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

http://ift.tt/2nkQEzn

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

http://ift.tt/2nkPpQw

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

http://ift.tt/2nkJScT

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

ATA HOME | 2017 SATELLITE SYMPOSIUM | BECOME A MEMBER

 

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 87^th 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 7^th. 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

Copyright © 2017 American Thyroid Association

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

Publication date: 1 July 2017
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

Publication date: Available online 29 March 2017
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

Publication date: Available online 29 March 2017
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

Publication date: Available online 16 March 2017
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.



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Chart-stimulated Recall as a Learning Tool for Improving Radiology Residents' Reports

Publication date: Available online 29 March 2017
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.



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An Interprofessional Learning Workshop for Mammography and Sonography Students Focusing on Breast Cancer Care and Management Via Simulation

Publication date: Available online 29 March 2017
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.



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Iterative Reconstructions in Reduced-Dose CT

Publication date: Available online 29 March 2017
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.



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Using the Analytic Hierarchy Process for Prioritizing Imaging Tests in Diagnosis of Suspected Appendicitis

Publication date: Available online 28 March 2017
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.



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