-Bahima, R. van Ree
http://ift.tt/2zgIIIK
Predictive biomarkers in allergen specific immunotherapy
Publication date: Available online 3 November 2017
Source:Allergologia et Immunopathologia
Author(s): D. Barber, M.M. Escribese
http://ift.tt/2hcKvHJ
Biologics in the treatment of severe asthma
Publication date: Available online 3 November 2017
Source:Allergologia et Immunopathologia
Author(s): S. Quirce, E. Phillips-Angles, J. Domínguez-Ortega, P. Barranco
Severe asthma is defined as asthma which requires treatment with high dose inhaled corticosteroids and with a second controller drug to prevent it from becoming uncontrolled or which remains uncontrolled despite this therapy. Patients with uncontrolled severe asthma require additional treatment options as add-on therapy, including biologics. Biologic therapies in asthma are designed to block key immune regulators, such as IgE, or certain pro-inflammatory cytokines, e.g. interleukin (IL)-5, IL-4, IL-13 or IL-17. Patients with severe asthma and eosinophilic phenotype may benefit from biologic therapies aimed at reducing blood and tissue eosinophils, such as mepolizumab, reslizumab and benralizumab. Patients with Th2-high phenotype may also benefit from therapy with anti-IL-4/anti-IL-13 monoclonal antibodies (dupilumab). The main limitations of asthma treatment with biologic agents are the crossover and overlap of the different pathways in the pathogenesis of asthma which may cause lack of complete success of these therapies, in addition of high costs, which make pharmacoeconomic studies necessary to identify the ideal target patient population to receive these biologic drugs.
http://ift.tt/2zg17VO
New insight into cancer immunotherapy
Publication date: Available online 3 November 2017
Source:Allergologia et Immunopathologia
Author(s): M.M. Escribese, D. Barber
A key point for maintenance of the immune system homeostasis is the balance between the capacity to recognize and fight exogenous molecules and the capacity to avoid auto reactivity. The disruption of this balance induces the progression of several immune diseases such as autoimmune diseases, allergies, infections or cancer.A promising therapeutic approach to treat these diseases is immunotherapy. In cancer, both active and passive immunotherapies have been tested with promising results, such as the blocking of immunological checkpoints like CTLA-4 and PD-1. These treatments, in the market since a few years ago, aim to redirect the patient's immunological response by inhibiting the induction of regulatory T cells, both in the priming and effector phases.This strategy sheds light on the immunological mechanisms that control the regulatory response mediated by T cells and opens new lines of research into other immunological diseases such as allergy, in which the induction of a regulatory response is necessary to avoid allergic progression and which is the main objective of allergen-specific immunotherapies available today.
http://ift.tt/2hgoqId
Biologics in chronic urticaria
Publication date: Available online 3 November 2017
Source:Allergologia et Immunopathologia
Author(s): M. Ferrer, R. Madamba
http://ift.tt/2zgIBgi
Worldwide allergen immunotherapy guidelines: Evidence and experience-based
Publication date: Available online 3 November 2017
Source:Allergologia et Immunopathologia
Author(s): D.E.S. Larenas-Linnemann
http://ift.tt/2hdLXK5
Proposals for harmonization of allergens regulation in the European Union
Publication date: Available online 3 November 2017
Source:Allergologia et Immunopathologia
Author(s): M. Timón
Allergen medicinal products in the European Union are regulated differently across the different Member States. Thus, whereas in some countries strict quality, safety and efficacy requirements are in place, in others, most allergens are on the market as Named Patient Products, without any regulatory oversight. This situation results on European allergic patients being exposed to totally different standards depending on where they live. Initiatives to correct this situation are needed.
http://ift.tt/2zdhgLU
Non-allergenic immunotherapy
Publication date: Available online 3 November 2017
Source:Allergologia et Immunopathologia
Author(s): E. Ibáñez Echevarría, J. Bartra Tomás, D. Hernández Fernández de Rojas
http://ift.tt/2hcwjyy
Epicutaneous immunotherapy
Publication date: Available online 3 November 2017
Source:Allergologia et Immunopathologia
Author(s): S. Scheurer, M. Toda
http://ift.tt/2zg138w
Gold nanostar-mediated neural activity control using plasmonic photothermal effects
Source:Biomaterials, Volume 153
Author(s): Jee Woong Lee, Hyunjun Jung, Hui Hun Cho, Jung Heon Lee, Yoonkey Nam
Nanomaterials have emerged as an essential tool for the understanding of cellular level mechanism in the fields of biology and medical science. Recently, researchers have been studying the regulation of neuronal activity using plasmonic nanoparticles and light, and it has been reported that photothermal effects could lead to both excitation and inhibition of neuronal cells. So far, only a few photothermal transducers have been applied to modulate neural activity. In this paper, we synthesized biocompatible gold nanostars (AuNSs) which generate heat by absorbing near-infrared (NIR) light. And we used the AuNS to inhibit the activity of neurons through light stimulation. We have demonstrated that AuNS inhibits the neural activity by NIR laser in both chip-attached mode and cell-attached mode. We also confirmed the suppression of single neuron signal by using digital micromirror device (DMD) set up. This approach is possible to inhibit the neural firing by controlling the intensity of light, and overcome the disadvantages of conventional electrochemical stimulation methods. This method of NIR-mediated stimulating neurons using light sensitive AuNS will be a powerful tool for neuromodulation researches and neuroscience studies.
http://ift.tt/2zwOXZh
A language non-specific speech test to evaluate the speech of cleft patients from different language and cultural backgrounds - A pilot study
Cleft speech tests are not universally available. We have developed a tool to fill this gap, especially in the context of a cleft mission setting. We performed a pilot study to evaluate the test's ability to differentiate between the speech of cleft patients and healthy individuals from three different language backgrounds.We used 78 made-up, nonsensical syllables to evaluate hypernasality, nasal emissions, and consonant errors. Cleft (n = 41) and non-cleft (n = 39) individuals from three countries were included in this study.
http://ift.tt/2j4k73v
Diagnostic dilemmas in chronic inflammatory bowel disease
Abstract
Histopathological assessment of biopsy and resection specimens of chronic inflammatory bowel disease (CIBD), or possible CIBD, forms a significant component of the routine workload in most tissue pathology laboratories. In this review, we have chosen selected areas of particular diagnostic difficulty in CIBD pathology, providing key advice for pathology reporting. Those mimics of CIBD which have the greatest potential for misdiagnosis are discussed, particularly the wide range of infectious colitides which represent possible diagnostic pitfalls. The most important distinguishing features between the two main forms of CIBD, ulcerative colitis and Crohn's disease, are addressed, first in relation to resection specimens, and then with emphasis on features which may also be diagnostically useful in endoscopic biopsy material. The importance of assessment of the index endoscopic specimen is stressed, before treatment has been instigated, along with careful correlation with clinical and endoscopic features. Problems in the assessment of post-surgical CIBD specimens are described and then the role of upper gastrointestinal pathology specimens in diagnosing both Crohn's disease and ulcerative colitis, with increased recognition of upper gastrointestinal tract involvement in the latter condition. Finally, with recent developments in endoscopic surveillance techniques and local excision options, modern approaches to reporting and managing neoplasia complicating CIBD are reviewed.
http://ift.tt/2A8w23r
Gypsophila elegans isoorientin-2″-O-α-l-arabinopyranosyl ameliorates porcine serum-induced immune liver fibrosis by inhibiting NF-κB signaling pathway and suppressing HSC activation
Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Facheng Bai, Quanfang Huang, Jinbin Wei, Shujuan Lv, Yuxin Chen, Chunhong Liang, Ling Wei, Zhongpeng Lu, Xing Lin
The present study was to investigate the inhibitory effect of Gypsophila elegans isoorientin-2″-O-α-l-arabinopyranosyl (GEI) on hepatic stellate cells (HSCs), to reveal the underlying mechanism of GEI against hepatic fibrosis. Our study showed that GEI significantly alleviated liver injury induced by porcine serum (PS) in rats; it notably alleviated collagen accumulation as evidenced by a significant decrease in the levels of collagen biomarkers including hyaluronic acid, laminin, hydroxyproline and procollagen III N-terminal peptide. Moreover, GEI treatment markedly decreased the secretion of inflammatory cytokines by inhibiting the NF-κB pathway and significantly inhibited the generation of excessive extracellular matrix (ECM) components by restoring the balance between matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases (TIMPs). Additionally, the cell experiments in vitro showed that GEI strongly inhibited HSC proliferation, migration and clonogenicity and markedly induced HSC apoptosis. Moreover, GEI caused cell cycle arrest at G2 phase. In conclusion, our study demonstrates that GEI significantly alleviates PS-induced hepatic fibrosis by inhibiting the NF-κB pathway, restoring the balance between MMPs and TIMPs, and suppressing HSC activation.
http://ift.tt/2zxEbC8
Elevated expression of miR-146, miR-139 and miR-340 involved in regulating Th1/Th2 balance with acute exposure of fine particulate matter in mice
Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Tianfang Hou, Jiping Liao, Cheng Zhang, Chao Sun, Xueying Li, Guangfa Wang
Airborne fine particulate matter (PM2.5) is detrimental to human health, and frequently leads to a variety of lung diseases. Recently, IARC conclude that particulate matter is carcinogenic to humans (level one). However, the pulmonary toxicological mechanism induced by PM2.5 remains obscure. Our previous studies confirmed that PM2.5 hurt the human immune system by means of causing the imbalance of Th1/Th2 lymphocytes. MicroRNAs (miRNAs) are post-transcriptional gene suppressors and potential mediators of environmental effects, which play an important role in the regulation of CD4+T lymphocyte differentiation. In order to further understand the roles of microRNAs in regulating the imbalance of Th1/Th2 differentiation triggered by PM2.5, mice were subjected to intratracheal instillation of 2.5, 10, or 20mg/kg PM2.5 in this study. Mice were euthanized on the 1st, 7th and 14th day to screen out differential miRNAs in lung tissue by employing the miRNA microarray. The expression levels of IL-4 and IFN-γ in bronchoalveolar lavage fluid (BALF) were quantified by ELISA and their mRNA expressions in lung tissue were detected by qRT-PCR. The experiment demonstrated that 10 differential miRNAs (miR-146a, -146b, -139, -129, -340, -691, -181a, -155, -21-3p, and -21-5p) were up-regulated. IL-4 levels were found decreased, nevertheless, IFN-γ levels were increased, and the IL-4/IFN-γ ratio was inclined to Th1 shifting. Besides that, we also found that miRNA-691, -181a, -146a, -146b, -21a-3p, -21a-5p, and -340 had a positive linear correlation with BALF IFN-γ, while a negative linear correlation between microRNAs (miR-146, -139, -340, -21, and -181a) and the IL-4/IFN-γ level of BALF was observed. In conclusion, elevated microRNAs profiles correlated with T lymphocyte immune imbalance, driving a Th1-biased immune response after acute PM2.5 exposure. These findings improve our understanding of the toxicological pathways of PM2.5 exposure.
http://ift.tt/2zljMzp
TRPM2 dependence of ROS-induced NLRP3 activation in Alzheimer's disease
Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Malihe Aminzadeh, Mehrdad Roghani, Azadeh Sarfallah, Gholam Hossein Riazi
Recent studies have shown that neuroinflammation plays an important role in Alzheimer's disease (AD). Microglial cells are responsible for the phagocytosis of Amyloid-β (Aβ). However, it has been demonstrated that in AD patients the efficiency of phagocytosis decreases due to proinflammatory cytokines, such as Interleukin-1β (IL-1β), which is produced through the activation of NLRP3 inflammasome. In this study, we aimed at deciphering the mechanism underlying the NLRP3 activation. The results showed that Aβ induces an increase in the level of reactive oxygen species (ROS). According to this study, ROS produced from both mitochondria and NADPH oxidase was responsible for NLRP3 activation. In addition, it was observed that this high level of ROS activated the transient receptor potential melastatin 2 (TRPM2) channel, which causes an increase in the level of intracellular calcium. The results demonstrated that in the absence of intracellular calcium, caspase-1 cannot be activated and therefore the level of IL-1β decreases. Altogether, our findings supported the role of TRPM2 channel in ROS-induced NLRP3 activation in microglial cells through the exposure to Aβ.
http://ift.tt/2zycf16
Study the effects of mesenchymal stem cell conditioned medium injection in mouse model of acute colitis
Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Sedigheh Pouya, Maryam Heidari, Kaveh Baghaei, Hamid Asadzadeh Aghdaei, Afshin Moradi, Saeed Namaki, Mohammad Reza Zali, Seyed Mahmoud Hashemi
Background and aimInflammatory bowel disease (IBD) is an autoimmune-inflammatory disorder that results in inflammatory responses in individuals who are genetically susceptible. Uncontrolled inflammation in Crohn's disease (CD) or Ulcerative colitis (UC) affects the patient quality of life. Current therapies are not completely effective while cell therapy, especially the treatment with mesenchymal stem cells (MSCs) absorb lots of attention due to its immunomodulatory properties. So, we examined the effects of mesenchymal stem cells-conditioned medium (MSC-CM) in the experimental model of acute colitis.Material and methodMSC-CM was isolated from C57Bl/6 male mice and stored. The acute colitis induction in C57BL/6 mice was performed by dissolving dextran sulfate sodium (DSS) in drinking water and then CM injected intraperitoneally. During the study body weight changes, bleeding, stool consistency, disease activity index (DAI), mortality rate, weight and length of the colon and histopathological analysis were recorded as well as changes in the percentage of Treg cells. The level of IL-17, IL-10, and TGF-β were measured, too. Data were reported as mean±SD and analyzed by One-Way ANOVA test.ResultsBased on the results it is recognized CM inhibited the weight loss and bleeding and improved fecal consistency and DAI. Macroscopic examination of the colon showed that after infusion, colon inflammation was reduced and histopathological analysis showed a decrease in mucosal degeneration. The percentage of Treg cells, secretion of IL-10 and TGF-β was increased while the IL-17 level was reduced.ConclusionThis study showed that mesenchymal stem cell secretion with immunomodulatory properties has the potential to reduce inflammatory responses.
Graphical abstract
http://ift.tt/2zir6M8
Corrigendum to “The possible role of interleukin-35 and its therapeutic potential in pemphigus” [Int. Immunol. 42 (2017) 11–17]
Publication date: Available online 4 November 2017
Source:International Immunopharmacology
Author(s): Soheil Tavakolpour, Forough Kheiry, Hajar SadatMirsafaei, Meisam Akhlaghdoust
http://ift.tt/2zkzwT1
Erratum to “Descendens vagohypoglossi: rare variant of the superior root of ansa cervicalis” [Br J Oral Maxillofac Surg 55 (2017) 834–5]
The publisher regrets that S. B. Nayak's initial appeared incorrectly in the original article. It appears correctly above.
http://ift.tt/2zf0SrQ
C-reactive protein concentration as a prognostic factor for inflammation in the management of odontogenic infections
Our aim was to find out if it is possible to correlate the duration of stay in hospital, the severity of infection, involvement of particular anatomical spaces, white cell count, efficacy of surgical treatment, and fever with C-reactive protein (CRP) concentrations on admission. One hundred patients met our inclusion criteria. After their notes had been examined they were subdivided according to whether the infection of the main facial space involved was less severe, moderately severe, or very severe.
http://ift.tt/2y1bQzF
Generations of oral and maxillofacial surgeons have read Maxillofacial Surgery for preparation for their...
Generations of oral and maxillofacial surgeons have read Maxillofacial Surgery for preparation for their FRCS examination or as "the" reference book. This third edition is led by Peter Brennan and continues to provide an update and review of the essential elements that encompass oral and maxillofacial surgical practice.
http://ift.tt/2zf10HP
Impact of rehabilitation intensity on mortality risk after stroke
Publication date: Available online 3 November 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Cheng-Yang Hsieh, Hsiu-Chen Huang, Darren Philbert Wu, Chung-Yi Li, Meng-Jun Chiu, Sheng-Feng Sung
ObjectiveTo determine the relationship between rehabilitation intensity and post-stroke mortality.DesignRetrospective cohort study.Setting: Nationwide claims data.ParticipantsFrom Taiwan's National Health Insurance claims databases, a total of 6737 patients (mean age 66.9 years; 40.3% women) hospitalized between 2001 and 2013 for a first-ever stroke who had mild to moderate stroke and survived the first 90 days of stroke were enrolled.InterventionThe intensity of rehabilitation therapy within 90 days after stroke was categorized into low, medium, or high based on the tertile distribution of the amount of rehabilitation sessions.Main Outcome MeasuresLong-term all-cause mortality. The Cox proportional hazard models with Bonferroni correction were used to assess the association between rehabilitation intensity and mortality, adjusting for age, comorbidities, stroke severity, and other covariates.ResultsPatients in the high-intensity group were younger but had a higher burden of comorbidities and greater stroke severity. During follow-up, the high-intensity group was associated with a significantly lower adjusted risk (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.63–0.84) of mortality compared with the low-intensity group, whereas the medium-intensity group carried a similar risk of mortality (HR 0.94, 95% CI 0.84–1.06) to the low-intensity group. This association was not modified by stroke severity.ConclusionsAmong stroke patients with mild to moderate severity, high-intensity rehabilitation therapy within the first 90 days was associated with a lower mortality risk compared to low-intensity therapy. Efforts to promote high-intensity rehabilitation therapy for this group of stroke patients should be encouraged.
http://ift.tt/2heo5pF
Dual-Task of Fine Motor skill and Problem-Solving in Individuals with Multiple Sclerosis: A pilot study
Publication date: Available online 3 November 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Y. Goverover, B.M. Sandroff, J. DeLuca
ObjectiveTo examine and compare dual-task performance in patients with Multiple Sclerosis (MS) and healthy controls (HC) using mathematical problem-solving questions that included an everyday competence component while performing an upper extremity fine motor task. Additionally, it examined whether difficulties in dual-task performance are associated with problems in performing an everyday internet task.DesignPilot study, mixed-design with both a within and between subjects' factorParticipantsand Setting: Participants included 19 persons with MS and 19 HC who were recruited from a nonprofit rehabilitation research institution and from the community.InterventionsNot applicableOutcomesParticipant were presented with two testing conditions—solving mathematical everyday problems or placing bolts into divots (single-task condition) vs. solving problems while putting bolts into divots (dual-task condition). Additionally, participants were required to perform a test of everyday Internet competence.ResultsAs expected, dual-task performance was significantly worse than either of the single-task tasks (i.e., number of bolts into divots or correct answers, and time to answer the questions). Cognitive but not motor dual-task cost was associated with worse performance in activities of everyday internet task.ConclusionsCognitive dual-task cost is significantly associated with worse performance of everyday technology. This was not observed in the motor dual-task cost. The implications of dual-task costs on everyday activity are discussed.
http://ift.tt/2zgAqk6
Isolated right ventricular thrombus in an adult patient with nephrotic syndrome: a case report
Venous thrombosis in nephrotic syndrome is a well-described phenomenon. We report a case of an adult patient with an isolated thrombus in the right ventricle due to nephrotic syndrome, which was initially susp...
http://ift.tt/2y29ikR
Isolated right ventricular thrombus in an adult patient with nephrotic syndrome: a case report
Venous thrombosis in nephrotic syndrome is a well-described phenomenon. We report a case of an adult patient with an isolated thrombus in the right ventricle due to nephrotic syndrome, which was initially susp...
http://ift.tt/2y29ikR
The different fate of antibiotics in the Thames River, UK, and the Katsura River, Japan
Abstract
Little is known about the mechanisms influencing the differences in attenuation of antibiotics between rivers. In this study, the natural attenuation of four antibiotics (azithromycin, clarithromycin, sulfapyridine, and sulfamethoxazole) during transport along the Thames River, UK, over a distance of 8.3 km, and the Katsura River, Japan, over a distance of 7.6 km was compared. To assist interpretation of the field data, the individual degradation and sorption characteristics of the antibiotics were estimated by laboratory experiments using surface water or sediment taken from the same rivers. Azithromycin, clarithromycin, and sulfapyridine were attenuated by 92, 48, and 11% in the Thames River stretch. The first-order decay constants of azithromycin and sulfapyridine were similar to those in the Katsura River, while that of clarithromycin was 4.4 times higher. For sulfamethoxazole, the attenuation was limited in both rivers. Loss of sulfapyridine was attributed to both direct and indirect photolysis in the Thames River, but to only direct photolysis in the Katsura River. Loss of azithromycin and clarithromycin was attributed to sorption to sediment in both rivers. The probable explanation behind the difference in loss rates of clarithromycin between the two rivers was considered to be sediment sorption capacity.
http://ift.tt/2h4nSRW
Comparing discrimination capabilities of fluorescence spectroscopy versus FT-ICR-MS for sources and hydrophobicity of sediment organic matter
Abstract
Characterizing the chemical and molecular composition of sediment organic matter (SeOM) provides critical information for a complete picture of global carbon and nutrient cycles, and helps to track the sources and the fate of organic carbon in aquatic environments. In this study, we examined fluorescence properties and the molecular composition of the alkaline-extractable organic matter (AEOM) of sediments in a coastal lake (Lake Sihwa) and its surrounding creeks (rural, urban, wetland, and industrial areas). Five fluorescence-based indices and 20 molecular parameters were selected from fluorescence spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS), respectively, and utilized to discriminate the AEOM among five different sources as well as the chemical composition of hydrophobic acid (HoA) and hydrophilic (Hi) fractions. Ordination based on Bray–Curtis dissimilarity matrices showed that the fluorescence-based indices distinguished among urban, lake, and the three other sources, while the molecular parameters from FT-ICR-MS performed better in discriminating among the sources of rural, wetland, and industrial areas. Irrespective of the sources, the two different chemical fractions were statistically distinguished by their relative distributions of the UVA-humic-like fluorescent component and the carbohydrate molecular group. However, a rigorous test based on percent dissimilarities indicated no superior capability of either of the two tools in discriminating the sources or their two chemical fractions, which might be attributed to the inherent structural heterogeneity of SeOM and the limited analytical window of FT-ICR-MS for relatively large-sized molecules.
http://ift.tt/2ivXMb8
Clinical survival of chair-side generated monolithic lithium disilicate crowns:10-year results
Abstract
Objectives
Nowadays, all-ceramic materials are routinely used within the treatment of patients in dentistry. The objective of this prospective clinical trial was the evaluation of chair-side generated monolithic lithium disilicate crowns after 10 years.
Materials and methods
Forty-one posterior full contour crowns made of lithium disilicate ceramics were inserted with a self-adhesive resin cement in 34 patients (20 university/14 private practice) using a chair-side CAD/CAM technique. One crown per patient was randomly selected for evaluation according to the modified US Public Health Service criteria.
Results
After a mean examination time of 10.1 years, 26 crowns were available for re-examination. Within the observation period, five failures occurred due to one crown fracture after 2.9 years, an abutment fracture after 6.0 years, one severe endodontic problem after 6.1 years, a root fracture after 7.0 years, and a replacement of one crown caused by a carious lesion after 10 years. Complications occurred as retention loss of one crown, two carious lesions, and a change in sensibility perception of two abutment teeth. All events were associated with molars. The Kaplan-Meier analysis revealed a survival rate of 83.5% and a complication-free rate of 71.0% after 10 years.
Conclusion
Due to the small amount of technical complications and failures, the clinical performance of monolithic lithium disilicate crowns was completely satisfying.
Clinical relevance
The insertion of chair-side fabricated monolithic lithium disilicate crowns can be recommended for long-term use in the posterior region.
http://ift.tt/2ywWg30
Distribution and migration of 239+240Pu in abiotic components of the Black Sea ecosystems during the post-Chernobyl period
Source:Journal of Environmental Radioactivity
Author(s): N.N. Tereshchenko, S.B. Gulin, V. Yu Proskurnin
Distribution of 239,240Pu in abiotic components (water and bottom sediment) of the Black Sea ecosystems was studied during the post-Chernobyl period at different offshore and near-shore locations. The trends of these radionuclides accumulation by sediments were analyzed. The spatial-temporal changes in the 239,240Pu distribution as well as effective half-life for these radionuclides in the Black Sea surface water in deep-sea area are presented. The estimations of the average annual removal fluxes of the 239,240Pu into the bottom sediments were obtained. The Black Sea sediments were characterized by a higher 239,240Pu concentration factor (Cf ≈ n·104–n·106) and radiocapacity factor (F(239,240Pu) was about 99.9% on the shelf, 94.5–99.1% on deep-sea basin for silty and 94.6–98.9% on the shelf for sandy bottom sediments) as compared with Cf and F for 137Cs and 90Sr. Silty bottom sediments play the role of 239,240Pu main depot in the Black Sea ecosystem. The studied radioecological characteristics of Pu allowed us to define the type of plutonium biogeochemical behavior in the Black Sea as a pedotropic one. The results of this complex radioecological monitoring of 239+240Pu contamination in the Black Sea and their analysis makes it possible to understand the plutonium redistribution pathways which will enable to carry out the tracing of its migration within the ecosystems.
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Evaluating the Protective Effect of Etazolate on Memory Impairment, Anxiety- and Depression- Like Behaviors Induced by Post Traumatic Stress Disorder
Source:Brain Research Bulletin
Author(s): Karem H. Alzoubi, Zeinab Y. Al Subeh, Omar F. Khabour
Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder that develops after an individual experiences severe life-threatening traumatic stress. Etazolate is a selective phosphodiesterase-4 inhibitor that is specific for cAMP. Etazolate showed anxiolytic and antidepressant activity, and could be useful in managing PTSD co-morbidities. The current study was done to evaluate the role of etazolate in preventing PTSD induced memory impairment, anxiety and depression- like symptoms. PTSD was induced in rats using single prolonged stress model. Etazolate was administered via oral gavage at a dose of 1mg/kg/day. The radial arm water maze was used to assess learning and memory. The elevated plus maze, open field, and tail suspension tests were conducted to test anxiety- and depression-like symptoms. The PTSD was associated with short- and long- term memory impairment, which was prevented by etazolate administration. Moreover, PTSD was associated with symptoms of anxiety and depression. Etazolate administration prevented these symptoms. In conclusion, our data suggests that memory impairment, anxiety, and depression symptoms that are induced by PTSD can be prevented using etazolate.
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Knowledge and practices of isolation precautions among nurses in Jordan
Source:American Journal of Infection Control
Author(s): Mohammad Suliman, Sami Aloush, Maen Aljezawi, Mohammed AlBashtawy
BackgroundImplementation of isolation precautions from the Centers for Disease Control and Prevention (CDC) has been justified through research and clinical evidence. However, nurses' understanding and compliance with these precautions is still unknown. The aim of this study was to assess nurses' knowledge and practices in relation to isolation precautions in Jordan.MethodsA cross-sectional, descriptive design was used. The study took place in 8 hospitals in Jordan. A self-reported questionnaire and an observational checklist were developed based on the CDC (2007) isolation precautions guidelines.ResultsA total of 247 questionnaires were returned out of 400, for a response rate of 61.7%. The results show that most nurses (90%) have good knowledge of isolation precautions. However, only 65% of nurses reported good compliance with isolation precautions. The results of a t test revealed that nurses with Bachelor's degrees perform better in knowledge examinations than nurses with 2-year diplomas (P < .001). However, there was no significant difference in knowledge and self-report practices scores based on nurses' previous training and existence of isolation guidelines in their units or wards (P > .05). The results of the checklists confirm that there is a low compliance with standard isolation practice. In addition, the checklist shows that a high percentage of units and wards do not use isolation signs (46.4%) and posters (34.5%).ConclusionsThis study revealed that educating nurses about isolation is not enough strategy to improve their compliance. It is important to adapt other strategies, such as supporting nurses by giving them a manageable workload, and providing more supplies and reminders of isolation precautions in the hospitals.
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Deployment of a touchless ultraviolet light robot for terminal room disinfection: The importance of audit and feedback
Source:American Journal of Infection Control
Author(s): Michele Fleming, Amie Patrick, Mark Gryskevicz, Nadia Masroor, Lisa Hassmer, Kevin Shimp, Kaila Cooper, Michelle Doll, Michael Stevens, Gonzalo Bearman
Touchless ultraviolet disinfection (UVD) devices effectively reduce the bioburden of epidemiologically relevant pathogens, including Clostridium difficile. During a 25-month implementation period, UVD devices were deployed facilitywide for the terminal disinfection of rooms that housed a patient who tested positive for C difficile. The deployment was performed with structured education, audit and feedback, and resulted in a multidisciplinary practice change that maximized the UVD capture rate from 20% to 100%.
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Socioeconomic differences in self- and family awareness of viral hepatitis status among carriers of hepatitis B or C in rural Korea
Source:American Journal of Infection Control
Author(s): Hye-Ran Ahn, Sung-Bum Cho, Ik Joo Chung, Sun-Seog Kweon
BackgroundHepatitis is the most important cause of hepatocellular carcinoma in Korea. This study evaluated the socioeconomic differences in self- and family awareness of hepatitis status among hepatitis B and C carriers and their cohabitants in rural Korea.MethodsIn total, 5,017 randomly selected rural residents participated in a seroepidemiologic and questionnaire survey. We found 326 hepatitis B surface antigen carriers or hepatitis C antibody carriers and 310 family members cohabiting with members of this group.ResultsAmong the hepatitis B carriers and their family members, 48.1% were aware of their own status and 36.7% were aware of their cohabitant's hepatitis status, respectively. Only 28.1% of the hepatitis C carriers were aware of their own status, and only 23.3% of their cohabiting family members knew about their family member's hepatitis C status. A multivariate analysis including health-related factors, such as alcohol consumption, family history of liver disease, and recent acupuncture history, found that self-awareness was significantly lower in the older group and significantly higher in the more educated and higher-income groups. Family awareness was also increased in those working in salaried jobs.ConclusionsSocioeconomic disparities in awareness of hepatitis status were found among hepatitis carriers and their families.
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A needs assessment of infection control training for American Red Cross personnel working in shelters
Source:American Journal of Infection Control
Author(s): Jocelyn J. Herstein, Janice Springer, Jono Anzalone, Sharon Medcalf, John J. Lowe
This pilot needs assessment aimed to identify gaps in infection prevention and control (IPC) training of American Red Cross shelter staff through an electronic survey of IPC background, knowledge, and perceived training needs. Respondents (n = 471) noted a greater need for training in several IPC areas, although no significant differences were found in IPC knowledge between those who had recently deployed to a shelter (n = 70) and trained personnel who had never deployed (n = 178).
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Hospital length of stay and cost burden of HIV, tuberculosis, and HIV-tuberculosis coinfection among pregnant women in the United States
Source:American Journal of Infection Control
Author(s): Adeola Falana, Vanessa Akpojiyovwi, Esther Sey, Andika Akpaffiong, Olive Agumbah, Samara Chienye, Jamie Banks, Erin Jones, Kiara K. Spooner, Jason L. Salemi, Omonike A. Olaleye, Sherri D. Onyiego, Hamisu M. Salihu
BackgroundWe sought to determine hospital length of stay (LOS) and cost burden associated with hospital admissions among pregnant women with HIV monoinfection, tuberculosis (TB) monoinfection, or HIV-TB coinfection in the United States.MethodsAnalysis covered the period from 2002-2014 using data from the Nationwide Inpatient Sample. Relevant ICD-9-CM codes were used to determine HIV and TB status. Costs associated with hospitalization were calculated and adjusted to 2010 dollars using the medical care component of the Consumer Price Index.ResultsWe found modest annual average reduction in HIV, TB, and HIV-TB coinfection rates over the study period. The mean LOS was lowest among mothers free of HIV or TB disease and highest among those with HIV-TB coinfection. The average LOS among mothers diagnosed with TB monoinfection was 60% higher than for those with HIV monoinfection. The cost associated with pregnancy-related hospital admissions among mothers with HIV was approximately 30% higher than disease-free mothers, and the cost more than doubled among patients with TB monoinfection or HIV-TB coinfection.ConclusionsTB significantly increased hospital care cost among HIV-positive and HIV-negative pregnant women.
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SOCS-1 ameliorates smoke inhalation-induced acute lung injury through inhibition of ASK-1 activity and DISC formation
Source:Clinical Immunology
Author(s): Leifang Zhang, Kairei Zhu, Yating Ma, Chenming Xu, Qiwen Shi, Xiaoming Chen, Weike Su, Hang Zhao
Smoke inhalation leads to acute lung injury (ALI), a devastating clinical problem associated with high mortality. Suppressor of cytokine signaling-1 (SOCS-1) is a negative regulator of apoptosis and pro-inflammatory cytokine signaling, two major contributors to the pathogenesis of ALI. We have found that SOCS-1 protects lung epithelial cells from smoke-induced apoptosis through two mechanisms. One is that SOCS-1 enhances degradation of ASK-1 and diminishes cleavage of pro-caspase-3 to repress smoke-triggered apoptosis in lung epithelial cells. The other is that SOCS-1 represses smoke-triggered DISC formation through altering TRADD-caspase-8 interaction rather than TNFR-1-TRADD interaction or TNFR-1-TRAF-2 interaction. In conclusion, SOCS-1 relieves smoke inhalation-induced lung injury by repressing ASK-1 and DISC-mediated epithelium apoptosis.
http://ift.tt/2hc8wOX
SOCS-1 ameliorates smoke inhalation-induced acute lung injury through inhibition of ASK-1 activity and DISC formation
Source:Clinical Immunology
Author(s): Leifang Zhang, Kairei Zhu, Yating Ma, Chenming Xu, Qiwen Shi, Xiaoming Chen, Weike Su, Hang Zhao
Smoke inhalation leads to acute lung injury (ALI), a devastating clinical problem associated with high mortality. Suppressor of cytokine signaling-1 (SOCS-1) is a negative regulator of apoptosis and pro-inflammatory cytokine signaling, two major contributors to the pathogenesis of ALI. We have found that SOCS-1 protects lung epithelial cells from smoke-induced apoptosis through two mechanisms. One is that SOCS-1 enhances degradation of ASK-1 and diminishes cleavage of pro-caspase-3 to repress smoke-triggered apoptosis in lung epithelial cells. The other is that SOCS-1 represses smoke-triggered DISC formation through altering TRADD-caspase-8 interaction rather than TNFR-1-TRADD interaction or TNFR-1-TRAF-2 interaction. In conclusion, SOCS-1 relieves smoke inhalation-induced lung injury by repressing ASK-1 and DISC-mediated epithelium apoptosis.
http://ift.tt/2hc8wOX
Interobserver variability in rectum contouring in high-dose-rate brachytherapy for prostate cancer: A multi-institutional prospective analysis
Source:Brachytherapy
Author(s): Rodolfo Chicas-Sett, Francisco Celada-Alvarez, Susana Roldan, Silvia Rodriguez-Villalba, Miguel Santos-Olias, Pablo Soler-Catalan, Blanca Ibanez-Rosello, Leoncio Arribas, Alejandro Tormo, Jose M. Benlloch, Jose Perez-Calatayud
PurposeThe aim of this study was to evaluate the interobserver variability (IOV) of rectum contouring, and its dosimetric consequences, for high-dose-rate brachytherapy in patients with prostate cancer across multiple institutions.Methods and MaterialsFive radiation oncologists contoured rectums in 10 patients on transperineal ultrasound image sets after establishing a delineation consensus. The D0.1cc, D1cc, and D2cc rectum volume parameters were determined. The mean, standard deviation, and range of each dose–volume histogram parameter were evaluated for each patient. The IOV was determined using the coefficient of variation, and the dosimetric impacts on the total dose were analyzed by estimating the biologically equivalent dose (EQD2α/β = 3).ResultsThe interobserver coefficients of variation (±standard deviation) for the reported D0.1cc, D1cc, and D2cc were 5 ± 1.84%, 4 ± 1.26%, and 4 ± 1.33%, respectively. As for the impact on the total dose, the mean dose differences for D0.1cc, D1cc, and D2cc were 10 Gy, 7.3 Gy, and 6.6 Gy, respectively.ConclusionsThe D2cc is robust as evident by the low IOV (<5%). However, some variability ranges almost overlap with the clinical threshold level, which may present dosimetric and clinical complications. General rectal contouring guidelines for prostate high-dose-rate brachytherapy are desirable to reduce discrepancies in delineation.
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Targeting interferons and their pathways in Systemic Lupus Erythematosus
Source:Autoimmunity Reviews
Author(s): François Chasset, Laurent Arnaud
Significant advances in the understanding of the molecular basis of innate immunity have led to the identification of interferons (IFNs), particularly IFN-α, as central mediators in the pathogenesis of Systemic Lupus Erythematosus. Therefore, targeting of IFNs and of their downstream pathways has emerged as important developments for novel drug research in SLE. Based on this, several specific interferon blocking strategies using anti-IFN-α antibodies, anti-type I interferon receptor antibodies, Interferon-α-kinoid, or anti-IFN-γ antibodies have all been assessed in recent clinical trials. Alternative strategies targeting the plasmacytoid dendritic cells (pDCs), Toll-Like Receptors (TLRs)-7/9 or their downstream pathways such as the myeloid differentiation primary-response protein 88 (MYD88), spleen tyrosine kinase (Syk), Janus-kinases (JAKs), interleukin-1 receptor-associated kinase 4 (IRAK4), or the Tyrosine Kinase 2 (TYK2) are also investigated actively in SLE, at more preliminary clinical development stages, except for JAK inhibitors which have reached phase 2 studies. In a near future, in-depth and personalized functional characterization of IFN pathways may provide further guidance for the selection of the most relevant therapeutic strategy in SLE, tailored at the patient-level.
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Vitamin D and systemic lupus erythematosus - the hype and the hope
Source:Autoimmunity Reviews
Author(s): Yehuda Shoenfeld, Roberto Giacomelli, Shir Azrielant, Onorina Berardicurti, John A. Reynolds, Ian N. Bruce
Over the past 20years, much has been written about the potential role of vitamin D in on adverse health outcomes. In recent years, evidence has accumulated regarding the effect of vitamin D on the immune system, and its different cells. Some studies have noted lower vitamin D concentrations in patients with SLE. These epidemiological data still not answer the question: is vitamin D deficiency the cause or the effect? To answer this, we will discuss the association between vitamin D deficiency and SLE and review the evidence from interventional studies.
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Cocaine and ANCA associated vasculitis-like syndromes – A case series
Source:Autoimmunity Reviews
Author(s): Sujith Subesinghe, Sander van Leuven, Leena Yalakki, Shirish Sangle, David D'Cruz
ObjectivesWe analysed the spectrum of clinical manifestations of cocaine associated pseudovasculitis.MethodsClinical, serological, radiological and histological features of 14 patients with cocaine pseudovasculitis syndromes were included.ResultsTwelve patients had significant sinus thickening or erosive disease. Other multi-system manifestations included vasculitic rashes, pulmonary lesions and peripheral neuropathy. All patients had positive ANCA titres at presentation. All patients were managed with corticosteroids +/− methotrexate and co-trimoxazole, 2 patients received cyclophosphamide.ConclusionsAdvanced erosive nasal septal defects and atypical ANCA patterns are suggestive of cocaine induced pseudovasculitis. Complete drug cessation may negate the need for exposure to potent immunosuppressive agents.
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Physical activity and autoimmune diseases: Get moving and manage the disease
Source:Autoimmunity Reviews
Author(s): Kassem Sharif, Abdulla Watad, Nicola Luigi Bragazzi, Micheal Lichtbroun, Howard Amital, Yehuda Shoenfeld
Physical activity, by definition, is any skeletal muscle body movement that results in energy expenditure. In the last few decades, a plethora of scientific evidences have accumulated and confirmed the beneficial role of physical activity as a modifiable risk factor for a wide variety of chronic diseases including cardiovascular diseases (CVDs), diabetes mellitus and cancer, among others. Autoimmune diseases are a heterogeneous group of chronic diseases, which occur secondary to loss of self-antigen tolerance. With the advent of biological therapies, better outcomes have recently been noted in the management of autoimmune diseases. Nonetheless, recent research highlights the salient role of modifiable behaviors such as physical inactivity on various aspects of the immune system and autoimmune diseases. Physical activity leads to a significant elevation in T-regulatory cells, decreased immunoglobulin secretion and produces a shift in the Th1/Th2 balance to a decreased Th1 cell production. Moreover, physical activity has been proven to promote the release of IL-6 from muscles. IL-6 released from muscles functions as a myokine and has been shown to induce an anti-inflammatory response through IL-10 secretion and IL-1β inhibition. Physical activity has been shown to be safe in most of autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), inflammatory bowel diseases (IBD), as well as others. Additionally, the incidence of RA, MS, IBD and psoriasis has been found to be higher in patients less engaged in physical activity. As a general trend, patients with autoimmune diseases tend to be less physically active as compared to the general population. Physically active RA patients were found to have a milder disease course, better cardiovascular disease (CVD) profile, and improved joint mobility. Physical activity decreases fatigue, enhances mood, cognitive abilities and mobility in patients with MS. In SLE patients, enhanced quality of life and better CVD profile were documented in more physically active patients. Physically active patients with type 1 diabetes mellitus have a decreased risk of autonomic neuropathy and CVD. Both fibromyalgia and systemic sclerosis patients report decreased disease severity, pain, as well as better quality of life with more physical activity. Further, SSc patients improve their grip strength, finger stretching and mouth opening with increased level of exercise. The purpose of this paper is to review the clinical evidence regarding the safety, barriers to engagement, and impact of physical activity on autoimmune diseases.
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Can we withdraw immunosuppressants in patients with lupus nephritis in remission? An expert debate
Source:Autoimmunity Reviews
Author(s): Gabriella Moroni, Mariele Gatto, Francesca Raffiotta, Valentina Binda, Eleni Frangou, Liz Lightstone, Dimitrios T. Boumpas
Lupus nephritis (LN) treatment requires an initial intensive period of therapy followed by a long-term maintenance treatment in order to stabilize disease control and eventually reach renal remission. In this section, Authors discuss the feasibility of safely lowering and even suspending maintenance therapy in LN patients having entered remission, highlighting hurdles in predicting the depth and durability of disease quiescence together with the need for minimizing potentially toxic therapies. Even though no firm conclusions can still be drawn, the treating physician has to find the wise balance between disease control and treatment-related drawbacks by following patients closely and recognizing as early as possible the ones who are likely to reach a deep and durable renal remission; there is consensus that is these are the only patients in whom a potential safe complete withdrawal can be foreseen so far.
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The Immunobiology and clinical features of type 1 autoimmune polyglandular syndrome (APS-1)
Source:Autoimmunity Reviews
Author(s): Can-Jie Guo, Patrick S.C. Leung, Weici Zhang, Xiong Ma, M. Eric Gershwin
Autoimmune Polyglandular Syndrome type 1 (APS-1) is a subtype of the autoimmune polyendocrine syndrome characterized by the simultaneous or sequential dysfunction of multiple endocrine or non-endocrine glands. A clinical diagnosis of APS-1 is typically based on the presence of at least two of three following criteria: chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal insufficiency. The first identified causative mutated gene for APS-1 is autoimmune regulator (AIRE) encoding a critical transcription factor, which is primarily expressed in the medullary thymic epithelial cells (mTECs) for generating central immune tolerance. A wide range of chronic, debilitating complications, with no obvious correlation with genetics, makes a diagnosis of APS-1 challenging early in the disease course. Managing APS-1 is difficult due to its complexity, especially the intricate relationships within manifestations and genetic mutations. The past decades have witnessed dramatic progress in elucidating the function of AIRE and conducting large-scale cohort studies in APS-1. However, no clear evidence-based guidelines have been established in APS-1. In this review, we provide a detailed critical overview of the study history, epidemiology, clinical features, and related mechanisms of autoimmunity in APS-1, as well as currently available therapies for this autoimmune disorder.
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TNF inhibitors in rheumatoid arthritis and spondyloarthritis: Are they the same?
Source:Autoimmunity Reviews
Author(s): Andrea Rubbert-Roth, Fabiola Atzeni, Ignazio Francesco Masala, Roberto Caporali, Carlomaurizio Montecucco, Piercarlo Sarzi-Puttini
The advent of anti-tumour necrosis factor (TNF) drugs for rheumatoid arthritis (RA) or spondyloarthritis (SpA) has revolutionised the approach to patients with active disease who do not respond to conventional therapy. Although there are differences in their structure, morphology, pharmacokinetic properties and activity, all anti-TNF drugs ultimately neutralise the TNFα pathway of inflammation. However, despite their similar clinical efficacy, there are disagreements concerning drug survival and safety, with systematic reviews and meta-analyses confirming one result or the other. The fact that 20–30% of patients fail to respond to TNFα inhibitors indicates the possibility of primary resistance or the development of an immune response to the drugs themselves, which may act as antigens. The overall benefit of switching to another anti-TNF drug or a biological agent with a different mechanism of action, may be a valuable option in individual patients. There are few data concerning the use of anti-TNF drugs in patients with SpA but it seems that there are fewer adverse advents and higher drug survival in comparison with patients with RA.
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Can we manage lupus nephritis without chronic corticosteroids administration?
Source:Autoimmunity Reviews
Author(s): Liz Lightstone, Andrea Doria, Hannah Wilson, Frank L. Ward, Maddalena Larosa, Joanne M. Bargman
The outcome of lupus nephritis (LN) has changed since the introduction of glucocorticoids (GCs), which dramatically reduced the mortality related to one of the most severe complications of systemic lupus erythematosus (SLE). Since the 1950′s, other immunosuppressants, including biologic drugs (i.e. rituximab) have aided in maintaining remission, preserving kidney function, but not preventing treatment-related toxicity.GCs still remain the cornerstone in the treatment of SLE, including LN, and they are widely used in clinical practice. However, GC administration represents a double-edged sword. Indeed, from one side they allow a fast and effective control of disease activity by dampening inflammation; from the other side, they have many and severe side effects leading to organ damage.In this paper, we will discuss pros and cons of the chronic use of GCs, especially focusing on LN.
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