Cochlear implantation using the underwater technique: long-term results

Abstract

Introduction

The opening of the round window and the insertion of the electrode array into the scala tympani during cochlear implant surgery can lead to a pressure shock of the delicate inner ear structures. By filling the tympanic cavity with Ringer Solution during these surgical steps (underwater technique), the hydrostatic pressure of the fluid acts as a smooth pressure stabilizer, avoiding a pressure shock of the inner ear structures. The aim of this retrospective study was to present long-term results of this new method of cochlear implantation in underwater technique.

Methods

Altogether, 47 implantations in 43 patients with residual hearing at the frequencies 250, 500 and 1000 Hz in the unaided preoperative pure tone audiometry were included. A cochlear implantation via round window with a conventional full-length electrode was performed in underwater technique. Changes of residual hearing 7 weeks and 24 months after surgery were analyzed.

Results

Overall postimplant hearing preservation 7 weeks after implantation was achieved in 22 ears (47%). Subsequent follow-up was performed on average 24 months after surgery (range 12 months–4.2 years) in all patients. At this late postoperative evaluation, preservation of hearing was recorded in 18 ears (38%). Neither the follow-up time nor the type of electrode had a significant impact on the postoperative hearing loss.

Conclusion

The underwater technique is an atraumatic cochlear implantation technique with hearing preservation rates comparable to results in literature and a very small hearing preservation decline rate over time even when using full-length CI electrodes.

http://ift.tt/2ENoEho

Stapes Surgery Teaching Tool: A Simple, Stable and Successful Technique

Abstract

Stapes surgery is a highly skilled surgery among otological procedures and needs a good dexterity. To improve the skills one may need to do procedures using temporal bone dissections. We describe a procedure that is simple, inexpensive and improves the skills and can be done using easily available materials like disposable syringe, stapler pin and a forceps.

http://ift.tt/2nHLKPe

Risk of depression among patients with acne in the U.K.: a population-based cohort study

http://ift.tt/2E8fb34

Risk of depression among patients with acne in the U.K.: a population-based cohort study

http://ift.tt/2E8fb34

A single channel sleep-spindle detector based on multivariate classification of EEG epochs: MUSSDET

Publication date: 1 March 2018
Source:Journal of Neuroscience Methods, Volume 297
Author(s): Daniel Lachner-Piza, Nino Epitashvili, Andreas Schulze-Bonhage, Thomas Stieglitz, Julia Jacobs, Matthias Dümpelmann
BackgroundStudies on sleep-spindles are typically based on visual-marks performed by experts, however this process is time consuming and presents a low inter-expert agreement, causing the data to be limited in quantity and prone to bias. An automatic detector would tackle these issues by generating large amounts of objectively marked data.New MethodOur goal was to develop a sensitive, precise and robust sleep-spindle detection method. Emphasis has been placed on achieving a consistent performance across heterogeneous recordings and without the need for further parameter fine tuning. The developed detector runs on a single channel and is based on multivariate classification using a support vector machine. Scalp-electroencephalogram recordings were segmented into epochs which were then characterized by a selection of relevant and non-redundant features. The training and validation data came from the Medical Center-University of Freiburg, the test data consisted of 27 records coming from 2 public databases.ResultsUsing a sample based assessment, 53% sensitivity, 37% precision and 96% specificity was achieved on the DREAMS database. On the MASS database, 77% sensitivity, 46% precision and 96% specificity was achieved. The developed detector performed favorably when compared to previous detectors. The classification of normalized EEG epochs in a multidimensional space, as well as the use of a validation set, allowed to objectively define a single detection threshold for all databases and participants.ConclusionsThe use of the developed tool will allow increasing the data-size and statistical significance of research studies on the role of sleep-spindles.



http://ift.tt/2E7z9Lo

Intracranial rat glioma model for tumor resection and local treatment

Publication date: Available online 6 February 2018
Source:Journal of Neuroscience Methods
Author(s): Zhiqun Wu, Makoto Nakamura, Joachim K. Krauss, Kerstin Schwabe, Nadine John
BackgroundAlthough tumor resection is among the most important prognostic factors, high grade gliomas regrow in most cases. Also, resection of glial tumors in eloquent brain regions is not or only partially possible. Despite these severe restraints, however, only a few in-vivo models have been established to investigate tumor recurrence and local treatment. Here we characterize the intracranial BT4Ca rat glioma as a model for these aspects.New MethodBT4Ca cells were stereotaxically implanted into the frontal cortex of BDIX rats. Rats were than allocated to (1) a control group, which received no further treatment; (2) a catheter group, where a catheter was implanted for repeated microinjection of vehicle every 3rd day as catheter-control; (3) a resection group, where the tumor was microsurgically removed eight days after cell injection. Postoperatively, survival time, weight and general health condition were scored and the tumor size was histologically assessed.ResultsInjection of BT4Ca cells induced fast-growing tumors with a mean survival time of 16 days in the control and catheter groups. Resection significantly prolonged survival time whereby the tumor regrew in all rats. Tumor size was similar between all groups.Comparison with Existing Method(s)We here present a robust and reliable intracranial rat glioma model, which is suitable to simulate tumor recurrence after surgical resection and local treatment. Importantly, this model does not require advanced imaging or elaborate surgical techniques.ConclusionsThe intracranial BT4Ca glioma model appears to be a feasible tool to investigate tumor recurrence after resection and to test local treatment.



http://ift.tt/2EMn5jz

Comparative safety and efficacy of topical mometasone furoate with other topical corticosteroids

Abstract

Derivatives of hydrocortisone, such as mometasone furoate, a (2′) furoate-17 ester with chlorine substitutions at positions 9 and 21, have been designed to improve efficacy and reduce the incidence of adverse effects. An extensive literature search of MEDLINE, Embase and other databases was conducted to review the safety and efficacy of various formulations of topical mometasone furoate. Mometasone furoate exhibits high potency with greater anti-inflammatory activity and a longer duration of action than betamethasone. In clinical trials, mometasone furoate shows comparable or significantly better efficacy, depending on the comparator, in all indications studied in both adults and children. It is well tolerated with only transient, mild to moderate local adverse effects. It is characterised by low systemic availability due to its high lipophilicity, low percutaneous absorption and rapid hepatic biotransformation, and consequently has no significant effect on the hypothalamic-pituitary-adrenal axis. The molecular biotransformation of mometasone furoate in the skin results in a lower affinity with dermal cells than epidermal cells, which contributes to its low atrophogenicity. Sensitisation to mometasone furoate is low. Overall, mometasone furoate is a highly efficacious potent corticosteroid with a low risk of both local and systemic adverse effects.

http://ift.tt/2E87r10

Comparative safety and efficacy of topical mometasone furoate with other topical corticosteroids

Abstract

Derivatives of hydrocortisone, such as mometasone furoate, a (2′) furoate-17 ester with chlorine substitutions at positions 9 and 21, have been designed to improve efficacy and reduce the incidence of adverse effects. An extensive literature search of MEDLINE, Embase and other databases was conducted to review the safety and efficacy of various formulations of topical mometasone furoate. Mometasone furoate exhibits high potency with greater anti-inflammatory activity and a longer duration of action than betamethasone. In clinical trials, mometasone furoate shows comparable or significantly better efficacy, depending on the comparator, in all indications studied in both adults and children. It is well tolerated with only transient, mild to moderate local adverse effects. It is characterised by low systemic availability due to its high lipophilicity, low percutaneous absorption and rapid hepatic biotransformation, and consequently has no significant effect on the hypothalamic-pituitary-adrenal axis. The molecular biotransformation of mometasone furoate in the skin results in a lower affinity with dermal cells than epidermal cells, which contributes to its low atrophogenicity. Sensitisation to mometasone furoate is low. Overall, mometasone furoate is a highly efficacious potent corticosteroid with a low risk of both local and systemic adverse effects.

http://ift.tt/2E87r10

Infant case of tinea faciei caused by Microsporum canis

http://ift.tt/2EIGBxr

Necrobiosis lipoidica with mucin deposition in a patient with autoimmune thyroiditis

http://ift.tt/2FS6Rou

Decrease in eosinophils infiltrating into the skin of patients with dipeptidyl peptidase-4 inhibitor-related bullous pemphigoid

Abstract

Bullous pemphigoid (BP) is an acquired autoimmune blistering disease in which autoantibodies against epitopes in the basement membrane zone of the skin such as BP180 or BP230 are produced. Dipeptidyl peptidase (DPP)-4 inhibitors have become commonly used to treat diabetes. As DPP-4 inhibitors are more commonly prescribed for diabetes, BP related to DPP-4 inhibitors has been reported and has attracted attention. Therefore, we retrospectively investigated patients who were diagnosed with BP in order to examine characteristics of DPP-4 inhibitor-related BP (nine patients; median age, 85 years) in comparison with non-DPP-4 inhibitor-related BP (21; median age, 85 years). There was no significant difference in Bullous Pemphigoid Disease Area Index between DPP-4 inhibitor-related BP patients and non-DPP-4 inhibitor-related BP patients, except for erosions/blisters score in mucosa. Laboratory tests revealed no significant differences between DPP-4 inhibitor-related BP patients and non-DPP-4 inhibitor-related BP patients in total white blood cell count, eosinophil count, neutrophil count and the titer of anti-BP180 antibody. The number of eosinophils infiltrating into the skin was significantly lower in patients with DPP4 inhibitor-related BP than in patients with non-DPP4 inhibitor-related BP. Our results showed that DPP-4 inhibitor-related BP has some distinct pathological characteristics from BP not associated with DPP-4 inhibitor.

http://ift.tt/2ENcaXd

Editorial Board

Publication date: February 2018
Source:Pathology - Research and Practice, Volume 214, Issue 2





http://ift.tt/2nJ4Kgl

Editorial Board

Publication date: January 2018
Source:Pathology - Research and Practice, Volume 214, Issue 1





http://ift.tt/2nSVVzR

De Novo Designed Proteins for Colloidal Stabilization and Improvement of Cellular Uptake

Publication date: 2 February 2018
Source:Biophysical Journal, Volume 114, Issue 3, Supplement 1
Author(s): Tingting Zheng, Felipe Perona Martínez, Ingeborg Maria Storm, Wolf Rombouts, Joris Sprakel, Renko de Vries, Romana Schirhagl




http://ift.tt/2nJ4dLn

Randomized investigator-blinded comparative study of moisturizer containing 4-t-butylcyclohexanol and licochalcone A versus 0.02% triamcinolone acetonide cream in facial dermatitis

Summary

Background

Facial dermatitis can result from various conditions, some of which are of a chronic and relapsing nature. The use of topical corticosteroid therapy may lead to additional adverse effects.

Objective

To compare the efficacy of moisturizer containing 4-t-butylcyclohexanol, which acts as a sensitivity regulator, and licochalcone A, an anti-inflammatory agent from the licorice plant Glycyrrhiza inflata, with that of 0.02% triamcinolone acetonide (TA) for the treatment of facial dermatitis.

Methods

This was a randomized, prospective, investigator-blinded study. Eighty participants with mild to moderate facial dermatitis were randomly treated with either the test facial moisturizer or 0.02% TA twice daily for the first 2 weeks. For the subsequent 2 weeks, all patients used only the test moisturizer. Clinical assessment by investigators, bioengineering measurements, patients' subjective evaluation, and clinical photography were performed at baseline, week 2, and week 4.

Results

Both treatments showed a statistically significant improvement with regard to physician clinical assessment, skin hydration, transepidermal water loss, and patient-assessed visual analog scale after 2 and 4 weeks of treatment compared with baseline. The test facial moisturizer produced better skin hydration than TCS. The improvement in TEWL after 4 weeks of using the test moisturizer was comparable with 2-week treatment with 0.02% TA cream. However, subjective evaluation by patients indicated that TA more rapidly improved sensation sensitivity.

Conclusion

The test facial moisturizer was slower than 0.02% TA in improving facial dermatitis, but showed greater benefit in erythema control and skin hydration.

http://ift.tt/2C3YOTu

Randomized investigator-blinded comparative study of moisturizer containing 4-t-butylcyclohexanol and licochalcone A versus 0.02% triamcinolone acetonide cream in facial dermatitis

Summary

Background

Facial dermatitis can result from various conditions, some of which are of a chronic and relapsing nature. The use of topical corticosteroid therapy may lead to additional adverse effects.

Objective

To compare the efficacy of moisturizer containing 4-t-butylcyclohexanol, which acts as a sensitivity regulator, and licochalcone A, an anti-inflammatory agent from the licorice plant Glycyrrhiza inflata, with that of 0.02% triamcinolone acetonide (TA) for the treatment of facial dermatitis.

Methods

This was a randomized, prospective, investigator-blinded study. Eighty participants with mild to moderate facial dermatitis were randomly treated with either the test facial moisturizer or 0.02% TA twice daily for the first 2 weeks. For the subsequent 2 weeks, all patients used only the test moisturizer. Clinical assessment by investigators, bioengineering measurements, patients' subjective evaluation, and clinical photography were performed at baseline, week 2, and week 4.

Results

Both treatments showed a statistically significant improvement with regard to physician clinical assessment, skin hydration, transepidermal water loss, and patient-assessed visual analog scale after 2 and 4 weeks of treatment compared with baseline. The test facial moisturizer produced better skin hydration than TCS. The improvement in TEWL after 4 weeks of using the test moisturizer was comparable with 2-week treatment with 0.02% TA cream. However, subjective evaluation by patients indicated that TA more rapidly improved sensation sensitivity.

Conclusion

The test facial moisturizer was slower than 0.02% TA in improving facial dermatitis, but showed greater benefit in erythema control and skin hydration.

http://ift.tt/2C3YOTu

Is Action Execution Part of the Decision-Making Process? An Investigation of the Embodied Choice Hypothesis.

Author: Aczel, Balazs; Szollosi, Aba; Palfi, Bence; Szaszi, Barnabas; Kieslich, Pascal J.

DOI: 10.1037/xlm0000484

Publication Date: POST AUTHOR CORRECTIONS, 5 February 2018

http://ift.tt/2E8IJSp

Ginseng phytochemicals as therapeutics in oncology: Recent perspectives

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Fatima Majeed, Fozia Zahur Malik, Zaheer Ahmed, Asma Afreen, Muhammad Naveed Afzal, Nauman Khalid
During the last few decades, cancer has mushroomed as a major health issue; and almost all drugs used for its therapy are very toxic with lethal side effects. Complementary and alternative medicines gain popularity among health professionals in recent era owing to its preventive mechanism against side effect chemotherapeutic drugs. Efforts are focused by scientists to isolate compounds from medicinal plant that have chemotherapeutic attributes; and ability to neutralize the side effects of chemotherapy. Ginseng is an oriental medicinal recipe from Araliceae family and Panax species. The chemotherapeutic effect of ginsenoside is resultant of its appetites, anti-proliferative, anti-angiogenic, anti-inflammatory and anti-oxidant properties. The anticancer effect of ginseng is proven in various types of cancer, including; breast, lung, liver, colon and skin cancer. It increases the mitochondrial accumulation of apoptosis protein and downregulate the expression of anti-apoptotic protein. It also aids in the reduction of alopecia, fatigue and nausea, the known side effects of chemotherapeutic drugs. The aim of the present review is to provide the brief review of the recent researches related to mechanism of action of ginseng in different types of cancer as complementary and alternative medicine on different body organs.

Graphical abstract

http://ift.tt/2BIA3QO

MicroRNA-204 protects H9C2 cells against hypoxia/reoxygenation-induced injury through regulating SIRT1-mediated autophagy

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Ruixia Qiu, Wen Li, Yunhai Liu
Ischemia/reperfusion (I/R) injury is a main cause of acute myocardial infarction, and the pathogenesis of I/R injury is still not definitely confirmed. In the present study, we aimed to explore the roles of miR-204 in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury in vitro. The H9C2 cells were subjected to hypoxia for 12 h followed by reoxygenation for another 24 h, and we found that miR-204 was significantly down-regulated after H/R treatment. Transfection of miR-204 mimics attenuated the H/R-induced impaired cell viability and increased apoptosis rates. Furthermore, SIRT1 was identified as a direct target of miR-204, and its expression is negatively regulated by miR-204. Forced expression of SIRT1 could partly rescue the effects of miR-204 on H/R-induced apoptosis and autophagy. Taken together, our study first revealed that overexpression of miR-204 has a protective effect against myocardial I/R injury.



http://ift.tt/2Bgg8b9

Long non-coding RNA ENST01108 promotes carcinogenesis of glioma by acting as a molecular sponge to modulate miR-489

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Dawei Xu, Ruihua Liu, Lei Meng, Yi Zhang, Guangjian Lu, Pengju Ma
Gliomas are the most common primary malignant tumor in the adult central nervous system with poor prognosis. Exploring novel biomarkers and elucidating underlying molecular mechanisms to provide effective therapeutic methods is in an urgent need. Long noncoding RNAs (lncRNAs) is involved in various human diseases including cancer. However, studies on lncRNAs and gliomas are limited. In this study, we explored the expression patterns of lncRNAs in 4 pairs of glioma samples and adjacent normal tissues via microarray and chose the most up-regulated lncRNA ENST01108 (ENST01108) to further verify its oncogenic role in glioma. Clinical data suggest that ENST01108 is closely associated with the malignant status in glioma. In vitro experiment demonstrated that overexpression of ENST01108 promoted glioma cell proliferation, migration, invasion, EMT process and survival, while knockdown of ENST01108 has an opposite effect, indicating that ENST01108 serves as an oncogenic property in glioma carcinogenesis. Further, we identified miR-489 as a direct target of ENST01108 and ENST01108 negatively regulate miR-489 by act as a sponge. SIK1 is verified as the direct target of miR-489 and it is negatively regulated by miR-489. ENST01108 also positively regulate SIKI and it promotes SIKI expression by suppressing miR-489. Taken together, the reciprocal repression of ENST011081 and miR-489 may be served as potential targets for cancer therapeutics in glioma.



http://ift.tt/2BLGtyw

Polyphenol-enriched extract of Rosa rugosa Thunb regulates lipid metabolism in diabetic rats by activation of AMPK pathway

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Liu Liu, Mireguli Yasen, Dan Tang, Jianping Ye, Haji Akber Aisa, Xuelei Xin
This study was designed to investigate the mechanism of polyphenol-enriched extract of Rosa rugosa Thunb (RPE) in the control of dyslipidemia in diabetic rats. RPE was tested at three dosages (37.5 mg/kg, 75 mg/kg and 150 mg/kg) in the rat dyslipidemia model established with high fat diet feeding in combination with STZ injection (30 mg/kg). The RPE effect was evaluated after 4 weeks of treatment. In the RPE-treated rats, hepatic total cholesterol (TC) and triglyceride (TG) were significantly reduced, lipoprotein lipase (LPL) and liver lipase (HL) were significantly increased. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were decreased in the serum. Those effects of RPE were observed primarily at the mediate and high dosages. Expression of FGF21 was increased in the liver tissue and hepatic cell line 1c1c7 by RPE. The signals of p-AMPK, p-ACC, ACC, p-SIRT, and PGC-1α were significantly induced in the liver by RPE. The results suggest that RPE may improve hepatic steatosis and liver function by induction of AMPK signaling activity in the control of dyslipidemia.



http://ift.tt/2BcHkaq

Ghrelin attenuates ultraviolet B radiation-induced impairment in capacities of epidermal stem cells

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Yue-hui Wang, Cheng-kuan Sun, Xiang-lan Li, Yan Huang, Jing Sun
Persistent exposure to solar ultraviolet radiation (UVR) causes continuous damages to skin, including progressive impairment of epidermal stem cells (ESCs) capacities. Ghrelin is the only known endogenous orexigenic hormone, which has displayed its various pharmacological functions. In the current study, we found that the specific receptor of ghrelin, growth hormone secretagogue receptor (GHS-R), is expressed in ESCs. Interestingly, GHS-R expression is significantly upregulated in response to ultraviolet B (UVB) radiation. We also found that ghrelin treatment prevented UVB radiation-induced reduction in cell viability and the release of lactate dehydrogenase (LDH). Additionally, ghrelin reduced UVB radiation-induced generation of reactive oxygen species (ROS) and restored the intracellular level of reduced glutathione (GSH). UVB radiation significantly suppressed the expressions of integrin β1 and Krt19, the two major ESC markers, which were restored by ghrelin. Notably, knockdown of GHS-R abolished the effects of ghrelin on the expressions of integrin β1 and Krt19, suggesting the involvement of GHS-R. Also, we found that ghrelin treatment inhibited UVB radiation- induced reduction of Wnt1, Wnt3a, Myc, and cyclin D1 at both the mRNA levels and the protein levels. Taken together, our findings identify a novel function of ghrelin on maintaining the capacities of ESCs against UVB radiation.



http://ift.tt/2BK7DG8

Therapeutic efficacy of osthole against dinitrobenzene sulphonic acid induced-colitis in rats

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Hanan Khairy, Hanan Saleh, Abeer M. Badr, Mohamed-Assem S. Marie
Several mediators were associated with the pathogenesis of inflammatory bowel disease such as oxidative stress through the production of reactive oxygen metabolites, neutrophils infiltration and release of pro-inflammatory cytokines. This study was designed to investigate the therapeutic efficacy of osthole against dinitrobenzene sulfonic acid (DNBS) induced-colitis in rats through its anti-oxidant and anti-inflammatory properties. Colitis was induced in rats by single intracolonic instillation of (250 μl DNBS-25 mg/rat). Then 4 days later, rats were received oral administration of either (osthole 50 mg/kg), (sulfasalazine 500 mg/kg) or both in combination for 7 consecutive days. Body weight, some hematological parameters, colonic malondialdehyde (MDA) and myeloperoxidase activity (MPO), antioxidant parameters, colon injury and mucosa architectures were assessed. T helper (Th1)-related cytokines [Tumor necrosis factor alpha (TNF-α) and interferon-gamma (INF-γ)], Th2-relarted cytokines (interleukin-4 [IL-4 and IL-10], and Th-17 related cytokines [IL-17] were determined by ELISA. Osthole significantly improved the loss in body weight. That was accompanied with a remarkable amelioration of the disruption of the colonic architecture as well as a significant improvement in the antioxidant defense system. A reduction in MPO and MDA was observed in flamed colon. Treatment with either osthole or combination therapy showed suppressive activities on pro-inflammatory Th2-related cytokines and upregulation of anti-inflammatory Th2-related cytokines The results of this study suggest that osthole exert beneficial therapeutic effect in experimental colitis and improved the efficacy of the synthetized drugs such as sulfasalazine. Therefore, osthole may have a valuable sound in the treatment of inflammatory bowel disease.



http://ift.tt/2BfGTMR

Icariside II attenuates myocardial fibrosis by inhibiting nuclear factor-κB and the TGF-β1/Smad2 signalling pathway in spontaneously hypertensive rats

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Shu Fu, Ye-Li Li, Yu-Ting Wu, Yun Yue, Zhi-Qiang Qian, Dan-Li Yang
Studies have demonstrated that icariin plays important roles in preventing hypertension and improving myocardial hypertrophy, inflammatory and infiltration. Icariside (ICS II) is the main metabolite of icariin, which has anti-inflammatory and anti-oxidant activities and protects against ischaemic brain injury. Whether ICS II improves myocardial fibrosis in spontaneously hypertensive rats (SHRs) and the related mechanism remain unknown. Some studies have suggested that TGF-β and the nuclear factor κB signalling pathway play a key role in the progression of myocardial fibrosis. Therefore, in the current study, we aimed to evaluate the effects of ICS II on induced myocardial fibrosis in SHRs and explore the mechanism underlying this activity. The SHRs were treated with ICS II (4, 8, and 16 mg/kg) via daily gavage for 12 weeks. Left ventricular function was detected using the Vevo2100 system, and the collagen area was measured by Masson staining. The results indicated that ICS II markedly improved left ventricular function and decreased the left ventricular myocardial collagen area compared with the SHR group. To further investigate the mechanism underlying this activity, we measured the protein expression of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), Smad2, inhibitory κB (IκB), and nuclear factor κB (NF-κB) p65 by Western blot. The results showed that ICS II inhibited NF-κB p65 expression and the TGF-β1/Smad2 signalling pathways. In conclusion, the present results suggest that ICS II suppresses myocardial fibrosis in SHRs, and this effect might be at least partially mediated through suppression of NF-kB signalling and the TGF-β1/Smad2 signalling pathway.



http://ift.tt/2BKTKaH

miR-145 overexpression triggers alteration of the whole transcriptome and inhibits breast cancer development

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Peng Ye, Yu Shi, Nairui An, Qian Zhou, Juan Guo, Xinghua Long
Cumulative evidence has associated microRNA (miRNA) with cancer development, and among those miRNAs, miR-145 has been identified as an anti-oncomiRNA. However, the comprehensive mechanisms of action of miR-145 in breast cancer development have not yet been fully elucidated. Herein, we performed next-generation sequencing to detect the expression profiles of the transcriptome and conducted cellular function experiments after miR-145 overexpression. The results verified the inhibitory effects of miR-145 on breast cancer cell proliferation, colony formation, migration and invasion. Sequencing data revealed that miR-145 triggered the alteration of the whole transcriptome and further led to regulation of the competing endogenous RNA (ceRNA) network. Our study also identified a list of 49 target mRNAs of miR-145 and specific non-coding RNAs, which could be utilized as potential breast cancer biomarkers. This study might serve as a significant platform for further research on miR-145 along with the ceRNA network in breast cancer.



http://ift.tt/2BeyPf2

Annona muricata Linn. leaf as a source of antioxidant compounds with in vitro antidiabetic and inhibitory potential against α-amylase, α-glucosidase, lipase, non-enzymatic glycation and lipid peroxidation

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Allisson Benatti Justino, Natália Carnevalli Miranda, Rodrigo Rodrigues Franco, Mário Machado Martins, Neide Maria da Silva, Foued Salmen Espindola
Annona muricata leaves are used in traditional medicine to manage diabetes mellitus and its complications. The aim of this study was to evaluate the potential in vitro antidiabetic properties of Annona muricata leaf by identifying its main phytochemical constituents and characterizing the phenolic-enriched fractions for their in vitro antioxidant capacity and inhibitory activities against glycoside and lipid hydrolases, advanced glycation end-product formation and lipid peroxidation. Ethanol extract of A. muricata leaf was subjected to a liquid-liquid partitioning and its fractions were used in enzymatic assays to evaluate their inhibitory potential against α-amylase, α-glucosidase and lipase, as well as their antioxidant (DPPH, ORAC, FRAP and Fe²⁺-ascorbate-induced lipid peroxidation assays) and anti-glycation (BSA-fructose, BSA-methylglyoxal and arginine-methylglyoxal models) capacities. In addition, identification of the main bioactive compounds of A. muricata leaf by HPLC-ESI-MS/MS analysis was carried out. Ethyl acetate (EtOAc) and n-butanol (BuOH) fractions showed, respectively, antioxidant properties (ORAC 3964 ± 53 and 2707 ± 519 μmol trolox eq g⁻¹, FRAP 705 ± 35 and 289 ± 18 μmol trolox eq g⁻¹, and DPPH IC50 4.3 ± 0.7 and 9.3 ± 0.8 μg mL⁻¹) and capacity to reduce liver lipid peroxidation (p < .01). Also, EtOAc and BuOH, respectively, inhibited glycation in BSA-fructose (IC50 45.7 ± 13.5 and 61.9 ± 18.2 μg mL⁻¹), BSA-methylglyoxal (IC50 166.1 ± 21.6 and 413.2 ± 49.5 μg mL⁻¹) and arginine-methylglyoxal (IC50 437.9 ± 89.0 and 1191.0 ± 199.0 μg mL⁻¹) assays, α-amylase (IC50 9.2 ± 2.3 and 6.1 ± 1.6 μg mL⁻¹), α-glucosidase (IC50 413.1 ± 121.1 and 817.4 ± 87.9 μg mL⁻¹) and lipase (IC50 74.2 ± 30.1 and 120.3 ± 50.5 μg.mL⁻¹), and presented lower cytotoxicity, when compared to the other fractions and crude extract. Various biomolecules known as potent antioxidants were identified in these fractions, such as chlorogenic and caffeic acids, procyanidins B2 and C1, (epi)catechin, quercetin, quercetin-hexosides and kaempferol. This study presents new biological activities not yet described for A. muricata, which contributes to the understanding of the potential effectiveness in the use of the A. muricata leaf, especially its polyphenols-enriched fractions, for the management of diabetes mellitus and its complications.

Graphical abstract

http://ift.tt/2BHTcCp

Ginsenoside Rb2 promotes glucose metabolism and attenuates fat accumulation via AKT-dependent mechanisms

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Shanshan Dai, Yilian Hong, Jing Xu, Yi Lin, Qiya Si, Xuejiang Gu
Ginsenosides, the major active constituents of ginseng, have been demonstrated possess anti-diabetic, anti-inflammatory effects. Ginsenoside Rb2 (Rb2) is the most abundant saponin in Panax ginseng, this study investigates the role of Rb2 in the anti-hyperglycemic mechanism of insulin-sensitive cell lines 3T3-L1 adipocytes as well as high fat diet-induced obesity mice. Glucose uptake of 3T3-L1 adipocytes was measured. The insulin signaling cascade, including insulin AKT, insulin receptor (IR) beta-subunit, IR substrate (IRS) -1, phosphatidylinositol 3-kinase (PI3K) were also examined. TNF-α-treated 3T3-L1 adipocytes were used as an insulin resistant model in which p-AKT, c-Jun NH2-terminal kinase (JNK), MAPK, and nuclear factor (NF) -κB signaling cascades were examined. As an in vivo study, C57BL/6J mice were fed with a high-fat diet for 9 weeks, with or without Rb2 supplementation. Then we investigated the effects of Rb2 on glycometabolism in these high fat diet-induced obesity mice. Our results demonstrate Rb2 increases glucose uptake in 3T3-L1 adipocytes, independent of insulin receptor β-subunit (IRβ) and principally through the insulin receptor substrate (IRS)-1-phosphatidylinositol 3-kinase (PI3K)-AKT/PKB pathway. Rb2 inhibited TNF-α-induced activation of MAPK and nuclear factor (NF)-κB signaling pathway as well as the expression of inflammatory factors. In high fat diet-induced obesity mice, Rb2 attenuated fat mass and regulated insulin resistance. In mouse adipose tissue, Rb2 phosphorylation of AKT was correlated with glycometabolism. Furthermore, Rb2 attenuates insulin resistance in 3T3-L1 adipocytes, reduces fat mass, and improves insulin sensitivity in high fat diet-obesity mice.



http://ift.tt/2BeyQ2A

LncRNA Uc.173 is a key molecule for the regulation of lead-induced renal tubular epithelial cell apoptosis

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Jiabi Qin, Huacheng Ning, Yao Zhou, Yue Hu, Bo Huang, Yue Wu, Ruixue Huang
Transcribed ultra-conserved region (T-UCR) transcripts are a novel class of long non-coding RNAs (lncRNAs) transcribed from ultra-conserved region which is highly conserved in human, rat, and mouse genome. LncRNA UC.173 has been found significantly down-regulated in lead-exposed population and lead-exposed animal mode, and had an inhibitory effect on lead-induced nerve cell apoptosis. We supposed that lncRNA UC.173 had an inhibitory effect on lead-induced renal tubular epithelial cell apoptosis. Thus, the aim of our study was to explore the function of lncRNA UC.173 in lead-exposed renal tubular epithelial cells. In our results, lead exposure inhibited renal tubular epithelial cells viability and promoted cell apoptosis and apoptosis-associated genes expression, but no effect on cell-cycle distribution. Lead exposure inhibited the expression of lncRNA UC.173 in renal tubular epithelial cells, and the inhibition effect was time-dependent and concentration-dependent. Up-regulation of lncRNA UC.173 had no effect on renal tubular epithelial cell viability, cell cycle and apoptosis, but significantly rescued lead-induced inhibition of renal tubular epithelial cell viability and suppressed lead-induced cell apoptosis. In summary, our experiments suggest that lncRNA UC.173 is certainly involved in the regulation of lead-induced renal tubular epithelial cell apoptosis, which may supply a new strategy to minimize lead-induced nephrotoxicity.



http://ift.tt/2BHBor2

Tumor suppressive ZBTB4 inhibits cell growth by regulating cell cycle progression and apoptosis in Ewing sarcoma

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Yongxin Yu, Ruguo Shang, Yunzhou Chen, Jiehua Li, Zhichao Liang, Jianwei Hu, Kai Liu, Chao Chen
Increasing studies identify that zinc finger and BTB domain containing 4 (ZBTB4) functions as a tumor suppressor in human cancer. Underexpression of ZBTB4 is correlated with poor survival of breast cancer patients. However, the expression of ZBTB4 and its possible function remain unknown in Ewing sarcoma (ES). To clarify these issues, we investigated the expression difference between ES and normal tissues based on Gene Expression Omnibus (GEO) data from R2: Genomics Analysis and Visualization Platform (http://r2.amc.nl). GEO data (GSE68776) indicated that the expression of ZBTB4 in ES tissues was prominently lower compare to normal tissues. Our data further confirmed the underexpression of ZBTB4 in ES tissues. GEO data (GSE63157 and GSE17679) demonstrated that ZBTB4 underexpression predicted a obvious shorter overall survival and event-free survival of ES patients. Interestingly, the expression of ZBTB4 was inversely correlated with proliferation makers Ki-67 and proliferating cell nuclear antigen (PCNA) in ES tissues. In vitro, ZBTB4 overexpression inhibited cell proliferation, and induced cell cycle arrest at G1 phase and apoptosis in SK-ES-1 and RD-ES cells. Moreover, ZBTB4 restoration suppressed the tumor growth of ES in mice. An inversely correlation between ZBTB4 and Survivin expression was observed in ES tissues. ZBTB4 overexpression reduced Survivin abundance in ES cells. Notably, Survivin restoration reversed the regulatory effect of ZBTB4 on ES cell proliferation, cell cycle progression and apoptosis. To conclude, our data indicated that ZBTB4 exhibited a tumor suppressive role in ES possibly by reducing Survivin expression. ZBTB4/Survivin axis might serve as a therapeutic target for ES.



http://ift.tt/2BdF036

Trends of incidence, mortality, and survival of multiple myeloma in Switzerland between 1994 and 2013

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Martin Andres, Anita Feller, Volker Arndt
BackgroundTreatment of multiple myeloma has changed considerably over the last two decades with remarkable reduction in mortality rates in clinical trials and in population-based studies. Since health care systems and patient management differ between countries, population-based data from cancer registries with high coverage may provide further insight into real-life achievements and unmet needs. We report on the first population-based nation-wide study of incidence, mortality and survival of multiple myeloma in Switzerland covering the era of autologous stem cell transplantation and the first proteasome inhibitors and immunomodulatory drugs.MethodsWe performed a retrospective registry study with data from the National Institute for Cancer Epidemiology and Registration (NICER) database in Switzerland from 1994 to 2013.ResultsWe identified 5770 patients with multiple myeloma. Incidence has increased from 419 new cases per year in 1994–1998 to 557 new cases per year in 2009–2013 while the age-adjusted incidence rate remained stable at 4.7–5.0 per 100′000 person-years. Five- and 10-year relative survival increased from 32.6% (95%CI 29.3–36.0) and 17.8% (95%CI 14.9–21.0) in 1994–1998 to 46.4% (95%CI 43.3–49.3) and 25.0% (95%CI 21.9–28.3) in 2009–2013.ConclusionThe increase in incidence can be attributed to demographic changes. There is a trend to longer relative survival in all age groups with substantial increase in myeloma patients aged less than 75 years and only minimal changes in older persons.



http://ift.tt/2Ep6gxy

Esophageal cancer male to female incidence ratios in Africa: A systematic review and meta-analysis of geographic, time and age trends

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Daniel R.S. Middleton, Liacine Bouaoun, Rachel Hanisch, Freddie Bray, Charles Dzamalala, Steady Chasimpha, Diana Menya, Charles Gombé Mbalawa, Guy N'Da, Mathewos A. Woldegeorgis, Ramou Njie, Moussa Koulibaly, Nathan Buziba, Josefo Ferro, Hassan Nouhou, Femi Ogunbiyi, Henry R. Wabinga, Eric Chokunonga, Margaret Z. Borok, Anne R. Korir, Amos O. Mwasamwaja, Blandina T. Mmbaga, Joachim Schüz, Valerie A. McCormack
Esophageal squamous cell carcinoma (ESCC) remains the predominant histological subtype of esophageal cancer (EC) in many transitioning countries, with an enigmatic and geographically distinct etiology, and consistently elevated incidence rates in many Eastern and Southern African countries. To gain epidemiological insights into ESCC patterns across the continent, we conducted a systematic review and meta-analysis of male-to-female (M:F) sex ratios of EC age-standardised (world) incidence rates in Africa according to geography, time and age at diagnosis. Data from 197 populations in 36 countries were included in the analysis, based on data from cancer registries included in IARC's Cancer Incidence in Five Continents, Cancer in Africa and Cancer in Sub-Saharan Africa reports, alongside a systematic search of peer-reviewed literature. A consistent male excess in incidence rates overall (1.7; 95% CI: 1.4, 2.0), and in the high-risk Eastern (1.6; 95% CI: 1.4, 1.8) and Southern (1.8; 95% CI: 1.5, 2.0) African regions was observed. Within the latter two regions, there was a male excess evident in 30–39 year olds that was not observed in low-risk regions. Despite possible referral biases affecting the interpretability of the M:F ratios in place and time, the high degree of heterogeneity in ESCC incidence implies a large fraction of the disease is preventable, and directs research enquiries to elucidate early-age exposures among young men in Africa.



http://ift.tt/2E9t94L

Development and validation of a prognostic index for survival in non-small cell lung cancer: Results from a Tunisian cohort study

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Ghassen Soussi, Nissaf Ben Alaya, Nawel Chaouch, Hajer Racil
IntroductionDespite the continuous efforts made with the TNM system, the issue of heterogeneity of prognosis within the stages of non-small cell lung cancer (NSCLC) could not be resolved. Our aim was to identify prognostic factors and develop an index to predict NSCLC survival with greater accuracy.MethodsWe conducted a survival study over 5 years on patients with NSCLC. Kaplan–Meier analysis followed by Cox regression modelling were used. Prognostic indices were derived, using either an additive or a multiplicative pattern, and were compared by their receiver operating characteristics (ROC) curves. We then proceeded to a risk stratification and validation of the index on the derivation cohort.ResultsTwo hundred and sixty-two NSCLC patients were included. Two models were constructed, using the following nine variables as prognostic factors: age, performance status, haemoglobin level, leucocyte count, calcium, lactate dehydrogenase, alkaline phosphatase levels, histological type and TNM stage. Four prognostic indices were derived, and the best one was picked and validated on a population of five risk groups. The higher the risk group, the shorter the survival.ConclusionsThis novel and simple prognostic tool could predict survival more accurately in patients with NSCLC.



http://ift.tt/2nPaLY5

Upper Lid Thick Skin Blepharoplasty

Facial plast Surg 2018; 34: 043-049
DOI: 10.1055/s-0037-1615824

While many of the basic tenants of upper lid blepharoplasty remain constant regardless of skin type, the thick-skinned eyelid patient requires special consideration. The brow may be naturally lower in the thick-skinned patient. These patients are more prone to having the brow pulled downward while attempting to remove redundant skin. There may also be more fat in the medial and central compartments. There may be fat in a lateral compartment overlying the lacrimal gland. Patient's expectations for a deep lid sulcus and complete excision of redundant skin may not be possible. They are more prone to an observable scar, a small dog ear at the lateral wound edge, and prolonged postoperative lid edema. Patients with lifelong upper lid fullness must get some input from significant others because their upper face aesthetic will change. In these patients, the eyelid surgery is not a rejuvenation, but a creation.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2BKeGyP

Integrated Management of the Thick-Skinned Rhinoplasty Patient

Facial plast Surg 2018; 34: 003-008
DOI: 10.1055/s-0037-1617445

Patients with thick skin are a challenge in facial plastic surgery. Rhinoplasty is still the most frequently performed facial plastic procedure worldwide and it becomes very difficult to obtain optimal consistent results in these patients. A systematic presurgical skin evaluation is performed dividing skin into type I–III depending on the elasticity, oiliness, presence of skin alterations, size of skin pores, and laxity. Depending on the skin type, presurgical, surgical, and postsurgical management of the epidermis and dermis is defined. Preconditioning and treating thick skin can improve postsurgical results and reduce postsurgical unwanted results.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2BcwYHA

Indications and Use of Isotretinoin in Facial Plastic Surgery

Facial plast Surg 2018; 34: 075-081
DOI: 10.1055/s-0037-1617446

Isotretinoin is a first generation retinoid with pleiotropic effects on keratinocyte differentiation, proliferation, and activity of sebaceous glands. For years, there has been intense debate on whether the use of isotretinoin combined with cosmetic or surgical procedures is safe and potentially more efficient than either therapy alone. Due to delays in wound healing and keloid formation, conservative recommendations were not to combine isotretinoin with any plastic surgery or local treatment at 6 to 12 months after discontinuation of the drug. However, there is increasing evidence that a combination approach is not only safe, but may also provide excellent cosmetic outcomes in acne scars, sebaceous gland hyperplasia, and thick-skinned patients undergoing facial plastic surgery. In particular, low-dose regimens of isotretinoin may offer advantages over standard dosage treatments because of better tolerability and safety in long-term use adjunct with surgical interventions. In this article, the authors aim to summarize the current evidence on the use of isotretinoin in facial plastic surgery and to share their experience from selected patients.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2BKLebJ

Use of 5-Fluorouracil for Management of the Thick-Skinned Nose

Facial plast Surg 2018; 34: 009-013
DOI: 10.1055/s-0037-1617420

Patients with a thick nasal skin and soft tissue envelope can have unpredictable results and irregular scarring after rhinoplasty surgery. These patients typically have sebaceous tissue over the nasal tip and are particularly susceptible to soft tissue polly beak formation and excess scar tissue in the radix, tip, and septum. Targeted injections of 5-fluorouracil alone or mixed with low concentrations of steroid can be useful to prevent and treat excess postoperative scar tissue deposition. Ideally, four to six injections are performed every 1 to 4 weeks beginning 1 week postoperatively. The injections are most beneficial when performed within the first 3 months after surgery. Even a single injection may improve outcomes with minimal side effects.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2BciTKq

Surgical Approach to the Thick Nasolabial Folds, Jowls and Heavy Neck—How to Approach and Suspend the Facial Ligaments

Facial plast Surg 2018; 34: 059-065
DOI: 10.1055/s-0037-1615283

Patients with thick skin typically present with a redundant, baggy, lax skin envelope together with prominent nasolabial folds, jowls, and a heavy neck. Durable and natural-appearing rejuvenation is not possible unless the deformities are addressed adequately and harmoniously in these patients. Traditional superficial musculoaponeurotic system techniques do not include surgical release of the zygomatic cutaneous ligaments and repositioning of descendent malar fat pad, and may lead to an unbalanced, unnatural appearance and the lateral sweep phenomenon. Additional attempts to improve unopposed nasolabial folds such as fat grafting to malar region are more likely to result with a "stuffed" look, far from a natural and rejuvenated appearance, and must therefore be avoided. The facelift techniques including true release of the anchoring ligaments of the midface and allowing adequate repositioning of saggy tissues are ideal for these patients to obtain harmonious, natural result. Despite the extensive dissections, maximal release, and maximal lateral pull, additional maneuvers, e.g., platysmaplasty, subplatysmal fat removal, or partial resection of submandibular glands may be required for satisfying result in patients with heavy neck. In this article, the authors outline the relevant anatomy of the facial retaining ligaments and their implications to surgical management of patients with heavy skin are discussed.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2BKKcMX

Reducing Periorbital Edema and Ecchymosis after Rhinoplasty: Literature Review and Personal Approach

Facial plast Surg 2018; 34: 014-021
DOI: 10.1055/s-0037-1617444

Postoperative periorbital edema and ecchymosis are most bothersome to rhinoplasty patients. The degree of swelling and bruising is influenced by several factors, and numerous prophylactic and therapeutic measures have been described in the literature. This article reviews the current literature and concludes with the author's suggestions on how to best minimize postoperative periorbital edema and ecchymosis.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2BevrAS

Managing the Thick Skin in Facial Plastic Surgery

Facial plast Surg 2018; 34: 001-002
DOI: 10.1055/s-0037-1617447

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2BJrg0S

Surgical Management of the Thick-Skinned Nose

Facial plast Surg 2018; 34: 022-028
DOI: 10.1055/s-0037-1617421

When executed properly, open structure rhinoplasty can dramatically improve the consistency, durability, and quality of the cosmetic surgical outcome. Moreover, in expert hands, dramatic transformations in skeletal architecture can be accomplished with minimal risk and unparalleled control, all while preserving nasal airway function. While skeletal enhancements have become increasingly more controlled and precise, the outer skin-soft tissue envelope (SSTE) often presents a formidable obstacle to a satisfactory cosmetic result. In noses with unusually thick skin, excessive skin volume and characteristically hostile healing responses frequently combine to obscure or sometimes even negate cosmetic skeletal modifications and taint the surgical outcome. For this challenging patient subgroup, care must be taken to optimize the SSTE using a graduated treatment strategy directed at minimizing skin thickness and controlling unfavorable healing responses. When appropriate efforts are implemented to manage thick nasal skin, cosmetic outcomes are often substantially improved, sometimes even negating the ill-effects of thick skin altogether.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2BbPfVH

Surgical Tips for the Management of the Wide Nasal Base

Facial plast Surg 2018; 34: 029-035
DOI: 10.1055/s-0037-1621714

Alar base reduction (ABR) was first described by Weir in 1892, but continues to be a controversial topic in rhinoplasty in terms of optimal techniques. The authors describe the techniques for ABR including internal, external and combined ABR, flare excisions, and alar hooding reductions. The techniques described have resulted in consistent outcomes with acceptable scarring and high patient satisfaction.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2BdyMjK

Cool Atmospheric Plasma (J-Plasma) and New Options for Facial Contouring and Skin Rejuvenation of the Heavy Face and Neck

Facial plast Surg 2018; 34: 066-074
DOI: 10.1055/s-0037-1621713

Treating patients with heavy or thick features comes with challenges not present in those patients lacking these physical characteristics. The authors report our experience with cool atmospheric plasma for facial contouring and skin rejuvenation of the heavy face and neck including rhinophyma. Cool atmospheric plasma is generated by running helium gas over radiofrequency energy. The resulting plasma is a fourth state of matter and has enhanced clinical effects for ablation and thinning of skin and soft tissues as well of contouring and tightening of deeper soft tissues and fascia. Cool helium plasma has been a very effective tool for skin rejuvenation and skin tightening as well as using it as a tool for nonexcisional microinvasive face and neck rejuvenation. Future research may indicate that it can help treat primary or recurrent superficial cutaneous malignancies.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2BIXw4f

Management of the Heavy Brows: Long-Term Surgical Options

Facial plast Surg 2018; 34: 036-042
DOI: 10.1055/s-0037-1617422

One of the first signs of aging belongs to the upper third of the face. With the aging process, mestizo facial features become more prominent. The thicker skin-soft tissue envelope (S-STE) has a tendency to sag more, hooding of the eyelids tends to be more pronounced, and there is a tendency for eyebrows to droop, specifically the tail of the brows, because of the loss of support. A "tired" or "sad" look implies that the complex eyebrow-upper eyelid is showing one or more of these signs. Different surgical as well as non-surgical techniques have been described to treat this area, every one of them aiming at making the patient look rested and natural. The objective of this study is to describe a technique for endoscopic brow lifting, consisting on minimal incisions, a biplanar dissection, and a different fixation technique designed for helping reshape the brow. This particular surgical technique has shown the advantage of being minimally invasive and effective. Careful analysis of the patient should be made to decide both the technique and the changes desired by the patient and the surgeon. The authors believe the technique described is another option for approaching and fixating the heavy eyebrows in mestizo patients.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2BdjPye

Brainstem Injury in Pediatric Patients With Posterior Fossa Tumors Treated With Proton Beam Therapy and Associated Dosimetric Factors

Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Michelle S. Gentile, Beow Y. Yeap, Harald Paganetti, Claire P. Goebel, Dillon E. Gaudet, Sara L. Gallotto, Elizabeth A. Weyman, Michael L. Morgan, Shannon M. MacDonald, Drosoula Giantsoudi, Judith Adams, Nancy J. Tarbell, Hanne Kooy, Torunn I. Yock
PurposeProton radiation therapy is commonly used in young children with brain tumors for its potential to reduce late effects. However, some proton series report higher rates of brainstem injury (0%-16%) than most photon series (2.2%-8.6%). We report the incidence of brainstem injury and a risk factor analysis in pediatric patients with posterior fossa primary tumors treated with proton radiation therapy at our institution.Methods and MaterialsThe study included 216 consecutive patients treated between 2000 and 2015. Dosimetry was available for all but 4 patients. Grade 2 to 5 late brainstem toxicity was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.ResultsThe histologies include medulloblastoma (n=154, 71.3%), ependymoma (n=56, 25.9%), and atypical teratoid rhabdoid tumor (n=6, 2.8%). The median age at irradiation was 6.6 years (range, 0.5-23.1 years); median dose, 54 gray relative biological effectiveness (Gy RBE) (range, 46.8-59.4 Gy RBE); and median follow-up period, 4.2 years (range, 0.1-15.3 years) among 198 survivors. Of the patients, 83.3% received chemotherapy; 70.4% achieved gross total resection. The crude rate of injury was 2.3% in all patients, 1.9% in those with medulloblastoma, 3.6% in those with ependymoma, and 0% in those with atypical teratoid rhabdoid tumor. The 5-year cumulative incidence of injury was 2.0% (95% confidence interval, 0.7%-4.8%). The median brainstem dose (minimum dose received by 50% of brainstem) in the whole cohort was 53.6 Gy RBE (range, 16.5-56.8 Gy RBE); maximum point dose within the brainstem (Dmax), 55.2 Gy RBE (range, 48.4-60.5 Gy RBE); and mean dose, 50.4 Gy RBE (range, 21.1-56.7 Gy RBE). In the 5 patients with injury, the median minimum dose received by 50% of the brainstem was 54.6 Gy RBE (range, 50.2-55.1 Gy RBE); Dmax, 56.2 Gy RBE (range, 55.0-57.1 Gy RBE); mean dose, 51.3 Gy RBE (range, 45.4-54.4 Gy RBE); and median volume of the brainstem receiving ≥55 Gy RBE (V55), 27.4% (range, 0%-59.4%). Of the 5 patients with injury, 4 had a brainstem Dmax in the highest quartile (≥55.8 Gy RBE, P = .016) and a V55 in the highest tertile (>6.0%) of the cohort distribution (P = .047). Of the 5 patients with injury, 3 were aged >6 years (age range, 4.1-22.8 years), and 4 of 5 patients received chemotherapy and achieved gross total resection.ConclusionsThe incidence of injury in pediatric patients with posterior fossa tumors is consistent with previous reports in the photon setting. Our data suggest that when Dmax and V55 are kept <55.8 Gy RBE and ≤6.0%, respectively, the 5-year rate of radiation brainstem injury would be <2%.



http://ift.tt/2FQfr76

In Reply to Daisne et al

Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Jean-Emmanuel Bibault, Philippe Giraud, Magali Morelle, Lionel Perrier, Marius Huguet




http://ift.tt/2EKLeXU

Stereotactic Radiosurgery for Resected Brain Metastases: New Evidence Supports a Practice Shift, but Questions Remain

Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Giuseppe Minniti, Scott G. Soltys, Lia M. Halasz, John C. Breneman, Michael Chan, Nadia N. Laack, John P. Kirkpatrick




http://ift.tt/2E7Wtsc

Enhancing Radiation Therapy Through Cherenkov Light-Activated Phototherapy

Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Suk W. Yoon, Vadim Tsvankin, Zachary Shrock, Boyu Meng, Xiaofeng Zhang, Mark Dewhirst, Peter Fecci, Justus Adamson, Mark Oldham
PurposeThis work investigates a new approach to enhance radiotherapy through a photo therapeutic agent activated by Cherenkov light produced from the megavoltage photon beam. The process is termed Radiotherapy Enhanced with Cherenkov photo-Activation (RECA). RECA is compatible with various photo-therapeutics, but here we focus on use with psoralen, an ultraviolet activated therapeutic with extensive history of application in superficial and extracorporeal settings. RECA has potential to extend the scope of psoralen treatments beyond superficial to deep seated lesions.Methods and MaterialsIn vitro studies in B16 melanoma and 4T1 murine breast cancer cells were performed to investigate the potential of RT plus RECA versus RT alone for increasing cytotoxicity (local control) and increasing surface expression of major histocompatibility complex I (MHC I). The latter represents potential for immune response amplification (increased antigen presentation), which has been observed in other psoralen therapies. Cytotoxicity assays included luminescence and clonogenics. The MHC I assays were performed using flow cytometry. In addition, Cherenkov light intensity measurements were performed to investigate the possibility of increasing the Cherenkov light intensity per unit dose from clinical megavoltage beams, to maximize psoralen activation.ResultsLuminescence assays showed that RECA treatment (2 Gy at 6 MV) increased cytotoxicity by up to 20% and 9.5% for 4T1 and B16 cells, respectively, compared with radiation and psoralen alone (ie, Cherenkov light was blocked). Similarly, flow cytometry revealed median MHC I expression was significantly higher in RECA-treated cells, compared with those receiving radiation and psoralen alone (approximately 450% and 250% at 3 Gy and 6 Gy, respectively, P << .0001). Clonogenic assays of B16 cells at doses of 6 Gy and 12 Gy showed decreases in tumor cell viability of 7% (P = .017) and 36% (P = .006), respectively, when Cherenkov was present.ConclusionThis work demonstrates for the first time the potential for photo-activation of psoralen directly in situ, from Cherenkov light generated by a clinical megavoltage treatment beam.



http://ift.tt/2FREkQ2

Radiation Oncology in Egypt: A Model for Africa

Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Mohamed S. Zaghloul, Mai K. Bishr




http://ift.tt/2En5jFV

Secondary Acute Leukemia in Sarcoma Patients: A Population-Based Study

Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Nina N. Sanford, Allison M. Martin, Andrew M. Brunner, Gregory M. Cote, Edwin Choy, Thomas F. DeLaney, Ayal A. Aizer, Yen-Lin Chen
PurposeTo compare rates of secondary acute leukemia between sarcoma patients and the general population, using data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) registry, and to examine whether various patient, tumor, and treatment factors were associated with development of a secondary acute leukemia.Methods and MaterialsPatients with a primary diagnosis of connective tissue malignancy between 1973 and 2008 in the SEER database were included. Multivariable competing risk analysis was used to determine risk factors associated with subsequent development of acute leukemia. Using observed-to-expected ratios, we compared incidence rates of secondary acute leukemia between sarcoma patients and the general population.ResultsA total of 72,945 patients were identified, with median follow-up of 131 months. On multivariable competing risk analysis, factors associated with increased risk of secondary acute leukemia included receipt of radiation therapy (hazard ratio [HR] 1.67, P=.02), distant disease (HR 2.67, P=.004), male gender (HR 1.53, P=.03), year of diagnosis (HR 0.98, P=.049), and Ewing sarcoma histology (HR 9.95, P < .0001) and osteosarcoma histology (HR 5.06, P=.0001). The observed-to-expected ratio for development of a secondary acute leukemia was 3.67 (95% confidence interval [CI] 1.95-6.28), 3.41 (95% CI 2.73-4.20), and 1.6 (95% CI 1.38-8.19) for acute lymphocytic leukemia, acute myeloid leukemia, and acute monocytic leukemia, respectively. The 10-year cumulative incidence of secondary acute leukemia for patients who did and did receive radiation therapy was 0.3% versus 0.1% (P=.02).ConclusionsPatients treated for sarcoma, in particular those with Ewing sarcoma and osteosarcoma histology, seem to have a higher incidence of secondary acute leukemia as compared with the general population. Treatment factors including radiation therapy and chemotherapy seem to play a role in this increased risk, although the absolute incidence nevertheless remains very small.



http://ift.tt/2Em2qW6

Seymour H. Levitt, MD, 1928-2017

Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Luther W. Brady




http://ift.tt/2E7GAC2

Involved-Site Radiation to Maximize Control

Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Parag Sanghvi




http://ift.tt/2E37Xx9

Curative Radiation Therapy at Time of Progression Under Active Surveillance Compared With Up-front Radical Radiation Therapy for Prostate Cancer

Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Alejandro Berlin, Ardalan E. Ahmad, Melvin L.K. Chua, Fabio Y. Moraes, Haiyan Jiang, Maria Komisarenko, Narhari Trimilshina, Hamid Raziee, Ali Hosni, Jure Murgic, Peter Chung, Robert G. Bristow, Antonio Finelli
PurposeTo describe and compare outcomes in men with initially presumed indolent prostate cancer receiving definitive radiation therapy after active surveillance (AS) versus those in a risk-matched cohort undergoing up-front radiation therapy.Methods and MaterialsMen prospectively enrolled in an AS program between 1992 and 2014 and subsequently undergoing curative radiation therapy (ie, image guided radiation therapy [IGRT] or low-dose-rate brachytherapy [LDR-BT]) were identified. Biochemical relapse–free rate (bRFR), metastasis-free rate (mFR), and overall survival (OS) were compared against a cohort of men treated up front, matched by age, clinical prognostic indices (risk group, prostate-specific antigen, cT category, Gleason score, percentage of involved biopsy cores), and radiation therapy modality.ResultsOf 1070 patients in the AS registry, 200 underwent definitive radiation therapy (143 IGRT and 57 LDR-BT) after a median of 32.9 (interquartile range [IQR] 20.6-59.8) months on surveillance. Main reasons for treatment were grade and volume upgrading (57.5% and 26%, respectively). Median follow-up after radiation therapy was 4.9 (IQR 3.1-7.5) years. At 5 years the bRFR, mFR, and OS were, respectively, 97%, 99%, and 98.5%. No patient died of prostate cancer. Adequate risk-matching was confirmed in an independent cohort comprising 359 patients receiving up-front IGRT (71%) or LDR-BT (29%) and followed for a median of 9 (IQR 3.1-7.5) years. There was no difference in the disease-specific outcomes (bRFR, mFR) between the 2 cohorts (Gray's P value of .257 and .934, respectively). In multivariate analyses, timing of radical radiation therapy (deferred vs up-front) was not correlated to biochemical relapse or metastases occurrence.ConclusionsCurative-intent radiation therapy (ie, dose-escalated IGRT or LDR-BT) after a period of AS renders excellent oncologic outcomes at 5 years. Deferring radical therapy after a period of AS does not seem to result in inferior oncologic outcomes compared with patients with similar risk characteristics undergoing up-front treatment.



http://ift.tt/2Em2nto

Observe, and Keep Chemotherapy Up the Sleeve

Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Carol Marquez




http://ift.tt/2E569Ul

Normal Tissue Complication Probability Modeling of Pulmonary Toxicity After Stereotactic and Hypofractionated Radiation Therapy for Central Lung Tumors

Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): H. Tekatli, M. Duijm, E. Oomen-de Hoop, W. Verbakel, W. Schillemans, B.J. Slotman, J.J. Nuyttens, S. Senan
PurposeTo evaluate clinical pulmonary and radiographic bronchial toxicity after stereotactic ablative radiation therapy and hypofractionated radiation therapy for central lung tumors, and perform normal tissue complication probability modeling and multivariable analyses to identify predictors for toxicity.Methods and MaterialsA pooled analysis was performed of patients with a central lung tumor treated using ≤12 fractions at 2 centers between 2006 and 2015. Airways were manually contoured on planning computed tomography scans, and doses were recalculated to an equivalent dose of 2 Gy per fraction with an α/β ratio of 3. Grade ≥3 (≥G3) clinical pulmonary toxicity was evaluated by 2 or more physicians. Radiographic toxicity was defined as a stenosis or an occlusion with or without atelectasis using follow-up computed tomography scans. Logistic regression analyses were used for statistical analyses.ResultsA total of 585 bronchial structures were studied in 195 patients who were mainly treated using 5 or 8 fractions (60%). Median patient survival was 27.9 months (95% confidence interval 22.3-33.6 months). Clinical ≥G3 toxicity was observed in 24 patients (12%) and radiographic bronchial toxicity in 55 patients (28%), both mainly manifesting ≤12 months after treatment. All analyzed dosimetric parameters correlated with clinical and lobar bronchial radiographic toxicity, with V130Gy,EQD having the highest odds ratio. Normal tissue complication probability modeling showed a volume dependency for the development of both clinical and radiographic toxicity. On multivariate analyses, significant predictors for ≥G3 toxicity were a planning target volume overlapping the trachea or main stem bronchus (P = .005), chronic obstructive pulmonary disease (P = .034), and the total V130Gy,EQD (P = .012). Radiographic bronchial toxicity did not significantly correlate with clinical toxicity (P = .663).ConclusionsWe identified patient and dosimetric factors associated with clinical and radiographic toxicity after high-dose radiation therapy for central lung tumors. Additional data from prospective studies are needed to validate these findings.



http://ift.tt/2E6f4oA

Development of a Radiation Oncology Resident Continuity Clinic to Improve Clinical Competency and Patient Compliance

Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Stella K. Yoo, Shelly X. Bian, Eugene Lin, Sukhjeet S. Batth, Lydia W. Ng, Jacob Andrade, Patrick A. Williams, Anthony H. Pham, Omar M. Ragab, Naomi R. Schechter, Eric L. Chang, Richard L.S. Jennelle




http://ift.tt/2EmTnE5

Complex DNA Damage Induced by High Linear Energy Transfer Alpha-Particles and Protons Triggers a Specific Cellular DNA Damage Response

Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Rachel J. Carter, Catherine M. Nickson, James M. Thompson, Andrzej Kacperek, Mark A. Hill, Jason L. Parsons
PurposeTo investigate the precise mechanism of recognition and processing of ionizing radiation (IR)-induced complex DNA damage (CDD), where two or more DNA lesions are in close proximity, in cellular DNA which is packaged with histones to form chromatin.Methods and MaterialsHeLa and oropharyngeal squamous cell carcinoma (UMSCC74A and UMSCC6) cells were irradiated with high linear energy transfer (LET) α-particles or protons, versus low-LET protons and X rays. At various time points after irradiation, site-specific histone post-translational modifications were analyzed by quantitative Western blotting; DNA damage and repair were measured by different versions of the comet assay; and cell survival was determined using clonogenic assays.ResultsSite-specific histone post-translational modifications after low- and high-LET radiation, particularly proton irradiation, were screened, aiming to identify those responsive to CDD. We demonstrate that histone H2B ubiquitylated on lysine 120 (H2Bub) is specifically induced several hours after irradiation in response to high-LET α-particles and protons but not by low-LET protons or X rays/γ-radiation. This is associated with increased levels of CDD, which contributes to decreased cell survival. We further discovered that modulation of H2Bub is under the control of two E3 ubiquitin ligases, MSL2 and RNF20/RNF40 complex, whose depletion leads to defective processing and further persistence of CDD, and to additional decreased cell survival after irradiation.ConclusionThis study demonstrates that the signaling and repair of CDD, particularly induced by high-LET IR is co-ordinated through the specific induction of H2Bub catalyzed by MSL2 and RNF20/40, a mechanism that contributes significantly to cell survival after irradiation.



http://ift.tt/2Ero4Ir

Utilizing 10-Year Results From the American Board of Radiology Clinical Examination to Identify Areas for Programmatic Improvement

Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Robert B. Den, Marlene Folino, Adam P. Dicker




http://ift.tt/2E7v9dT

In Reply to Leddy

Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Nishant K. Shah, Brad Zehr, Ankit Agarwal, Apar Gupta, Ariel E. Hirsch




http://ift.tt/2E9OMC8

In Reply to Overgaard et al

Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): William A. Stokes, Sana D. Karam




http://ift.tt/2EnZloh

Radiation Safety for Pregnant Workers at a Proton Facility

Publication date: 1 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 100, Issue 3
Author(s): Genevieve Maquilan, Marc R. Bussière, Joseph McCormack, Tara Medich, Andrzej Niemierko, Helen A. Shih
PurposeTo quantify radiation exposure of radiation therapy technologists (RTTs) in a proton treatment facility in comparison with a photon therapy facility, to inform and establish these specialized occupational safety guidelines.Methods and MaterialsTwo groups of RTTs, consisting of 12 full-time passive scattering proton RTTs and 18 full-time conventional photon RTTs, wore an additional dosimetry badge at the waist for a period of 14 weeks. The 2 groups of RTTs were given identical instructions on the proper use of the badges. To compare exposures between passive scatter and scanning beam systems, exposure rates from activated equipment in both systems were measured.ResultsOver the 14-week period, the mean and standard deviation background-corrected dose for the passively scattered proton RTTs was 39.9 ± 5.4 mrem. The mean and standard deviation background-corrected dose for the conventional photon RTTs was similar at 39.9 ± 9.0 mrem (P = .6). Exposure rates were lower in equipment activated in a scanning beam system in comparison with those from a passive scatter system.ConclusionsRadiation dose to passively scattered proton and photon radiation therapy technologists was similar when measured with a dosimeter worn at the waist over a period of 14 weeks. On the basis of these data, the departmental policy permits pregnant radiation workers to work in proton treatment areas, and the policy for pregnant workers does not differ between proton and photon radiation workers or between passive scatter and scanning beam systems. All employees are encouraged to limit time near and proximity to activated equipment.



http://ift.tt/2E37YRJ

Using the "ligamentum flavum gap" to identify originally missed type B vertebral fractures.

Related Articles

Using the "ligamentum flavum gap" to identify originally missed type B vertebral fractures.

Surg Neurol Int. 2018;9:5

Authors: Alfredo G, Carlos Z, Nelson P, Alfredo S, Alejandro MC, Asdrúbal F

Abstract
Background: Spine fractures may involve the ligamentum flavum (LF). Here, we utilized the "ligamentum flavum gap," defined by the discontinuity of the LF at the level of a vertebral fracture, to document a vertebral fracture.
Methods: Utilizing X-rays, computed tomography (CT), and magnetic resonance (MR) studies, 10 patients with type B vertebral fractures were diagnosed with the ligamentum flavum gap (LFG: discontinuity of the LF) at the fracture levels. The fractures were located in 2 patients in the cervical and 8 in the thoracolumbar spine.
Results: All 10 patients with vertebral fractures had complained of axial pain. Four also showed progressive thoracic kyphosis. Notably, all demonstrated a loss of continuity in the LF at the level of fracture "ligamentum flavum gap." T2-weighted and short tau inversion recovery (STIR) MR sagittal studies were best at locating LFG at the level of a fracture.
Conclusion: Here, we identified best on sagittal T2 and STIR-weighted MR studies 10 patients for whom discontinuity of the ligamentum flavum (LFG) correlated with the location of type B vertebral fractures.

PMID: 29399377 [PubMed]

http://ift.tt/2FTkPqe

Isolated ligamentum flavum ossification in primary hypoparathyroidism.

Related Articles

Isolated ligamentum flavum ossification in primary hypoparathyroidism.

Surg Neurol Int. 2018;9:4

Authors: Sohail AH, Maan MAA, Khan MS, Masood Q

Abstract
Background: The ligamenta flava can undergo ossification and calcification resulting in myelopathy. Only seven cases of ligamentum flavum ossification in association with hypoparathyroidism have been reported, most of which had concurrent osseous changes in other spinal ligaments. Here, we report a patient with hypoparathyroidism who presented with ligamentum flavum ossification causing both cervical and thoracic myelopathy.
Case Description: A 43-year-old male presented with backache, urinary retention, and lower limb weakness for the last few days. Magnetic resonance imaging scan showed ossification of the ligamentum flavum in the cervical and thoracic regions, with severe spinal stenosis. Following spinal decompressive surgery, the patient made a complete recovery. Primary hypoparathyroidism was found to be the underlying cause for ligamentum flavum ossification.
Conclusion: Ossification of ligamentum flavum secondary to hypoparathyroidism should be considered as a possible cause of myelopathy in all patients presenting with symptoms of spinal cord compression.

PMID: 29399376 [PubMed]

http://ift.tt/2EKyErA

Editorial Board

Publication date: 16 April 2018
Source:Behavioural Brain Research, Volume 342





http://ift.tt/2EoDehz

Clinical implementation of contrast-enhanced four-dimensional dual-energy computed tomography for target delineation of pancreatic cancer

Publication date: Available online 6 February 2018
Source:Radiotherapy and Oncology
Author(s): Shingo Ohira, Kentaro Wada, Takero Hirata, Naoyuki Kanayama, Toshiki Ikawa, Tsukasa Karino, Yuya Nitta, Masaru Isono, Yoshihiro Ueda, Masayoshi Miyazaki, Masahiko Koizumi, Teruki Teshima
Background and purposeThe accurate delineation of pancreatic tumor with respiratory motion is challenging. This study demonstrates the application of contrast-enhanced four-dimensional dual-energy computed tomography (CE-4D-DECT) for tumor delineation and assesses the objective and subjective image quality.Material and methodsTwelve patients underwent CE-4D-DECT, and quantitative spectral analysis was performed on the resulting virtual monochromatic images (VMI) to determine the optimal VMI (O-VMI) with the highest contrast-to-noise ratio (CNR). The objective value of the CNR between pancreatic parenchyma and tumor, and the subjective measurement with five-point scale were compared between O-VMI, standard VMI (S-VMI, 77 keV) and single energy CT (SECT, 120 kVp).ResultsThe CNR was the highest in the VMI at 60 keV, and the corresponding CNR in the O-VMI (3.4) was significantly higher (p < 0.05) than that in the S-VMI (2.4) and the SECT (2.7). The overall mean subjective measurements among 4 radiation oncologists were higher for the O-VMI over the S-VMI and SECT with respect to overall image quality (4.0, 3.3 and 3.7, respectively), tumor enhancement (3.4, 2.6 and 3.2, respectively), and vessel delineation (4.2, 3.6 and 4.2, respectively).ConclusionsThe O-VMI derived from the CE-4D-DECT demonstrated its superiority over the S-VMI and SECT in depicting pancreatic tumor.



http://ift.tt/2Err2wm

Lower fluidity of supported lipid bilayers promotes neuronal differentiation of neural stem cells by enhancing focal adhesion formation

Publication date: April 2018
Source:Biomaterials, Volume 161
Author(s): Wangping Hao, Jie Han, Yun Chu, Lei Huang, Jie Sun, Yan Zhuang, Xiaoran Li, Hongwei Ma, Yanyan Chen, Jianwu Dai
Extensive studies have been performed to understand how the mechanical properties of a stem cell's microenvironment influence its behaviors. Supported lipid bilayers (SLBs), a well-known biomimetic platform, have been used to mimic the dynamic characteristics of the extracellular matrix (ECM) because of their fluidity. However, the effect of the fluidity of SLBs on stem cell fate is unknown. We constructed SLBs with different fluidities to explore the influence of fluidity on the differentiation of neural stem cells (NSCs). The results showed that the behavior of NSCs was highly dependent on the fluidity of SLBs. Low fluidity resulted in enhanced focal adhesion formation, a dense network of stress fibers, stretched and elongated cellular morphology and increased neuronal differentiation, while high fluidity led to less focal adhesion formation, immature stress fibers, round cellular morphology and more astrocyte differentiation. Mechanistic studies revealed that low fluidity may have enhanced focal adhesion formation, which activated FAK-MEK/ERK signaling pathways and ultimately promoted neuronal differentiation of NSCs. This work provides a strategy for manipulating the dynamic matrix surface for the development of culture substrates and tissue-engineered scaffolds, which may aid the understanding of how the dynamic ECM influences stem cell behaviors as well as improve the efficacy of stem cell applications.

Graphical abstract

http://ift.tt/2BbPaBj

Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation

Publication date: April 2018
Source:Biomaterials, Volume 161
Author(s): Hong Ji Yan, Tommaso Casalini, Gry Hulsart-Billström, Shujiang Wang, Oommen P. Oommen, Matteo Salvalaglio, Sune Larsson, Jöns Hilborn, Oommen P. Varghese
Synthetic scaffolds that possess an intrinsic capability to protect and sequester sensitive growth factors is a primary requisite for developing successful tissue engineering strategies. Growth factors such as recombinant human bone morphogenetic protein-2 (rhBMP-2) is highly susceptible to premature degradation and to provide a meaningful clinical outcome require high doses that can cause serious side effects. We discovered a unique strategy to stabilize and sequester rhBMP-2 by enhancing its molecular interactions with hyaluronic acid (HA), an extracellular matrix (ECM) component. We found that by tuning the initial protonation state of carboxylic acid residues of HA in a covalently crosslinked hydrogel modulate BMP-2 release at physiological pH by minimizing the electrostatic repulsion and maximizing the Van der Waals interactions. At neutral pH, BMP-2 release is primarily governed by Fickian diffusion, whereas at acidic pH both diffusion and electrostatic interactions between HA and BMP-2 become important as confirmed by molecular dynamics simulations. Our results were also validated in an in vivo rat ectopic model with rhBMP-2 loaded hydrogels, which demonstrated superior bone formation with acidic hydrogel as compared to the neutral counterpart. We believe this study provides new insight on growth factor stabilization and highlights the therapeutic potential of engineered matrices for rhBMP-2 delivery and may help to curtail the adverse side effects associated with the high dose of the growth factor.



http://ift.tt/2BKCIJR

Exogenous ROS-induced cell sheet transfer based on hematoporphyrin-polyketone film via a one-step process

Publication date: April 2018
Source:Biomaterials, Volume 161
Author(s): Min-Ah Koo, Mi Hee Lee, Byeong-Ju Kwon, Gyeung Mi Seon, Min Sung Kim, Dohyun Kim, Ki Chang Nam, Jong-Chul Park
To date, most of invasive cell sheet harvesting methods have used culture surface property variations, such as wettability, pH, electricity, and magnetism, to induce cell detachment. These methods that rely on surface property changes are effective when cell detachment prior to application is necessary, but of limited use when used for cell sheet transfer to target regions. The study reports a new reactive oxygen species (ROS)-induced strategy based on hematoporphyrin-incorporated polyketone film (Hp-PK film) to transfer cell sheets directly to target areas without an intermediate harvesting process. After green LED (510 nm) irradiation, production of exogenous ROS from the Hp-PK films induces cell sheet detachment and transfer. The study suggests that ROS-induced cell detachment property of the Hp-PK film is closely related to conformational changes of extracellular matrix (ECM) proteins. Also, this strategy with the Hp-PK film can be applied by regulating production rate of exogenous ROS in various types of cells, including fibroblasts, mesenchymal stem cells and keratinocytes. In conclusion, ROS-induced method using the Hp-PK film can be used for one-step cell sheet transplantation and has potential in biomedical applications.

Graphical abstract

http://ift.tt/2Ben34m

Harnessing macrophage-mediated degradation of gelatin microspheres for spatiotemporal control of BMP2 release

Publication date: April 2018
Source:Biomaterials, Volume 161
Author(s): Ramkumar T. Annamalai, Paul A. Turner, William F. Carson, Benjamin Levi, Steven Kunkel, Jan P. Stegemann
Biomaterials-based approaches to harnessing the immune and inflammatory responses to potentiate wound healing hold important promise. Bone fracture healing is characterized by an acute inflammatory phase, followed by a transition to a regenerative and repair phase. In this study, we developed genipin-crosslinked gelatin microspheres designed to be preferentially degraded by inflammatory (M1) macrophages. Highly crosslinked (>90%) microspheres allowed efficient incorporation of bioactive bone morphogenetic protein 2 (BMP2), a potent stimulator of osteogenesis in progenitor cells, via electrostatic interactions. Release of BMP2 was directly correlated with degradation of the gelatin matrix. Exposure of microspheres to polarized murine macrophages showed that degradation was significantly higher in the presence of M1 macrophages, relative to alternatively activated (M2) macrophages and unpolarized controls. Microsphere degradation in the presence of non-inflammatory cells resulted in very low degradation rates. The expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMP (TIMPs) by macrophages were consistent with the observed phenotype-dependent degradation rates. Indirect co-culture of BMP2-loaded microspheres and macrophages with isolated adipose-derived mesenchymal stem cells (MSC) showed that M1 macrophages produced the strongest osteogenic response, comparable to direct supplementation of the culture medium with BMP2. Controlled release systems that are synchronized with the inflammatory response have the potential to provide better spatiotemporal control of growth factor delivery and therefore may improve the outcomes of recalcitrant wounds.



http://ift.tt/2BN0R2q

A self-delivery membrane system for enhanced anti-tumor therapy

Publication date: April 2018
Source:Biomaterials, Volume 161
Author(s): Wen-Xiu Qiu, Ming-Kang Zhang, Li-Han Liu, Fan Gao, Lu Zhang, Shi-Ying Li, Bo-Ru Xie, Chi Zhang, Jun Feng, Xian-Zheng Zhang
Nowadays, cell membrane targeting therapy has drawn much attention for its high anti-tumor effect by avoiding the cellular barriers. In this study, therapeutic agent conjugated chimeric peptide (Cp) was anchored in cracked cancer cell membranes (CCCM) to construct a self-delivery membrane system (M-Cp), which could relize precise cell membrane targeting therapy. It was found that compared with Cp, M-Cp could target to the cancer cell membrane with longer retention time, which is very crucial for in vivo applications. And the superior cell membrane targeting ability was attributed to the specific proteins (focal adhesion proteins, focal adhesion kinase, RHO family proteins, and integrin) on the CCCM surface. Importantly, the M-Cp could promote tumor-specific immune response, which further enhanced anti-tumor effect when combined with therapeutic agents in M-Cp. What's more, this self-delivery membrane system could be used as a template for cell membrane targeting therapy by changing the therapeutic agents as well as the CCCM, and this strategy would open a new window for various cell membrane targeting therapy.

Graphical abstract

http://ift.tt/2BN0RPY

Hacking macrophage-associated immunosuppression for regulating glioblastoma angiogenesis

Publication date: April 2018
Source:Biomaterials, Volume 161
Author(s): Xin Cui, Renee-Tyler Tan Morales, Weiyi Qian, Haoyu Wang, Jean-Pierre Gagner, Igor Dolgalev, Dimitris Placantonakis, David Zagzag, Luisa Cimmino, Matija Snuderl, Raymond H.W. Lam, Weiqiang Chen
Glioblastoma (GBM) is the most lethal primary adult brain tumor and its pathology is hallmarked by distorted neovascularization, diffuse tumor-associated macrophage infiltration, and potent immunosuppression. Reconstituting organotypic tumor angiogenesis models with biomimetic cell heterogeneity and interactions, pro-/anti-inflammatory milieu and extracellular matrix (ECM) mechanics is critical for preclinical anti-angiogenic therapeutic screening. However, current in vitro systems do not accurately mirror in vivo human brain tumor microenvironment. Here, we engineered a three-dimensional (3D), microfluidic angiogenesis model with controllable and biomimetic immunosuppressive conditions, immune-vascular and cell-matrix interactions. We demonstrate in vitro, GL261 and CT-2A GBM-like tumors steer macrophage polarization towards a M2-like phenotype for fostering an immunosuppressive and proangiogenic niche, which is consistent with human brain tumors. We distinguished that GBM and M2-like immunosuppressive macrophages promote angiogenesis, while M1-like pro-inflammatory macrophages suppress angiogenesis, which we coin "inflammation-driven angiogenesis." We observed soluble immunosuppressive cytokines, predominantly TGF-β1, and surface integrin (αvβ3) endothelial-macrophage interactions are required in inflammation-driven angiogenesis. We demonstrated tuning cell-adhesion receptors using an integrin (αvβ3)-specific collagen hydrogel regulated inflammation-driven angiogenesis through Src-PI3K-YAP signaling, highlighting the importance of altered cell-ECM interactions in inflammation. To validate the preclinical applications of our 3D organoid model and mechanistic findings of inflammation-driven angiogenesis, we screened a novel dual integrin (αvβ3) and cytokine receptor (TGFβ-R1) blockade that suppresses GBM tumor neovascularization by simultaneously targeting macrophage-associated immunosuppression, endothelial-macrophage interactions, and altered ECM. Hence, we provide an interactive and controllable GBM tumor microenvironment and highlight the importance of macrophage-associated immunosuppression in GBM angiogenesis, paving a new direction of screening novel anti-angiogenic therapies.



http://ift.tt/2BejECw

Inhibition of tumor-promoting stroma to enforce subsequently targeting AT1R on tumor cells by pathological inspired micelles

Publication date: April 2018
Source:Biomaterials, Volume 161
Author(s): Yun Zhu, Lijuan Wen, Shihong Shao, Yanan Tan, Tingting Meng, Xiqin Yang, Yupeng Liu, Xuan Liu, Hong Yuan, Fuqiang Hu
Cancer associated fibroblasts (CAFs) are the most abundant, genetically stable stroma cells and localize near blood vessels within "finger-like" collagen-rich stroma, which lead to restrained drug transport in dense stroma instead of tumor cells inside tumor mass, especially for targeting micelles. Meanwhile, the bioactive cytokines secreted by stroma cells result in microenvironment mediated drug resistance (TMDR). Hence, a biologically inspired Telmisartan (Tel) grafting glycolipid micelles (Tel-CSOSA) are constructed, which can sequentially target angiotensin II type I receptor (AT1R) overexpressed on both CAFs and tumor cells. More Tel-CSOSA are demonstrated to specifically accumulate in tumor site compared to CSOSA. In addition, the retention of Tel-CSOSA is primarily prolonged around tumor vessel in virtue of CAFs targeting and the stroma barrier. In contrast, the elimination of "finger-like" ECM resulting from CAFs apoptosis by Tel-CSOSA/DOX contributes to a more uniform and deeper penetration post-administration, which can enforce subsequently tumor cells targeting. Meanwhile, cytokines are decreased along with CAFs apoptosis so that tumor cells are more vulnerable to chemotherapeutics. Collectively, this strategy of sequentially targeting CAFs and tumor cells could synergistically increase antitumor therapy with reversed TMDR.

Graphical abstract

http://ift.tt/2BK6xKL