The cholesterol biosynthesis pathway, also referred to as the mevalonate (MVA) pathway, is responsible for the biosynthesis of two key isoprenoids: farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). Post-translational modification of small GTPases by FPP and GGPP has captured much attention due to their potential contribution to cancer, cardiovascular and neurodegenerative diseases. The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) catalyzes the conversion of HMG-CoA to MVA, and is the rate-limiting step in the biosynthesis of cholesterol. Statins are HMGCR inhibitors that are used extensively in the treatment of hypercholesterolemia. Inhibitors of the MVA pathway exhibit anti-tumor effects and may reduce cancer incidence and cancer-related mortality in humans. </p> <p> In this review, we will focus on the mevalonate cascade and its regulation in cholesterol metabolism as well as polymorphisms of the MVA cascade in cancer development, infectious and cardiovascular disease (CVD).
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Τετάρτη 29 Μαρτίου 2017
Mevalonate Cascade and its Regulation in Cholesterol Metabolism in Different Tissues in Health and Disease
Patient Engagement in Randomized Controlled Tai Chi Clinical Trials among the Chronically Ill
Background: Physicians encounter various symptom-based complaints each day. While physicians strive to support patients with chronic illnesses, evidence indicates that patients who are actively involved in their health care have better health outcomes and sometimes lowers costs. <p></p> Aim: This article is to analyze how patient engagement is described when complex interventions such as Tai Chi were delivered in Randomized Controlled clinical Trials (RCTs). It reviews the dynamic patient- physician relationship in chronic illness management and to illustrate the patient engagement process, using Tai Chi as an example intervention. <p></p> Methods: RCTs are considered the gold standard in clinical research. This study is a qualitative analysis of RCTs using Tai Chi as an intervention. A systematic literature search was performed to identify quality randomized controlled clinical trials that investigated the effects of Tai Chi. Selected clinical trials were classified according to research design, intervention style, patient engagement, and outcomes. Patient engagement was classified based on levels of patient participation, compliance, and selfmanagement. The chronic health conditions included in this paper are Parkinson's disease, polyneuropathy, hypertension, stroke, chronic insomnia, chronic heart failure, fibromyalgia, osteoarthritis, central obesity, depression, deconditioning in the elderly, or being pre-clinically disabled. <p></p> Results and Conclusion: We found that patient engagement, as a concept, was not well defined in literature. It covers a wide range of related terms, such as patient involvement, participation, shared decision- making, patient activation, adherence, compliance, and self-management. Tai Chi, as a very complex practice system, is to balance all aspects of a patient's life; however, the level of patient engagement is difficult to describe using conventional clinical trial design. To accurately illustrate the effect of a complex intervention, novel research design must explore ways to measure patient engagement in the intervention in order to clarify its specific role on health. <p></p>
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A Magnetic Resonance Spectroscopy Study of Lovastatin for Treating Bipolar Mood Disorder: A 4-Week Randomized Double-Blind, Placebo- Controlled Clinical Trial
Background: No trial has examined the effect of lovastatin on the brain metabolites in patients with bipolar mood disorder. <p></p> Objectives: Current medications for treating bipolar disorders cause metabolic syndrome. It is supposed that lovastatin not only decreases the rate of metabolic syndrome but also impacts some brain metabolites and their ratio like common treatments that are measured by Magnetic Resonance Spectroscopy. <p></p> Methods: 27 Manic phase patients were randomly allocated into two groups, lovastatin and placebo as their adjuant medication. Clinical symptoms were assessed at baseline, weeks 2, 4. The brain metabolites were measured at baseline and week 4. <p></p> Result: Regarding the change of clinical symptoms, no significant difference was found between two groups. However, lovastatin significantly increased the level of NAA in cingulate gyrus in comparison to the placebo group. Moreover, lovastatin more than placebo increased creatine in the left basal ganglia. Furthermore, choline/ creatine showed a significant decrease in the left basal ganglia in lovastatin group. <p></p> Conclusion: Using MRS after treating with lovastatin showed lovastatin increases NAA in cingulate gyrus, indicating the possible effect of NAA for increasing the reduced viable neuron. Moreover, the increment of Cr by lovastatin in the left basal ganglia suggests the role of lovastatin for maintaining energy homeostasis, anti-apoptotic activity and ATP production in bipolar disorder. Some patents using lovastatin as an adjuant therapy for treating bipolar patients and depression in MDD patients are also outlined. This trial was registered in the Iranian Clinical Trials Registry (http://www.irct.ir/) (IRCT201302203930N18). <p></p>
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Snacking and Diet Quality Are Associated With the Coping Strategies Used By a Socioeconomically Diverse Urban Cohort of African-American and White Adults
Publication date: Available online 29 March 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Marie Fanelli Kuczmarski, Nancy Cotugna, Ryan T. Pohlig, May A. Beydoun, Erica L. Adams, Michele K. Evans, Alan B. Zonderman
BackgroundStress affects health-related quality of life through several pathways, including physiological processes and health behaviors. There is always a relationship between stress (the stimulus) and coping (the response). The relationship between snacking and snackers' diet quality and stress coping is a topic overlooked in research.ObjectiveThe study was primarily designed to determine whether energy provided by snacks and diet quality were associated with coping behaviors to manage stress.DesignWe analyzed a baseline cohort of the Healthy Aging in Neighborhoods of Diversity across the Life Span study (2004 to 2009).ParticipantsThe sample was composed of 2,177 socioeconomically diverse African-American and white adults who resided in Baltimore, MD.Main outcome measuresEnergy from snacks was calculated from 2 days of 24-hour dietary recalls collected using the US Department of Agriculture's Automated Multiple Pass Method. Snack occasions were self-reported as distinct eating occasions. Diet quality was evaluated by the Healthy Eating Index-2010.Statistical analyses performedMultiple regression analyses were used to determine whether coping factors were associated with either energy provided by snacks or Healthy Eating Index-2010, adjusting for age, sex, race, socioeconomic status, education, literacy, and perceived stress. Coping was measured by the Brief COPE Inventory with instrument variables categorized into three factors: problem-focused coping, emotion-focused coping, and use of support. Perceived stress was measured with the 4-item Perceived Stress Scale.ResultsAdjusting for perceived stress and selected demographic characteristics, emotion-focused coping strategies were associated with greater energy intakes from snacks (P=0.020), and use of coping strategies involving support was positively associated with better diet quality (P=0.009).ConclusionsEnergy contributed by snacks and diet quality were affected by the strategy that an individual used to cope with stress. The findings suggest that health professionals working with individuals seeking guidance to modify their eating practices should assess a person's coping strategies to manage stress.
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The Telemark Breast Score: a Valid Method for Evaluation of Outcome after Breast Surgery
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Functional and Aesthetic Thorax Reconstruction after Desmoid Tumor Resection
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Tumefactive demyelination associated with developmental venous anomaly: Report of two cases
Publication date: May–June 2017
Source:Clinical Imaging, Volume 43
Author(s): Mingming Ma, James Y. Chen, Edward D. Plowey, Nancy Fischbein, Michael Iv
We present two cases of tumefactive demyelination (TD) occurring in close association with a developmental venous anomaly (DVA). Our purpose is to describe the association between demyelinating lesions and venous anomalies, as only one case of TD associated with a DVA has been published in the literature. Appropriate recognition of this "do not touch" lesion may avoid invasive and potentially harmful procedures such as biopsy or resection.
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Experimental and numerical investigation of V-bent anisotropic 304L SS sheet with spring-forward considering deformation-induced martensitic transformation
Publication date: 5 June 2017
Source:Materials & Design, Volume 123
Author(s): Masoud Ahmadi, Bagher Mohammad Sadeghi, Hossein Arabi
Spring-back/forward phenomenon usually occurs during various kinds of bending tests of sheet metals. In this study, using a digital image correlation (DIC) technique coupled with uniaxial tensile test, mechanical properties of AISI 304L austenitic stainless steel were determined and the results were applied into finite element analysis (FEA) for further investigations. In order to examine various parameters affecting spring-forward in V-bending, a novel V-bending die equipped with data acquisition system was designed and used to perform V-bending tests of the AISI 304L stainless steel samples. For investigating crystallographic texture evolution in the bent sample, electron backscatter diffraction (EBSD) analysis was conducted. Furthermore, microstructural characterization, micro-hardness test and residual magnetic field measurement were utilized to investigate the transformation of austenite to α′-martensite in the bent samples. The results revealed that spring-forward angle raised by increasing sample thickness and lowering bending angle and anisotropy parameter. The fraction of transformed α′-martensite was affected by mode of deformation (stress state). An empirical model was suggested to relate residual magnetic field to volume fraction of α′-martensite for bent samples. In order to control the spring-forward efficiently, the contribution of microstructural evolution in V-bent samples was discussed.
Graphical abstract
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Characterization of moisture vapor diffusion in fine aggregate mixtures using Fickian and non-Fickian models
Publication date: 15 June 2017
Source:Materials & Design, Volume 124
Author(s): Huining Xu, Jing Zhou, Qifeng Dong, Yiqiu Tan
Moisture vapor diffusion resulting from the difference in relative humidity between air and pavement material contributes to moisture damage. Understanding moisture vapor diffusion in asphalt pavement is the first task in the analysis of moisture damage. Analysis was conducted in an automated environmental chamber with a temperature precision of ±0.5°C and relative humidity precision of ±3%. Moisture uptake profiles for fine aggregate mixtures (FAMs) under various environmental conditions (relative humidity and ambient air temperature) and constituent materials (aggregate and asphalt binder) were measured. Preliminary data analysis showed the existence of Non-Fickian diffusion behavior. Therefore, two non-Fickian and one Fickian models were introduced to fit the measured moisture uptake data and determine FAM diffusion characteristics, such as diffusion coefficient, diffused moisture phase, and time-variable diffusion. Based on the variation in FAM diffusion characteristics under various experimental conditions and constituent material combinations, sensitivity analysis was conducted with one-way ANOVA and the determinants of FAM vapor diffusion characteristics were proposed.
Graphical abstract
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The left intraparietal sulcus adapts to symbolic number in both the visual and auditory modalities: Evidence from fMRI
Source:NeuroImage, Volume 153
Author(s): Stephan E. Vogel, Celia Goffin, Joshua Bohnenberger, Karl Koschutnig, Gernot Reishofer, Roland H. Grabner, Daniel Ansari
A growing body of evidence from functional Magnetic Resonance Imaging adaptation (fMRIa) has implicated the left intraparietal sulcus (IPS) as a crucial brain region representing the semantic of number symbols. However, it is currently unknown to what extent the left IPS brain activity can be generalized across modalities (e.g., Arabic digits and spoken number words) and how robust and reproducible numerical adaptation effects are.In two separate fMRIa experiments we habituated the brain response of 20 native English-speaking (Experiment 1) and 34 native German-speaking (Experiment 2) adults to Arabic digits or spoken number words. Consistent with previous findings, experiment 1 revealed numerical ratio dependent adaptation to Arabic numerals in the left IPS using both conventional and cortex-based alignment techniques. Experiment 2 revealed numerical ratio dependent signal recovery in the left IPS following adaptation to both Arabic numerals and spoken number words using both conventional and cortex-based alignment techniques. Together, these findings suggest that the left IPS is involved in symbolic number processing across modalities.
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Factor analysis linking functions for simultaneously modeling neural and behavioral data
Source:NeuroImage, Volume 153
Author(s): Brandon M. Turner, Ting Wang, Edgar C. Merkle
A growing number of researchers have advocated for the advancement of cognitive neuroscience by blending cognitive models with neurophysiology. The recently proposed joint modeling framework is one way to bridge the gap between the abstractions assumed by cognitive models and the neurophysiology obtained by modern methods in neuroscience. Despite this advancement, the current method for linking the two domains is hindered by the dimensionality of the neural data. In this article, we present a new linking function based on factor analysis that allows joint models to grow linearly in complexity with increases in the number of neural features. The new linking function is then evaluated in two simulation studies. The first simulation study shows how the model parameters can be accurately recovered when there are many neural features, that mimics real-world applications. The second simulation shows how the new linking function can (1) properly recover a representation of the data generating model, even in the case of model misspecification, and (2) outperform the previous linking function in a cross-validation test. We close by applying a model equipped with the new linking function to real-world data from a perceptual decision making task. The model allows us to understand how differences in the model parameters emerge as a function of differences in brain function across speed and accuracy instruction.
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Predictive position computations mediated by parietal areas: TMS evidence
Source:NeuroImage, Volume 153
Author(s): Grace Edwards, Céline Paeye, Philippe Marque, Rufin VanRullen, Patrick Cavanagh
When objects move or the eyes move, the visual system can predict the consequence and generate a percept of the target at its new position. This predictive localization may depend on eye movement control in the frontal eye fields (FEF) and the intraparietal sulcus (IPS) and on motion analysis in the medial temporal area (MT). Across two experiments we examined whether repetitive transcranial magnetic stimulation (rTMS) over right FEF, right IPS, right MT, and a control site, peripheral V1/V2, diminished participants' perception of two cases of predictive position perception: trans-saccadic fusion, and the flash grab illusion, both presented in the contralateral visual field. In trans-saccadic fusion trials, participants saccade toward a stimulus that is replaced with another stimulus during the saccade. Frequently, predictive position mechanisms lead to a fused percept of pre- and post-saccade stimuli (Paeye et al., 2017). We found that rTMS to IPS significantly decreased the frequency of perceiving trans-saccadic fusion within the first 10min after stimulation. In the flash grab illusion, a target is flashed on a moving background leading to the percept that the target has shifted in the direction of the motion after the flash (Cavanagh and Anstis, 2013). In the first experiment, the reduction in the flash grab illusion after rTMS to IPS and FEF did not reach significance. In the second experiment, using a stronger version of the flash grab, the illusory shift did decrease significantly after rTMS to IPS although not after rTMS to FEF or to MT. These findings suggest that right IPS contributes to predictive position perception during saccades and motion processing in the contralateral visual field.
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Optical-flow analysis toolbox for characterization of spatiotemporal dynamics in mesoscale optical imaging of brain activity
Source:NeuroImage, Volume 153
Author(s): Navvab Afrashteh, Samsoon Inayat, Mostafa Mohsenvand, Majid H. Mohajerani
Wide-field optical imaging techniques constitute powerful tools to investigate mesoscale neuronal activity. The sampled data constitutes a sequence of image frames in which one can investigate the flow of brain activity starting and terminating at source and sink locations respectively. Approaches to the analyses of information flow include qualitative assessment to identify sources and sinks of activity as well as their trajectories, and quantitative measurements based on computing the temporal variation of the intensity of pixels. Furthermore, in a few studies estimates of wave motion have been reported using optical-flow techniques from computer vision. However, a comprehensive toolbox for the quantitative analyses of mesoscale brain activity data is still lacking. We present a graphical-user-interface toolbox based in Matlab® for investigating the spatiotemporal dynamics of mesoscale brain activity using optical-flow analyses. The toolbox includes the implementation of three optical-flow methods namely Horn-Schunck, Combined Local-Global, and Temporospatial algorithms for estimating velocity vector fields of flow of mesoscale brain activity. From the velocity vector fields we determined the locations of sources and sinks as well as the trajectories and temporal velocities of flow of activity. Using simulated data as well as experimentally derived sensory-evoked voltage and calcium imaging data from mice, we compared the efficacy of the three optical-flow methods for determining spatiotemporal dynamics. Our results indicate that the combined local-global method we employed, yields the best results for estimating wave motion. The automated approach permits rapid and effective quantification of mesoscale brain dynamics and may facilitate the study of brain function in response to new experiences or pathology.
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Hippocampal CA3-dentate gyrus volume uniquely linked to improvement in associative memory from childhood to adulthood
Source:NeuroImage, Volume 153
Author(s): Ana M. Daugherty, Robert Flinn, Noa Ofen
Associative memory develops into adulthood and critically depends on the hippocampus. The hippocampus is a complex structure composed of subfields that are functionally-distinct, and anterior-posterior divisions along the length of the hippocampal horizontal axis that may also differ by cognitive correlates. Although each of these aspects has been considered independently, here we evaluate their relative contributions as correlates of age-related improvement in memory. Volumes of hippocampal subfields (subiculum, CA1-2, CA3-dentate gyrus) and anterior-posterior divisions (hippocampal head, body, tail) were manually segmented from high-resolution images in a sample of healthy participants (age 8–25 years). Adults had smaller CA3-dentate gyrus volume as compared to children, which accounted for 67% of the indirect effect of age predicting better associative memory via hippocampal volumes. Whereas hippocampal body volume demonstrated non-linear age differences, larger hippocampal body volume was weakly related to better associative memory only when accounting for the mutual correlation with subfields measured within that region. Thus, typical development of associative memory was largely explained by age-related differences in CA3-dentate gyrus.
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SEEG dipole source localization based on an empirical Bayesian approach taking into account forward model uncertainties
Source:NeuroImage, Volume 153
Author(s): S. Le Cam, R. Ranta, V. Caune, G. Korats, L. Koessler, L. Maillard, V. Louis-Dorr
Electromagnetic brain source localization consists in the inversion of a forward model based on a limited number of potential measurements. A wide range of methods has been developed to regularize this severely ill-posed problem and to reduce the solution space, imposing spatial smoothness, anatomical constraint or sparsity of the activated source map. This last criteria, based on physiological assumptions stating that in some particular events (e.g., epileptic spikes, evoked potential) few focal area of the brain are simultaneously actives, has gained more and more interest. Bayesian approaches have the ability to provide sparse solutions under adequate parametrization, and bring a convenient framework for the introduction of priors in the form of probabilistic density functions. However the quality of the forward model is rarely questioned while this parameter has undoubtedly a great influence on the solution. Its construction suffers from numerous approximation and uncertainties, even when using realistic numerical models. In addition, it often encodes a coarse sampling of the continuous solution space due to the computational burden its inversion implies. In this work we propose an empirical Bayesian approach to take into account the uncertainties of the forward model by allowing constrained variations around a prior physical model, in the particular context of SEEG measurements. We demonstrate on simulations that the method enhance the accuracy of the source time-course estimation as well as the sparsity of the resulting source map. Results on real signals prove the applicability of the method in real contexts.
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A simple post-synthesis conversion approach to Zn(OH)F and the effects of fluorine and hydroxyl on the photodegradation properties of dye wastewater
Publication date: 5 July 2017
Source:Journal of Hazardous Materials, Volume 333
Author(s): Hao Yang, Fei Teng, Wenhao Gu, Zailun Liu, Yunxuan Zhao, An Zhang, Zhe Liu, Yiran Teng
In this work, Zn(OH)F is prepared by an initiative, simple post-synthesis method, in which the molar ratio of F/Zn (RF) was varied to investigate the effect of the NH4F amounts added on the samples. Further, we have mainly investigated their energy bands and photochemical properties. Under UV light irradiation (λ£420nm), the samples (RF=0,1,2) show the high degradation activities of methylene blue (MB) dye, namely, 80% of MB can be degraded after 8min. It is found that the hydroxyl and fluorine have greatly down shifted the conduction band (CB, 0.99eV) and valence band (VB, 4.17eV) of Zn(OH)F, compared with ZnO (CB=−0.31eV, VB=2.89eV), but with the nearly same band gap. For the degradation of MB dye, the main oxidative species are holes and hydroxyl radicals for ZnO and Zn(OH)F, respectively. This study suggests that this simple post-synthesis fluorination approach could be extended to develop the other photocatalysts; moreover, we can facilely tune the band structure and photocatalytic activity by introducing or removing hydroxyl and fluorine, which could benefit to develop new photocatalysts.
Graphical abstract
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Oxygen accumulation on metal surfaces investigated by XPS, AES and LEIS, an issue for sputter depth profiling under UHV conditions
Publication date: 31 July 2017
Source:Applied Surface Science, Volume 411
Author(s): R. Steinberger, C.E. Celedón, B. Bruckner, D. Roth, J. Duchoslav, M. Arndt, P. Kürnsteiner, T. Steck, J. Faderl, C.K. Riener, G. Angeli, P. Bauer, D. Stifter
Depth profiling using surface sensitive analysis methods in combination with sputter ion etching is a common procedure for thorough material investigations, where clean surfaces free of any contamination are essential. Hence, surface analytic studies are mostly performed under ultra-high vacuum (UHV) conditions, but the cleanness of such UHV environments is usually overrated. Consequently, the current study highlights the in principle known impact of the residual gas on metal surfaces (Fe, Mg, Al, Cr and Zn) for various surface analytics methods, like X-ray photoelectron spectroscopy (XPS), Auger electron spectroscopy (AES) and low-energy ion scattering (LEIS). The investigations with modern, state-of-the-art equipment showed different behaviors for the metal surfaces in UHV during acquisition: (i) no impact for Zn, even after long time, (ii) solely adsorption of oxygen for Fe, slight and slow changes for Cr and (iii) adsorption accompanied by oxide formation for Al and Mg. The efficiency of different counter measures was tested and the acquired knowledge was finally used for ZnMgAl coated steel to obtain accurate depth profiles, which exhibited before serious artifacts when data acquisition was performed in an inconsiderate way.
Graphical abstract
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Treatment Options for Metastatic Colorectal Cancer in Patients with Liver Dysfunction due to Malignancy
Publication date: Available online 29 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): L. Faugeras, A. Dili, A. Druez, B. Krug, Decoster, L. D'Hondt
BackgroundThe survival of colorectal cancer patients is frequently determined by the extent of metastatic invasion to the liver; in cases of major involvement, therapeutic strategies are limited because the liver is necessary for drug metabolism.Material and methodsWe have reviewed articles about the pharmacokinetic profiles of each drug used in colorectal cancer patients with hepatic dysfunction to determine which of these treatments are most feasible.ResultsSome drugs appear to be feasible options for patients with hepatic insufficiency. Agents such as 5-fluorouracil and oxaliplatin, as well as monoclonal antibodies such as bevacizumab, cetuximab, and panitumumab, can potentially be used in these cases. On the other hand, irinotecan and regorafenib cannot be recommended because of the risk of increased toxicity.ConclusionTreatment of patients with colorectal cancer and liver dysfunction represents a major challenge because the prognosis is usually very poor and alteration of liver function is normally an exclusion criterion in clinical trials. In this review, we present evidence regarding the use of each drug in patients with colorectal cancer and hepatic impairment.
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Morbidity of the Free Fibula Flap Reconstruction in Head and Neck Malignancies
J reconstr Microsurg
DOI: 10.1055/s-0037-1601402
Thieme Medical Publishers, Inc. 333 Seventh Avenue, New York, NY 10001, USA
Article in Thieme eJournals:
Table of contents | Full text
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Cognitive deficits in obstructive sleep apnea: insights from a meta-review and comparison with deficits observed in COPD, insomnia, and sleep deprivation
Obstructive sleep apnea (OSA) is a nocturnal breathing disorder that is associated with cognitive impairment. The primary determinants of cognitive deficits in OSA are thought to be sleep disruption and blood gas abnormalities. Cognitive impairment is also seen in other disorders that are characterised primarily by sleep disturbance (e.g., sleep restriction/deprivation, insomnia) or hypoxia/hypercarbia (e.g. chronic obstructive pulmonary disease (COPD). Assessment of the cognitive defects observed in these other disorders could help better define the mechanisms underlying cognitive deficits in OSA.
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pH-Responsive pHLIP (pH Low Insertion Peptide) Nanoclusters of Superparamagnetic Iron Oxide Nanoparticles as a Tumor-selective MRI Contrast Agent
Publication date: Available online 29 March 2017
Source:Acta Biomaterialia
Author(s): Yushuang Wei, Rufang Liao, Abdulrahman Ahmed Mahmood, Haibo Xu, Qibing Zhou
Superparamagnetic iron oxide nanoparticles (SPION) are contrast agents used for noninvasive tumor magnetic resonance imaging (MRI). SPION with active targeting by tumor-specific ligands can effectively enhance the MRI sensitivity and specificity of tumors. However, the challenge remains when the tumor specific markers are yet to be determined, especially in the case of early tumor detection. In this study, the effectiveness of pH-responsive SPION via a pH low insertion peptide (pHLIP) to target tumor acidic microenvironments was investigated. Polylysine polymers were first successfully modified with pHLIP to have the pH-responsive capability. SPION pHLIP nanoclusters of 64, 82, 103, and 121 nm size were then assembled by the pH-responsive polymers in a size-controlled manner. The pH-responsive SPION nanoclusters of the 64 nm size exhibited the most effective pH-responsive retention in cells and tumor selective imaging in MRI. More importantly, the unique contrast enhancement of tumor inner core by the pH-responsive SPION in three different tumor models demonstrated the clinical potential to target tumor acidic microenvironment through pHLIP for tumor early detection and diagnosis by MRI.Statement of SignificanceDetection and diagnosis of tumors at early stage are critical for the improvement of the survival rate of cancer patients. However, the challenge remains when the tumor specific markers are unto be determined, especially in early tumor detection. pH low insertion peptide (pHLIP) has been used as a specific ligand to target the tumor acidic microenvironment for tumors at early and metastatic stages. Superparamagnetic iron nanoparticles (SPION) are contrast enhancing agents used in the noninvasive magnetic resonance imaging for tumors. This research has demonstrated that pH-responsive pHLIP nanoclusters of SPION were able to target different tumors and facilitate the noninvasive diagnosis of tumors by MRI.
Graphical abstract
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Targeted delivery of hyaluronic acid to the ocular surface by a polymer-peptide conjugate system for dry eye disease
Publication date: Available online 29 March 2017
Source:Acta Biomaterialia
Author(s): David Lee, Qiaozhi Lu, Sven D. Sommerfeld, Amanda Chan, Nikhil G. Menon, Tannin A. Schmidt, Jennifer H. Elisseeff, Anirudha Singh
Hyaluronic acid (HA) solutions effectively lubricate the ocular surface and are used for the relief of dry eye related symptoms. However, HA undergoes rapid clearance due to limited adhesion, which necessitates frequent instillation. Conversely, highly viscous artificial tear formulations with HA blur vision and interfere with blinking. Here, we developed an HA-eye drop formulation that selectively binds and retains HA for extended periods of time on the ocular surface. We synthesized a heterobifunctional polymer-peptide system with one end binding HA while the other end binding either sialic acid-containing glycosylated transmembrane molecules on the ocular surface epithelium, or type I collagen molecule within the tissue matrix. HA solution was mixed with the polymer-peptide system and tested on both ex vivo and in vivo models to determine its ability to prolong HA retention. Furthermore, rabbit ocular surface tissues treated with binding peptides and HA solutions demonstrated superior lubrication with reduced kinetic friction coefficients compared to tissues treated with conventional HA solution. The results suggest that binding peptide-based solution can keep the ocular surface enriched with HA for prolonged times as well as keep it lubricated. Therefore, this system can be further developed into a more effective treatment for dry eye patients than a standard HA eye drop.Statement of SignificanceEye drop formulations containing HA are widely used to lubricate the ocular surface and relieve dry eye related symptoms, however its low residence time remains a challenge. We designed a polymer-peptide system for the targeted delivery of HA to the ocular surface using sialic acid or type I collagen as anchors for HA immobilization. The addition of the polymer-peptide system to HA eye drop exhibited a reduced friction coefficient, and it can keep the ocular surface enriched with HA for prolonged time. This system can be further developed into a more effective treatment for dry eye than a standard HA eye drop.
Graphical abstract
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Comparative analysis of biological effect of corannulene and graphene on developmental and sleep/wake profile of zebrafish larvae
Publication date: Available online 29 March 2017
Source:Acta Biomaterialia
Author(s): Xiang Li, Yuan Zhang, Xu Li, DaoFu Feng, ShuHui Zhang, Xin Zhao, DongYan Chen, ZhiXiang Zhang, XiZeng Feng
Little is known about the biological effect of non-planar polycyclic aromatic hydrocarbons (PAH) such as corannulene on organisms. In this study, we compared the effect of corannulene (non-planar PAH) and graphene (planar PAH) on embryonic development and sleep/wake behaviors of larval zebrafish. First, the toxicity of graded doses of corannulene (1, 10, and 50 μg/mL) was tested in developing zebrafish embryos. Corannulene showed minimal developmental toxicity only induced an epiboly delay. Further, a significant decrease in locomotion/increase in sleep was observed in larvae treated with the highest dose (50 μg/mL) of corannulene while no significant locomotion alterations were induced by graphene. Finally, the effect of corannulene or graphene on the hypocretin (hcrt) system and sleep/wake regulators such as hcrt, hcrt G-protein coupled receptor (hcrtr), and arylalkylamine N-acetyltransferase-2 (aanat2) was evaluated. Corannulene increased sleep and reduced locomotor activity and the expression of hcrt and hcrtr mRNA while graphene did not obviously disturb the sleep behavior and gene expression patterns. These results suggest that the corannulene has the potential to cause hypnosis-like behavior in larvae and provides a fundamental comparative understanding of the effects of corannulene and graphene on biology systems.Statement of significanceLittle is known about the biological effect of non-planar polycyclic aromatic hydrocarbons (PAH) such as corannulene on organisms. Here, we compare the effect of corannulene (no-planar PAH) and graphene (planar PAH) on embryonic development and sleep/wake behaviours of larval zebrafish. And we aim to investigate the effect of curvature on biological system. First, toxicity of corannulene over the range of doses (1 μg/mL, 10 μg/mL and 50 μg/mL) was tested in developing zebrafish embryos. Corannulene has minimal developmental toxicity, only incurred epiboly delay. Subsequently, a significant decrease in locomotion/increase in sleep at the highest dose (50 μg/mL) was detected in corannulene treated larvae while no significant locomotion alterations was induced by graphene. Finally, the impact of corannulene or graphene on hypocretin system and sleep/wake regulator such as hcrt, hcrtr and aanat2 was evaluated. Corannulene increased sleep, reduced locomotor activity and the expression of hcrt and hcrtr mRNA while graphene did not obviously disturb the sleep behaviours and gene expression patterns. This result may indicate the potential effect of corannulene to cause hypnosia-like behaviour in larvae and provide the fundamental understanding for the biological effect of curvature on biology system.
Graphical abstract
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Non-invasive Monitoring of In Vivo Degradation of a Radiopaque Thermoreversible Hydrogel and Its Efficacy in Preventing Post-operative Adhesions
Publication date: Available online 29 March 2017
Source:Acta Biomaterialia
Author(s): Kewen Lei, Yipei Chen, Jinyao Wang, Xiaochun Peng, Lin Yu, Jiandong Ding
In vivo behavior of hydrogel-based biomaterials is very important for rational design of hydrogels for various biomedical applications. Herein, we developed a facile method for in situ fabrication of radiopaque hydrogel. An iodinated functional diblock copolymer of poly(ethylene glycol) and aliphatic polyester was first synthesized by coupling the hydroxyl end of the diblock copolymer with 2, 3, 5-triiodobenzoic acid (TIB) and then a radiopaque thermoreversible hydrogel was obtained by mixing it with the virgin diblock copolymer. A concentrated aqueous solution of the copolymer blend was injectable at room temperature and spontaneously turned into an in situ hydrogel at body temperature after injection. The introduction of TIB moieties affords the capacity of X-ray opacity, enabling in vivo visualization of the hydrogel using Micro-CT. A rat model with cecum and abdominal defects was utilized to evaluate the efficacy of the radiopaque hydrogel in the prevention of post-operative adhesions, and a significant reduction of the post-operative adhesion formation was confirmed. Meanwhile, the maintenance of the radiopaque hydrogel in the abdomen after administration was non-destructively detected via Micro-CT scanning. The reconstructed three-dimensional images showed that the radiopaque hydrogel with an irregular morphology was located on the injured abdominal wall. The time-dependent profile of the volume of the radiopaque hydrogel determined by Micro-CT imaging was well consistent with the trend obtained from the dissection observation. Therefore, the radiopaque thermoreversible hydrogel can serve as a potential visualized biomedical implant and this practical mixing approach is also useful for further extension into the in vivo monitoring of other biomaterials.Statement of SignificanceWhile a variety of biomaterials have been extensively studied, it is rare to monitor in vivo degradation and medical efficacy of a material after being implanted deeply into the body. Herein, the radiopaque thermoreversible hydrogel developed by us not only holds desirable performance on the prevention of post-operative abdominal adhesions, but also allows non-invasive monitoring of its in vivo degradation with CT imaging in a real-time, quantitative and three-dimensional manner. The methodology based on CT imaging provides important insights into the in vivo fate of the hydrogel after being deeply implanted into mammals for different biomedical applications and significantly reduces the amount of animals sacrificed.
Graphical abstract
http://ift.tt/2nkNUlt
Oligomeric proanthocyanidins released from dentin induce regenerative dental pulp cell response
Publication date: Available online 29 March 2017
Source:Acta Biomaterialia
Author(s): Daniel Kulakowski, Ariene A Leme-Kraus, Joo-won Nam, James McAlpine, Shao-Nong Chen, Guido F. Pauli, Sriram Ravindran, Ana K. Bedran-Russo
Proanthocyanidins (PACs) are plant-derived, multifunctional compounds that possess high interactivity with extracellular matrix (ECM) components. The documented affinity of PACs for type-I collagen is directly correlated with their structural features and degree of polymerization. In this investigation, centrifugal partition chromatography (CPC) was used to sequentially deplete less active monomeric and polymeric PACs from a crude Pinus massoniana bark extract to create refined mixtures enriched in oligomeric PACs. The ability of these oligomeric PACs to modify the mechanical properties of the dentin collagen matrix and their biocompatibility with dental pulp cells (DPCs) was evaluated in an innovative biomimetic environment. The refined mixtures displayed high interactivity with dentin collagen as demonstrated by a significant increase (> 5-fold) in the modulus of elasticity of the dentin matrix. In a simplified model of the dentin-DPC complex, DPCs embedded within their native ECM in the presence of PAC-treated dentin exhibited increased proliferation. Quantitative gene expression analyses indicated that exposure to PAC-treated dentin increased the expression of key biomineralization and odontogenic differentiation regulators, including RUNX2, BMP2, OCN, and DSPP. LC-MS/MS analysis revealed that PACs two to four units long (dimers, trimers, and tetramers) were being released from dentin into media, influencing cell behavior. Overall, the results suggested that PAC dimers, trimers, and tetramers are not only biocompatible, but enhance the differentiation of DPCs towards a phenotype that favors biomineralization. PAC-enriched refined mixtures can influence the field of biomaterials and regeneration by serving as renewable, non-cytotoxic agents that can increase the mechanical properties of biomaterials.Statement of SignificancePine bark extract is a renewable source of structurally diverse proanthocyanidins (PACs), multifunctional compounds whose interaction with collagen can be tailored to specific purposes by enrichment of selected PACs from the complex mixture. Oligomeric PACs were enriched from the extract and were shown here to sustain desired tissue modification and were thus assessed for cellular response in a model of the dentin-pulp interface. This model was developed to mimic leaching of potentially reactive compounds into pulp tissue. Dental pulp cells exposed to PAC-treated dentin showed increased proliferation and expression of genes necessary for extracellular matrix deposition and biomineralization, processes crucial for forming new dentin. Thus, collagen-interactive PACs may also enhance tissue regeneration and have broad impact in tissue engineering.
Graphical abstract
http://ift.tt/2nkLkMv
Mesenchymal Stem Cell Fate Following Non-viral Gene Transfection Strongly Depends on the Choice of Delivery Vector
Publication date: Available online 29 March 2017
Source:Acta Biomaterialia
Author(s): T. Gonzalez-Fernandez, B.N. Sathy, C. Hobbs, G.M. Cunniffe, H.O. McCarthy, N.J. Dunne, V. Nicolosi, F.J. O'Brien, D.J. Kelly
Controlling the phenotype of mesenchymal stem cells (MSCs) through the delivery of regulatory genes is a promising strategy in tissue engineering (TE). Essential to effective gene delivery is the choice of gene carrier. Non-viral delivery vectors have been extensively used in TE, however their intrinsic effects on MSC differentiation remain poorly understood. The objective of this study was to investigate the influence of three different classes of non-viral gene delivery vectors: (1) cationic polymers (polyethylenimine, PEI), (2) inorganic nanoparticles (nanohydroxyapatite, nHA) and (3) amphipathic peptides (RALA peptide) on modulating stem cell fate after reporter and therapeutic gene delivery. Despite facilitating similar reporter gene transfection efficiencies, these nanoparticle-based vectors had dramatically different effects on MSC viability, cytoskeletal morphology and differentiation. After reporter gene delivery (pGFP or pLUC), the nHA and RALA vectors supported an elongated MSC morphology, actin stress fibre formation and the development of mature focal adhesions, while cells appeared rounded and less tense following PEI transfection. These changes in MSC morphology correlated with enhanced osteogenesis following nHA and RALA transfection and adipogenesis following PEI transfection. When therapeutic genes encoding for transforming growth factor beta 3 (TGF-β3) and/or bone morphogenic protein 2 (BMP2) were delivered to MSCs, nHA promoted osteogenesis in 2D culture and the development of an endochondral phenotype in 3D culture, while RALA was less osteogenic and appeared to promote a more stable hyaline cartilage-like phenotype. In contrast, PEI failed to induce robust osteogenesis or chondrogenesis of MSCs, despite effective therapeutic protein production. Taken together, these results demonstrate that the differentiation of MSCs through the application of non-viral gene delivery strategies depends not only on the gene delivered, but also on the gene carrier itself.Statement of SignificanceNanoparticle-based non-viral gene delivery vectors have been extensively used in regenerative medicine, however their intrinsic effects on mesenchymal stem cell (MSC) differentiation remain poorly understood. This paper demonstrates that different classes of commonly used non-viral vectors are not inert and they have a strong effect on cell morphology, stress fiber formation and gene transcription in MSCs, which in turn modulates their capacity to differentiate towards osteogenic, adipogenic and chondrogenic lineages. These results also point to the need for careful and tissue-specific selection of nanoparticle-based delivery vectors to prevent undesired phenotypic changes and off-target effects when delivering therapeutic genes to damaged or diseased tissues.
Graphical abstract
http://ift.tt/2o9Txqi
Distributed Vasculogenesis from Modular Agarose-Hydroxyapatite-Fibrinogen Microbeads
Publication date: Available online 29 March 2017
Source:Acta Biomaterialia
Author(s): Ana Y. Rioja, Ethan L.H. Daley, Julia C. Habif, Andrew J. Putnam, Jan P. Stegemann
Critical limb ischemia impairs circulation to the extremities, causing pain, disrupted wound healing, and potential tissue necrosis. Therapeutic angiogenesis seeks to repair the damaged microvasculature directly to restore blood flow. In this study, we developed modular, micro-scale constructs designed to possess robust handling qualities, allow in vitro pre-culture, and promote microvasculature formation. The microbead matrix consisted of an agarose (AG) base to prevent aggregation, combined with cell-adhesive components of fibrinogen (FGN) and/or hydroxyapatite (HA). Microbeads encapsulating a co-culture of human umbilical vein endothelial cells (HUVEC) and fibroblasts were prepared and characterized. Microbeads were generally 80-100 microns in diameter, and the size increased with the addition of FGN and HA. Addition of HA increased the yield of microbeads, as well as the homogeneity of distribution of FGN within the matrix. Cell viability was high in all microbead types. When cell-seeded microbeads were embedded in fibrin hydrogels, HUVEC sprouting and inosculation between neighboring microbeads were observed over seven days. Pre-culture of microbeads for an additional seven days prior to embedding in fibrin resulted in significantly greater HUVEC network length in AG+HA+FGN microbeads, as compared to AG, AG+HA or AG+FGN microbeads. Importantly, composite microbeads resulted in more even and widespread endothelial network formation, relative to control microbeads consisting of pure fibrin. These results demonstrate that AG+HA+FGN microbeads support HUVEC sprouting both within and between adjacent microbeads, and can promote distributed vascularization of an external matrix. Such modular microtissues may have utility in treating ischemic tissue by rapidly re-establishing a microvascular network.Statement of SignificanceCritical limb ischemia (CLI) is a chronic disease that can lead to tissue necrosis, amputation, and death. Cell-based therapies are being explored to restore blood flow and prevent the complications of CLI. In this study, we developed small, non-aggregating agarose-hydroxyapatite-fibrinogen microbeads that contained endothelial cells and fibroblasts. Microbeads were easy to handle and culture, and endothelial sprouts formed within and between microbeads. Our data demonstrates that the composition of the microbead matrix altered the degree of endothelial sprouting, and that the addition of hydroxyapatite and fibrinogen resulted in more distributed sprouting compared to pure fibrin microbeads. The microbead format and control of the matrix formulation may therefore be useful in developing revascularization strategies for the treatment of ischemic disease.
Graphical abstract
http://ift.tt/2o9ENrw
ATA Signal e-News March 2017 Secretary’s Update
| Victor J. Bernet, MD Secretary/Chief Operating Officer |
Secretary's Update, March 2017
Well, Spring is here and so is the ATA Spring 2017 Satellite Symposium in Orlando, Hypothyroidism: Where Are We Now? This activity is being held 31 March, 2017 between 1:00 and 5:30 pm in the Orange County Convention and Exhibition Center. We hope to see you there! Also, we would very much like to hear your thoughts on potential topics for future symposia.
To indirectly quote Bobbi Smith: we have so many ATA irons in the fire to the point of inducing dizziness. Hyperbole, maybe, but actually not so far from the truth. ATA leadership and committees continue to move forward on initiatives related to our strategic plan. So let's review: Strategic focus on efforts for patients. Well, the Spring Symposia will include a first ever patient panel and a remarkable 11,969 patients have completed a survey, the results of which will be discussed at the symposium. The ATA is also reaching out to patients thru Philip James who hosts the "Doctor Thyroid" podcast series at www.docthyroid.com. He has already interviewed several ATA members and these excellent podcasts are available on the listed website. Furthermore, the ATA headquarters' staff, with support from our consultants at Just Write Solutions, has just submitted an application to participate in the NIH Program "All of Us." If successful, the ATA will receive funding to support patient recruitment and education for this initiative with a special focus on underrepresented groups with thyroid disease within the United States.
Strategic focus on global leadership. We have made several advances. Members Elizabeth Pearce and Angela Leung, composed a letter to request that iodine be included as an essential micronutrient within the strategic plan for the NIH Nutrition Research Task Force (NRTF). The ATA is also involved in an effort to develop modules for primary care thyroid education in India. Furthermore, arrangements have been made with sister societies such as SNMMI to have shared symposia at our respective national meetings. The ATA expressed our concerns about the unintended negative consequences on medical research and international collaboration that the proposed executive order on travel restrictions can be anticipated to engender in several ways: a letter to the White House, a press release on the website and to the public media through NewsWise.
Strategic focus to support research efforts. With support from Rebecca Schweppe, the Research Committee plus assists by Tony Hollenberg and Tony Bianco, the ATA is in negotiations with representatives from the Nuclear Receptor Signaling Atlas (NURSA) soon to be known as Signaling Pathways to develop a data repository for thyroid diseases. This partnership is expected to make a panoply of raw data from various basic science projects available for further analysis with the intent of leading to additional research and meaningful discoveries. The Research Committee is also in the midst of reviewing submissions for awarding of research grants. We appreciate the continuing support from ThyCa, Bite Me Cancer, and the ATA Campaign endowment which make these research funds available.
The ATC Guidelines Policy Task Force continues its efforts. A new initiative with these guidelines is that arrangements have been made to support very methodical literature reviews which will hopefully strengthen the guidelines and facilitate guideline acceptance by the National Guidelines Clearinghouse which represents the newest in guideline standards.
Finally, the webpage for the 87th Annual Meeting of the ATA in Victoria, British Columbia, is open with preliminary information on program http://ift.tt/2oj2wTB. Regular abstract submissions open 29 March, 2017 with a submission deadline of June 7th. The annual program this year is shaping to be a great one and the Program Committee will be adding a Pediatric Symposium to the annual meeting agenda as well.
And with that, are you dizzy yet?
We hope to see you at the symposium in Orlando and please visit the ATA exhibit booth at the ENDO Expo – come see us and say hello. I'll be looking for you!
Sincerely,
Victor J. Bernet, MD
Secretary/Chief Operating Officer
The post ATA Signal e-News March 2017 Secretary's Update appeared first on American Thyroid Association.
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What makes dietary restraint problematic? Development and validation of the Inflexible Eating Questionnaire
Source:Appetite, Volume 114
Author(s): Cristiana Duarte, Cláudia Ferreira, José Pinto-Gouveia, I.A. Trindade, A. Martinho
This study presents the Inflexible Eating Questionnaire (IEQ), which measures the inflexible adherence to subjective eating rules.The scale's structure and psychometric properties were examined in distinct samples from the general population comprising both men and women.IEQ presented an 11-item one-dimensional structure, revealed high internal consistency, construct and temporal stability, and discriminated eating psychopathology cases from non-cases. The IEQ presented significant associations with dietary restraint, eating psychopathology, body image inflexibility, general psychopathology symptoms, and decreased intuitive eating. IEQ was a significant moderator on the association between dietary restraint and eating psychopathology symptoms.Findings suggested that the IEQ is a valid and useful instrument with potential implications for research on psychological inflexibility in disordered eating.
http://ift.tt/2oiOaT5
Liraglutide relieves myocardial damage by promoting autophagy via AMPK-mTOR signaling pathway in zucker diabetic fatty rat
Source:Molecular and Cellular Endocrinology
Author(s): Ya Zhang, Yuanna Ling, Li Yang, Yanzhen Cheng, Pingzhen Yang, Xudong Song, Huixiong Tang, Yongkang Zhong, Lu Tang, Shangfei He, Shuangli Yang, Aihua Chen, Xianbao Wang
Liraglutide, a glucose-lowering agent used to treat type 2 diabetic mellitus is reported to exert cardioprotective effects in clinical trials and animal experiments. However, the cardioprotective mechanism of liraglutide on diabetic cardiomyopathy has not been fully illustrated. The present study was performed to investigate whether liraglutide alleviates diabetic myocardium injury by promoting autophagy and its underlying mechanisms. Our results show that liraglutide significantly reduced the levels of creatine kinase (CK) and lactate dehydrogenase (LDH), improved left ventricular functional status and alleviated myocardial fibrosis in the Zucker diabetic fatty (ZDF) rat model. Liraglutide also mitigated high glucose-induced injury in NRCs. However these effects were partly reversed by the autophagic inhibitor chloroquine (CQ). Liraglutide promoted myocardial autophagy in the vivo and in the vitro models. Furthermore, liraglutide-induced enhancement of autophagy was related to increased AMPK phosphorylation and decreased mTOR phosphorylation, which was partially abolished by the AMPK inhibitor compound C (Comp C). Collectively, our data provide evidence that liraglutide mediated diabetic myocardium injury by promoting AMPK-dependent autophagy.
http://ift.tt/2nkprg3
Utility of baseline serum phosphorus levels for predicting remission in acromegaly patients
Abstract
Purpose
High GH and IGF I levels increase tubular phosphate reabsorption in patients with acromegaly. We aimed to investigate the utility of serum phosphorus levels as an indicator for predicting chance of remission in acromegaly patients.
Design
Fifty-one patients (n: 51; F: 24, M: 27) with diagnosis of acromegaly were included in the study. Plasma IGF-1, Phosphorus (P) and nadir GH levels on oral glucose tolerance test (OGTT) at the time of diagnosis were analysed retrospectively. Patients were classified into two groups according to their plasma P levels; P ≤ 4.5 mg/dl (Group-1, n: 23, 45.1%), P > 4.5 mg/dl (Group-2, n: 28, 54.9%). Two groups were compared according to remission status; remission (n: 27) and non-remission (n: 24). Remission was defined with absence of clinical symptoms, normal plasma IGF-1 (adjusted for age and gender) and GH levels (<1 mcg/dl) at least 3 months after initial treatment.
Results
Serum P levels decreased significantly after treatment in both groups (p < 0.001). There was a significant correlation between baseline phosphorus levels and remission rates, nadir GH in OGTT, pituitary adenoma size and Ki-67 scores (p = 0.001, r: −0.51; p = 0.01, r: 0.44; p = 0.001, r: 0.52; p = 0.02, r: 0.71, respectively). Mean baseline P levels were significantly higher in patients with non-remission (4.8 vs 4.2, P < 0.001). Logistic regression analysis did not reveal an independent effect on remission with any of these risk factors.
Conclusion
High serum P levels may be an indicator for a low likelihood of onset of remission in acromegaly patients. Further studies with wider spectrum are needed to make specific suggestions.
http://ift.tt/2oyAHFS
Psychological characteristics of Italian gender dysphoric adolescents: a case–control study
Abstract
Purpose
Gender dysphoria (GD) is associated with clinically significant distress and impairment in social, scholastic, and other important areas of functioning, especially when early onset is reported. The aim of the present study is to assess the psychopathological features associated with GD in adolescence, comparing a group of gender dysphoric adolescents (GDs) with a group of non-referred adolescents (NRs), in terms of body uneasiness, suicide risk, psychological functioning, and intensity of GD.
Methods
A sample of 46 adolescents with GD and 46 age-matched NRs was evaluated (mean ± SD age = 16.00 ± 1.49 and 16.59 ± 1.11 respectively, p > 0.05). Subjects were asked to complete the Body Uneasiness Test (BUT) to explore body uneasiness, the Youth Self Report (YSR) to measure psychological functioning, the Multi-Attitude Suicide Tendency Scale (MAST) for suicide risk, and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA) for GD assessment.
Results
Adolescents with GD reported significantly higher levels of body uneasiness (BUT-GSI, F = 380.13, p < 0.0001), as well as a worse psychological functioning (YSR, F = 13.06 and p < 0.0001 for "total problem scale" and F = 12.53, p = 0.001 for "internalizing" scale) as compared to NRs. When YSR subscales were considered, GDs showed significantly higher scores in the "withdrawal/depression", "anxiety/depression", and "social problems" (all p < 0.0001). In addition, GDs showed significantly higher levels in the "attraction to death" and "repulsion by life" scales and lower scores in the "attraction to life" scale (all p < 0.0001). Finally, GIDYQ-AA score was significantly lower (meaning a higher level of gender dysphoria symptoms) in GDs vs. NRs (p < 0.0001).
Conclusions
GD adolescents reported significantly higher body dissatisfaction and suicidal risk compared to NRs. In addition, results confirmed a significant impairment in social psychological functioning in adolescents with GD.
http://ift.tt/2o7Deul
Diabetic retinopathy: new therapeutic perspectives based on pathogenic mechanisms
Abstract
Diabetic retinopathy (DR) is the leading cause of visual impairment and preventable blindness and represents a significant socioeconomic cost for healthcare systems worldwide. In early stages of DR the only therapeutic strategy that physicians can offer is a tight control of the risk factors for DR (mainly blood glucose and blood pressure). The currently available treatments for DR are applicable only at advanced stages of the disease and are associated with significant adverse effects. Therefore, new treatments for the early stages of DR are needed. However, in early stages of DR invasive treatments such as intravitreal injections are too aggressive, and topical treatment seems to be an emerging route. In the present review, therapeutic strategies based on the main pathogenic mechanisms involved in the development of DR are reviewed. The main gap in the clinical setting is the treatment of early stages of DR and, therefore, this review emphasizes in this issue by giving an overview of potential druggable targets. By understanding of disease-specific pathogenic mechanisms, biological heterogeneity and progression patterns in early and advanced DR a more personalised approach to patient treatment will be implemented.
http://ift.tt/2o9j8Qn
Bactericidal effect of the photocatalystic reaction of titanium dioxide using visible wavelengths on Streptococcus mutans biofilm
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Chan-Hee Kim, Eun-Song Lee, Si-Mook Kang, Elbert de Josselin de Jong, Baek-Il Kim
BackgroundThe aim of this study was to determine the effect of titanium dioxide (TiO2) photocatalysis induced by the application of clinically acceptable visible light at 405nm on the growth of Streptococcus mutans biofilms.MethodsS. mutans biofilms were grown on a hydroxyapatite (HA) disk and deposited in a rutile-type TiO2 solution at a concentration of 0.1mg/mL. TiO2 photocatalysis was measured for exposure to visible light (405 nm) and ultraviolet (UV) light (254 nm) produced by light-emitting diodes for 10, 20, 30, and 40 minutes. After two treatments, the number of colonies formed in the final S. mutans biofilm on the HA disk were measured to confirm their viability, and the morphological changes of S. mutans were evaluated using scanning electronic microscopy.ResultsThe bactericidal effects of 254- and 405-nm light resulted in >5-log and 4-log reductions, respectively (p < 0.05), after 20minutes of treatment and a > 7-log reduction after 40minutes of treatment in both treatment groups relative to the control group.ConclusionIt was confirmed that the antibacterial effect could be shown by causing the photocatalytic reaction of TiO2 in S. mutans biofilm even at the wavelength of visible light (405nm) as at the wavelength of ultraviolet light (254nm).
http://ift.tt/2o9qtzd
Salvage radiotherapy with or without concurrent chemotherapy for pelvic recurrence after hysterectomy alone for early-stage uterine cervical cancer
Abstract
Purpose
Treatment outcomes of patients with pelvic recurrence after hysterectomy alone for uterine cervical cancer who received salvage radiotherapy (RT) with or without concurrent chemotherapy were investigated.
Methods
Salvage RT for recurrent cervical cancer confined to the pelvic cavity after hysterectomy alone was received by 33 patients. The median interval between initial hysterectomy and recurrence was 26 months. Whole-pelvic irradiation was delivered to median dose of 45 Gy, followed by a boost with a median dose of 16 Gy to the gross tumor volume. Cisplatin-based concurrent chemotherapy was administered to 29 patients.
Results
The median follow-up period was 53 months for surviving patients. Most patients (97.0%) completed salvage RT of ≥45 Gy. Complete response (CR) was achieved in 23 patients (69.7%). Pelvic sidewall involvement and evaluation with positron-emission tomography-computed tomography were significantly associated with CR. The 5‑year progression-free survival (PFS), local control (LC), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 62.7, 79.5, 72.5, and 60.1%, respectively. Initial International Federation of Gynecology and Obstetrics stage, pelvic sidewall involvement, and CR status were significant factors for PFS and OS rates in multivariate analysis. The incidence of severe acute and late toxicities (≥grade 3) was 12.1 and 3.0%, respectively.
Conclusion
Aggressive salvage RT with or without concurrent chemotherapy for recurrent cervical cancer confined to the pelvic cavity was feasible, with promising treatment outcomes and acceptable toxicities. However, even more intensive novel treatment strategies should be investigated for patients with unfavorable prognostic factors.
http://ift.tt/2ogXqXM
Ethical issues in non-intervention trials for thyroid cancer
Source:European Journal of Surgical Oncology (EJSO)
Author(s): P. Angelos, D.M. Hartl, J.P. Shah, I.J. Nixon, R.P. Owen, A. Rinaldo, J.P. Rodrigo, A.R. Shaha, C.E. Silver, C. Suárez, A. Ferlito
In recent years, the increasing numbers of small, apparently indolent thyroid cancers diagnosed in the world have encouraged investigators to consider non-intervention as an alternative to surgical management. In the following pages, the prospect of a non-intervention trial for thyroid cancer is considered with attention to the ethical issues that such a trial might raise. Such a non-intervention trial is analyzed relative to 7 ethical considerations: the social or scientific value of the research, the scientific validity of the trial, the necessity of fair selection of participants, a favorable risk-benefit ratio for trial participants, independent review of the trial, informed consent, and allowing the study participants to withdraw from the trial. A non-intervention trial for thyroid cancer is also considered relative to the central concept of equipoise.
http://ift.tt/2oikPbq
Chart-stimulated Recall as a Learning Tool for Improving Radiology Residents' Reports
Source:Academic Radiology
Author(s): Naila Nadeem, Abdul Mueed Zafar, Sonia Haider, Rukhsana W. Zuberi, Muhammad Nadeem Ahmad, Vijayanadh Ojili
Rationale and ObjectivesWorkplace-based assessments gauge the highest tier of clinical competence. Chart-stimulated recall (CSR) is a workplace-based assessment method that complements chart audit with an interview based on the residents' notes. It allows evaluation of the residents' knowledge and heuristics while providing opportunities for feedback and self-reflection. We evaluated the utility of CSR for improving the radiology residents' reporting skills.Materials and MethodsResidents in each year of training were randomly assigned to an intervention group (n = 12) or a control group (n = 13). Five pre-intervention and five post-intervention reports of each resident were independently evaluated by three blinded reviewers using a modified Bristol Radiology Report Assessment Tool. The study intervention comprised a CSR interview tailored to each individual resident's learning needs based on the pre-intervention assessment. The CSR process focused on the clinical relevance of the radiology reports. Student's t test (P < .05) was used to compare pre- and post-intervention scores of each group.ResultsA total of 125 pre-intervention and 125 post-intervention reports were evaluated (total 750 assessments). The Cronbach's alpha for the study tool was 0.865. A significant improvement was seen in the cumulative 19-item score (66% versus 73%, P < .001) and the global rating score (59% versus 72%, P < .001) of the intervention group after the CSR. The reports of the control group did not demonstrate any significant improvement.ConclusionCSR is a feasible workplace-based assessment method for improving reporting skills of the radiology residents.
http://ift.tt/2oiqhuT
An Interprofessional Learning Workshop for Mammography and Sonography Students Focusing on Breast Cancer Care and Management Via Simulation
Source:Academic Radiology
Author(s): Eileen M. Giles, Nayana Parange, Bronwyn Knight
Rationale and ObjectivesThe literature surrounding interprofessional education claims that students who learn with, from, and about one another in well-designed interprofessional programs will practice together collaboratively upon graduation, given the skills to do so. The objective of this study was to examine attitudes to interprofessional practice before and after an interprofessional learning (IPL) activity.Materials and MethodsA total of 35 postgraduate medical imaging students attended a week-long mammography workshop. The sessions provided a range of didactic sessions related to diagnosis and management of breast cancer. An IPL session was incorporated on completion of the workshop to consolidate learning. Props and authentic resources were used to increase the fidelity of the simulation. Participants completed pre- and post-workshop questionnaires comprising an interprofessional education and collaboration scale and a quiz to gauge knowledge of specific content related to professional roles. Responses to each statement in the scale and quiz score, pre or post workshop, were compared, whereas responses to open-ended questions in post-workshop survey were thematically analyzed.ResultsSeventeen paired surveys were received. There was a significant total improvement of 10.66% (P = .036). After simulation, there was a statistically significant improvement in participants' understanding (P < .05) that IPL offers holistic care to the patient and that teamwork is useful for reducing errors in patient care. Simulation helped participants develop more awareness of their role within the profession, improve their understanding of other professionals, and gain more realistic expectations of team members.ConclusionThis pilot study confirmed learning within an IPL simulation improved attitudes toward shared learning, teamwork, and communication. Simulation provides opportunities for learning in a safe environment, and technology can be used in diverse ways to provide authentic learning.
http://ift.tt/2oc1WKf
Iterative Reconstructions in Reduced-Dose CT
Source:Academic Radiology
Author(s): Bastien Pauchard, Kai Higashigaito, Aicha Lamri-Senouci, Jean-Francois Knebel, Dominik Berthold, Francis Robert Verdun, Hatem Alkadhi, Sabine Schmidt
Rationale and ObjectivesTo compare adaptive statistical iterative reconstruction (ASIR) and model-based iterative reconstruction (MBIR) algorithms for reduced-dose computed tomography (CT).Materials and MethodsForty-four young oncology patients (mean age 30 ± 9 years) were included. After routine thoraco-abdominal CT (dose 100%, average CTDIvol 9.1 ± 2.4 mGy, range 4.4–16.9 mGy), follow-up CT was acquired at 50% (average CTDIvol 4.5 ± 1.2 mGy, range 2.2–8.4 mGy) in 29 patients additionally at 20% dose (average CTDIvol 1.9 ± 0.5 mGy, range 0.9–3.4 mGy). Each reduced-dose CT was reconstructed using both ASIR and MBIR. Four radiologists (two juniors and two seniors) blinded to dose and technique read each set of CT images regarding objective and subjective image qualities (high- or low-contrast structures), subjective noise or pixilated appearance, diagnostic confidence, and lesion detection.ResultsAt all dose levels, objective image noise was significantly lower with MBIR than with ASIR (P < 0.001). The subjective image quality for low-contrast structures was significantly higher with MBIR than with ASIR (P < 0.001).Reduced-dose abdominal CT images of patients with higher body mass index (BMI) were read with significantly higher diagnostic confidence than images of slimmer patients (P < 0.001) and had higher subjective image quality, regardless of technique.Although MBIR images appeared significantly more pixilated than ASIR images, they were read with higher diagnostic confidence, especially by juniors (P < 0.001).ConclusionsReduced-dose CT during the follow-up of young oncology patients should be reconstructed with MBIR to ensure diagnostic quality. Elevated body mass index does not hamper the quality of reduced-dose CT.
http://ift.tt/2oilpGd
Using the Analytic Hierarchy Process for Prioritizing Imaging Tests in Diagnosis of Suspected Appendicitis
Source:Academic Radiology
Author(s): Maria Agapova, Brian W. Bresnahan, Ken F. Linnau, Louis P. Garrison, Mitchell Higashi, Larry Kessler, Beth Devine
Rationale and ObjectivesIn clinical guideline or criteria development processes, such as those used in developing American College of Radiology Appropriateness Criteria (ACR AC), experts subjectively evaluate benefits and risks associated with imaging tests and make complex decisions about imaging recommendations. The analytic hierarchy process (AHP) decomposes complex decisions into structured smaller decisions, incorporates quantitative evidence and qualitative expert opinion, and promotes structured consensus building. AHP may supplement and/or improve the transparency of expert opinion contributions to developing guidelines or criteria.Materials and MethodsTo conduct an empirical test using health services research tools, we convened a mock ACR AC panel of emergency department radiology and nonradiology physicians to evaluate by multicriteria decision analysis, the relative appropriateness of imaging tests for diagnosing suspected appendicitis. Panel members selected benefit-risk criteria via an online survey and assessed contrast-enhanced computed tomography, magnetic resonance imaging, and ultrasound using an AHP-based software. Participants were asked whether the process was manageable, transparent, and improved shared understanding. Priority scores were converted to rankings and compared to the rank order of ACR AC ratings.ResultsWhen compared to magnetic resonance and ultrasound imaging, participants agreed with the ACR AC that contrast-enhanced computed tomography is the most appropriate test. Contrary to the ACR AC ratings, study results suggest that magnetic resonance is preferable to ultrasound. When compared to nonradiologists, radiologists' priority scores reflect a stronger preference for computed tomography.ConclusionsStudy participants addressed decision-making challenges using a relatively efficient data collection mechanism, suggesting that AHP may benefit the ACR AC guideline development process in identifying the relative appropriateness of imaging tests. With additional development, AHP may improve transparency when expert opinion is used in clinical guideline or appropriateness criteria development.
http://ift.tt/2oc3Qut
A Phase Ib Study of the Dual PI3K/mTOR Inhibitor Dactolisib (BEZ235) Combined with Everolimus in Patients with Advanced Solid Malignancies
Abstract
Background
The combination of everolimus and the imidazoquinoline derivative, BEZ235 (dactolisib), a dual PI3K/mTOR inhibitor, demonstrated synergy in a preclinical model.
Objective
To establish clinical feasibility, a phase Ib dose-escalation trial investigating safety and pharmacokinetics of this combination in patients with advanced tumors was performed.
Patients and Methods
BEZ235 was orally administered daily in escalating doses of 200, 400, and 800 mg along with everolimus at 2.5 mg daily in 28-day cycles. Nineteen patients were enrolled. Adverse events and tumor responses were evaluated using CTCAE v4.0 and RECIST 1.1, respectively. Pharmacokinetic analyses were performed.
Results
Common toxicities observed included fatigue, diarrhea, nausea, mucositis, and elevated liver enzymes. No confirmed responses were observed. BEZ235 pharmacokinetics exhibited dose-proportional increases in Cmax and AUC0-24 over the three doses, with high inter-individual variability. Non-compartmental and population pharmacokinetic-based simulations indicated significant increases in everolimus Cmax and AUC0-24 on day 28 and decreased clearance to 13.41 L/hr.
Conclusions
The combination of BEZ235 and everolimus demonstrated limited efficacy and tolerance. BEZ235 systemic exposure increased in a dose-proportional manner while oral bioavailability was quite low, which may be related to gastrointestinal-specific toxicity. The changes in steady-state pharmacokinetics of everolimus with BEZ235 highlight potential drug–drug interactions when these two drugs are administered together.
Clinicaltrials.gov: NCT01508104
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Gemcitabine in Combination with a Second Cytotoxic Agent in the First-Line Treatment of Locally Advanced or Metastatic Pancreatic Cancer: a Systematic Review and Meta-Analysis
Abstract
Background
It remains controversial whether the addition of a second cytotoxic agent can further improve the therapeutic effect of gemcitabine monotherapy in advanced or metastatic pancreatic cancer (LA/MPC).
Objective
The objective of the present systematic review and meta-analysis was to investigate the efficacy and safety of gemcitabine-based doublet chemotherapy regimens compared to single-agent gemcitabine in the first-line treatment of unresectable LA/MPC.
Methods
We searched for randomized controlled trials (RCTs) of gemcitabine monotherapy versus gemcitabine in combination with a second cytotoxic agent in patients with LA/MPC. The last search date was December 31, 2016.
Results
Twenty-seven RCTs were identified and included in the present systematic review and meta-analysis, involving a total of 7343 patients. The meta-analysis showed that gemcitabine-based combination therapy significantly improved overall survival (OS) (HR: 0.89; 95% confidence interval (CI): 0.85-0.94; P < 0.0001), progression-free survival (PFS) (HR: 0.80; 95% CI: 0.73-0.88; P < 0.0001), and overall response rate (ORR) (RR: 1.83; 95% CI: 1.62-2.07; P < 0.0001) in comparison to single-agent gemcitabine. Subgroup analysis suggested that the antitumor activity differed between gemcitabine-based combination regimens: doublet regimens of gemcitabine plus a taxoid, and gemcitabine plus a fluoropyrimidine, in particular an oral fluoropyrimidine, resulted in a significant OS benefit for the patients. However, the combination of gemcitabine with other cytotoxic agents, such as platinum compounds or topoisomerase inhibitors failed to reduce the mortality risk. Combination therapy caused more grade 3/4 toxicities, including neutropenia, thrombocytopenia, vomiting, diarrhea, and fatigue.
Conclusions
Gemcitabine-based doublet regimens demonstrated superiority over gemcitabine monotherapy in overall efficacy, but were associated with increased toxicity. Different gemcitabine-based combinations showed different antitumor activity, and doublet regimens of gemcitabine in combination with a taxoid or a fluoropyrimidine, in particular an oral fluoropyrimidine provided significant survival benefits in the first-line treatment of unresectable LA/MPC.
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Effect of Ongoing Assessment of Resident Operative Autonomy on the Operating Room Environment
Publication date: Available online 28 March 2017
Source:Journal of Surgical Education
Author(s): Jonathan P. Fryer, Ezra N. Teitelbaum, Brian C. George, Mary C. Schuller, Shari L. Meyerson, Christina M. Theodorou, Joseph Kang, Amy Yang, Lihui Zhao, Debra A. DaRosa
ObjectiveWe have previously demonstrated the feasibility and validity of a smartphone-based system called Procedural Autonomy and Supervision System (PASS), which uses the Zwisch autonomy scale to facilitate assessment of the operative performances of surgical residents and promote progressive autonomy. To determine whether the use of PASS in a general surgery residency program is associated with any negative consequences, we tested the null hypothesis that PASS implementation at our institution would not negatively affect resident or faculty satisfaction in the operating room (OR) nor increase mean OR times for cases performed together by residents and faculty.MethodsMean OR times were obtained from the electronic medical record at Northwestern Memorial Hospital for the 20 procedures most commonly performed by faculty members with residents before and after PASS implementation. OR times were compared via two-sample t-test. The OR Educational Environment Measure tool was used to assess OR satisfaction with all clinically active general surgery residents (n = 31) and full-time general surgery faculty members (n = 27) before and after PASS implementation. Results were compared using the Mann-Whitney rank sum test.ResultsA significant prolongation in mean OR time between control and study period was found for only 1 of the 20 operative procedures performed at least 20 times by participating faculty members with residents. Based on the overall survey score, no significant differences were found between resident and faculty responses to the OR Educational Environment Measure survey before and after PASS implementation. When individual survey items were compared, while no differences were found with resident responses, differences were noted with faculty responses for 7 of the 35 items addressed although after Bonferroni correction none of these differences remained significant.ConclusionsOur data suggest that PASS does not increase mean OR times for the most commonly performed procedures. Resident OR satisfaction did not significantly change during PASS implementation, whereas some changes in faculty satisfaction were noted suggesting that PASS implementation may have had some negative effect with them. Although the effect on faculty satisfaction clearly requires further investigation, our findings support that use of an autonomy-based OR performance assessment system such as PASS does not appear to have a major negative influence on OR times nor OR satisfaction.
http://ift.tt/2o8DhG8
Assessment of Female Medical Students’ Interest in Careers in Cardiothoracic Surgery
Publication date: Available online 28 March 2017
Source:Journal of Surgical Education
Author(s): Darci C. Foote, James M. Meza, Vikram Sood, Rishindra M. Reddy
ObjectiveAlthough over half of medical students are females, women comprise only 21% of cardiothoracic (CT) surgery residency applicants and 5% of the CT workforce. We sought to gain insight into female medical students' perceptions of CT surgery and identify targets to increase interest.DesignA 33-question survey queried career selection factors, perceptions of CT surgery, and ways to increase interest in the field. Responses were stratified by sex and preclinical versus clinical years.SettingWomen at 13 US medical schools were compared to men at a Midwest medical school.ParticipantsSurveys were distributed to approximately 4400 women and were completed by 372 (8.5%) women. Comparison surveys were distributed to approximately 170 preclinical men and were completed by 98 (57.6%) men.ResultsPreclinical woman had broad interests, whereas clinical women were more interested in primary care (p = 0.0124). Intellectual interest and lifestyle were important in specialty selection for men and women (91% versus 90%; 78% versus 86%). Although preclinical men valued perceived prestige and salary significantly more than preclinical women (39% versus 20%, p = 0.0014; 64% versus 48%, p = 0.0173), preclinical women valued caring for specific ethnicities and addressing health disparities significantly more than preclinical men (26% versus 15%, p = 0.0173; 53% versus 33%, p = 0.0019). Making family plans was cited by 83% of women as difficult if they choose to become a CT surgeon. Women thought that attaining their career interests and life goals (76%) or access to female CT surgery mentors (63%) would make the field more appealing. Over 70% of preclinical women were interested in shadowing a CT surgeon. Of these women, 12% attempted to shadow.ConclusionsAlthough baseline interest in CT surgery is low among women, there are many targets for increasing interest especially during preclinical years. Residency programs have the opportunity to entice women to the field by addressing their priorities of lifestyle, family planning, and addressing health disparities.
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Variable Operative Experience in Hand Surgery for Plastic Surgery Residents
Publication date: Available online 29 March 2017
Source:Journal of Surgical Education
Author(s): Jason Silvestre, Ines C. Lin, Lawrence Scott Levin, Benjamin Chang
BackgroundEfforts to standardize hand surgery training during plastic surgery residency remain challenging. We analyze the variability of operative hand experience at U.S. plastic surgery residency programs.MethodsOperative case logs of chief residents in accredited U.S. plastic surgery residency programs were analyzed (2011-2015). Trends in fold differences of hand surgery case volume between the 10th and 90th percentiles of residents were assessed graphically. Percentile data were used to calculate the number of residents achieving case minimums in hand surgery for 2015.ResultsCase logs from 818 plastic surgery residents were analyzed of which a minority were from integrated (35.7%) versus independent/combined (64.3%) residents. Trend analysis of fold differences in case volume demonstrated decreasing variability among procedure categories over time. By 2015, fold differences for hand reconstruction, tendon cases, nerve cases, arthroplasty/arthrodesis, amputation, arterial repair, Dupuytren release, and neoplasm cases were below 10-fold. Congenital deformity cases among independent/combined residents was the sole category that exceeded 10-fold by 2015. Percentile data suggested that approximately 10% of independent/combined residents did not meet case minimums for arterial repair and congenital deformity in 2015.ConclusionsVariable operative experience during plastic surgery residency may limit adequate exposure to hand surgery for certain residents. Future studies should establish empiric case minimums for plastic surgery residents to ensure hand surgery competency upon graduation.
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Country-level predictors of vaccination coverage and inequalities in Gavi-supported countries
Source:Vaccine
Author(s): Catherine Arsenault, Mira Johri, Arijit Nandi, José M. Mendoza Rodríguez, Peter M. Hansen, Sam Harper
BackgroundImportant inequalities in childhood vaccination coverage persist between countries and population groups. Understanding why some countries achieve higher and more equitable levels of coverage is crucial to redress these inequalities. In this study, we explored the country-level determinants of (1) coverage of the third dose of diphtheria-tetanus-pertussis- (DTP3) containing vaccine and (2) within-country inequalities in DTP3 coverage in 45 countries supported by Gavi, the Vaccine Alliance.MethodsWe used data from the most recent Demographic and Health Surveys (DHS) conducted between 2005 and 2014. We measured national DTP3 coverage and the slope index of inequality in DTP3 coverage with respect to household wealth, maternal education, and multidimensional poverty. We collated data on country health systems, health financing, governance and geographic and sociocultural contexts from published sources. We used meta-regressions to assess the relationship between these country-level factors and variations in DTP3 coverage and inequalities. To validate our findings, we repeated these analyses for coverage with measles-containing vaccine (MCV).ResultsWe found considerable heterogeneity in DTP3 coverage and in the magnitude of inequalities across countries. Results for MCV were consistent with those from DTP3. Political stability, gender equality and smaller land surface were important predictors of higher and more equitable levels of DTP3 coverage. Inequalities in DTP3 coverage were also lower in countries receiving more external resources for health, with lower rates of out-of-pocket spending and with higher national coverage. Greater government spending on heath and lower linguistic fractionalization were also consistent with better vaccination outcomes.ConclusionImproving vaccination coverage and reducing inequalities requires that policies and programs address critical social determinants of health including geographic and social exclusion, gender inequality and the availability of financial protection for health. Further research should investigate the mechanisms contributing to these associations.
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Editorial Board/Aims and Scope
Source:Vaccine, Volume 35, Issue 16
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Sociodemographic predictors of variation in coverage of the national shingles vaccination programme in England, 2014/15
Source:Vaccine
Author(s): Charlotte Ward, Lisa Byrne, Joanne M. White, Gayatri Amirthalingam, Karen Tiley, Michael Edelstein
IntroductionIn September 2013, England introduced a shingles vaccination programme to reduce incidence and severity of shingles in the elderly. This study aims to assess variation in vaccine coverage with regards to selected sociodemographic factors to inform activities for improving equity of the programme.MethodsEligible 70year-olds were identified from a national vaccine coverage dataset in 2014/15 that includes 95% of GPs in England. NHS England Local Team (LT) and index of multiple deprivation (IMD) scores were assigned to patients based on GP-postcode. Vaccine coverage (%) with 95% confidence intervals (CIs), were calculated overall and by LT, ethnicity and IMD, using binomial regression.ResultsOf 502,058 eligible adults, 178,808 (35.6%) had ethnicity recorded. Crude vaccine coverage was 59.5% (95%CI: 59.3–59.7). Coverage was lowest in London (49.6% coverage, 95%CI: 49.0–50.2), and compared to this coverage was significantly higher in all other LTs (+6.3 to +10.4, p<0.001) after adjusting for ethnicity and IMD. Coverage decreased with increasing deprivation and was 8.2% lower in the most deprived (95%CI: 7.3–9.1) compared with the least deprived IMD quintile (64.1% coverage, 95%CI: 63.6–64.6), after adjustment for ethnicity and LT. Compared with White-British (60.7% coverage, 95%CI: 60.5–61.0), other ethnic groups had between 4.0% (Indian) and 21.8% (Mixed: White and Black African) lower coverage. After adjusting for IMD and LT, significantly lower coverage by ethnicity persisted in all groups, except in Mixed: Other, Indian and Bangladeshi compared with White-British.ConclusionsAfter taking geography and deprivation into account, shingles vaccine coverage varied by ethnicity. White-British, Indian and Bangladeshi groups had highest coverage; Mixed: White and Black African, and Black-other ethnicities had the lowest. Patients' ethnicity and IMD are predictors of coverage which contribute to, but do not wholly account for, geographical variation coverage. Interventions to address service-related, sociodemographic and ethnic inequalities in shingles vaccine coverage are required.
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A different scintigraphic approach to evaluate the glomerular filtration rate
Publication date: Available online 29 March 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): T. Haciosmanoglu, A.O. Karacalioglu, T. Eyileten, S. Ince, N. Arslan
ObjectiveMultiple nuclear medicine techniques for measuring renal glomerular filtration rate (GFR) are available but some of them are not practical in daily routine use and others have some accuracy issues. Hence the aim of the study was to design a new camera-based approach to measure the GFR and to compare our results with other measured GFR (mGFR) and estimated GFRs (eGFRs) derived from available measurements and equations used in daily clinical practice.Material and methods34 patients were included in the study. ∼74MBq (2mCi) Technetium 99m diethylene-triamine-pentaacetic acid (99mTc-DTPA) was administered to the patients during 5min. A simple formula based on a dilution principle was used to measure GFR (ScinGFR).ResultsOur formula provided similar mGFR results in narrower range as creatinine clearance did and our results correlated well with results derived from other equations. When ScinGFR values were compared to others, there was a significant difference among them (p=0.031) due to difference between the ScinGFR and Cockroft–Gault. When the results of the ScinGFR compared to others without Cockroft-Gault, the difference among them was not significant (p=0.164).ConclusionA simple formula considering the extracellular fluid volume was used to predict the split and global kidney functions and despite some discrepancies, good correlation among our results and those derived from available formulas was detected.
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Definition: Apraxia
Source:Cortex
Author(s): Roberto Cubelli
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In search of a shared language in neuropsychology
Source:Cortex
Author(s): Roberto Cubelli, Sergio Della Sala
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Definition: Limb Apraxia
Source:Cortex
Author(s): François Osiurak, Yves Rossetti
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Pulsed Low Dose Rate Radiation With Concurrent Chemotherapy for Non-Small Cell Lung Cancer and Esophageal Cancer
Interventions: Radiation: Pulsed Low Dose Radiation; Drug: Carboplatin; Drug: Paclitaxel
Sponsor: Fox Chase Cancer Center
Recruiting - verified March 2017
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Observation Study of Patients With Non-Small Cell Lung Cancer and Esophageal Cancer Treated With Chemo-Radiation Followed by Surgery
Interventions: Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation Therapy
Sponsor: Fox Chase Cancer Center
Recruiting - verified March 2017
http://ift.tt/2obdGNk
Robot-assisted Thoraco-laparoscopic Esophagectomy Versus Minimally Invasive Conventional Thoraco-laparoscopic Esophagectomy
Interventions: Procedure: esophagectomy; Procedure: esophagectomy
Sponsor: Zhiang Li
Not yet recruiting - verified March 2017
http://ift.tt/2oyWMUR
Stop or Go? Endosome Positioning in the Establishment of Compartment Architecture, Dynamics, and Function
Publication date: Available online 28 March 2017
Source:Trends in Cell Biology
Author(s): Jacques Neefjes, Marlieke M.L. Jongsma, Ilana Berlin
The endosomal system constitutes a key negotiator between the environment of a cell and its internal affairs. Comprised of a complex membranous network, wherein each vesicle can in principle move autonomously throughout the cell, the endosomal system operates as a coherent unit to optimally face external challenges and maintain homeostasis. Our appreciation of how individual endosomes are controlled in time and space to best serve their collective purpose has evolved dramatically in recent years. In light of these efforts, the endoplasmic reticulum (ER) – with its expanse of membranes permeating the cytoplasmic space – has emerged as a potent spatiotemporal organizer of endosome biology. We review the latest advances in our understanding of the mechanisms underpinning endosomal transport and positioning, with emphasis on the contributions from the ER, and offer a perspective on how the interplay between these aspects shapes the architecture and dynamics of the endosomal system and drives its myriad cellular functions.
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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