Background: Brain abscess is a rare but serious, life-threatening infection in children. It may arise from parameningeal infections such as otitis media, sinusitis and mastoiditis.Case descriptionA ten-year-old boy with the diagnosis of glycogen-storage disease and obesity was admitted to the emergency room with complaints of vomiting, decreased level of consciousness, imbalance on walking. On neurological examination, the patient was ataxic. His cranial magnetic resonance imaging (MRI) examination showed mastoiditis on the right side and 39 × 34 mm abscess formation with surrounding edema on the right cerebellar hemisphere. The patient underwent surgery to drain the abscess, microbiological samples were obtained and empirical antibiotic treatment with vancomycin and piperacillin–tazobactam were started. Postoperative cranial MRI examination showed that the lesion regressed 10 × 10 mm with a reduction in the edema. On the second week of the treatment, the antibiotics were switched to vancomycin and meropenem because of the relapsing fever. The therapy was continued for 6 weeks. A final MRI (after completing antibiotherapy) showed resolution of the cerebellar abscess. The child's clinical condition improved and he was discharged without any sequelae.Discussion and evaluationChildren with congenital heart disease and an immonocompromised state are particularly at risk. Streptococcus intermedius is usually a commensal microorganism in the normal flora of the mouth which can cause brain abscess rarely in children. Brain abscess induced mortality rates are still relatively high, even with the advancement of imaging technologies, the combination of surgical drainage and antimicrobial therapy. Conclusion: This case is one of the few reported cases of cerebellar abscess caused by S. intermedius in an immunocompetent child, due to its low virulence, a rare occurence and timely management resulting in fully healed.
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Τετάρτη 23 Δεκεμβρίου 2015
Braın abscess due to Streptococcus intermedius secondary to mastoiditis in a child
Terlipressin and albumin for type 1 hepatorenal syndrome: does bacterial infection affect the response?
Vasoconstrictor therapy with terlipressin and concomitant albumin can improve renal function in patients with hepatorenal syndrome (HRS) type 1, but the efficacy of therapy in patients with active infection is controversial. The aim of this study was to investigate the efficacy, adverse effects, and predictors of terlipressin therapy and to find out whether there was a difference in response rates between the patients with or without active infections. Data of 58 patients with type 1 HRS treated with terlipressin and albumin were retrospectively evaluated. Twenty-six patients (44.8 %) showed complete response to treatment. Response rates of patients with or without active bacterial infection were 47 and 43.9 %, respectively (p > 0.05). Only baseline serum creatinine level was significantly related to response in univariate/multivariate analyses (p < 0.05). Twenty-three patients (39.6 %) developed adverse effects probably related to treatment. In 8.6 % of patients, treatment was discontinued because of adverse effects of therapy. Four patients (6.9 %) developed ischemic adverse events, including nonfatal myocardial infarction, intestinal ischemia, and cutaneous necrosis. Terlipressin plus albumin therapy improved renal function in nearly half of patients with type 1 HRS. Thus, it seems a reasonable treatment for patients with active bacterial infections. Baseline serum creatinine level is a potential predictor of terlipressin response.
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CT-guided biopsy of lung lesions using two needles in difficult and poorly cooperative patients
The purpose of our study was to evaluate the feasibility and safety of CT-guided percutaneous lung biopsy using two needles in difficult and poorly cooperative patients; and to examine the usefulness of the malpositioned first needle in tissue sampling with a second needle. This study included 17 consecutive patients with unsuccessful first insertion of the biopsy needle in the normal lung parenchyma and re-attempted tissue sampling through another puncture site using a second needle with the first needle retained in position until completion of the biopsy. We examined the difficult factors in biopsy that led to a failed first attempt, success rate of tissue sampling, procedure-related complications, and usefulness of the malpositioned needle. There were 1 or multiple difficult factors in all patients. In all 17 patients, core samples were successfully obtained using a second needle. Post-procedure pneumothorax and parenchymal hemorrhage occurred in 4 and 3 patients, respectively. The first needle was used as a navigational reference point for lesion localization in all patients and as an anchor restricting the mobility of the lung in patients with pneumothorax or poor breath holding capacity. CT-guided needle biopsy of the lung using a second needle without removing the first malpositioned needle is feasible and safe. During biopsy procedures in difficult or poorly cooperative patients, the malpositioned needle provides a navigational reference point or serves as an anchor to hold the movable lung.
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Evaluation of a systematic approach to weaning of tracheotomized neurological patients: an early interrupted randomized controlled trial
Background: While a systematic approach to weaning reduces the rate of extubation failure in intubated brain-injured patients, no data are available on the weaning outcome of these patients after tracheotomy. We aimed to assess whether a systematic approach to disconnect tracheotomized neurological and neurosurgical patients off the ventilator (intervention) is superior to the sole physician's judgment (control). Based on previous work in intubated patients, we hypothesized a reduction of the rate of failure within 48 h from 15 to 5 %. Secondary endpoints were duration of mechanical ventilation, ICU length of stay and mortality. Methods: We designed a single center randomized controlled study. Since no data are available on tracheotomized patients, we based our a priori power analysis on results derived from intubated patients and calculated an overall sample size of 280 patients. Results: After inclusion of 168 consecutive patients, the trial was interrupted because the attending physicians judged the observed rate of reconnection to be much greater than expected. The overall rate of failure was 29 %, confirming the physicians' judgment. Twenty-one patients (24 %) in the intervention group and 27 (33 %) controls were reconnected to the ventilator within 48 h (p = 0.222). The main reasons for failure were respiratory distress (80 and 88 % in the treatment and control group, respectively), hemodynamic impairment (15 and 4 % in the treatment and control group, respectively), neurological deterioration (4 % in the control group only). The duration of mechanical ventilation was of 412 ± 202 h and 402 ± 189 h, in the control and intervention group, respectively. ICU length of stay was on average of 23 days for both groups. ICU mortality was 6 % in the control and 2 % in the intervention group without significant differences. Conclusion: We found no difference between the two groups under evaluation, with a rate of failure much higher than expected. Consequent to the early interruption, our study results to be underpowered. Based on the results of the present study, a further trial should overall enroll 790 patients.Trial registration: ACTRN12612000372886
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The impact of system matrix dimension on small FOV SPECT reconstruction with truncated projections
A dedicated cardiac hybrid single photon emission computed tomography (SPECT)/CT scanner that uses cadmium zinc telluride detectors and multiple pinhole collimators for stationary acquisition offers many advantages. However, the impact of the reconstruction system matrix (SM) dimension on the reconstructed image quality from truncated projections and 19 angular samples acquired on this scanner has not been extensively investigated. In this study, the authors aimed to investigate the impact of the dimensions of SM and the use of body contour derived from adjunctive CTimaging as an object support in reconstruction on this scanner, in relation to background extracardiac activity.
The authors first simulated a generic SPECT/CT system to image four NCAT phantoms with various levels of extracardiac activity and compared the reconstructions using SM in different dimensions and with/without body contour as a support for quantitative evaluations. The authors then compared the reconstructions of 18 patient studies, which were acquired on a GE Discovery NM570c scanner following injection of different radiotracers, including 99mTc-Tetrofosmin and 123I-mIBG, comparing the scanner's default SM that incompletely covers the body with a large SM that incorporates a patient specific full body contour.
The simulation studies showed that the reconstructions using a SM that only partially covers the body yielded artifacts on the edge of the field of view (FOV), overestimation of activity and increased nonuniformity in the blood pool for the phantoms with higher relative levels of extracardiac activity. However, the impact on the quantitative accuracy in the high activity region, such as the myocardium, was subtle. On the other hand, an excessively large SM that enclosed the entire body alleviated the artifacts and reduced overestimation in the blood pool, but yielded slight underestimation in myocardium and defect regions. The reconstruction using the larger SM with body contour yielded the most quantitatively accurate results in all the regions of interest for a range of uptake levels in the extracardiac regions. In patient studies, the SM incorporating patient specific body contour minimized extracardiac artifacts, yielded similar myocardial activity, lower blood pool activity, and subsequently improved myocardium-to-blood pool contrast (p reconstructions using the scanner's default SM.
Their results demonstrate that using a large SM that incorporates a CT derived body contour in the reconstruction could improve quantitative accuracy within the FOV for clinical studies with high extracardiac activity.
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Effect of deformable registration uncertainty on lung SBRT dose accumulation
Deformable image registration (DIR) plays an important role in dose accumulation, such as incorporating breathing motion into the accumulation of the delivered dose based on daily 4DCBCT images. However, it is not yet well understood how the uncertainties associated with DIR methods affect the dose calculations and resulting clinical metrics. The purpose of this study is to evaluate the impact of DIR uncertainty on the clinical metrics derived from its use in dose accumulation.
A biomechanical model based DIR method and a biomechanical-intensity-based hybrid method, which reduced the average registration error by 1.6 mm, were applied to ten lungcancer patients. A clinically relevant dose parameter [minimum dose to 0.5 cm3 (Dmin)] was calculated for three dose scenarios using both algorithms. Dose scenarios included static (no breathing motion), predicted (breathing motion at the time of planning), and total accumulated (interfraction breathing motion). The relationship between the dose parameter and a combination of DIR uncertainty metrics, tumor volume, and dose heterogeneity of the plan was investigated.
Depending on the dose heterogeneity, tumor volume, and DIR uncertainty, in over 50% of the patients, differences greater than 1.0 Gy were observed in the Dmin of the tumor in the static dose calculation on exhale phase of the 4DCT. Such differences were due to the errors in propagating the tumor contours from the reference planning 4DCT phase onto a subsequent 4DCT phase using each DIR algorithm and calculating the dose on that phase. The differences in predicted dose were more subtle when breathing motion was modeled explicitly at the time of planning with only one patient exhibiting a greater than 1.0 Gy difference in Dmin. Dmin differences of up to 2.5 Gy were found in the total accumulated delivered dose due to difference in quantifying the interfraction variations. Such dose uncertainties could potentially be clinically significant.
Reductions in average uncertainty in DIR algorithms by 1.6 mm may have a clinically significant impact on the decision-making metrics used in dose planning and dose accumulation assessment.
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Osmotic potential calculations of inorganic and organic aqueous solutions over wide solute concentration levels and temperatures
To demonstrate that the authors' new "aqueous solution vs pure water" equation to calculate osmotic potential may be used to calculate the osmotic potentials of inorganic and organic aqueous solutions over wide ranges of solute concentrations and temperatures. Currently, the osmotic potentials of solutions used for medical purposes are calculated from equations based on the thermodynamics of the gas laws which are only accurate at low temperature and solute concentration levels. Some solutions used in medicine may need their osmotic potentials calculated more accurately to take into account solute concentrations and temperatures.
The authors experimented with their new equation for calculating the osmotic potentials of inorganic and organic aqueous solutions up to and beyond body temperatures by adjusting three of its factors; (a) the volume property of pure water, (b) the number of "free" water molecules per unit volume of solution, "Nf," and (c) the "t" factor expressing the cooperative structural relaxation time of pure water at given temperatures. Adequate information on the volume property of pure water at different temperatures is available in the literature. However, as little information on the relative densities of inorganic and organic solutions, respectively, at varying temperatures needed to calculate Nf was available, provisional equations were formulated to approximate values. Those values together with tentative t values for different temperatures chosen from values calculated by different workers were substituted into the authors' equation to demonstrate how osmotic potentials could be estimated over temperatures up to and beyond bodily temperatures.
The provisional equations formulated to calculate Nf, the number of free water molecules per unit volume of inorganic and organic solute solutions, respectively, over wide concentration ranges compared well with the calculations of Nf using recorded relative density data at 20 °C. They were subsequently used to estimate Nf values at temperatures up to and excess of body temperatures. Those values, together with t values at temperatures up to and in excess of body temperatures recorded in the literature, were substituted in the authors' equation for the provisional calculation of osmotic potentials. The calculations indicated that solutiontemperatures and solute concentrations have a marked effect on osmotic potentials.
Following work to measure the relative densities of aqueous solutions for the calculation of Nf values and the determination of definitive t values up to and beyond bodily temperatures, the authors' equation would enable the accurate estimations of the osmotic potentials of wide concentrations of aqueous solutions of inorganic and organic solutes over the temperature range. The study illustrates that not only solute concentrations but also temperatures have a marked effect on osmotic potentials, an observation of medical and biological significance.
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Flattening filter free beams from TrueBeam and Versa HD units: Evaluation of the parameters for quality assurance
Flattening filter free (FFF) beams generated by medicallinear accelerators are today clinically used for stereotactical and non-stereotactical radiotherapy treatments. Such beams differ from the standard flattened beams (FF) in the high dose rate and the profile shape peaked on the beam central axis. Definition of new parameters as unflatness and slope for FFF beams has been proposed based on a renormalization factor for FFF profiles. The present study aims to assess the dosimetric differences between FFF beams generated by linear accelerators from different vendors, and to provide renormalization and parameter data of the two kinds of units.
Dosimetric data from two Varian TrueBeam and two Elekta Versa HD linear accelerators, all with 6 and 10 MV nominal accelerating potentials, FF and FFF modes have been collected. Renormalization factors and related fit parameters according to Fogliata et al. ["Definition of parameters for quality assurance of flattening filter free (FFF) photon beams in radiation therapy," Med. Phys. 39, 6455–6464 (2012)] have been evaluated for FFF beams of both units and energies. Unflatness and slope parameters from profile curves were evaluated. Dosimetric differences in terms of beam penetration and near-the-surface dose were also assessed.
FFF profile parameters have been updated; renormalization factors and unflatness from the Varian units are consistent with the published data. Elekta FFF beam qualities, different from the Varian generated beams, tend to express similar behaviour as the FF beam of the corresponding nominal energy. TPR20,10 for 6 and 10 MV FF and FFF TrueBeam beams are 0.665, 0.629 (6 MV) and 0.738, 0.703 (10 MV). The same figures for Versa HD units are 0.684, 0.678 (6 MV) and 0.734, 0.721 (10 MV).
Renormalization factor and unflatness parameters evaluated from Varian and Elekta FFF beams are provided, in particular renormalization factors table and fit parameters.
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Discontinuous finite element space-angle treatment of the first order linear Boltzmann transport equation with magnetic fields: Application to MRI-guided radiotherapy
The advent of magnetic resonance imaging(MRI) guided radiotherapy systems demands the incorporation of the magnetic field into dose calculation algorithms of treatment planning systems. This is due to the fact that the Lorentz force of the magnetic field perturbs the path of the relativistic electrons, hence altering the dose deposited by them. Building on the previous work, the authors have developed a discontinuous finite element space-angle treatment of the linear Boltzmann transport equation to accurately account for the effects of magnetic fields on radiotherapy doses.
The authors present a detailed description of their new formalism and compare its accuracy to geant4Monte Carlo calculations for magnetic fields parallel and perpendicular to the radiation beam at field strengths of 0.5 and 3 T for an inhomogeneous 3D slab geometry phantom comprising water, bone, and air or lung. The accuracy of the authors' new formalism was determined using a gamma analysis with a 2%/2 mm criterion.
Greater than 98.9% of all points analyzed passed the 2%/2 mm gamma criterion for the field strengths and orientations tested. The authors have benchmarked their new formalism against Monte Carlo in a challenging radiationtransport problem with a high density material (bone) directly adjacent to a very low density material (dry air at STP) where the effects of the magnetic field dominate collisions.
A discontinuous finite element space-angle approach has been proven to be an accurate method for solving the linear Boltzmann transport equation with magnetic fields for cases relevant to MRI guided radiotherapy. The authors have validated the accuracy of this novel technique against geant4, even in cases of strong magnetic field strengths and low density air.
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Constructing the ecstasy of MDMA from its component mental organs: Proposing the primer/probe method
Publication date: Available online 23 December 2015
Source:Medical Hypotheses
Author(s): Thomas S. Ray
The drug MDMA, commonly known as ecstasy, produces a specific and distinct open hearted mental state, which led to the creation of a new pharmacological class, "entactogens". Extensive literature on its mechanisms of action has come to characterize MDMA as a "messy" drug with multiple mechanisms, but the consensus is that the distinctive entactogenic effects arise from the release of neurotransmitters, primarily serotonin. I propose an alternative hypothesis:• The entactogenic mental state is due to the simultaneous direct activation of imidazoline-1 (I1) and serotonin-2 (5-HT2) receptors by MDMA.• "Mental organs" are populations of neurons that all express their defining metabotropic receptor, and each mental organ plays a distinct role in the mind, a role shaped by evolution as mental organs evolve by duplication and divergence. Mental organs are the mechanism by which evolution sculpts the mind.• Mental organs can be in or out of consciousness.• In order for a mental organ to enter consciousness, three things must happen:○ The mental organ must be activated directly at its defining receptor.○ 5-HT2 must be simultaneously activated. One of the functions of activated 5-HT2 is to load other simultaneously activated mental organs fully into consciousness.○ In some cases THC must be introduced to remove long-term blocks mediated by the cannabinoid system.This hypothesis emerges from "mental organ" theory, which embodies many hypotheses, the most relevant of which are:I propose the "primer/probe" method to test these hypotheses. A "primer" is a drug that selectively activates 5-HT2 (e.g. DOB or MEM) or serotonin-1 (5-HT1) and 5-HT2 (e.g. DOET or 2C-B-fly). A "probe" is a drug that activates a receptor whose corresponding mental organ we wish to load into consciousness in order to understand its role in the mind. The mental organ is loaded into consciousness when the primer and probe are taken together, but not when taken separately. For example, the blood pressure medications rilmenidine and moxonidine are selective for imidazoline-1 and can be used to test the hypothesis that the entactogenic mental effects of MDMA are due to loading the imidazoline-1 mental organ into consciousness. The primer/probe method is not limited to testing the specific hypothesis about MDMA and imidazoline, but is a general method for studying the role of mental organs in the mind. For example, the role of dopamine mental organs can be studied by using Parkinson's drugs such as ropinirole or pramipexole as probes.
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Strategy To Fabricate Naked-Eye Readout Ultrasensitive Plasmonic Nanosensor Based on Enzyme Mimetic Gold Nanoclusters
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Enhanced Mass Defect Filtering To Simplify and Classify Complex Mixtures of Lignin Degradation Products
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Cross-sector surveys assessing perceptions of key stakeholders towards barriers, concerns and facilitators to the appropriate use of adaptive designs in confirmatory trials
Background: Appropriately conducted adaptive designs (ADs) offer many potential advantages over conventional trials. They make better use of accruing data, potentially saving time, trial participants, and limited resources compared to conventional, fixed sample size designs. However, one can argue that ADs are not implemented as often as they should be, particularly in publicly funded confirmatory trials. This study explored barriers, concerns, and potential facilitators to the appropriate use of ADs in confirmatory trials among key stakeholders. Methods: We conducted three cross-sectional, online parallel surveys between November 2014 and January 2015. The surveys were based upon findings drawn from in-depth interviews of key research stakeholders, predominantly in the UK, and targeted Clinical Trials Units (CTUs), public funders, and private sector organisations. Response rates were as follows: 30(55 %) UK CTUs, 17(68 %) private sector, and 86(41 %) public funders. A Rating Scale Model was used to rank barriers and concerns in order of perceived importance for prioritisation. Results: Top-ranked barriers included the lack of bridge funding accessible to UK CTUs to support the design of ADs, limited practical implementation knowledge, preference for traditional mainstream designs, difficulties in marketing ADs to key stakeholders, time constraints to support ADs relative to competing priorities, lack of applied training, and insufficient access to case studies of undertaken ADs to facilitate practical learning and successful implementation. Associated practical complexities and inadequate data management infrastructure to support ADs were reported as more pronounced in the private sector. For funders of public research, the inadequate description of the rationale, scope, and decision-making criteria to guide the planned AD in grant proposals by researchers were all viewed as major obstacles. Conclusions: There are still persistent and important perceptions of individual and organisational obstacles hampering the use of ADs in confirmatory trials research. Stakeholder perceptions about barriers are largely consistent across sectors, with a few exceptions that reflect differences in organisations' funding structures, experiences and characterisation of study interventions. Most barriers appear connected to a lack of practical implementation knowledge and applied training, and limited access to case studies to facilitate practical learning.
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Diagnosis of early-stage esophageal cancer by Raman spectroscopy and chemometric techniques
DOI: 10.1039/C5AN01323B, Paper
We evaluated the potential of Raman spectroscopy for the diagnosis of early stage esophageal cancer with chemometric techniques.
To cite this article before page numbers are assigned, use the DOI form of citation above.
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Micro movements of the upper limb in fibromyalgia: The relation to proprioceptive accuracy and visual feedback
Publication date: Available online 22 December 2015
Source:Journal of Electromyography and Kinesiology
Author(s): Ellen Marie Bardal, Karin Roeleveld, Espen Ihlen, Paul Jarle Mork
The purpose of this study was to explore the role of visual and proprioceptive feedback in upper limb posture control in fibromyalgia (FM) and to assess the coherence between acceleration measurements of upper limb micro movements and surface electromyography (sEMG) of shoulder muscle activity (upper trapezius and deltoid). Twenty-five female FM patients and 25 age- and sex-matched healthy controls (HCs) performed three precision motor tasks: 1) maintain a steady shoulder abduction angle of 45˚ while receiving visual feedback about upper arm position and supporting external loads (0.5, 1, or 2 kg), 2) maintain the same shoulder abduction angle without visual feedback (eyes closed) and no external loading, and 3) a joint position sense test (i.e., assessment of proprioceptive accuracy). Patients had more extensive increase in movement variance than HCs when visual feedback was removed (P<0.03). Proprioceptive accuracy was related to movement variance in HCs (R⩾0.59, P⩽0.002), but not in patients (R⩽0.25, P⩾0.24). There was no difference between patients and HCs in coherence between sEMG and acceleration data. These results may indicate that FM patients are more dependent on visual feedback and less reliant on proprioceptive information for upper limb posture control compared to HCs.
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The curative efficacy of arthroscopic therapy in treating anterior cruciate ligament rupture with secondary osteoarthritis
OBJECTIVE: To compare and analyze the clinical effects of arthroscopic therapy and drug therapy in treating anterior cruciate ligament (ACL) rupture with secondary osteoarthritis (OA).
PATIENTS AND METHODS: A total of 68 patients that were diagnosed as ACL rupture with secondary OA in our hospital from February 2014 to February 2015 were enrolled in our study. All of the patients were randomly divided into control group (n = 30) and observation group (n = 38) according to the order of admission. Patients in control group were given analgesic, anti-inflammatory drugs + functional rehabilitation training whereas patients in observation group were given ACL reconstruction + OA debridement and functional rehabilitation training under arthroscopy.
RESULTS: The success rate of the observation group was 92.1%. After 3-month follow-up, the clinical total effective rate of the observation group was significantly higher than that of the control group, the prevalence of complications in the observation group was significantly lower than in the control group, and differences were statistically significant (p < 0.05). Lysholm scale scoring of observation group was significantly higher than of the control group, modified McGill pain scale score was significantly lower than that of the control group, and differences were statistically significant (p < 0.05). Quadriceps muscle peak torque, average power, and the optimal single work at 60°/s, 120°/s, and 180°/s were significantly higher than those of the control group, and differences were statistically significant (p < 0.05).
CONCLUSIONS: Arthroscopic operative therapy was safe and effective for the treatment of ACL with secondary OA. Compared with drug therapy, it can significantly improve the movement function of knee joint, so it was worthy of clinical application.
L'articolo The curative efficacy of arthroscopic therapy in treating anterior cruciate ligament rupture with secondary osteoarthritis sembra essere il primo su European Review.
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Does statin use have a disease modifying effect in symptomatic knee osteoarthritis? Study protocol for a randomised controlled trial
Background: Osteoarthritis (OA) is a major clinical and public health problem, with no current medications approved as having disease modifying effects. HMG-CoA reductase inhibitors, or "statins", a drug class widely used to prevent cardiovascular events, could potentially affect OA progression via a number of mechanisms including their effects on lipid metabolism and inflammation. The aim of this multicentre, randomised, double-blind, placebo-controlled trial is to determine whether atorvastatin reduces the progression of knee structural changes and symptoms over 2 years in patients with symptomatic knee OA.Methods/design350 patients with symptomatic knee OA will be recruited through the OA Clinical Trial Network (in Melbourne, Hobart and Adelaide). They will be randomly allocated to the two arms of the study, receiving either 40 mg of atorvastatin or identical placebo once daily for 2 years. Magnetic resonance imaging of the knee will be performed at baseline and 2 years later. Knee structure, symptoms and function will be assessed using validated methods. The primary outcome is annual percentage change in knee cartilage volume. Secondary outcomes include progression of cartilage defects, bone marrow lesions, knee pain and function. The primary analysis will be by intention to treat, but per protocol analyses will also be performed.DiscussionThe study will provide high-quality evidence to address whether atorvastatin has a novel disease modifying effect in OA by delaying the structural and symptomatic progression of knee OA. Thus, the trial has major public health and clinical importance, as if found to be beneficial, atorvastatin could produce substantial cost savings by delaying and possibly reducing the need for joint replacement surgery, and provide marked improvements in quality of life for people with OA.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12613000190707, registered on 18 February 2013.
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Plasmonic nanostructures for surface enhanced spectroscopic methods
DOI: 10.1039/C5AN02057C, Critical Review
A comprehensive review of theoretical approaches to simulate plasmonic-active metallic nano-arrangements is given. Further, various fabrication methods based on bottom-up, self-organization and top-down techniques are introduced. Here, analytical approaches are...
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Study of Oral Ceritinib in Patients With ALK-Activated Gastrointestinal Malignancies
Intervention: Drug: ceritinib
Sponsors: Criterium, Inc.; University of Colorado, Denver; Novartis
Not yet recruiting - verified December 2015
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The neurophysiology of failed visual perceptions: some implications for medical teaching
Failed perceptions of clinical abnormalities may have a neurophysiological explanation including three major covert eye problems and seven major brain-processing problems. Seven suggestions are made in an attempt to minimise their effect. We see in detail much less than we think and there is no substitute for seeing real-life clinical abnormalities.
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Life, Vol. 6, Pages 1: Landmarks in the Evolution of (t)-RNAs from the Origin of Life up to Their Present Role in Human Cognition
How could modern life have evolved? The answer to that question still remains unclear. However, evidence is growing that, since the origin of life, RNA could have played an important role throughout evolution, right up to the development of complex organisms and even highly sophisticated features such as human cognition. RNA mediated RNA-aminoacylation can be seen as a first landmark on the path from the RNA world to modern DNA- and protein-based life. Likewise, the generation of the RNA modifications that can be found in various RNA species today may already have started in the RNA world, where such modifications most likely entailed functional advantages. This association of modification patterns with functional features was apparently maintained throughout the further course of evolution, and particularly tRNAs can now be seen as paradigms for the developing interdependence between structure, modification and function. It is in this spirit that this review highlights important stepping stones of the development of (t)RNAs and their modifications (including aminoacylation) from the ancient RNA world up until their present role in the development and maintenance of human cognition. The latter can be seen as a high point of evolution at its present stage, and the susceptibility of cognitive features to even small alterations in the proper structure and functioning of tRNAs underscores the evolutionary relevance of this RNA species.
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Healthcare, Vol. 4, Pages 1: Shortening a Patient Experiences Survey for Medical Homes
The Consumer Assessment of Healthcare Providers and Systems—Patient-Centered Medical Home (CAHPS PCMH) Survey assesses patient experiences reflecting domains of care related to general patient experience (access to care, communication with providers, office staff interaction, provider rating) and PCMH-specific aspects of patient care (comprehensiveness of care, self-management support, shared decision making). The current work compares psychometric properties of the current survey and a proposed shortened version of the survey (from 52 to 26 adult survey items, from 66 to 31 child survey items). The revisions were based on initial psychometric analysis and stakeholder input regarding survey length concerns. A total of 268 practices voluntarily submitted adult surveys and 58 submitted child survey data to the National Committee for Quality Assurance in 2013. Mean unadjusted scores, practice-level item and composite reliability, and item-to-scale correlations were calculated. Results show that the shorter adult survey has lower reliability, but still it still meets general definitions of a sound survey for the adult version, and resulted in few changes to mean scores. The impact was more problematic for the pediatric version. Further testing is needed to investigate approaches to improving survey response and the relevance of survey items in informing quality improvement.
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Molbank, Vol. 2016, Article M882: 1,3-Bis(5′-methyl-4′-phenyl-2′-thiazolylimino)isoindoline
A new sterically hindered isoindoline-based 1,3-bis(5′-methyl-4′-phenyl-2′-thiazolylimino)isoindoline (1) was synthesized by fusion method with satisfyingly good yield. The structure of the newly synthesized compound was identified by FT-IR, UV-Vis, 1H-NMR, 13C-NMR and X-ray analysis.
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Marine Drugs, Vol. 14, Pages 2: In Vitro and in Vivo Anticancer Activity of Pardaxin against Proliferation and Growth of Oral Squamous Cell Carcinoma
Pardaxin (H-GFFALIPKIISSPLFKTLLSAVGSALSSSGGQE-OH), a 33-amino-acid polypeptide, is an antimicrobial peptide (AMP) isolated from the marine fish species Pardachirus marmoratus. Pardaxin shows antibacterial and antitumor activities. However, pardaxin-induced inhibition of oral cancer and the mechanism of tumor reduction in buccal pouch carcinogenesis after pardaxin painting remain undetermined. Additionally, the toxic effects of pardaxin on normal tissue remain unclear. The present study investigated the anticancer activity of pardaxin in oral squamous cell carcinoma (OSCC) cells in the hamster buccal pouch model with or without 7,12-dimethylbenz[a]anthracene (DMBA) pretreatment. This is the first study to confirm the effects of pardaxin on normal tissue and its nontoxic effects in vivo. Cell viability assays and colony formation tests in OSCC cell lines (SCC-4) demonstrated that pardaxin reduced cell viability in a dose-dependent manner. Immunofluorescence staining of cleaved caspase-3 in SCC-4 cells revealed that expression of activated caspase-3 in SCC-4 cells significantly increased after 24-h treatment with pardaxin. Additionally, a cell cycle analysis indicated that pardaxin treatment resulted in the cell cycle arrest of SCC-4 cells in the G2/M phase, thereby limiting cell proliferation. Furthermore, pardaxin treatment substantially alleviated carcinogenesis in the DMBA-induced hamster buccal pouch model by lowering prostaglandin E2 levels. These results suggest that pardaxin is a potential marine drug for adjuvant chemotherapy for human OSCC and oral cancer.
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Humanities, Vol. 5, Pages 1: Double Blind Peer-Review in Humanities
Pre-publication peer-review forms the basis of how scholarly journals assess whether an article is suitable for publication. [...]
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JDB, Vol. 4, Pages 1: Beyond the Mammalian Heart: Fish and Amphibians as a Model for Cardiac Repair and Regeneration
The epidemic of heart disease, the leading cause of death worldwide, is made worse by the fact that the adult mammalian heart is especially poor at repair. Damage to the mammal heart—such as that caused by myocardial infarction—leads to scarring, resulting in cardiac dysfunction and heart failure. In contrast, the hearts of fish and urodele amphibians are capable of complete regeneration of cardiac tissue from multiple types of damage, with full restoration of functionality. In the last decades, research has revealed a wealth of information on how these animals are able to perform this remarkable feat, and non-mammalian models of heart repair have become a burgeoning new source of data on the morphological, cellular, and molecular processes necessary to heal cardiac damage. In this review we present the major findings from recent research on the underlying mechanisms of fish and amphibian heart regeneration. We also discuss the tools and techniques that have been developed to answer these important questions.
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Laws, Vol. 5, Pages 1: Services in the Field of Law within the Internal Market: Promoting e-Justice through Interoperability
The paper addresses the problem of intra-European services provided to professionals in the legal sector. Through a brief overview of the main services that are or may be offered in the internal market in this field, the author identifies the lack of interoperability as one of the most critical barriers currently preventing effective intra-community competition. The author wonders to what degree and under which rules of the treaties a European intervention could be justified and, therefore, what purposes could be pursued through European legislation. The author analyses the rail transport sector to assess if, and to what degree, existing barriers to entry could be reduced and innovation could be fostered by defining certain standards at a European level for the interoperability of IT systems in the field of law. In particular, the example of the rail sector is analyzed to determine the degree to which the solutions already in place for the "telematics applications for the passenger services subsystem" could be replicated in the context of the services addressed by the paper. In conclusion, the author suggests that addressing the issues of interoperability in the legal services sector could be a useful first step towards the digitalization of the internal market, as advocated by the Commission in its recent Communication on the digital single market.
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JoF, Vol. 2, Pages 1: Colliding Epidemics and the Rise of Cryptococcosis
Discovered more than 100 years ago as a human pathogen, the Cryptococcus neoformans–Cryptococcus gattii (C. neoformans–C. gattii) complex has seen a large global resurgence in its association with clinical disease in the last 30 years. First isolated in fermenting peach juice, and identified as a human pathogen in 1894 in a patient with bone lesions, this environmental pathogen has now found niches in soil, trees, birds, and domestic pets. Cryptococcosis is well recognized as an opportunistic infection and was first noted to be associated with reticuloendothelial cancers in the 1950s. Since then, advances in transplant immunology, medical science and surgical techniques have led to increasing numbers of solid organ transplantations (SOT) and hematological stem cell transplantations being performed, and the use of biological immunotherapeutics in increasingly high-risk and older individuals, have contributed to the further rise in cryptococcosis. Globally, however, the major driver for revivification of cryptococcosis is undoubtedly the HIV epidemic, particularly in Sub-Saharan Africa where access to care and antiretroviral therapy remains limited and advanced immunodeficiency, poverty and malnutrition remains the norm. As a zoonotic disease, environmental outbreaks of both human and animal cryptococcosis have been reported, possibly driven by climate change. This is best exemplified by the resurgence of C. gattii infection in Vancouver Island, Canada, and the Pacific Northwest of the United States since 1999. Here we describe how the colliding epidemics of HIV, transplantation and immunologics, climate change and migration have contributed to the rise of cryptococcosis.
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Diagnostics, Vol. 6, Pages 2: Ultrasonography of the Kidney: A Pictorial Review
Ultrasonography of the kidneys is essential in the diagnosis and management of kidney-related diseases. The kidneys are easily examined, and most pathological changes in the kidneys are distinguishable with ultrasound. In this pictorial review, the most common findings in renal ultrasound are highlighted.
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Insects, Vol. 7, Pages 1: Antagonistic Interactions between the African Weaver Ant Oecophylla longinoda and the Parasitoid Anagyrus pseudococci Potentially Limits Suppression of the Invasive Mealybug Rastrococcus iceryoides
The ant Oecophylla longinoda Latreille forms a trophobiotic relationship with the invasive mealybug Rastrococus iceryoides Green and promotes the latter's infestations to unacceptable levels in the presence of their natural enemies. In this regard, the antagonistic interactions between the ant and the parasitoid Anagyrus pseudococci Girault were assessed under laboratory conditions. The percentage of parasitism of R. iceryoides by A. pseudococci was significantly higher on "ant-excluded" treatments (86.6% ± 1.27%) compared to "ant-tended" treatments (51.4% ± 4.13%). The low female-biased sex-ratio observed in the "ant-tended" treatment can be attributed to ants' interference during the oviposition phase, which disrupted parasitoids' ability to fertilize eggs. The mean foraging time, host handling time and number of successful oviposition in "ant-excluded" treatment were significantly higher compared to "ant-tended" treatments. When ant workers were allowed access to sterilized sand grains, mummified and unmummified R. iceryoides, they selectively removed the mummified mealybugs, indicating that they recognized the mummies as potential foods (1.2 ± 0.46 to 7.8 ± 1.17 mummies at 10 min intervals for 2 h). Percentage emergence from mummified R. iceryoides removed by the ants was significantly lower compared to emergence from mummies not exposed to ants. Although, host seeking parasitoids frequently evaded attacks, some were killed by the foraging ant workers (2.0 ± 0.38 to 6.0 ± 0.88 at 10 min intervals for 2 h). These results suggest for the first time that the presence of O. longinoda has a detrimental effect on the abundance, reproductive success and possibly oviposition strategy of female parasitoids, which might be a delimiting factor in field conditions if both natural enemies are to be recommended for use within the same agro-ecosystem.
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Making the invisible visible: Improved electrospray ion formation of metalloporphyrins/-phthalocyanines by attachment of the formate anion (HCOO-)
DOI: 10.1039/C5AN02148K, Paper
A protocol is developed for the coordination of the formate anion (HCOO-) to neutral metallo-porphyrins (Pors) and -phthalocyanines (Pcs) containing divalent metals as a means to improve their ion formation...
The content of this RSS Feed (c) The Royal Society of Chemistry
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Preclinical mouse models for assessing axial compression of long bones during exercise
The aim of this laboratory method is to describe two approaches for the investigation of bone responses to mechanical loading in mice in vivo. The first is running exercise, because it is easily translatable clinically, and the second is axial compression of the tibia, because it is precisely controllable. The effects of running exercise, and in general physical activity, on bone tissue have been shown to be both direct through mechanical loading (ground impact and muscle tension) and indirect through metabolic changes. Therefore, running exercise has been considered the most convenient preclinical model for demonstrating the general idea that exercise is good for bone health, either early in age for increasing peak bone mass or later in age by slowing down bone loss. However, numerous combinations of protocols have been reported, which makes it difficult to formulate a simple take-home message. This laboratory method also provides a detailed description of in vivo direct mechanical axial compression of the mouse tibia. The effects of mechanical loading depend on the force (strain), frequency, waveform and duration of application, and they range from bone anabolism with low bone remodeling, inducing lamellar bone accumulation, to bone catabolism with high bone remodeling, leading to microdamage, woven bone formation and bone loss. Direct in vivo loading models are extensively used to study mechanotransduction pathways, and contribute by this way to the development of new bone anabolism treatments. Although it is particularly difficult to assemble an internationally adopted protocol description, which would give reproducible bone responses, here we have attempted to provide a comprehensive guide for best practice in performing running exercise and direct in vivo mechanical loading in the laboratory.
BoneKEy Reports 4 doi: 10.1038/bonekey.2015.138
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Role of Irisin on the bone–muscle functional unit
Irisin was originally recognized as a hormone-like myokine secreted as a product of fibronectin type III domain containing 5 from skeletal muscle in response to exercise both in mice and humans. The first role attributed to Irisin was its ability to induce trans-differentiation of white adipose tissue into brown, but we recently demonstrated that Irisin also has a central role in the control of bone mass, even at lower concentration than required to induce the browning response. Considering how physical exercise is important for the development of an efficient load-bearing skeleton, we can now consider this myokine as one of the molecules responsible for the positive correlation between exercise and healthy bone, linking to the well-established relationship between muscle and bone. Recombinant Irisin (r-Irisin), administered at low dose in young mice, increases cortical bone mineral density and positively modifies bone geometry. Irisin exerts its effect prevalently on osteoblast lineage by enhancing differentiation and activity of bone-forming cells, through the increase in activating transcription factor 4 expression. Low-dose r-Irisin also increases osteopontin and decreases sclerostin synthesis but did not affect Uncoupling protein 1 expression in white adipose tissue, whose upregulation is known to cause browning of fat, when Irisin is administered at a higher dose. These findings offer an explanation to the positive outcome on the skeleton triggered by skeletal muscle during physical activity and prove that the bone tissue is more sensitive than the adipose tissue to the Irisin action.
BoneKEy Reports 4 doi: 10.1038/bonekey.2015.134
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Skeletal stem cells for bone development, homeostasis and repair: one or many?
BoneKEy Reports 4 doi: 10.1038/bonekey.2015.139
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Sulfiredoxin inhibitor induces preferential death of cancer cells through reactive oxygen species-mediated mitochondrial damage
Publication date: Available online 23 December 2015
Source:Free Radical Biology and Medicine
Author(s): Hojin Kim, Gong-Rak Lee, Jiwon Kim, Jin Young Baek, You-Jin Jo, Seong-Eun Hong, Sung Hoon Kim, Jiae Lee, Hye In Lee, Song-Kyu Park, Hwan Mook Kim, Hwa Jeong Lee, Tong-Shin Chang, Sue Goo Rhee, Ju-Seog Lee, Woojin Jeong
Recent studies have shown that many types of cancer cells have increased levels of reactive oxygen species (ROS) and enhance antioxidant capacity as an adaptation to intrinsic oxidative stress, suggesting that cancer cells are more vulnerable to oxidative insults and are more dependent on antioxidant systems compared with normal cells. Thus, disruption of redox homeostasis caused by a decline in antioxidant capacity may provide a method for the selective death of cancer cells. Here we show that ROS-mediated selective death of tumor cells can be caused by inhibiting sulfiredoxin (Srx), which reduces hyperoxidized peroxiredoxins, leading to their reactivation. Srx inhibitor increased the accumulation of sulfinic peroxiredoxins and ROS, which led to oxidative mitochondrial damage and caspase activation, resulting in the death of A549 human lung adenocarcinoma cells. Srx depletion also inhibited the growth of A549 cells like Srx inhibition, and the cytotoxic effects of Srx inhibitor were considerably reversed by Srx overexpression or antioxidants such as N-acetyl cysteine and butylated hydroxyanisol. Moreover, Srx inhibitor rendered tumorigenic ovarian cells more susceptible to ROS-mediated death compared with nontumorigenic cells and significantly suppressed the growth of A549 xenografts without acute toxicity. Our results suggest that Srx might serve as a novel therapeutic target for cancer treatment based on ROS-mediated cell death.
Graphical abstract
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Down-regulation of the mitochondrial matrix peptidase ClpP in muscle cells causes mitochondrial dysfunction and decreases cell proliferation
Publication date: Available online 23 December 2015
Source:Free Radical Biology and Medicine
Author(s): Sathyaseelan S. Deepa, Shylesh Bhaskaran, Rojina Ranjit, Rizwan Qaisar, Binoj C. Nair, Yuhong Liu, Michael E. Walsh, Wilson C. Fok, Holly Van Remmen
The caseinolytic peptidase P (ClpP) is the endopeptidase component of the mitochondrial matrix ATP-dependent ClpXP protease. ClpP degrades unfolded proteins to maintain mitochondrial protein homeostasis and is involved in the initiation of the mitochondrial unfolded protein response (UPRmt). Outside of an integral role in the UPRmt, the cellular function of ClpP is not well characterized in mammalian cells. To investigate the role of ClpP in mitochondrial function, we generated C2C12 muscle cells that are deficient in ClpP using siRNA or stable knockdown using lentiviral transduction. Reduction of ClpP levels by ~70% in C2C12 muscle cells resulted in a number of mitochondrial alterations including reduced mitochondrial respiration and reduced oxygen consumption rate in response to electron transport chain (ETC) complex I and II substrates. The reduction in ClpP altered mitochondrial morphology, changed the expression level of mitochondrial fission protein Drp1 and blunted UPRmt induction. In addition, ClpP deficient cells showed increased generation of reactive oxygen species (ROS) and decreased membrane potential. At the cellular level, reduction of ClpP impaired myoblast differentiation, cell proliferation and elevated phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) suggesting an inhibition of translation. Our study is the first to define the effects of ClpP deficiency on mitochondrial function in muscle cells in vitro. In addition, we have uncovered novel effects of ClpP on mitochondrial morphology, cell proliferation and protein translation pathways in muscle cells.
Graphical abstract
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Neuroprotective potential of molecular hydrogen against perinatal brain injury via suppression of activated microglia
Publication date: February 2016
Source:Free Radical Biology and Medicine, Volume 91
Author(s): Kenji Imai, Tomomi Kotani, Hiroyuki Tsuda, Yukio Mano, Tomoko Nakano, Takafumi Ushida, Hua Li, Rika Miki, Seiji Sumigama, Akira Iwase, Akihiro Hirakawa, Kinji Ohno, Shinya Toyokuni, Hideyuki Takeuchi, Tetsuya Mizuno, Akio Suzumura, Fumitaka Kikkawa
Exposure to inflammation in utero is related to perinatal brain injury, which is itself associated with high rates of long-term morbidity and mortality in children. Novel therapeutic interventions during the perinatal period are required to prevent inflammation, but its pathogenesis is incompletely understood. Activated microglia are known to play a central role in brain injury by producing a variety of pro-inflammatory cytokines and releasing oxidative products. The study is aimed to investigate the preventative potential of molecular hydrogen (H2), which is an antioxidant and anti-inflammatory agent without mutagenicity. Pregnant ICR mice were injected with lipopolysaccharide (LPS) intraperitoneally on embryonic day 17 to create a model of perinatal brain injury caused by prenatal inflammation. In this model, the effect of maternal administration of hydrogen water (HW) on pups was also evaluated. The levels of pro-inflammatory cytokines, oxidative damage and activation of microglia were determined in the fetal brains. H2 reduced the LPS-induced expression of pro-inflammatory cytokines, oxidative damage and microglial activation in the fetal brains. Next, we investigated how H2 contributes to neuroprotection, focusing on microglia, using primary cultured microglia and neurons. H2 prevented LPS- or cytokine-induced generation of reactive oxidative species by microglia and reduced LPS-induced microglial neurotoxicity. Finally, we identified several molecules influenced by H2, involved in the process of activating microglia. These results suggested that H2 holds promise for the prevention of inflammation related to perinatal brain injury.
Graphical abstract
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ZYZ451 Protects Cardiomyocytes from Hypoxia-induced Apoptosis via Enhancing MnSOD and STAT3 Interaction
Publication date: Available online 23 December 2015
Source:Free Radical Biology and Medicine
Author(s): Shanshan Luo, Xianfeng Gu, Fenfen Ma, Chunhua Liu, Yaqi Shen, Ruowen Ge, Yizhun Zhu
3, 5-dimethoxy-4-(2-amino-3-prop-2-ynylsulfanyl-propionyl)-benzoic acid 4-guanidino-butyl ester (ZYZ451) were found to be an excellent cardio-protective agent in the previous research in our lab. However, its potential therapeutic effects on myocardial infarction and the underlying mechanism remain elusive. In the present study, we demonstrate that ZYZ451 protects neonatal rat ventricular cardiomyocytes (NRVCs) from hypoxia-induced apoptosis via increasing manganese-containing superoxide dismutase (MnSOD) activity and inhibiting mitochondrial reactive oxidative species (mitoROS) production. MnSOD knockdown impairs the anti-apoptotic effects of ZYZ451. We report here for the first time that signal transducer and activator of transcription 3 (STAT3), an important nuclear transcriptional factor also identified in mitochondria, co-localizes with MnSOD and interacts with it, as determined by using methods of co-immunofluorescence and co-immunoprecipitation. Knockdown of STAT3 rather than inhibition of STAT3 phosphorylation results in a significant reduction in MnSOD activity. Furthermore, interaction between MnSOD and STAT3 is diminished in STAT3 deficient H9C2 cells. Its novel subcellular localization and interaction with MnSOD suggest that STAT3 may be involved in regulation of MnSOD activity beyond its transcriptional potential. Consistent with the results in vitro, ZYZ451 reduces myocardial infarct size as well as cardiomyocytes apoptosis, inhibits lactate dehydrogenase (LDH) and malondialchehyche (MDA) release, and restores MnSOD activity in peri-infarct hearts. These benefits appear to be attributed to the enhanced interaction between STAT3 and MnSOD. These findings shed a light on a new role of STAT3 in oxidative stress and suggest that ZYZ451 is likely an effective cardio-protective agent.
Graphical abstract
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Caffeic acid prevents acetaminophen-induced liver injury by activating the Keap1-Nrf2 antioxidative defense system
Publication date: Available online 23 December 2015
Source:Free Radical Biology and Medicine
Author(s): Chun Pang, Zhiyong Zheng, Liang Shi, Yuchen Sheng, Hai Wei, Zhengtao Wang, Lili Ji
Acute liver failure induced by acetaminophen (APAP) overdose is the main cause of drug-induced liver injury (DILI). Caffeic acid (CA) is a phenolic compound from many natural products. This study aims to investigate the protective mechanism of CA in APAP-induced liver injury. The results of serum alanine/aspartate aminotransferases (ALT/AST), liver myeloperoxidase (MPO) activity, liver glutathione (GSH) and reactive oxygen species (ROS) levels demonstrated the protection of CA against APAP-induced liver injury. Liver histological observation provided further evidences of CA-induced protection. CA was found to reverse the APAP-induced decreased cell viability in human normal liver l-02 cells and HepG2 cells. CA also reduced the increased cellular ROS level induced by APAP in hepatocytes. The results of luciferase assay and Western-blot analysis showed that CA increased the transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2) in the presence of APAP. Nrf2 siRNA reduced the protection of CA against APAP-induced hepatotoxicity. CA also reversed the APAP-induced decreased mRNA and protein expression of heme oxygenase 1 (HO-1) and NAD(P)H: quinone oxidoreductase 1(NQO1). In addition, HO-1 inhibitor zinc protoporphyrin (ZnPP) and NQO1 inhibitor diminutol (Dim) reduced the protection of CA against APAP-induced hepatotoxicity. CA also decreased the expression of kelch-like ECH-associated protein-1(Keap1). Molecular docking indicated the potential interacting of CA with Nrf2 binding site in the Keap1 protein. CA had little effect on the enzymatic activity of cytochrome P450 (CYP) 3A4 and CYP2E1 in vitro. In conclusion, we demonstrated that CA prevented APAP-induced hepatotoxicity by decreasing Keap1 expression, inhibiting binding of Keap1 to Nrf2, and thus activating Nrf2 and leading to increased expression of antioxidative signals including HO-1 and NQO1.
Graphical abstract
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Fructose-derived advanced glycation end-products drive lipogenesis and skeletal muscle reprogramming via SREBP-1c dysregulation in mice.
Publication date: Available online 22 December 2015
Source:Free Radical Biology and Medicine
Author(s): R. Mastrocola, D. Nigro, F. Chiazza, C. Medana, F. Dal Bello, G. Boccuzzi, M. Collino, M. Aragno
Advanced Glycation End-Products (AGEs) have been recently related to the onset of metabolic diseases and related complications. Moreover, recent findings indicate that AGEs can endogenously be formed by high dietary sugars, in particular by fructose which is widely used as added sweetener in foods and drinks. The aim of the present study was to investigate the impact of a high-fructose diet and the causal role of fructose-derived AGEs in mice skeletal muscle morphology and metabolism. C57Bl/6J mice were fed a standard diet (SD) or a 60% fructose diet (HFRT) for 12 weeks. Two subgroups of SD and HFRT mice received the anti-glycative compound pyridoxamine (150mg/kg/day) in the drinking water. At the end of protocol high levels of AGEs were detected in both plasma and gastrocnemius muscle of HFRT mice associated to impaired expression of AGE-detoxifying AGE-receptor 1. In gastrocnemius, AGEs upregulated the lipogenesis by multiple interference on SREBP-1c through downregulation of the SREBP-inihibiting enzyme SIRT-1 and increased glycation of the SREBP-activating protein SCAP. The AGEs-induced SREBP-1c activation affected the expression of myogenic regulatory factors leading to alterations in fiber type composition, associated with reduced mitochondrial efficiency and muscular strength. Interestingly, pyridoxamine inhibited AGEs generation, thus counteracting all the fructose-induced alterations. The unsuspected involvement of diet-derived AGEs in muscle metabolic derangements and proteins reprogramming opens new perspectives in pathogenic mechanisms of metabolic diseases.
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Polymers, Vol. 8, Pages 1: Comparative Indoor and Outdoor Degradation of Organic Photovoltaic Cells via Inter-laboratory Collaboration
We report on the degradation of organic photovoltaic (OPV) cells in both indoor and outdoor environments. Eight different research groups contributed state of the art OPV cells to be studied at Pomona College. Power conversion efficiency and fill factor were determined from IV curves collected at regular intervals over six to eight months. Similarly prepared devices were measured indoors, outdoors, and after dark storage. Device architectures are compared. Cells kept indoors performed better than outdoors due to the lack of temperature and humidity extremes. Encapsulated cells performed better due to the minimal oxidation. Some devices showed steady aging but many failed catastrophically due to corrosion of electrodes not active device layers. Degradation of cells kept in dark storage was minimal over periods up to one year.
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Biology, Vol. 5, Pages 1: Cell Adhesion Molecules and Ubiquitination—Functions and Significance
Cell adhesion molecules of the immunoglobulin (Ig) superfamily represent the biggest group of cell adhesion molecules. They have been analyzed since approximately 40 years ago and most of them have been shown to play a role in tumor progression and in the nervous system. All members of the Ig superfamily are intensively posttranslationally modified. However, many aspects of their cellular functions are not yet known. Since a few years ago it is known that some of the Ig superfamily members are modified by ubiquitin. Ubiquitination has classically been described as a proteasomal degradation signal but during the last years it became obvious that it can regulate many other processes including internalization of cell surface molecules and lysosomal sorting. The purpose of this review is to summarize the current knowledge about the ubiquitination of cell adhesion molecules of the Ig superfamily and to discuss its potential physiological roles in tumorigenesis and in the nervous system.
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Micromachines, Vol. 7, Pages 1: Miniature Microwave Notch Filters and Comparators Based on Transmission Lines Loaded with Stepped Impedance Resonators (SIRs)
In this paper, different configurations of transmission lines loaded with stepped impedance resonators (SIRs) are reviewed. This includes microstrip lines loaded with pairs of SIRs, and coplanar waveguides (CPW) loaded with multi-section SIRs. Due to the high electric coupling between the line and the resonant elements, the structures are electrically small, i.e., dimensions are small as compared to the wavelength at the fundamental resonance. The circuit models describing these structures are discussed and validated, and the potential applications as notch filters and comparators are highlighted.
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Chemosensors, Vol. 4, Pages 1: Building Selectivity for NO Sensing in a NOx Mixture with Sonochemically Prepared CuO Structures
Several technologies are available for decreasing nitrogen oxide (NOx) emissions from combustion sources, including selective catalytic reduction methods. In this process, ammonia reacts with nitric oxide (NO) and nitrogen dioxide (NO2). As the stoichiometry of the two reactions is different, electrochemical sensor systems that can distinguish between NO and NO2 in a mixture of these two gases are of interest. Since NO and NO2 can be brought to equilibrium, depending on the temperature and the surfaces that they are in contact with, the detection of NO and NO2 independently is a difficult problem and has not been solved to date. In this study, we explore a high surface area sonochemically prepared CuO as the resistive sensing medium. CuO is a poor catalyst for NOx equilibration, and requires temperatures of 500 C to bring about equilibration. Thus, at 300 C, NO and NO2 retain their levels after interaction with CuO surface. In addition, NO adsorbs more strongly on the CuO over NO2. Using these two concepts, we can detect NO with minimal interference from NO2, if the latter gas concentration does not exceed 20% in a NOx mixture over a range of 100–800 ppm. Since this range constitutes most of the range of total NOx concentrations in diesel and other lean burn engines, this sensor should find application in selective detection of NO in this combustion application. A limitation of this sensor is the interference with CO, but with combustion in excess air, this problem should be alleviated.
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Bioengineering, Vol. 3, Pages 1: Sustained Release of Antibacterial Agents from Doped Halloysite Nanotubes
The use of nanomaterials for improving drug delivery methods has been shown to be advantageous technically and viable economically. This study employed the use of halloysite nanotubes (HNTs) as nanocontainers, as well as enhancers of structural integrity in electrospun poly-e-caprolactone (PCL) scaffolds. HNTs were loaded with amoxicillin, Brilliant Green, chlorhexidine, doxycycline, gentamicin sulfate, iodine, and potassium calvulanate and release profiles assessed. Selected doped halloysite nanotubes (containing either Brilliant Green, amoxicillin and potassium calvulanate) were then mixed with poly-e-caprolactone (PLC) using the electrospinning method and woven into random and oriented-fibered nanocomposite mats. The rate of drug release from HNTs, HNTs/PCL nanocomposites, and their effect on inhibiting bacterial growth was investigated. Release profiles from nanocomposite mats showed a pattern of sustained release for all bacterial agents. Nanocomposites were able to inhibit bacterial growth for up to one-month with only a slight decrease in bacterial growth inhibition. We propose that halloysite doped nanotubes have the potential for use in a variety of medical applications including sutures and surgical dressings, without compromising material properties.
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Cancers, Vol. 8, Pages 2: Diverse Mechanisms of Sp1-Dependent Transcriptional Regulation Potentially Involved in the Adaptive Response of Cancer Cells to Oxygen-Deficient Conditions
The inside of a tumor often contains a hypoxic area caused by a limited supply of molecular oxygen due to aberrant vasculature. Hypoxia-inducible factors (HIFs) are major transcription factors that are required for cancer cells to adapt to such stress conditions. HIFs, complexed with the aryl hydrocarbon receptor nuclear translocator, bind to and activate target genes as enhancers of transcription. In addition to this common mechanism, the induction of the unfolded protein response and mTOR signaling in response to endoplasmic reticulum stress is also known to be involved in the adaptation to hypoxia conditions. Sp1 is a ubiquitously-expressed transcription factor that plays a vital role in the regulation of numerous genes required for normal cell function. In addition to the well-characterized stress response mechanisms described above, increasing experimental evidence suggests that Sp1 and HIFs collaborate to drive gene expression in cancer cells in response to hypoxia, thereby regulating additional adaptive responses to cellular oxygen deficiency. However, these characteristics of Sp1 and their biological merits have not been summarized. In this review, we will discuss the diverse mechanisms of transcriptional regulation by Sp1 and their potential involvement in the adaptive response of cancer cells to hypoxic tumor microenvironments.
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Catalysts, Vol. 6, Pages 1: Catalytic Conversion of Glucose into 5-Hydroxymethylfurfural by Hf(OTf)4 Lewis Acid in Water
A series of Lewis acidic metal salts were used for glucose dehydration to 5-hydroymethylfurfural (HMF) in water. Effect of valence state, ionic radii of Lewis acidic cation, and the type of anions on the catalytic performance have been studied systematically. The experimental results showed that the valence state played an important role in determining catalytic activity and selectivity. It was found that a higher glucose conversion rate and HMF selectivity could be obtained over high valent Lewis acid salts, where the ionic radii of these Lewis acidic metal salts are usually relatively small. Analysis on the effect of the anions of Lewis acid salts on the catalytic activity and the selectivity suggested that a higher glucose conversion and HMF selectivity could be readily obtained with Cl−. Furthermore, the recyclability of high valence state Lewis acid salt was also studied, however, inferior catalytic performance was observed. The deactivation mechanism was speculated to be the fact that high valence state Lewis acid salt was comparatively easier to undergo hydrolysis to yield complicated metal aqua ions with less catalytic activity. The Lewis acidic activity could be recovered by introducing a stoichiometric amount of hydrochloric acid (HCl) to the catalytic before the reaction.
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Behavioral Sciences, Vol. 6, Pages 1: Adolescent Pornography Use and Dating Violence among a Sample of Primarily Black and Hispanic, Urban-Residing, Underage Youth
This cross-sectional study was designed to characterize the pornography viewing preferences of a sample of U.S.-based, urban-residing, economically disadvantaged, primarily Black and Hispanic youth (n = 72), and to assess whether pornography use was associated with experiences of adolescent dating abuse (ADA) victimization. The sample was recruited from a large, urban, safety net hospital, and participants were 53% female, 59% Black, 19% Hispanic, 14% Other race, 6% White, and 1% Native American. All were 16–17 years old. More than half (51%) had been asked to watch pornography together by a dating or sexual partner, and 44% had been asked to do something sexual that a partner saw in pornography. Adolescent dating abuse (ADA) victimization was associated with more frequent pornography use, viewing pornography in the company of others, being asked to perform a sexual act that a partner first saw in pornography, and watching pornography during or after marijuana use. Approximately 50% of ADA victims and 32% of non-victims reported that they had been asked to do a sexual act that their partner saw in pornography (p = 0.15), and 58% did not feel happy to have been asked. Results suggest that weekly pornography use among underage, urban-residing youth is common, and may be associated with ADA victimization.
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Minerals, Vol. 6, Pages 1: New Insights in the Ontogeny and Taphonomy of the Devonian Acanthodian Triazeugacanthus affinis From the Miguasha Fossil-Lagerstätte, Eastern Canada
Progressive biomineralization of a skeleton occurs during ontogeny in most animals. In fishes, larvae are poorly mineralized, whereas juveniles and adults display a progressively more biomineralized skeleton. Fossil remains primarily consist of adult specimens because the fossilization of poorly-mineralized larvae and juveniles necessitates exceptional conditions. The Miguasha Fossil-Lagerstätte is renowned for its Late Devonian vertebrate fauna, revealing the exceptional preservation of fossilized ontogenies for 14 of the 20 fish species from this locality. The mineralization of anatomical structures of the acanthodian Triazeugacanthus affinis from Miguasha are compared among larval, juvenile and adult specimens using Energy Dispersive X-ray Spectrometry. Chemical composition of anatomical structures of Triazeugacanthus reveals differences between cartilage and bone. Although the histology and anatomy is well-preserved, Fourier transform infrared spectrometry shows that the original chemical composition of bone is altered by diagenesis; the mineral phase of the bone (i.e., hydroxyapatite) is modified chemically to form more stable carbonate-fluorapatite. Fluorination occurring in mineralized skeletal structures of adult Triazeugacanthus is indicative of exchanges between groundwater and skeleton at burial, whereas the preservation of larval soft tissues is likely owing to a rapid burial under anoxic conditions. The exceptional state of preservation of a fossilized ontogeny allowed us to characterize chemically the progressive mineralization of the skeleton in a Devonian early vertebrate.
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Algorithms, Vol. 9, Pages 2: Offset-Assisted Factored Solution of Nonlinear Systems
This paper presents an improvement to the recently-introduced factored method for the solution of nonlinear equations. The basic idea consists of transforming the original system by adding an offset to all unknowns. When searching for real solutions, a real offset prevents the intermediate values of unknowns from becoming complex. Reciprocally, when searching for complex solutions, a complex offset is advisable to allow the iterative process to quickly abandon the real domain. Several examples are used to illustrate the performance of the proposed algorithm, when compared to Newton's method.
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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