Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τετάρτη 20 Ιουλίου 2016
Membrane protein reconstitution into giant unilamellar vesicles: a review on current techniques
Abstract
Studying membrane proteins at the molecular level represents a major challenge in biochemistry due to the complexity of the membrane in which they are embedded. As an important step towards a detailed understanding of their action and molecular functioning, current studies focus on membrane proteins reconstituted into artificial lipid environments. Such reconstituted systems allow for a more flexible choice of biochemical, biophysical, and microscopy techniques for characterizing the proteins. This review gives an overview of the methods currently available for reconstituting membrane proteins in a functional state into giant unilamellar vesicles, and discusses some key methods to verify successful reconstitution.
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Stay up to date with online EMS training and education
The citizens EMS providers care for every day have high expectations for the care they will receive when they call for help. Beginning with the television show "Emergency!" in the 1970s, and continuing to the present day with shows like "Chicago Fire," the public has been "informed and educated" about EMS in pop culture. (Perhaps not in all the ways we in EMS would like, but it's happening nonetheless.)
Such an awesome responsibility can only be met by EMTs and paramedics who are knowledgeable, skilled and experienced in a wide variety of subject matter, including but not limited to:
- Provision of emergency medical care.
- Patient rescue from auto crashes, collapsed trenches and confined spaces.
- Containment of and patient rescue from hazardous materials spills and releases.
- Response to the consequences of natural disasters, such as tornadoes, hurricanes, winter storms and floods.
The need for EMS agencies to provide required training and education isn't only applicable to care providers. In today's world, EMS paramedic chiefs are faced with ensuring that their personnel complete a wide variety of training requirements, such as:
- Vehicle operations courses that cover defensive driving techniques and strategies, safe backing procedures, fatigue and stress management, severe weather and distracted driving.
- OSHA-required workplace training — entry-level and annual or bi-annual refresher training — courses on avoiding slips, trips and falls; bloodborne pathogens, fire safety and extinguisher training, hazardous communication and safety data sheets; hearing conservation; office ergonomics; personal protective equipment; preventing back injuries; wellness and fitness; and workplace violence risk management.
- Soft skills courses that help build stronger and more resilient organizations through training in interpersonal communications, stress management, written and oral communications and employee/supervisor relations.
- Awareness courses that provide personnel with fundamental knowledge of various subject areas including workplace inspections, accident investigation, cultural diversity and discrimination, workplace harassment prevention and substance abuse [1].
Criteria for EMS training
To meet these challenges, EMTs and paramedics — and the supervisors who lead them — have a great need for quality training and education that is current, accessible and affordable. The body of knowledge expected of EMS providers continues to grow, yet for EMS agency leaders the challenge of providing the training that meets those three criteria is becoming increasingly difficult. Here is why:
1. Current
Many EMS agencies lack the resources to develop their own training programs to meet new threats. It is also challenging to keep the programs they have current regarding new information, technologies and methods.
2. Accessible
Many departments lack the resources to handle training in house and must depend on state or regional EMS training programs. At the same time, most state or regional agencies have seen significant reductions in their funding and their ability to deliver programs to meet the growing needs of local EMS agencies.
3. Affordable
All agencies across different types of EMS delivery models have seen their operating budgets reduced, or those budgets have not kept pace with the demands placed upon the organizations. Training programs are frequently the first target for budget cuts by an organization or its oversight or funding authority.
Online training and education
Online training is not new. Online training 1.0, such as Blackboard and other educational portals, provided dedicated email systems and electronic drop boxes for assignments and PowerPoint slide presentations, but such systems were primarily about inserting technology into the teacher/student relationship.
Today the huge technical advances in the content creation and development and delivery processes for online training have revolutionized the industry. Online training 2.0 brings the interactive experience of learning into the educational experience. Technology facilitates the student's ability to interact with the material in ways heretofore unimaginable through the use of 3-D modeling, modular curriculum that requires students to demonstrate that they've learned before allowing them to proceed in the course and much more.
The rub (and there's always a rub!)
Online training for EMTs and paramedics" It sounds impossible, or at best, a little shady. How is it possible for anyone to sufficiently train for such important hands-on jobs without working face-to-face" That's actually a little presumptuous, with the presumption being that a person taking an online EMT or paramedic course receives all of his or her training that way. That's simply not the case.
Preparing for any profession or occupation that by its very nature involves physical contact with something or someone else will invariably require both hands-on experience and, for lack of a more modern term, book learning. In fact, the non-hands-on part of EMT and paramedic education is rather extensive, and distance education is a very good delivery system for that component of the formal education process [2].
People are earning undergraduate and graduate degrees through online learning every year. Doctors are diagnosing diseases and treating patients and conducting the research to find cures for diseases every day using computers. Architects learn how to design buildings and engineers learn how to build them every day through online learning.
We should embrace this new capability to teach a person what he or she needs to know to be a safe, effective and efficient EMT, paramedic or instructor. Delivery and attendance of lectures online frees up our most precious teaching resource — the knowledgeable and experienced EMS instructor — for the critical task of teaching new and experienced EMS providers the skills that they need to do the job. Reserving our face-to-face instructor to student time for skills, scenarios and discussions instead of lectures enables us to use our diminished financial resources to pay for those instructors capable of conducting skills-development training.
A sampling of online training programs for EMS
Combining online coursework with in-class or in-the-field training is referred to as the hybrid format. Hybrid courses are a proven successful method of emergency medical training [3].
EMS1 Academy offers 240 hours of EMS continuing education to EMS agencies and fire departments. All of its Medic Monthly courses, as well as licensed courses from Jones & Bartlett Publishing Company, are approved by the Commission on Accreditation for Pre-Hospital Continuing Education for first responders, EMTs and paramedics and recognized by the National Registry of EMTs. Most states recognize CECBEMS-approved credit for state license renewal [4].
Individuals in need of credits or without an agency affiliation can also complete online CE courses. BoundTree University is one of many online CE options for EMS providers.
Students who successfully complete PERCOM's EMT, AEMT or paramedic programs are eligible to sit for the National Registry of EMTs exams for registration. PERCOM's training programs are recognized by most states in the United States for certification or reciprocity [5].
EMT & Fire Training Inc. is a proprietary school registered with the Idaho Board of Education. In addition, the school is recognized as a training institution by the Idaho Department of Emergency Medical Services. Their online EMT training course is a self-directed, interactive, distance-learning course that also prepares students to sit for the NREMT exam. Practical skills and testing take place during a six-day program of hands-on instruction at the company's training facilities [6].
Online training is important for personnel in leadership and support functions as well as for first-line care providers. Creighton University offers online training courses in EMS management and EMS instruction [7].
What are you waiting for" This is just a sample of the online training programs available for EMTs, paramedics and EMS leaders. Get started on a career in EMS or advance your current EMS career through online learning.
References
1. PCI. Basic Safety Training Online Review. [Available online] http://ift.tt/2aavxOG
2. FireScienceOnline. Online Paramedic & EMT Programs. [Available online] http://ift.tt/2a8teZt
3. Ibid.
4. EMS1. FireEMS Academy. [Available online] http://ift.tt/2a8tqYK
5. PERCOM On-line. EMS Education for the Modern Professional. [Available online] http://ift.tt/2aavwtX
6. EMT and Fire Training, Inc. EMT Certification Course Online. [Available online] http://ift.tt/2a8thEs
7. Creighton University. Training and Certifications. [Available online] http://ift.tt/2aavnqs
About the author
Battalion Chief Robert Avsec (Ret.) served with the Chesterfield (Va.) Fire & EMS Department for 26 years beginning as a firefighter/EMT; he retired as an EMT-Cardiac Technician (ALS provider) certified by the Commonwealth of Virginia. During his career he was an active instructor, beginning as an EMT Instructor, who later became an instructor for fire, hazardous materials, and leadership courses at the local, state, and federal levels, which included more than 10 years as a Contract Instructor with the National Fire Academy. Chief Avsec earned his bachelor of science degree from the University of Cincinnati and his master of science degree in Executive Fire Service Leadership from Grand Canyon University. He is a 2001 graduate of the National Fire Academy's Executive Fire Officer Program. Since his retirement in 2007, he has continued to be a life-long learner working in both the private and public sectors to further develop his "management sciences mechanic" credentials. He makes his home near Charleston, W.Va. Contact Robert at Robert.Avsec@FireRescue1.com
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Regional advisory council improves patient care
SAN ANTONIO ― The Southwest Texas Regional Advisory Council has a mission to deliver the right patient, in the right time to the right place in an area of Texas that is bigger than West Virginia. The STRAC serves 2.4 million people in a 22-county, 26,000 square mile area. The region has 73 EMS provider agencies, 16 PCI Centers, 11 Stroke Centers, and two Level I Trauma Centers.
Eric Epley, executive director, described the innovative STRAC projects with an emphasis on the purpose ― or "why" ― of regional collaboration in a session at the Pinnacle EMS conference.
STRAC coordinates 60 monthly meetings for representatives from every hospital and EMS agency to refine or create systems to improve patient care across the region. Epley refers to the meeting interactions and positive results that come from those meetings as "co-op-petition."
Memorable quotes
Here are three memorable quotes from Epley on the role of the STRAC.
"We want to be the model regional trauma and disaster medical system in the country."
"Why we do things ― coming together and making decisions ― is important."
"Processes are developed through deliberate consensus. Consensus means I may not get what I want, but I will get what I need."
Key Takeaways on improving care across a region
Epley's presentation, part of a Pinnacle power seminar on innovation, focused on the approach of the STRAC to bring together a diverse coalition of health care providers to use process improvement and consensus to improve patient care. Here are the key takeaways for EMS leaders.
- Systems improve care. Where you become sick or injured should not determine whether you live. A system of care equalizes care across a region.
- Systems hardwire processes. Mutual terminology and processes, developed by the caregivers within the system, is the only way to hardwire processes, like transfer of patients from rural hospitals to a level I trauma hospital, into a system.
- System design is deliberate. Development and implementation of process takes time to ensure buy-in among the participants. An EMS Time Out process took 18-months to develop. A Regional blood/body fluids exposure process took 14-months to develop and widely implement.
- System transparency builds trust. Transparency allowed the STRAC to rapidly develop a multiple-phase Ebola virus disease alert patient flow diagram for a broad coalition that had come to trust each other through previous collaborations. The patient flow encompassed pre-arrival, on-scene and EMS/ER.
- System improvement is by people. Technology doesn't solve problems. System-wide problems are solved by people and the solutions are enhanced by available technology. The STRAC brings people involved in problems together, such as transporting patients with mental health emergencies to the emergency department, to identify solutions through consensus.
- Systems solve the underlying problem. Mandatory hospital diversion in the STRAC, triggered by EMS crews waiting for an emergency department bed for more than 20 minutes, doesn't solve the hospital's patient flow problem, but it keeps the problem at the emergency department from getting worse. The STRAC can motivate and facilitate the hospital's solution to the underlying problem of patient flow into and out of the emergency department.
Learn more:
- Epley recommended the TED Talk: How great leaders inspire action to attendees.
- How to improve EMS patient handoffs at the emergency department
- How to use the MIST for an EMS radio or bedside report
- Southwest Texas Regional Advisory Council website
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Correction: Decarboxylative Csp3-Csp3 coupling for benzylation of unstable ketone enolates: synthesis of p-(acylethyl)phenols
Chem. Commun., 2016, Advance Article
DOI: 10.1039/C6CC90325H, Correction
DOI: 10.1039/C6CC90325H, Correction
Sasa Wang, Xinzheng Chen, Qiaoqiao Ao, Huifei Wang, Hongbin Zhai
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
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Toxins, Vol. 8, Pages 224: No Association between Mycotoxin Exposure and Autism: A Pilot Case-Control Study in School-Aged Children
Evaluation of environmental risk factors in the development of autism spectrum disorder (ASD) is needed for a more complete understanding of disease etiology and best approaches for prevention, diagnosis, and treatment. A pilot experiment in 54 children (n = 25 ASD, n = 29 controls; aged 12.4 ± 3.9 years) screened for 87 urinary mycotoxins via liquid chromatography-tandem mass spectrometry to assess current exposure. Zearalenone, zearalenone-4-glucoside, 3-acetyldeoxynivalenol, and altenuene were detected in 9/54 (20%) samples, most near the limit of detection. No mycotoxin/group of mycotoxins was associated with ASD-diagnosed children. To identify potential correlates of mycotoxin presence in urine, we further compared the nine subjects where a urinary mycotoxin was confirmed to the remaining 45 participants and found no difference based on the presence or absence of mycotoxin for age (t-test; p = 0.322), gender (Fisher's exact test; p = 0.456), exposure or not to selective serotonin reuptake inhibitors (Fisher's exact test; p = 0.367), or to other medications (Fisher's exact test; p = 1.00). While no positive association was found, more sophisticated sample preparation techniques and instrumentation, coupled with selectivity for a smaller group of mycotoxins, could improve sensitivity and detection. Further, broadening sampling to in utero (mothers) and newborn-toddler years would cover additional exposure windows.
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Allosteric modulators of the NMDA receptors – a review
N-methyl-D-aspartate (NMDA) receptors are primarily involved in the rapid excitatory neurotransmission that underlies learning and memory formation. Moreover, NMDA receptors are also implicated in a variety of neurological disorders. Further, studies on allosteric modification of these receptors have resulted in better understanding of NMDA receptor functions and roles that in turn helps in the development of better and efficient drugs. It has been observed in the recent studies that amino terminal domain (ATD) of NMDA is responsible for the conformational changes in the NMDA receptors upon allosteric binding. The present review article aimed to highlight and discuss the recent allosteric modulating approach responsible for modulation of NMDA receptor, important modulators and their influences.
L'articolo Allosteric modulators of the NMDA receptors – a review sembra essere il primo su European Review.
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Hormetic response triggers multifaceted anti-oxidant strategies in immature king penguins (Aptenodytes patagonicus)
Publication date: Available online 19 July 2016
Source:Free Radical Biology and Medicine
Author(s): Benjamin Rey, Cyril Dégletagne, Jacques Bodennec, Pierre-Axel Monternier, Mathieu Mortz, Damien Roussel, Caroline Romestaing, Jean-Louis Rouanet, Jeremy Tornos, Claude Duchamp
Repeated deep dives are highly pro-oxidative events for air-breathing aquatic foragers such as penguins. At fledging, the transition from a strictly terrestrial to a marine lifestyle may therefore trigger a complex set of anti-oxidant responses to prevent chronic oxidative stress in immature penguins but these processes are still undefined. By combining in vivo and in vitro approaches with transcriptome analysis, we investigated the adaptive responses of sea-acclimatized (SA) immature king penguins (Aptenodytes patagonicus) compared with pre-fledging never-immersed (NI) birds. In vivo, experimental immersion into cold water stimulated a higher thermogenic response in SA penguins than in NI birds, but both groups exhibited hypothermia, a condition favouring oxidative stress. In vitro, the pectoralis muscles of SA birds displayed increased oxidative capacity and mitochondrial protein abundance but unchanged reactive oxygen species (ROS) generation per g tissue because ROS production per mitochondria was reduced. The genes encoding oxidant-generating proteins were down-regulated in SA birds while mRNA abundance and activity of the main antioxidant enzymes were up-regulated. Genes encoding proteins involved in repair mechanisms of oxidized DNA or proteins and in degradation processes were also up-regulated in SA birds. Sea life also increased the degree of fatty acid unsaturation in muscle mitochondrial membranes resulting in higher intrinsic susceptibility to ROS. Oxidative damages to protein or DNA were reduced in SA birds. Repeated experimental immersions of NI penguins in cold-water partially mimicked the effects of acclimatization to marine life, modified the expression of fewer genes related to oxidative stress but in a similar way as in SA birds and increased oxidative damages to DNA. It is concluded that the multifaceted plasticity observed after marine life may be crucial to maintain redox homeostasis in active tissues subjected to high pro-oxidative pressure in diving birds. Initial immersions in cold-water may initiate an hormetic response triggering essential changes in the adaptive antioxidant response to marine life.
Graphical abstract
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Enhanced base excision repair capacity in carotid atherosclerosis may protect nuclear DNA but not mitochondrial DNA
Publication date: August 2016
Source:Free Radical Biology and Medicine, Volume 97
Author(s): Tonje Skarpengland, Tuva B. Dahl, Mona Skjelland, Katja Scheffler, Mirta Mittelsted Leal de Sousa, Ida Gregersen, Anna Kuśnierczyk, Animesh Sharma, Geir Slupphaug, Lars Eide, Filip M. Segers, Karolina Ryeng Skagen, Christen P. Dahl, David Russell, Lasse Folkersen, Kirsten Krohg-Sørensen, Sverre Holm, Magnar Bjørås, Pål Aukrust, Bente Halvorsen
BackgroundLesional and systemic oxidative stress has been implicated in the pathogenesis of atherosclerosis, potentially leading to accumulation of DNA base lesions within atherosclerotic plaques. Although base excision repair (BER) is a major pathway counteracting oxidative DNA damage, our knowledge on BER and accumulation of DNA base lesions in clinical atherosclerosis is scarce. Here, we evaluated the transcriptional profile of a wide spectrum of BER components as well as DNA damage accumulation in atherosclerotic and non-atherosclerotic arteries.MethodsBER gene expression levels were analyzed in 162 carotid plaques, 8 disease-free carotid specimens from patients with carotid plaques and 10 non-atherosclerotic control arteries. Genomic integrity, mitochondrial (mt) DNA copy number, oxidative DNA damage and BER proteins were evaluated in a subgroup of plaques and controls.ResultsOur major findings were: (i) The BER pathway showed a global increased transcriptional response in plaques as compared to control arteries, accompanied by increased expression of several BER proteins. (ii) Whereas nuclear DNA stability was maintained within carotid plaques, mtDNA integrity and copy number were decreased. (iii) Within carotid plaques, mRNA levels of several BER genes correlated with macrophage markers. (iv) In vitro, some of the BER genes were highly expressed in the anti-inflammatory and pro-resolving M2 macrophages, showing increased expression upon exposure to modified lipids.ConclusionsThe increased transcriptional response of BER genes in atherosclerosis may contribute to lesional nuclear DNA stability but appears insufficient to maintain mtDNA integrity, potentially influencing mitochondrial function in cells within the atherosclerotic lesion.
Graphical abstract
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Mitochondrial Oxygen Metabolism in Primary Human Lens Epithelial Cells: Association with Age, Diabetes and Glaucoma
Source:Free Radical Biology and Medicine
Author(s): M. Kubota, Y.B. Shui, M. Liu, F. Bai, A.J. Huang, N. Ma, D.C. Beebe, C.J. Siegfried
PurposeThe hypoxic environment around the lens is important for maintaining lens transparency. Lens epithelial cells (LECs) play a key role in lens metabolism. We measured oxygen consumption to assess the role of human LECs in maintaining hypoxia around the lens, as well as the impact of systemic and ocular diagnosis on these cells.MethodsBaseline cellular respiration was measured in rabbit LECs (NN1003A), canine kidney epithelial cells (MDCK), trabecular meshwork cells (TM-5), and bovine corneal endothelial cells (CCEE) using a XF96 Extracellular Flux Analyzer (Seahorse Bioscience, North Billerica, MA), which measures oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in vitro. Following informed written consent, lens capsule epithelial cells were obtained from patients during cataract surgery and were divided into small explants in 96-well plates. Capsules were removed when LECs became confluent. OCR was normalized to the number of cells per well using rabbit LECs as a standard. The effect of patient age, sex, race, and presence of diabetes or glaucoma on oxygen consumption was assessed by using the Mann-Whitney U test and multivariate regression analysis.ResultsPrimary LECs were obtained from 69 patients. The OCR from donors aged 70 and over was lower than that of those under 70 years (2.21 ± 1.037 vs. 2.86 ± 1.383 fmol/min/cell; p<0.05). Diabetic patients had lower OCR than non-diabetic patients (2.02 ± 0.911 vs. 2.79 ± 1.332 fmol/min/cell; p<0.05), and glaucoma patients had lower OCR than non-glaucoma patients (2.27 ± 1.19 vs. 2.83 ± 1.286 fmol/min/cell; p<0.05). Multivariate regression analysis confirmed that donors aged 70 and over (p<0.05), diabetic patients (p<0.01), and glaucoma patients (p<0.05) had significantly lower OCR, independent of other variables. Gender and race had no significant effect on OCR.ConclusionsThe lower oxygen consumption rate of human LECs in older donors and patients with diabetes or glaucoma could contribute to cataract development. Diabetes and glaucoma are particularly important factors associated with decreased OCR, independent of age. Ongoing studies are examining pO2 at the anterior surface of the lens in vivo and oxygen consumption in the patient's LECs.The hypoxic environment around the lens is important for maintaining lens transparency. Lens epithelial cells (LECs) play a key role in lens metabolism. Using a XF96 Extracellular Flux Analyzer (Seahorse Bioscience), we measured oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) of various cell types (rabbit LECs, canine kidney epithelial cells, trabecular meshwork cells, bovine corneal endothelial cells, and human LECs from 69 patients of cataract surgery) to assess the role of human LECs in maintaining hypoxia around the lens, as well as the impact of systemic and ocular diagnosis on human LECs. Multivariate regression analysis confirmed that donors aged 70 and over (p<0.05), diabetic patients (p<0.01), and glaucoma patients (p<0.05) had significantly lower OCR, independent of other variables. Gender and race had no significant effect on OCR. The lower OCR of human LECs in older donors and patients with diabetes or glaucoma could contribute to cataract development.
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Angiotensin(1-7) attenuated Angiotensin II-induced hepatocyte EMT by inhibiting NOX-derived H2O2-activated NLRP3 inflammasome/IL-1β/Smad circuit
Publication date: Available online 18 July 2016
Source:Free Radical Biology and Medicine
Author(s): Li-Li Zhang, Shan Huang, Xiao-Xin Ma, Wen-Yong Zhang, Dan Wang, Si-Yi Jin, Yan-Ping Zhang, Yang Li, Xu Li
Epithelial-mesenchymal transition (EMT) is correlated with NAPDH oxidase (NOX)-derived reactive oxygen species (ROS). The ROS-induced NOD-like receptor pyrin domain containing-3 (NLRP3) inflammasome is a novel mechanism of EMT. Angiotensin II (AngII) induces EMT by regulating intracellular ROS. Nevertheless, it has not been reported whether AngII could induce hepatocyte EMT. Angiotensin-(1-7) [Ang-(1-7)] can inhibit the effects of AngII via a counter-regulatory mechanism. However, whether Ang-(1-7) attenuated the effects of AngII on hepatocyte EMT remains unclear. The aim of this study was to determine whether Ang-(1-7) attenuated AngII-induced hepatocyte EMT by inhibiting the NOX-derived ROS-mediated NLRP3 inflammasome/IL-1ß/Smad circuit. In vivo, two animal models were established. In the first model, rats were infused AngII. In the second model, Ang-(1-7) was constantly infused into double bile duct ligated (BDL) rats. In vitro, hepatocytes were pretreated with antioxidant, NLRP3 siRNA, NOX4 siRNA, or Ang-(1-7) before exposure to AngII. In vitro, AngII induced hepatocyte EMT, which was inhibited by N-acetylcysteine (NAC), diphenylene iodonium (DPI), and NOX4 siRNA. NLRP3 inflammasome, which was activated by hydrogen peroxide (H2O2), mediated AngII-induced hepatocyte EMT. Ang-(1-7) suppressed AngII-induced EMT by inhibiting the NOX-derived H2O2-activated NLRP3 inflammasome/IL-1ß/Smad circuit. In vivo, infusion of AngII induced activation of H2O2-correlated NLRP3 inflammasome in rat livers and accumulation of α-collagen I (Col1A1) in hepatocytes. Infusion of Ang-(1-7) alleviated BDL-induced liver fibrosis and inhibited the expression of Col1A1 and the activation of NLRP3 inflammasome in hepatocytes. Ang-(1-7) attenuated AngII-induced hepatocyte EMT by inhibiting the NOX-derived H2O2-activated NLRP3 inflammasome/IL-1ß/Smad circuit.
Graphical abstract
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Inhibitory nitrosylation of mammalian thioredoxin reductase 1: Molecular characterization and evidence for its functional role in cellular nitroso-redox imbalance
Publication date: August 2016
Source:Free Radical Biology and Medicine, Volume 97
Author(s): Rotem Engelman, Tamar Ziv, Elias S.J. Arnér, Moran Benhar
Mammalian thioredoxin 1 (Trx1) and the selenoprotein Trx reductase 1 (TrxR1) are key cellular enzymes that function coordinately in thiol-based redox regulation and signaling. Recent studies have revealed that the Trx1/TrxR1 system has an S-nitrosothiol reductase (denitrosylase) activity through which it can regulate nitric oxide-related cellular processes. In this study we revealed that TrxR1 is itself susceptible to nitrosylation, characterized the underlying mechanism, and explored its functional significance. We found that nitrosothiol or nitric oxide donating agents rapidly and effectively inhibited the activity of recombinant or endogenous TrxR1. In particular, the NADPH-reduced TrxR1 was partially and reversibly inhibited upon exposure to low concentrations (<10μM) of S-nitrosocysteine (CysNO) and markedly and continuously inhibited at higher doses. Concurrently, TrxR1 very efficiently reduced low, but not high, levels of CysNO. Biochemical and mass spectrometric analyses indicated that its active site selenocysteine residue renders TrxR1 highly susceptible to nitrosylation-mediated inhibition, and revealed both thiol and selenol modifications at the two redox active centers of the enzyme. Studies in HeLa cancer cells demonstrated that endogenous TrxR1 is sensitive to nitrosylation-dependent inactivation and pointed to an important role for glutathione in reversing or preventing this process. Notably, depletion of cellular glutathione with l-buthionine-sulfoximine synergized with nitrosating agents in promoting sustained nitrosylation and inactivation of TrxR1, events that were accompanied by significant oxidation of Trx1 and extensive cell death. Collectively, these findings expand our knowledge of the role and regulation of the mammalian Trx system in relation to cellular nitroso-redox imbalance. The observations raise the possibility of exploiting the nitrosylation susceptibility of TrxR1 for killing tumor cells.
Graphical abstract
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Biochemical indices of oxidative stress and inflammation in the evaluation of peripheral artery disease
Source:Free Radical Biology and Medicine
Author(s): Isabel Fort-Gallifa, Anabel García-Heredia, Anna Hernández-Aguilera, Josep M. Simó, Julio Sepúlveda, Vicente Martín-Paredero, Jordi Camps, Jorge Joven
BackgroundThe aims of this study were: (1) to investigate changes in indices of oxidative stress and inflammation in the evaluation of peripheral artery disease (PAD); (2) to compare the diagnostic efficacy of these parameters with that of classical clinical laboratory routine parameters.Design and methodsWe studied 115 patients with PAD and 300 healthy volunteers.ResultsPAD patients had significantly increased circulating concentrations of F2-isoprostanes, protein carbonyls, chemokine (C-C motif) ligand 2 (CCL2), high-sensitivity C-reactive protein (hs-CRP), β−2-microglobulin (B2M), and decreased paraoxonase-1 (PON1) levels. When patients were classified according to the Fontaine score, we observed important increases in plasma F2-isoprostanes and CCL2 that appeared in milder stages of the disease, and remained so at similar levels in more advanced stages; almost no overlapping with the control group was noted. Receiver operating characteristics analysis comparing patients and controls revealed that the areas under the curve for F2-isoprostanes and CCL2 approached unity [0.999 (0.998 – 1.000) and 0.993 (0.985 – 1.000), respectively, and significantly higher to those of the other measured parameters.ConclusionOur data suggest that F2-isoprostanes and CCL2 measurements may be useful tools for the diagnosis of PAD.
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NOX4-derived reactive oxygen species limit fibrosis and inhibit proliferation of vascular smooth muscle cells in diabetic atherosclerosis
Publication date: Available online 19 July 2016
Source:Free Radical Biology and Medicine
Author(s): Elyse Di Marco, Stephen P. Gray, Kit Kennedy, Cedric Szyndralewiez, Alicia N. Lyle, Bernard Lassègue, Kathy K. Griendling, Mark E. Cooper, Harald H.H.W. Schmidt, Karin A.M. Jandeleit-Dahm
Smooth muscle cell (SMC) proliferation and fibrosis contribute to the development of advanced atherosclerotic lesions. Oxidative stress caused by increased production or unphysiological location of reactive oxygen species (ROS) is a known major pathomechanism. However, in atherosclerosis, in particular under hyperglycaemic/diabetic conditions, the hydrogen peroxide-producing NADPH oxidase type 4 (NOX4) is protective. Here we aim to elucidate the mechanisms underlying this paradoxical atheroprotection of vascular smooth muscle NOX4 under conditions of normo- and hyperglycaemia both in vivo and ex vivo. Following 20-weeks of streptozotocin- induced diabetes, Apoe-/- mice showed a reduction in SM-alpha-actin and calponin gene expression with concomitant increases in platelet-derived growth factor (PDGF), osteopontin (OPN) and the extracellular matrix (ECM) protein fibronectin when compared to non-diabetic controls. Genetic deletion of Nox4 (Nox4-/-Apoe-/-) exacerbated diabetes-induced expression of PDGF, OPN, collagen I, and proliferation marker Ki67. Aortic SMCs isolated from NOX4-deficient mice exhibited a dedifferentiated phenotype including loss of contractile gene expression, increased proliferation and ECM production as well as elevated levels of NOX1-associated ROS. Mechanistic studies revealed that elevated PDGF signaling in NOX4-deficient SMCs mediated the loss of calponin and increase in fibronectin, while the upregulation of NOX1 was associated with the increased expression of OPN and markers of proliferation. These findings demonstrate that NOX4 actively regulates SMC pathophysiological responses in diabetic Apoe-/- mice and in primary mouse SMCs through the activities of PDGF and NOX1.
Graphical abstract
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Molecular basis of reactive oxygen species-induced inactivation of α4β2 nicotinic acetylcholine receptors
Source:Free Radical Biology and Medicine
Author(s): Junjun Zhao, Yan Zheng, Fenqin Xue, Yongchang Chang, Hui Yang, Jianliang Zhang
The α4β2 neuronal nicotinic acetylcholine receptors (nAChRs) are the most widespread heteromeric nAChR subtype in the brain, mediating fast synaptic transmission. Previous studies showed that α4β2 nAChRs could be inactivated by reactive oxygen species (ROS), but the underlying mechanism is still obscure. We found that H2O2 induced the rundown of ACh-evoked currents in human α4β2 nAChRs and the replacement of the conserved cysteine in the M1-M2 linker of either α4 Cys245 or β2 Cys237 with an alanine residue could prevent the current rundown. Structurally, α4 Cys245 and β2 Cys237 are hypothesized to be in close proximity when the receptor is activated. Western blotting results showed that α4 and β2 subunits were cross-linked when the agonist-bound receptor encountered H2O2, which could be prevented by the substitution of the conserved cysteine in the M1-M2 linker to an alanine. Thus, when agonist bound to the receptor, α4 Cys245 and β2 Cys237 came close to each other and ROS oxidized these conserved cysteines, leading subunits to be cross-linked and trapping α4β2 nAChRs into the inactivation state. In addition, we mimicked an experimental Parkinson's disease (PD) model in PC12 cells and found that ROS, generated by 6-hydroxydopamine (6-OHDA), could cause the current rundown in α4β2 nAChRs, which may play a role in PD.
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3D structure determination of a protein in living cells using paramagnetic NMR spectroscopy
Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC05490K, Communication
DOI: 10.1039/C6CC05490K, Communication
Xun-Cheng Su, Thomas Huber, Conggang Li, Bin-Bin Pan, Feng Yang, Yansheng Ye, Qiong Wu
Determining the three-dimensional (3D) structure of a protein in living cells remains particularly challenging. We herein demonstrated that the integration of site-specific tagging proteins and GPS-Rosetta calculations provides a fast...
The content of this RSS Feed (c) The Royal Society of Chemistry
Determining the three-dimensional (3D) structure of a protein in living cells remains particularly challenging. We herein demonstrated that the integration of site-specific tagging proteins and GPS-Rosetta calculations provides a fast...
The content of this RSS Feed (c) The Royal Society of Chemistry
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Potential of Inducible Nitric Oxide Synthase as a Therapeutic Target for Allergen-Induced Airway Hyperresponsiveness: A Critical Connection to Nitric Oxide Levels and PARP Activity
Although expression of inducible NO synthase (iNOS) in the lungs of asthmatics and associated nitrosative damage are established, iNOS failed as a therapeutic target for blocking airway hyperresponsiveness (AHR) and inflammation in asthmatics. This dichotomy calls for better strategies with which the enzyme is adequately targeted. Here, we confirm iNOS expression in the asthmatic lung with concomitant protein nitration and poly(ADP-ribose) polymerase (PARP) activation. We show, for the first time, that iNOS is highly expressed in peripheral blood mononuclear cells (PBMCs) of asthmatics with uncontrolled disease, which did not correspond to protein nitration. Selective iNOS inhibition with L-NIL protected against AHR upon acute, but not chronic, exposure to ovalbumin or house dust mite (HDM) in mice. Supplementation of NO by nitrite administration significantly blocked AHR in chronically HDM-exposed mice that were treated with L-NIL. Protection against chronic HDM exposure-induced AHR by olaparib-mediated PARP inhibition may be associated with the partial but not the complete blockade of iNOS expression. Indeed, L-NIL administration prevented olaparib-mediated protection against AHR in chronically HDM-exposed mice. Our study suggests that the amount of iNOS and NO are critical determinants in the modulation of AHR by selective iNOS inhibitors and renews the potential of iNOS as a therapeutic target for asthma.
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Identification of V-ATPase as a molecular sensor of SOX11-levels and potential therapeutic target for mantle cell lymphoma
Abstract
Background
Mantle cell lymphoma (MCL) is an aggressive disease with short median survival. Molecularly, MCL is defined by the t(11;14) translocation leading to overexpression of the CCND1 gene. However, recent data show that the neural transcription factor SOX11 is a disease defining antigen and several involved signaling pathways have been pin-pointed, among others the Wnt/β-catenin pathway that is of importance for proliferation in MCL. Therefore, we evaluated a compound library focused on the Wnt pathway with the aim of identifying Wnt-related targets that regulate growth and survival in MCL, with particular focus on SOX11-dependent growth regulation.
Methods
An inducible SOX11 knock-down system was used to functionally screen a library of compounds (n = 75) targeting the Wnt signaling pathway. A functionally interesting target, vacuolar-type H+-ATPase (V-ATPase), was further evaluated by western blot, siRNA-mediated gene silencing, immunofluorescence, and flow cytometry.
Results
We show that 15 out of 75 compounds targeting the Wnt pathway reduce proliferation in all three MCL cell lines tested. Furthermore, three substances targeting two different targets (V-ATPase and Dkk1) showed SOX11-dependent activity. Further validation analyses were focused on V-ATPase and showed that two independent V-ATPase inhibitors (bafilomycin A1 and concanamycin A) are sensitive to SOX11 levels, causing reduced anti-proliferative response in SOX11 low cells. We further show, using fluorescence imaging and flow cytometry, that V-ATPase is mainly localized to the plasma membrane in primary and MCL cell lines.
Conclusions
We show that SOX11 status affect V-ATPase dependent pathways, and thus may be involved in regulating pH in intracellular and extracellular compartments. The plasma membrane localization of V-ATPase indicates that pH regulation of the immediate extracellular compartment may be of importance for receptor functionality and potentially invasiveness in vivo.
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Incorporating Yttrium-90 trans-arterial radioembolization (TARE) in the treatment of metastatic pancreatic adenocarcioma: a single center experience
Abstract
Background
The purpose of this retrospective study was to evaluate the efficacy of incorporating trans-arterial radioembolization (TARE) with systemic chemotherapy in the treatment of liver-dominant metastatic pancreatic ductal adenocarcinoma, with the aim of destroying liver metastases and improving patient outcomes.
Methods
We retrospectively evaluated 16 patients with liver-dominant metastatic pancreatic ductal adenocarcinoma who underwent TARE between February 2012 and August 2015; 15 of these patients also underwent concurrent systemic chemotherapy. Patient outcomes were assessed using Response Evaluation Criteria In Solid Tumors (RECIST), Version 1.1 and included disease response, median overall survival from the time of diagnosis of metastatic disease, and median overall survival following receipt of TARE. Treatment-related adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03.
Results
The median overall survival from the time of diagnosis of metastatic disease and following receipt of TARE was 22.0 and 12.5 months, respectively. Overall and liver specific disease response were assessed for 13 patients with follow-up imaging available at the time of study (range 2–13 weeks post TARE). Four patients (31 %) demonstrated partial response and five patients (38 %) had stable disease in the liver at follow-up. One patient developed grade 3 elevation of total bilirubin three months post-treatment and another patient developed radiation cholecystitis directly following TARE. No treatment-related grade 4 or 5 toxicities were seen.
Conclusion
TARE can be safely combined with systemic chemotherapy for the treatment of liver-dominant metastatic pancreatic cancer. Patient outcomes following this treatment strategy are promising but prospective evaluations are needed to validate these preliminary findings.
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MICAL1 controls cell invasive phenotype via regulating oxidative stress in breast cancer cells
Abstract
Background
Molecules Interacting with CasL (MICAL1), a multidomain flavoprotein monoxygenase, is strongly involved in the mechanisms that promote cancer cell proliferation and survival. Activation of MICAL1 causes an up-regulation of reactive oxygen species (ROS) in HeLa cells. ROS can function as a signaling molecule that modulates protein phosphorylation, leading to malignant phenotypes of cancer cells such as invasion and metastasis. Herein, we tested whether MICAL1 could control cell migration and invasion through regulating ROS in breast cancer cell lines.
Methods
The effects of depletion/overexperssion of MICAL1 on cell invasion rate were measured by matrigel-based transwell assays. The contents of ROS in breast cancer cells were evaluated by CM2-DCFHDA staining and enhanced lucigenin chemiluminescence method. RAB35 activity was assessed by pulldown assay. The relationship of RAB35 and MICAL1 was evaluated by immunofluorescence, coimmunoprecipitation, immunoblotting and co-transfection techniques. Immunoblotting assays were also used to analyze Akt phosphorylation level.
Results
In this study, we found that depletion of MICAL1 reduced cell migration and invasion as well as ROS generation. Phosphorylation of Akt was also attenuated by MICAL1 depletion. Likewise, the over-expression of MICAL1 augmented the generation of ROS, increased Akt phosphorylation, and favored invasive phenotype of breast cancer cells. Moreover, we investigated the effect of EGF signaling on MICAL1 function. We demonstrated that EGF increased RAB35 activation and activated form of RAB35 could bind to MICAL1. Silencing of RAB35 repressed ROS generation, prevented Akt phosphorylation and inhibited cell invasion in response to EGF.
Conclusions
Taken together, our results provide evidence that MICAL1 plays an essential role in the activation of ROS/Akt signaling and cell invasive phenotype and identify a novel link between RAB35 and MICAL1 in regulating breast cancer cell invasion. These findings may provide a basis for designing future therapeutic strategy for blocking breast cancer metastasis.
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The role of formyl peptide receptor 1 (FPR1) in neuroblastoma tumorigenesis
Abstract
Background
Formyl peptide receptor 1 (FPR1) is a G protein-coupled receptor mainly expressed by the cells of myeloid origin, where it mediates the innate immune response to bacterial formylated peptides. High expression of FPR1 has been detected in various cancers but the function of FPR1 in tumorigenesis is poorly understood.
Methods
Expression of FPR1 in neuroblastoma cell lines and primary tumors was studied using RT-PCR, western blotting, immunofluorescence and immunohistochemistry. Calcium mobilization assays and western blots with phospho-specific antibodies were used to assess the functional activity of FPR1 in neuroblastoma. The tumorigenic capacity of FPR1 was assessed by xenografting of neuroblastoma cells expressing inducible FPR1 shRNA, FPR1 cDNA or control shRNA in nude mice.
Results
FPR1 is expressed in neuroblastoma primary tumors and cell lines. High expression of FPR1 corresponds with high-risk disease and poor patient survival. Stimulation of FPR1 in neuroblastoma cells using fMLP, a selective FPR1 agonist, induced intracellular calcium mobilization and activation of MAPK/Erk, PI3K/Akt and P38-MAPK signal transduction pathways that were inhibited by using Cyclosporin H, a selective receptor antagonist for FPR1. shRNA knock-down of FPR1 in neuroblastoma cells conferred a delayed xenograft tumor development in nude mice, whereas an ectopic overexpression of FPR1 promoted augmented tumorigenesis in nude mice.
Conclusion
Our data demonstrate that FPR1 is involved in neuroblastoma development and could represent a therapy option for the treatment of neuroblastoma.
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AT-101 enhances gefitinib sensitivity in non-small cell lung cancer with EGFR T790M mutations
Abstract
Background
Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) have become the standard care of patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC), development of acquired resistance is inevitable. A secondary mutation of threonine 790 (T790M) is associated with approximately half of the cases of acquired resistance. Strategies or agents to overcome this type of resistance are still limited. In this study, enhanced antitumor effect of AT-101, a-pan-Bcl-2 inhibitor, on gefitinib was explored in NSCLC with T790M mutation.
Methods
The effect of cotreatment with AT-101 and gefitinib on the viability of NSCLC cell lines harboring acquired T790M mutation was investigated using the MTT assay. The cellular apoptosis of NSCLC cells after cotreatment with AT-101 and gefitinib was assessed by FITC-annexin V/PI assay and Western blots analysis. The potential underlying mechanisms of the enhanced therapeutic effect for AT-101 was also studied using Western blots analysis. The in vivo anti-cancer efficacy of the combination with AT-101 and gefitinib was examined in a mouse xenograft model.
Results
In this study, we found that treatment with AT-101 in combination with gefitinib significantly inhibited cell proliferation, as well as promoted apoptosis of EGFR TKIs resistant lung cancer cells. The apoptotic effects of the use of AT-101 was related to the blocking of antiapoptotic protein: Bcl-2, Bcl-xl, and Mcl-1 and downregrulation of the molecules in EGFR pathway. The observed enhancements of tumor growth suppression in xenografts supported the reverse effect of AT-101 in NSCLC with T790M mutation, which has been found in in vitro studies before.
Conclusions
AT-101 enhances gefitinib sensitivity in NSCLC with EGFR T790M mutations. The addition of AT-101 to gefitinib is a promising strategy to overcome EGFR TKIs resistance in NSCLC with EGFR T790M mutations.
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Serum MMP7, MMP10 and MMP12 level as negative prognostic markers in colon cancer patients
Abstract
Background
Matrixmetalloproteinases (MMPs) comprise a family of zinc-dependent endopeptidases which are involved in angiogenesis, tumor invasion and metastatic formation. Up to date, the prognostic relevance of MMPs in serum of patients with colon cancer remains unknown. Thus, we wanted to assess an expression pattern of MMPs in a homogenous cohort of colon cancer patients to assess their potential as prognostic biomarkers.
Methods
Differences in the expression pattern of MMP7, MMP10 and MMP12 in 78 serum specimens of patients with an adenocarcinoma of the colon and serum specimens of a healthy control group were assessed using Luminex-100 technologies. Subsequently, we correlated these results with histopathological and clinical data of the patients.
Results
Luminex based expression analysis revealed a significant overexpression of MMP7 and an overexpression of MMP10 and MMP12 in the sera of colon cancer patients compared to the healthy control group. Patients with vascular invasion showed a significantly higher MMP12 expression than V0-staged patients. Moreover overexpression of MMP7, MMP10 and MMP12 in colon cancer patients´ sera displayed a significantly impaired overall survival. Multivariate analysis revealed high MMP10 serum levels to be an independent adverse prognostic marker in colon cancer patients.
Conclusions
Expression patterns of MMP7, MMP10 and MMP12 in colon cancer patients´ sera are different compared to serum specimens of healthy individuals. Furthermore, overexpression of MMP7, MMP10 and MMP12 in colon cancer patients´ sera correlates with a dismal prognosis and may help to stratify patients into different risk groups.
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Effect of progressive normobaric hypoxia on dynamic cerebral autoregulation
Cerebral blood flow is maintained at relatively constant levels over a wide range of perfusion pressures via cerebral autoregulation (CA). Although acute hypoxia reduces dynamic CA, it is unclear what level of hypoxia is necessary to exert this effect. We evaluated dynamic CA during progressive normobaric hypoxia (∼1 hour each at 21%, 18%, 15%, and 12% O2) using duplex ultrasonography to measure volumetric changes in common carotid artery blood flow of 11 healthy young males. Dynamic CA was evaluated by the thigh-cuff method and represented as rate of regulation (RoR) in vascular conductance. On a separate occasion, symptoms of acute mountain sickness (AMS) were evaluated over 6 hours of prolonged hypoxia (FiO2 = 14.1%) using the Lake Louise Questionnaire. Repeated measures ANOVA with linear trend analysis indicated that dynamic CA decreased progressively as FiO2 was reduced (P < 0.001). Spearman rank order analysis revealed that AMS symptoms were related to changes in RoR from 21% to 15% (r = -0.869, P = 0.006) and from 21% to 12% O2 (r = -0.648, P = 0.040), respectively. These results suggest that dynamic CA worsens with progressive hypoxia and that reductions in dynamic CA during moderate-to-severe hypoxia (<15% O2) may be related to the severity of AMS.
This article is protected by copyright. All rights reserved
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Special Issue of NeuroRehabilitation Investigates the Effectiveness of Treatment for Individuals with Brain Injury or Stroke
"The goal of this special issue is to present real world applications of neurorehabilitation that showcase a diverse spectrum of effective therapeutic interventions after brain injury and stroke," explained guest editor Rick Parente, PhD, Professor, Psychology Department, Towson University, Towson, MD, USA. "The characteristics of these therapies that make them effective are that they are adaptable, measurable, and they provide gains that are tangible for patients and family members. All of these therapies are evidence based, which makes them excellent candidates for future research and development."
The Editors-in-Chief of NeuroRehabilitation, Nathan D. Zasler, MD, FAAPM&R, and Jeffrey S. Kreutzer, PhD, ABPP, have selected three articles that represent the advances in neurorehabilitation that contribute to patient care. These articles have been made freely available online as a service to the neurorehabilitation community.
Goodwin, Lincoln and Bateman evaluate whether a holistic neuropsychological rehabilitation program reduced reported symptoms of everyday dysexecutive behavior and carer strain. They also assessed whether aetiology interacts with the effects of rehabilitation. "Neuropsychological rehabilitation is effective in reducing client and carer reports of dysexecutive behaviors and carer strain. Rehabilitation can benefit clients with acquired brain injury and their families, even after the spontaneous recovery period. Also implicated is the importance of considering aetiology in practice," they commented. Their findings highlight the importance of service evaluation to assure efficacy of rehabilitation.
Nickels and Osborne look at how a treatment for aphasia that has a strong evidence base can be implemented cost-effectively by speech and language therapists. "Constraint Induced Aphasia Therapy (CIAT) has been shown to be effective in the treatment of aphasia, but clinicians have expressed concern regarding how far CIAT was practical to implement in clinical practice," they explained. They examine whether a more clinically viable form of CIAT is possible.
Shaw investigates the effectiveness of cognitive remediation strategies, as well as their efficacy in a range of settings, particularly in school. "As traumatic brain injury (TBI) survivors spend a majority of their time in school, school personnel should be trained and prepared to continue the rehabilitation process. Schools are also agents for successful community reintegration. Most importantly, with increased problem-solving abilities and social coping skills, TBI survivors will more successfully reintegrate into the community," she commented.
Full contents of the current issue of NeuroRehabilitation are available at http://ift.tt/2atyDJA
# # #
NOTES FOR EDITORS
Full text of the articles is available to credentialed journalists. Contact Diana Murray, IOS Press, at +1 718 640-5678, d.murray@iospress.com to obtain full text of the articles listed below. Journalists wishing to request interviews with the guest editor or authors should contact Dr. Rick Parente at fparente@towson.edu.
Special Feature: Effectiveness of Neurorehabilitation Treatment for Individuals with Brain Injury or Stroke
NeuroRehabilitation: An Interdisciplinary Journal, 39(1), July 2016
Guest Editor: Rick Parente, PhD, Towson University, Towson, MD, USA
Featured Articles:
"Effectiveness of Neurorehabilitation Treatment for Individuals with Brain Injury or Stroke: Editorial," Rick Parente
"Restoring one's language edifice: A case study of long-term effects of intensive aphasia therapy," David Anaki, Rosalind Goldenberg, Haim Devisheim, Diana Rosenfelder, Lou Falik and Idit Harif
"Significance of the Feuerstein approach in neurocognitive rehabilitation," Jo Lebeer
"Self-Appraisal: Estimates of Intellectual Performance for Persons with Acquired Brain Injury," Grace-Anna S. Chaney and Rick Parente
"Efficacy of Self-Perception after Traumatic Brain Injury," Megan English, Maria E. St. Pierre, Anita Delahay and Rick Parente
"Dysexecutive symptoms and carer strain following acquired brain injury: changes measured before and after holistic neuropsychological rehabilitation," Rachel A. Goodwin, Nadina B. Lincoln and Andrew Bateman (openly available)
"Selection and Visualisation of Outcome Measures for Complex Post-Acute Acquired Brain Injury Rehabilitation Interventions," Catherine Elaine Longworth Ford, Donna Malley, Andrew Bateman, Isabel C.H. Clare, Adam P. Wagner and Fergus Gracey
"The impact of group therapy on word retrieval in people with chronic aphasia," Lyndsey Nickels, Belinda McDonald and Catherine Mason
"Constraint Induced Aphasia Therapy: Volunteer-led, unconstrained and less intense delivery can be effective," Lyndsey Nickels and Amanda Osborne (openly available)
"Seeing red: Relearning to read in a case of Balint's Syndrome," Anita Rose, Barbara A. Wilson, Rumen Manolov and Gerhard Florschutz
"A Systematic Review of Pediatric Cognitive Rehabilitation in the Elementary and Middle School Systems," Dorothy R. Shaw (openly available)
"Efficacy of Legal Judgements for Defendants with Traumatic Brain Injury," Maria E. St. Pierre and Rick Parente
"Effectiveness of Animal Assisted Therapy After Brain Injury : A Bridge To Improved Outcomes in CRT," Mary Stapleton
"Transcranial Direct Current Stimulation in Post Stroke Aphasia and Primary Progressive Aphasia: Current Knowledge and Future Clinical Applications," Rajani Sebastian, Kyrana Tsapkini and Donna C. Tippett
"Perspective training to treat anger problems after brain injury: Two case studies," Jill Winegardner, Clare Keohane, Leyla Prince and Dawn Neumann
"Treatments and technologies in the rehabilitation of Apraxia and Action Disorganisation Syndrome: A review," Andrew Worthington
ABOUT NEUROREHABILITATION: AN INTERDISCIPLINARY JOURNAL
NeuroRehabilitation; An Interdisciplinary Journal is an international journal that emphasizes publication of scientifically based, practical information relevant to all aspects of neurologic rehabilitation. Founded in 1991, it features peer-reviewed articles that are interdisciplinary in nature and cover the full life span and range of neurological disabilities including stroke, spinal cord injury, traumatic brain injury, neuromuscular disease, and other neurological disorders. Information is intended for an interdisciplinary audience. Issues of the journal are thematically organized. Themes have focused on specific clinical disorders, types of therapy, and age groups.
ABOUT IOS PRESS
Commencing its publishing activities in 1987, IOS Press is headquartered in Amsterdam with satellite offices in the USA, Germany, India and China and serves the information needs of scientific and medical communities worldwide. IOS Press now publishes over 100 international journals and about 75 book titles each year on subjects ranging from computer sciences and mathematics to medicine and the natural sciences.
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EV-A71 vaccine licensure: a first step for multivalent enterovirus vaccine to control HFMD and other severe diseases
EV-A71 vaccine licensure: a first step for multivalent enterovirus vaccine to control HFMD and other severe diseases
Emerging Microbes & Infections 5, e75 (July 2016). doi:10.1038/emi.2016.73
Authors: Qunying Mao, Yiping Wang, Lianlian Bian, Miao Xu & Zhenglun Liang
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Molecular characterization of H6 subtype influenza viruses in southern China from 2009 to 2011
Molecular characterization of H6 subtype influenza viruses in southern China from 2009 to 2011
Emerging Microbes & Infections 5, e73 (July 2016). doi:10.1038/emi.2016.71
Authors: Shumei Zou, Rongbao Gao, Ye Zhang, Xiaodan Li, Wenbing Chen, Tian Bai, Libo Dong, Dayan Wang & Yuelong Shu
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Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections
Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections
Emerging Microbes & Infections 5, e70 (July 2016). doi:10.1038/emi.2016.69
Authors: Srey Viseth Horm, Arnaud Tarantola, Sareth Rith, Sowath Ly, Juliette Gambaretti, Veasna Duong, Phalla Y, San Sorn, Davun Holl, Lotfi Allal, Wantanee Kalpravidh, Philippe Dussart, Paul F Horwood & Philippe Buchy
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MicroRNAs differentially expressed in Behçet disease are involved in interleukin-6 production
Abstract
Background
Behcet's disease (BD) is characterized by systemic recurrent inflammation with increased production of tumor necrosis factor (TNF)–α and interleukin (IL)-6 by peripheral blood mononuclear cells (PBMCs). To gain insight into the underlying mechanisms of this disease, the expression levels of distinct microRNAs in PBMCs of BD patients were determined and their association with TNF-α and IL-6 production was evaluated.
Findings
The expression levels of microRNAs, miR-638 and miR-4488, were reduced in patients with stable BD in comparison with healthy controls. In addition, the expression of miR-3591-3p was increased in patients with active BD when compared to patients with stable BD. Transfection of miR-638 and miR-4488 inhibitors, together with miR-3591-3p mimics, increased IL-6 mRNA levels in THP-1 cells in response to LPS stimulation.
Conclusions
We observed differential expression of microRNAs associated with increased production of IL-6 in BD patients.
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Treatment of Acne Keloidalis Nuchae: A Systematic Review of the Literature
Abstract
Acne keloidalis nuchae (AKN) is a chronic inflammatory condition that leads to fibrotic plaques, papules and alopecia on the occiput and/or nape of the neck. Traditional medical management focuses on prevention, utilization of oral and topical antibiotics, and intralesional steroids in order to decrease inflammation and secondary infections. Unfortunately, therapy may require months of treatment to achieve incomplete results and recurrences are common. Surgical approach to treatment of lesions is invasive, may require general anesthesia and requires more time to recover. Light and laser therapies offer an alternative treatment for AKN. The present study systematically reviews the currently available literature on the treatment of AKN. While all modalities are discussed, light and laser therapy is emphasized due to its relatively unknown role in clinical management of AKN. The most studied modalities in the literature were the 1064-nm neodymium-doped yttrium aluminum garnet laser, 810-nm diode laser, and CO2 laser, which allow for 82–95% improvement in 1–5 sessions. Moreover, side effects were minimal with transient erythema and mild burning being the most common. Overall, further larger-scale randomized head to head control trials are needed to determine optimal treatments.
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Superior Efficacy with Ivermectin 1% Cream Compared to Metronidazole 0.75% Cream Contributes to a Better Quality of Life in Patients with Severe Papulopustular Rosacea: A Subanalysis of the Randomized, Investigator-Blinded ATTRACT Study
Abstract
Introduction
Ivermectin 1% cream (IVM 1%) is indicated for the treatment of inflammatory lesions of rosacea. The objective of this subanalysis was to compare IVM 1% vs. metronidazole 0.75% cream (MTZ 0.75%) in the treatment of severe inflammatory lesions of rosacea.
Methods
A subanalysis of the investigator-assessed severe subjects from a Phase 3, investigator-blinded, randomized study comparing IVM 1% once daily (QD) with MTZ 0.75% twice daily (BID) over 16 weeks followed by a 36-week extension period was performed. Efficacy assessments were Dermatology Life Quality Index (DLQI) and EuroQol-5 Dimension (EQ-5D) questionnaires, investigator's global assessment (IGA), subject assessment of rosacea improvement, and inflammatory lesion counts. Adverse events (AEs) were monitored throughout the study.
Results
A total of 161 subjects (16.7% of overall study population; 80 IVM 1% and 81 MTZ 0.75%) had an IGA score of 4 at baseline representing severe papulopustular rosacea. Significantly more IVM 1% subjects had a minimal clinically important difference (MCID, defined as a decrease from baseline of ≥4 points) in DLQI score than MTZ 0.75% subjects at week 16 (65.4% vs. 39.2%; P = 0.001) and week 52 (68.8% vs. 40.4%; P = 0.003). At week 16, the mean EQ-5D score for the IVM 1% subjects was higher (better quality of life) than for MTZ 0.75% subjects (0.941 vs. 0.896). Significantly more IVM 1% subjects were IGA "clear" or "almost clear" at week 16 compared to MTZ 0.75% (82.5% vs. 63.0%; P = 0.005). Incidence of AEs was comparable between groups.
Conclusion
Better efficacy with IVM 1% cream (QD) compared to MTZ 0.75% cream (BID) contributes to an improved quality of life with significantly more patients achieving an MCID in DLQI score at week 16 and higher mean EQ-5D score. IVM 1% cream is thus a better alternative than MTZ 0.75% cream for severe papulopustular rosacea patients.
Trial registration
EUDRACT number: 2011-004791-11.
Funding
Galderma R&D.
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Factors affecting observer agreement in morphological evaluation of mandibular cortical bone on panoramic radiographs
Abstract
Objectives
To assess intra- and inter-observer agreement in the morphological evaluation of mandibular cortical bone on panoramic radiographs, to examine factors affecting the diagnosis, and to determine causes of diagnostic discrepancy.
Methods
Three experienced observers evaluated mandibular cortical shape on panoramic radiographs of 228 females, and divided the images into three classes. The intra- and inter-observer agreements were calculated. The effect of mandibular cortical width on shape classification was examined. Causes of diagnostic discrepancy were investigated.
Results
Overall intra- and inter-observer kappa values in diagnosing mandibular cortical shape were 0.58–0.76 and 0.62–0.69, respectively. The kappa values in diagnosing Class 2 were low. In radiographs diagnosed as Class 2 and Class 3, the ranges of mandibular cortical width overlapped. Discrepancies in diagnosis were caused by slight resorption at the endosteal margin of the cortical bone, endosteal cortical residues near the thinned smooth cortex, and superimposition of the hyoid bone over the mandible.
Conclusions
Inter-observer agreement in evaluating mandibular cortical shape was moderate to substantial. Diagnostic discrepancies were mainly caused by differences in evaluation of the endosteum near the cortical bone.
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Spatial and temporal pyramid-based real-time gesture recognition
Abstract
This paper proposes a novel method for real-time gesture recognition. Aiming at improving the effectiveness and accuracy of HGR, spatial pyramid is applied to linguistically segment gesture sequence into linguistic units and a temporal pyramid is proposed to get a time-related histogram for each single gesture. Those two pyramids can help to extract more comprehensive information of human gestures from RGB and depth video. A two-layered HGR is further exploited to further reduce the computation complexity. The proposed method obtains high accuracy and low computation complexity performance on the ChaLearn Gesture Dataset, comprising more than 50, 000 gesture sequences recorded.
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The potential to expand antiretroviral therapy by improving health facility efficiency: evidence from Kenya, Uganda, and Zambia
Background: Since 2000, international funding for HIV has supported scaling up antiretroviral therapy (ART) in sub-Saharan Africa. However, such funding has stagnated for years, threatening the sustainability and reach of ART programs amid efforts to achieve universal treatment. Improving health system efficiencies, particularly at the facility level, is an increasingly critical avenue for extending limited resources for ART; nevertheless, the potential impact of increased facility efficiency on ART capacity remains largely unknown. Through the present study, we sought to quantify facility-level technical efficiency across countries, assess potential determinants of efficiency, and predict the potential for additional ART expansion. Methods: Using nationally-representative facility datasets from Kenya, Uganda and Zambia, and measures adjusting for structural quality, we estimated facility-level technical efficiency using an ensemble approach that combined restricted versions of Data Envelopment Analysis and Stochastic Distance Function. We then conducted a series of bivariate and multivariate regression analyses to evaluate possible determinants of higher or lower technical efficiency. Finally, we predicted the potential for ART expansion across efficiency improvement scenarios, estimating how many additional ART visits could be accommodated if facilities with low efficiency thresholds reached those levels of efficiency. Results: In each country, national averages of efficiency fell below 50 % and facility-level efficiency markedly varied. Among facilities providing ART, average efficiency scores spanned from 50 % (95 % uncertainty interval (UI), 48–62 %) in Uganda to 59 % (95 % UI, 53–67 %) in Zambia. Of the facility determinants analyzed, few were consistently associated with higher or lower technical efficiency scores, suggesting that other factors may be more strongly related to facility-level efficiency. Based on observed facility resources and an efficiency improvement scenario where all facilities providing ART reached 80 % efficiency, we predicted a 33 % potential increase in ART visits in Kenya, 62 % in Uganda, and 33 % in Zambia. Given observed resources in facilities offering ART, we estimated that 459,000 new ART patients could be seen if facilities in these countries reached 80 % efficiency, equating to a 40 % increase in new patients. Conclusions: Health facilities in Kenya, Uganda, and Zambia could notably expand ART services if the efficiency with which they operate increased. Improving how facility resources are used, and not simply increasing their quantity, has the potential to substantially elevate the impact of global health investments and reduce treatment gaps for people living with HIV.
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Momentum distribution of charged particles in jets in dijet events and comparison to perturbative QCD predictions
Abstract
Inclusive momentum distributions of charged particles are measured in dijet events. Events were produced at the AMY detector with a centre of mass energy of 60 GeV. Our results were compared, on the one hand to those obtained from other e +e −, ep as well as CDF data, and on the other hand to the perturbative QCD calculations carried out in the framework of the modified leading log approximation (MLLA) and assuming local parton–hadron duality (LPHD). A fit of the shape of the distributions yields Q eff = 263±13 MeV for the AMY data. In addition, a fit to the evolution of the peak position with dijet mass using all data from different experiments gives Q eff = 226±18 MeV. Next, α s was extracted using the shape of the distribution at the Z 0 scale, with a value of 0.118 ± 0.013. This is consistent, within the statistical errors, with many accurate measurements. We conclude that it is the success of LPHD + MLLA that the extracted value of α s is correct. Possible explanations for all these features will be presented in this paper.
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Association of Aortic Compliance and Brachial Endothelial Function with Cerebral Small Vessel Disease in Type 2 Diabetes Mellitus Patients: Assessment with High-Resolution MRI
Objective. To assess the possible association of aortic compliance and brachial endothelial function with cerebral small vessel disease in type 2 diabetes mellitus (DM2) patients by using 3.0 T high-resolution magnetic resonance imaging. Methods. Sixty-two clinically confirmed DM2 patients (25 women and 37 men; mean age: years) were prospectively enrolled for noninvasive MR examinations of the aorta, brachial artery, and brain. Aortic arch pulse wave velocity (PWV), flow-mediated dilation (FMD) of brachial artery, lacunar brain infarcts, and periventricular and deep white matter hyperintensities (WMHs) were assessed. Pearson and Spearman correlation analysis were performed to analyze the association between PWV and FMD with clinical data and biochemical test results. Univariable logistic regression analyses were used to analyze the association between PWV and FMD with cerebral small vessel disease. Multiple logistic regression analyses were used to find out the independent predictive factors of cerebral small vessel disease. Results. Mean PWV was m/s and FMD was %. After adjustment for compounding factors, PWV was found significantly associated with lacunar brain infarcts (OR = 2.00; 95% CI: 1.14–3.2; ) and FMD was significantly associated with periventricular WMHs (OR = 0.82; 95% CI: 0.71–0.95; ). Conclusions. Quantitative evaluation of aortic compliance and endothelial function by using high-resolution MRI may be potentially useful to stratify DM2 patients with risk of cerebral small vessel disease.
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Recent perspectives of fusion genes in glioblastoma
Fusion genes are the result of chromosomal instability where two previously separate genes rearrange and fuse together, forming a hybrid gene. The first fusion gene was reported in a leukemia case but at present many studies have confirmed their existence in several solid tumors. Recent studies have evidenced the influence of fusion genes in glioblastoma too. The fusion genes have been observed to cause activated ERK, STAT3 signaling, that in turn lead to the development of resistance against frontline chemotherapy. The present review article is focused on the current views of fusion genes in glioblastoma.
L'articolo Recent perspectives of fusion genes in glioblastoma sembra essere il primo su European Review.
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Indications for total-body computed tomography in blunt trauma patients: a systematic review
Abstract
Purpose
Total-body CT scanning (TBCT) could improve the initial in-hospital evaluation of severe trauma patients. Indications for TBCT, however, differ between trauma centers, so more insight in how to select patients that could benefit from TBCT is required. The aim of this review was to give an overview of currently used indications for total-body CT in trauma patients and to describe mortality and Injury Severity Scores of patient groups selected for TBCT.
Methods
A systematic review was performed by searching MEDLINE and Embase databases. Studies evaluating or describing criteria for selection of patients with potentially severe injuries for TBCT during initial trauma care were included. Also, studies comparing total-body CT during the initial assessment of injured patients with conventional imaging and selective CT in specific patient groups were included.
Results
Thirty eligible studies were identified. Three studies evaluated indications for TBCT in trauma with divergent methods. Combinations of compromised vital parameters, severe trauma mechanisms and clinical suspicion on severe injuries are often used indications; however, clinical judgement is used as well. Studies describing TBCT indications selected patients in different ways and were difficult to compare regarding mortality and injury severity.
Conclusions
Indications for TBCT in trauma show a wide variety in structure and cut-off values for vital parameters and trauma mechanism dimensions. Consensus on indications for TBCT in trauma is lacking.
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Colonoscopic decompression should be used before neostigmine in the treatment of Ogilvie’s syndrome
Abstract
Background
Performance of urgent colonoscopy for the purposes of diagnosis and treatment of Ogilvie's syndrome remains controversial. However, no trials have directly compared neostigmine with endoscopic therapy. This study aimed to compare the effect of neostigmine and colonoscopic decompression in the treatment of Ogilvie's syndrome.
Methods
This study was designed as a retrospective, non-randomized clinical study of sequential patients. Patients who were diagnosed as having acute colonic pseudo-obstruction were separated into two groups after conservative treatment. Group 1 comprised patients who underwent colonoscopic decompression, because they had a poor first response to neostigmine treatment. Group 2 constituted patients who had a poor first response to colonoscopic decompression, and neostigmine was added to the treatment regimen. Groups 1 and 2 were compared for the success of disease management.
Results
In groups 1 and 2, the average age of the patients was 63.19 years (±14.71 years) and 59.45 years (±15.31 years) (p = 0.312), respectively. No significant difference was determined between the groups in terms of distribution of sex, hospital stay, etiologies, and initial cecal sizes in imaging (p > 0.05). Response to first intervention was statistically significant (p < 0.01). Also, the total response was determined statistically significant for hospital stay if colonoscopic decompression was performed (p < 0.01). No recurrence was determined during the 1-month follow-up in both groups. Although there was no etiologic factor for neostigmine response according to univariate analysis results, colonoscopic success was decreased due to age, sex, and the presence of a cardiac disease.
Conclusions
Although the success rate of neostigmine treatment was significantly lower in our homogeneous groups, no significant decrease was determined in terms of hospital stay, intensive care unit stay, and requirement of colostomy compared with colonoscopic decompression. By comparison, colonoscopic decompression, which was performed by experienced endoscopists as a first-line treatment option, was more effective as an initial therapy and was more effective at avoiding a second treatment modality.
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Usability and effectiveness of Suprathel ® in partial thickness burns in children
Abstract
Purpose
Evaluation of usability and effectiveness of Suprathel® in the treatment of partial thickness burns in children.
Methods
A prospective, observational study to evaluate adherence of Suprathel® to the wound bed, reepithelialization time, grafting, wound colonization and infection, pain, dressing changes, length of hospital stay (LOS) and scar formation.
Results
Twenty-one children (median age 2.4 years, range 5 months–14 years) with a median total body surface area (TBSA) of 4 % (range 1–18) were included. Median LOS was 10 days (range 3–20). Median outer layer dressing changes was 3 (range 1–14). Suprathel® was only adherent in wounds debrided with Versajet®. Median reepithelialization time was 13 days (range 7–29). Three patients needed a split skin graft. There were 7 (33 %) patients with wound colonization before application of Suprathel®. This increased to 12 (57 %) patients during treatment. One patient developed a wound infection. Median visual analog scale (VAS) scores for background and procedural pain in patients >7 years were 3.2 (range 2–5) and 3.5 (range 2–5), respectively. In younger patients, median background and procedural COMFORT-B scores were 13.8 (range 10–23) and 14.8 (range 13–23, p = 0.03), respectively. Patient and Observer Scar Assessment Scale (POSAS) scores were favorable after 3 and 6 months post burn.
Conclusions
Suprathel® provides potential advantages regarding pain and scar formation, but extensive wound debridement is needed to achieve adequate adherence.
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Rapid detection of Clostridium difficile via magnetic bead aggregation in cost-effective polyester microdevices with cell phone image analysis
Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C6AN00674D, Paper
DOI: 10.1039/C6AN00674D, Paper
Jacquelyn A. DuVall, Scott T. Cabaniss, Morgan L. Angotti, John H. Moore, Mayuresh Abhyankar, Nishant Shukla, Daniel L. Mills, Bryan G. Kessel, Gavin Garner, Nathan S. Swami, James Landers
Pathogen detection has traditionally been accomplished by utilizing methods such as cell culture, immunoassays, and nucleic acid amplification tests; however, these methods are not easily implemented in resource-limited settings because...
The content of this RSS Feed (c) The Royal Society of Chemistry
Pathogen detection has traditionally been accomplished by utilizing methods such as cell culture, immunoassays, and nucleic acid amplification tests; however, these methods are not easily implemented in resource-limited settings because...
The content of this RSS Feed (c) The Royal Society of Chemistry
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