Past, current, and future research on microalga-derived biodiesel: a critical review and bibliometric analysis

Abstract

Microalga-derived biodiesel plays a crucial role in the sustainable development of biodiesel in recent years. Literature related to microalga-derived biodiesel had an increasing trend with the expanding research outputs. Based on the Science Citation Index Expanded (SCI-Expanded) of the Web of Science, a bibliometric analysis was conducted to characterize the body of knowledge on microalga-derived biodiesel between 1993 and 2016. From the 30 most frequently used author keywords, the following research hotspots are extracted: lipid preparation from different microalga species, microalga-derived lipid and environmental applications, lipid-producing microalgae cultivation, microalgae growth reactor, and microalga harvest and lipid extraction. Other keywords, i.e., microalga mixotrophic cultivation, symbiotic system between microalga and other oleaginous yeast, microalga genetic engineering, and other applications of lipid-producing microalga are future focal points of research.

Graphical abstract

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Association between serum autotaxin or phosphatidylserine-specific phospholipase A1 levels and melanoma

Abstract

Autotaxin (ATX), a producing enzyme for lysophosphatidic acids, was first identified from the medium of a melanoma cell line and has been considered to be one of the candidate targets to treat melanoma; however, the association between serum ATX and melanoma in human subjects has not been elucidated. Along with ATX, phosphatidylserine-specific phospholipase A1 (PS-PLA₁) is a producing enzyme for lysophosphatidylserine, a similar glycero-lysophospholipid mediator to lysophosphatidic acids. In the present study, we aimed to investigate the association between serum ATX or PS-PLA₁ levels and melanoma. We measured the serum levels of ATX, ATX isoforms and PS-PLA₁ in subjects with melanoma (n = 57) and healthy subjects (n = 58). We further investigated the existence of trends according to the clinical stages of melanoma. We observed that serum total ATX and classical ATX levels were significant higher and serum novel ATX levels tended to be higher in male subjects with melanoma, while no significant difference was observed between the two groups in female subjects. The trend test revealed that the serum total ATX and ATX isoforms were significantly associated with the clinical stages of female subjects with melanoma. Regarding PS-PLA₁, serum PS-PLA₁ levels were significantly higher in the melanoma subjects and associated with the clinical stages. The present study is the first study which revealed the association between ATX or PS-PLA₁ and melanoma, suggesting the possible involvement of ATX/lysophosphatidic acids or PS-PLA₁/lysophosphatidylserine axis in the pathogenesis of melanoma.

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Case of punctate palmoplantar keratoderma type I treated with combination of low-dose oral acitretin and topical salicylic acid and steroid

Abstract

Palmoplantar keratodermas (PPK) are heterogeneous disorders characterized by abnormal keratinization. Especially, punctate PPK (PPPK), one of the subtypes of hereditary PPK, is a rare punctate keratoderma characterized by tiny "raindrop" keratoses having a tendency to coalesce on the edge of soles, which are exposed to sustained pressure. If typical punctate lesions are confined to the palms and soles and the patient has a family history and late onset, it can be considered as PPPK type I (PPKP1), also called Buschke–Fisher–Brauer disease. The exact etiology of PPPK has not been fully understood. Furthermore, no standardized treatment for PPPK has been established and treatment options are limited. Above all, traditional systemic retinoids have been used in several cases, but dose-related adverse effects are common. Therefore, combination of low-dose systemic retinoids and adjuvant topical therapy can be an alternative treatment option for PPPK. Herein, we report a case of PPKP1 treated with combination of low-dose oral acitretin (10 mg/day) and topical salicylic acid and steroid. Despite low capacity, low-dose acitretin showed excellent regression of the lesions by combined use of topical ointments. The supplementary topical therapy may be useful in reducing the dose of systemic retinoids and preventing potential toxicity.

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Changes in salivary chromogranin A levels in adults with atopic dermatitis are correlated with changes in their condition

Abstract

Stress-induced scratching is an issue in patients with adult atopic dermatitis (AD). Symptoms of stress-induced AD are common in clinical practise. Salivary chromogranin A (CgA) level has research value as a possible index related to a patient's psychological stress. Using saliva, which is easily collectable, we compared two assessments of the severities of AD and stress with the levels of stress proteins in the saliva of 30 patients with AD in the Department of Dermatology of Shimane University between April 2015 and May 2017. The severities of AD and stress were assessed using the Scoring Atopic Dermatitis (SCORAD) score and State–Trait Anxiety Inventory score, respectively. Additionally, the assessments included those of personality using the Tokyo University Egogram (TEG)-II score and quality of life using the Dermatology Life Quality Index score. Simultaneously, we measured their salivary CgA levels. The change in salivary CgA per protein in patients with AD was correlated with their changes in SCORAD score (correlation coefficient, r = 0.596, P = 0.001) and objective SCORAD (r = 0.608, P < 0.001). The changes in CgA per protein correlated with those in TEG-II A (r = 0.370, P = 0.022), while the changes in SCORAD score correlated with those in DLQI (r = 0.309, P = 0.048). Our results suggest that changes in a patient's condition are reflective of the changes in the patient's stress. The changes in salivary CgA level in patients with AD correlated with the changes in their condition.

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Cutaneous sarcoidosis in a patient with rheumatoid arthritis receiving tocilizumab

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Splice site mutation in COL7A1 resulting in aberrant in-frame transcripts identified in a case of recessive dystrophic epidermolysis bullosa, pretibial

Abstract

Dystrophic epidermolysis bullosa (DEB), pretibial, a rare subtype of epidermolysis bullosa (EB), is characterized by recurrent blisters and erosions predominantly on the pretibial region. We report the case of a 60-year-old Japanese woman with persistent blistering eruptions and scar formation on the pretibial region and elbows. Mutational analysis revealed a previously reported c.5797C>T mutation in exon 70 (p.R1933X) and a novel c.6348+1G>A mutation in intron 76 of COL7A1. Reverse transcription polymerase chain reaction revealed that the c.6348+1G>A mutation resulted in the skipping of exon 76 (69 bp) and the retention of intron 76 (75 bp), and both transcripts were in-frame. From these results, we diagnosed the patient as having recessive DEB, pretibial. A review of previously reported mutations in DEB, pretibial, revealed that one-third of DEB, pretibial, cases showed a recessive inheritance pattern, and no case had a combination of premature termination codon (PTC)/PTC mutations. The DEB, pretibial, case described herein is the first reported case of a compound heterozygote with PTC/in-frame mutations. Although no special characteristic features of the mutations were identified, a high diversity of COL7A1 mutations was shown even in DEB, pretibial.

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Overexpression of PIK3CA in head and neck squamous cell carcinoma is associated with poor outcome and activation of the YAP pathway

Publication date: April 2018
Source:Oral Oncology, Volume 79
Author(s): Ramón García-Escudero, Carmen Segrelles, Marta Dueñas, María Pombo, Claudio Ballestín, Marina Alonso-Riaño, Pablo Nenclares, Roberto Álvarez-Rodríguez, Gregorio Sánchez-Aniceto, Ana Ruíz-Alonso, José Luis López-Cedrún, Jesús M. Paramio, Corina Lorz
ObjectivesPhosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) is commonly altered in many human tumors, leading to the activation of p110α enzymatic activity that stimulates growth factor-independent cell growth. PIK3CA alterations such as mutation, gene amplification and overexpression are common in head and neck squamous cell carcinoma (HNSCC) and. We aim to explore how these alterations and clinical outcome are associated, as well as the molecular mechanisms involved.Material and methodsMutation and copy-number variation in PIK3CA, and whole-genome expression profiles, were analyzed in primary HNSCC tumors from The Cancer Genome Atlas (TCGA) cohort (n = 243). The results were validated in an independent cohort form the University Hospital of A Coruña (UHAC, n = 62). Expression of the PIK3CA gene protein product (PI3K p110α) and nuclear YAP were assessed in tissue microarrays in a cohort from the University Hospital 12 de Octubre (UH12O, n = 91).ResultsOnly high expression of the PIK3CA gene was associated with poor clinical outcome. The study of gene expression, transcription factor and protein signatures suggested that the activation of the Hippo-YAP pathway, involved in organ size, stem cell maintenance and tumorigenesis, could underlie tumor progression in PI3KCA overexpressing tumors. Tissue arrays showed that PI3K p110α levels correlated with YAP nuclear localization in HNSCC tumors.ConclusionsHigh expression of PIK3CA in HNSCC primary tumors identifies patients at high risk for recurrence. In these tumors, progression could rely on the Hippo-YAP pathway instead of the canonical Akt/mTOR pathway. This observation could have important implications in the therapeutic options for patients.

Graphical abstract

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Whole genome analysis of six organophosphate-degrading rhizobacteria reveals putative agrochemical degradation enzymes with broad substrate specificity

Abstract

Six organophosphate-degrading bacterial strains collected from farm and ranch soil rhizospheres across the Houston-metropolitan area were identified as strains of Pseudomonas putida (CBF10-2), Pseudomonas stutzeri (ODKF13), Ochrobactrum anthropi (FRAF13), Stenotrophomonas maltophilia (CBF10-1), Achromobacter xylosoxidans (ADAF13), and Rhizobium radiobacter (GHKF11). Whole genome sequencing data was assessed for relevant genes, proteins, and pathways involved in the breakdown of agrochemicals. For comparative purposes, this analysis was expanded to also include data from deposited strains in the National Center for Biotechnology Information's (NCBI) database. This study revealed Zn-dependent metallo-β-lactamase (MBL)-fold proteins similar to OPHC2 first identified in P. pseudoalcaligenes as the likely agents of organophosphate (OP) hydrolysis in A. xylosoxidans ADAF13, S. maltophilia CBF10-1, O. anthropi FRAF13, and R. radiobacter GHKF11. A search of similar proteins within NCBI identified over 200 hits for bacterial genera and species with a similar OPHC2 domain. Taken together, we conclude from this data that intrinsic low-level OP hydrolytic activity is likely prevalent across the rhizosphere stemming from widespread OPHC2-like metalloenzymes. In addition, P. stutzeri ODKF13, P. putida CBF10-2, O. anthropi FRAF13, and R. radiobacter GHKF11 were found to harbor glycine oxidase (GO) enzymes that putatively possess low-level activity against the herbicide glyphosate. These bacterial GOs are reported to catalyze the degradation of glyphosate to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and suggest a possible link to AMPA that can be found in glyphosate-contaminated agricultural soil. The presence of aromatic degradation proteins were also detected in five of six study strains, but are attributed primarily to components of the widely distributed β-ketoadipate pathway found in many soil bacteria.

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La azatioprina reduce el riesgo de recaída audiométrica en hipoacusia inmunomediada

Publication date: Available online 2 March 2018
Source:Acta Otorrinolaringológica Española
Author(s): Nieves Mata-Castro, Javier Gavilanes-Plasencia, Rafael Ramírez-Camacho, Alfredo García-Fernández, José Ramón García-Berrocal
IntroducciónLos esquemas actuales de tratamiento de la hipoacusia inmunomediada con corticoides, a dosis baja y pauta corta, son insuficientes.MétodosPara determinar el papel de la azatioprina en el control del deterioro auditivo se ha llevado a cabo un estudio observacional descriptivo longitudinal con 20 pacientes tratados con azatioprina por vía oral (1,5-2,5mg/kg/día en dos dosis) durante 1año. Se consideró recaída la pérdida de 10dB en dos frecuencias consecutivas o de 15dB en una frecuencia aislada.ResultadosLa edad media de los pacientes fue de 52,50años (IC95%: 46,91-58,17), y la mitad fueron mujeres. La afectación bilateral fue del 65%. Un 75% presentaban enfermedad organoespecífica y un 25%, enfermedad autoinmune sistémica. La diferencia entre la PTA basal (46,49 dB; DE18,90) y la PTA a los 12meses (45,47dB; DE18,88) no alcanzó significación estadística (p=0,799). Existía una correlación positiva moderada entre sexo femenino y presencia de enfermedad sistémica (R=0,577). Aplicando t de Student para datos apareados se obtuvo una diferencia significativa (p=0,042) entre el descenso de la PTA en frecuencias hasta 1.000Hz (PTA125-1.000Hz). La tasa relativa de incidencia de recaída por año fue de 0,52 recaídas/año (IC95%: 0,19-1,14). El tiempo medio de supervivencia libre de recaída audiométrica fue de 9,70meses (DE1,03).ConclusionesLa azatioprina mantiene el umbral de audición, disminuye el riesgo de recaída y frena la velocidad con la que los pacientes recaen, alterando el curso de la enfermedad inmunomediada del oído interno.IntroductionCurrent schemes for treatment of immune-mediated hearing loss with sporadic short-course, low-dose corticosteroids, are insufficient.MethodsTo determine the role of azathioprine in the control of auditory impairment, a longitudinal, observational, descriptive study was performed with 20 patients treated with azathioprine (1.5-2.5mg/kg/day into two doses) for 1year. The loss of 10dB on two consecutive frequencies or 15dB on an isolated frequency was considered as relapse.ResultsThe mean age of the patients was 52.50years (95%CI: 46.91-58.17), half were women. Bilateral affectation was 65%. 75% had organ specific disease and 25% had systemic autoimmune disease. The difference between baseline PTA (46.49dB; DS18.90) and PTA at 12months (45.47dB; DS18.88) did not reach statistical significance (P=.799). There was a moderate positive correlation between female sex and the presence of systemic disease (R=.577). By applying Student's t for paired data, a significant difference (P=.042) was obtained between the PTA in frequencies up to 1000 Hz (PTA125-1000Hz). The relative incidence rate of relapse per year was .52 relapses/year (95%CI: .19-1.14]). The median time to audiometric relapse-free was 9.70months (DS1.03).ConclusionsAzathioprine maintains the hearing threshold, decreases the risk of relapse, and slows down the rate at which patients relapse, altering the course of immune-mediated inner ear disease.



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Modified purse-string closure: a lymphatic channel and tissue sparing technique for biopsy of suspicious pigmented lesions on extremities

Publication date: Available online 2 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): David Oberlin, Dennis A. Porto, Matteo Lopiccolo, Laurie L. Kohen




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Inflammatory response and cytokine levels induced by intralesional photodynamic therapy and 630nm laser in a case series of basal cell carcinoma

Publication date: Available online 2 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): M.J. Suárez-Valladares, S. Calleja-Antolin, J.M. Ruíz-deMorales, M.A. Rodríguez-Prieto, J. Vega-Gutierrez




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Patients prioritize local recurrence risk over other attributes for surgical treatment of facial melanomas - results of a stated preference survey and choice-based conjoint analysis

Publication date: Available online 2 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Jeremy R. Etzkorn, Scott D. Tuttle, Ilya Lim, Elea M. Feit, Joseph F. Sobanko, Thuzar M. Shin, Donald E. Neal, Christopher J. Miller
BackgroundSurgical treatment options for facial melanomas include conventional excision with postoperative margin assessment (CE-POMA), Mohs micrographic surgery with immunostains (MMS-I) or slow Mohs. Patient preferences for these surgical options have not been studied.ObjectivesTo evaluate patient preferences for surgical treatment of facial melanoma and to determine how patients value the relative importance of different surgical attributes.MethodsParticipants completed a two-part study consisting of a stated preference survey and a choice-based conjoint analysis (CBCA) experiment.ResultsPatients overwhelmingly (94.3%) rate local recurrence risk as "very important" and rank it as the most important attribute of surgical treatment for facial melanoma. Via CBCA, patients ranked the following surgical attributes from highest to lowest importance: local recurrence rate, out-of-pocket cost, chance of second surgical visit, timing of reconstruction, travel time, and time in office for the procedure. Consistent with their prioritization of low local recurrence rates, over 73% of respondents selected MMS-I or slow Mohs as their preferred treatment option for a facial melanoma.LimitationsData were obtained from a single health system.ConclusionPatients prefer surgical treatment options that minimize risk for local recurrence. Logistics for travel and treatment have less influence on patient preferences. Most survey participants chose MMS-I to maximize local cure and convenience of care.



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Impact of Topical Fluorouracil Cream on Costs of Treating Keratinocyte Carcinoma (Nonmelanoma Skin Cancer) and Actinic Keratosis

Publication date: Available online 2 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Jean Yoon, Ciaran S. Phibbs, Adam Chow, Martin A. Weinstock
BackgroundIt is unknown whether treatment costs of Keratinocyte Carcinoma (KC) and Actinic Keratosis (AK) can be lowered by spending more on chemoprevention.ObjectiveWe examine the impact of one-course treatment of topical fluorouracil on the face and ears on KC and AK treatment costs over three years.MethodsThe VAKCC trial compared the efficacy of topical fluorouracil cream, 5%, vs vehicle control cream for reducing KC risk. Trial data and administrative data on costs and utilization were analyzed to measure post-randomization encounters and treatment costs for KC and AK care. Adjusted models were used to test for statistically significant differences between treatment arms for number of treatment encounters and costs.ResultsOne year after randomization, the control arm had higher mean number of treatment encounters for SCC (0.04) than the intervention arm (0.01) (P<0.01). At one year the intervention arm had lower treatment and dermatologic costs of $2,106 (SD=$2,079) compared to $2,444 (SD=$2,716) for control patients (P=0.02). After three years, the intervention arm incurred $771 less per patient.LimitationsCare not provided or paid by VA was not included. Results may not be generalizable to other payers.ConclusionWe found significant cost savings for patients treated with 5-FU.



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Discriminatory miRNAs for the Management of Papillary Thyroid Carcinoma and Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features

Thyroid , Vol. 0, No. 0.


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Prediction of Tubulointerstitial Injury in Chronic Kidney Disease Using a Non-Invasive Model: Combination of Renal Sonography and Laboratory Biomarkers

Publication date: Available online 2 March 2018
Source:Ultrasound in Medicine & Biology
Author(s): Wen-Qi Yang, Shan Mou, Li Xu, Feng-Hua Li, Hong-Li Li
The goal of the study described here was to evaluate the degree of tubulointerstitial injury in patients with chronic kidney disease (CKD) using a more accurate model that combines renal sonographic parameters and laboratory biomarkers. A total of 308 patients were enrolled. The study protocol included conventional ultrasound, contrast-enhanced ultrasonography and renal biopsy. CKD patients were divided into normal and mild (≤25%), moderate (26%–50%) and severe (>50%) tubulointerstitial injury groups. We created a model comprising peak intensity, time to peak, urinary retinol-binding protein and β2-microglobulin that could discriminate severe (>50%) tubulointerstitial injury. The area under the receiver operating characteristic curve of this model was 0.832, which had better accuracy than other individual indexes, and the sensitivity and specificity were 74.2% and 82.8%, respectively. Therefore, this model may be used to evaluate the severity of tubulointerstitial injury and may have the potential to serve as an effective auxiliary method to help nephrologists evaluate patients with CKD.



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The Assessment of Diagnostic Accuracy for Basilar Artery Stenosis by Transcranial Color-Coded Sonography

Publication date: Available online 2 March 2018
Source:Ultrasound in Medicine & Biology
Author(s): Jie Yang, Yang Hua, Xiang Li, Mingjie Gao, Qiuping Li, Beibei Liu, Liqun Jiao
This study aimed to determine the optimal criteria for evaluating basilar artery stenosis (BAS) by transcranial color-coded sonography (TCCS). A total of 403 cases with both TCCS and digital subtraction angiography (DSA) were enrolled. Peak systolic velocity (PSV), end diastolic velocity (EDV) and mean flow velocity (MFV) of the basilar artery (BA), intracranial vertebral artery (IVA) and posterior cerebral artery (PCA) were measured. The ratios PSVBA/PSVIVA and PSVBA/PSVPCA were calculated. With DSA as the reference, the optimal criteria for grading BAS were determined by receiver operating characteristic analysis. They were as follows: PSV ≥110 cm/s, MFV ≥70 cm/s and PSVBA/PSVIVA ≥1.5 for <50% BAS; PSV ≥150 cm/s, MFV ≥90 cm/s and PSVBA/PSVIVA ≥2.0 for 50%–69% BAS; PSV ≥210 cm/s, MFV ≥120 cm/s and PSVBA/PSVIVA ≥3.0 for 70%–99% BAS. The combination of PSV, MFV and PSVBA/PSVIVA may increase the accuracy for diagnosing 70%–99% BAS.



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Engrafting human regulatory T cells with a flexible modular chimeric antigen receptor technology

Publication date: Available online 2 March 2018
Source:Journal of Autoimmunity
Author(s): Stefanie Koristka, Alexandra Kegler, Ralf Bergmann, Claudia Arndt, Anja Feldmann, Susann Albert, Marc Cartellieri, Armin Ehninger, Gerhard Ehninger, Jan Moritz Middeke, Martin Bornhäuser, Marc Schmitz, Jens Pietzsch, Katja Akgün, Tjalf Ziemssen, Jörg Steinbach, Michael P. Bachmann
As regulatory T cells (Tregs) play a fundamental role in immune homeostasis their adoptive transfer emerged as a promising treatment strategy for inflammation-related diseases. Preclinical animal models underline the superiority of antigen-specific Tregs compared to polyclonal cells. Here, we applied a modular chimeric antigen receptor (CAR) technology called UniCAR for generation of antigen-specific human Tregs. In contrast to conventional CARs, UniCAR-endowed Tregs are indirectly linked to their target cells via a separate targeting module (TM). Thus, transduced Tregs can be applied universally as their antigen-specificity is easily adjusted by TM exchange. Activation of UniCAR-engrafted Tregs occurred in strict dependence on the TM, facilitating a precise control over Treg activity. In order to augment efficacy and safety, different intracellular signaling domains were tested. Both 4-1BB (CD137) and CD28 costimulation induced strong suppressive function of genetically modified Tregs. However, in light of safety issues, UniCARs comprising a CD137-CD3ζ signaling domain emerged as constructs of choice for a clinical application of redirected Tregs. In that regard, Tregs isolated from patients suffering from autoimmune or inflammatory diseases were, for the first time, successfully engineered with UniCAR 137/ζ and efficiently suppressed patient-derived effector cells. Overall, the UniCAR platform represents a promising approach to improve Treg-based immunotherapies for tolerance induction.



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Complementary roles of two resilient neotropical mammalian seed dispersers

Publication date: April 2018
Source:Acta Oecologica, Volume 88
Author(s): Adriana de Almeida, Rebecca J. Morris, Owen T. Lewis, Sandra B. Mikich
Capuchin monkeys (Cebus spp. and Sapajus spp.) and coatis (Nasua spp.) coexist in most neotropical forests, including small forest remnants. Both capuchins and coatis eat fruit and disperse seeds, but little is known about whether their roles in seed dispersal are redundant or complementary. We compiled 49 studies from the literature on feeding by capuchins and/or coatis, of which 19 were comprehensive enough for our analyses. We determined the relative importance of fruit eating to each species and compared their diets. Additionally, we analysed the structure of three fruit–frugivore networks built with both animal groups and the fruits they eat and evaluated whether fruit traits influenced the network topology. Fruits represented the largest part of capuchin and coati diets, even though coatis have been known for their opportunistic and generalist diets. Capuchins and coatis also exhibited similar general diet parameters (niche breadth and trophic diversity). The three networks exhibited high connectance values and variable niche overlap. A Multiple Correspondence Analysis, failed to detect any trait or trait combination related to food use. In conclusion, capuchins and coatis both have generalist diets; they feed on many different species of fruits and exhibit important complementarity as seed dispersers. Both are likely to be particularly important seed dispersers in disturbed and fragmented forests.



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Multimodal Imaging of Pathologic Response to Chemoradiation in Esophageal Cancer

Publication date: Available online 2 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Penny Fang, Benjamin C. Musall, Jong Bum Son, Amy C. Moreno, Brian P. Hobbs, Brett W. Carter, Bryan M. Fellman, Osama Mawlawi, Jingfei Ma, Steven H. Lin
PurposeTo examine the value of early changes in quantitative diffusion-weighted imaging (DWI) and ¹⁸F-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for discriminating complete pathologic response (pCR) to chemoradiation (CRT) in esophageal cancer.MethodsTwenty esophageal cancer patients treated with chemoradiation followed by surgery were prospectively enrolled. Patients underwent MRI and FDG-PET/CT scans at baseline (BL), interim (IM, 2 weeks after CRT start), and first follow-up (FU). Based on pathologic findings at surgery, patients were categorized into tumor regression groups (TRG1, TRG2, and TRG3+). Distributions of summary statistics in apparent diffusion coefficient (ADC) and FDG-PET at BL and relative change at IM and FU scans were compared between pCR/TRG1 and non-pCR/TRG2+ groups and across readers. Receiver operating characteristics (ROCs) were evaluated for summary measures to characterize discrimination of pCR from non-pCR.ResultsRelative changes in tumor volume ADC (ΔADC) mean, 25^th and 10^th percentiles were able to completely discriminate (AUC=1, p<0.0011) between pCR and non-pCR (thresholds = 27.7%, 29.2%, and 32.1%, respectively) and were found to have high inter-reader reliability (95% limits of agreement of 1.001, 0.944 and 0.940, respectively). Relative change in total lesion glycolysis (TLG) from BL to IM was significantly different among pCR and non-pCR groups (p=0.0117) and yielded AUC of 0.947 (95% CI: 0.8505-1.043). An optimal threshold of 59% decrease in TLG provided optimal sensitivity (specificity) of 1.000 (0.867). Changes in ADC summary measures were negatively correlated with that of TLG (Spearman, -0.495, p=0.027).ConclusionQuantitative volume ΔADC and TLG during treatment may serve as early imaging biomarkers for discriminating pathologic response to chemoradiation in esophageal cancer. Validation of this data in larger prospective multicenter studies is essential.



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A Phase II Study of Stereotactic Body Radiotherapy and Stereotactic Body Proton Therapy for High-Risk Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

Publication date: Available online 2 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Chonnipa Nantavithya, Daniel R. Gomez, Xiong Wei, Ritsuko Komaki, Zhongxing Liao, Steven H. Lin, Melenda Jeter, Quynh-Nhu Nguyen, Heng Li, Xiaodong Zhang, Falk Poenisch, X Ronald Zhu, Peter A. Balter, Lei Feng, Noah C. Choi, Radhe Mohan, Joe Y. Chang
PurposeTo report the feasibility of conducting a randomized study to compare the toxicity and efficacy of stereotactic body radiotherapy (SBRT) versus stereotactic body proton therapy (SBPT) for high-risk medically inoperable early-stage non-small cell lung cancer (NSCLC).Methods and MaterialsWe randomly assigned patients with medically inoperable NSCLC with high-risk features (centrally located or <5 cm-T3 tumor or isolated lung parenchymal recurrences) to SBRT or SBPT. Radiation dose was 50 Gy(RBE) in four 12.5-Gy(RBE) fractions prescribed to the planning target volume. SBRT was given using 3-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT), and SBPT was given using passive scattering. Consistency in patient setup was ensured with on-board cone-beam computed tomography for the SBRT group and with orthogonal X-rays for the SBPT group.ResultsThe study closed early owing to poor accrual, largely because of insurance coverage, and lack of volumetric imaging in the SBPT group. Ultimately, 21 patients were enrolled, and 19 patients who received 50 Gy in 4 fractions were included for analysis (9 SBRT, 10 SBPT). At a median follow-up time of 32 months, median overall survival (OS) time was 28 months in the SBRT group and not reached in the SBPT group. Three-years OS was 27.8% and 90%, 3-year local control (LC) was 87.5% (8/9) and 90.0% (9/10) and 3-years regional control (RC) was 47.6% (5/9) and 90% (9/10) in SBRT and SBPT respectively. One patient in the SBPT group developed grade 3 skin fibrosis. No patients experienced grade 4/5 toxicity.ConclusionPoor accrual, due to lack of volumetric image and insurance coverage for proton therapy led to early closure of the trial and precluded accurate assessment of efficacy and toxicity. Comparable maturity of two radiotherapy modalities, particularly on-board image, and better insurance coverage for SBPT should be considered for the future studies.

Teaser

A phase II randomized study to compare SBRT vs. SBPT was terminated early due to poor accrual; treatment outcomes after SBPT appeared no worse than those after SBRT numerically with low treatment related toxicity in both groups. Lack of volumetric imaging and insurance coverage for patients treated with SBPT were the major barriers to accrual. In addition to financial issues, similar maturity of treatment planning and imaged-guided delivery are essential for future comparison studies between proton and photon therapy.


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Correlation Between Tumor Metabolism and Semiquantitative Perfusion MRI Metrics in Non-small Cell Lung Cancer

Publication date: Available online 2 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Sang Ho Lee, Andreas Rimner, Emily Gelb, Joseph O. Deasy, Margie A. Hunt, John L. Humm, Neelam Tyagi
PurposeTo correlate semiquantitative parameters derived from dynamic contrast-enhanced MRI (DCE-MRI) and ¹⁸F-FDG-PET for non-small cell lung cancer (NSCLC).MethodsTwenty-four NSCLC patients who underwent pretreatment ¹⁸F-FDG-PET and DCE-MRI were analyzed. The maximum standardized uptake value (SUVmax) was measured from ¹⁸F-FDG-PET. DCE-MRI was obtained on 3T MRI scanner using four-dimensional T1-weighted high-resolution imaging with volume excitation sequence. DCE-MRI parameters consisting of mean, median, standard deviation (SD), and median absolute deviation (MAD) of peak enhancement, time-to-peak (TTP), time-to-half-peak (TTHP), wash-in slope (WIS), wash-out slope (WOS), initial gradient, wash-out gradient, signal enhancement ratio, and initial area under the relative signal enhancement curve taken up to 30, 60, 90, 120, 150, and 180 s, TTP, and TTHP (IAUCtthp) were calculated for each lesion. Univariate analysis (UVA) was performed using Spearman correlation. A linear regression model to predict SUVmax from DCE-MRI parameters was developed by multivariate analysis (MVA) using least absolute shrinkage selection operator in combination with leave-one-out cross-validation (LOOCV).ResultsIn UVA, mean(WOS) (ρ = -0.456, p = 0.025), mean(IAUCtthp) (ρ = -0.439, p = 0.032), median(IAUCtthp) (ρ = -0.543, p = 0.006), and MAD(IAUCtthp) (ρ = -0.557, p = 0.005) were statistically significant; all these parameters were negatively correlated with SUVmax. In MVA, a linear combination of SD(WIS), SD(TTP), MAD(TTHP), and MAD(IAUCtthp) was statistically significant for predicting SUVmax (LOOCV-based adjusted R² = 0.298, p = 0.0006). A decrease in SD(WIS), MAD(TTHP), and MAD(IAUCtthp) and an increase in SD(TTP) were associated with a significant increase in SUVmax.ConclusionAssociation was found between SUVmax, the SD, and MAD of DCE-MRI metrics derived during contrast uptake in NSCLC, reflecting that intratumoral heterogeneity in wash-in contrast kinetics is associated with tumor metabolism. Although MAD(IAUCtthp) was a significant feature in both UVA and MVA, the LASSO-based multivariate regression model yielded better predictability of SUVmax than a univariate regression model using MAD(IAUCtthp). This study will facilitate understanding of the complex relationship between tumor vascularization and metabolism, and eventually help in guiding targeted therapy.

Teaser

Balance between vascularity and glucose metabolism in tumor could prove to be an important indicator of its biological status and resistance to treatment. This study evaluates the use of semiquantitative dynamic contrast-enhanced MRI parameters for predicting the ¹⁸F-FDG-PET maximum standardized uptake value in non-small cell lung cancer (NSCLC). It was found that intratumoral heterogeneity in wash-in contrast kinetics is associated with tumor metabolism. Investigating vascular-metabolic relationship will help in guiding personalized targeted therapy in NSCLC.


http://ift.tt/2FaAi5t

Using Big Data Analytics to Advance Precision Radiation Oncology

Publication date: Available online 2 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Todd R. McNutt, Stanley H. Benedict, Daniel A. Low, Kevin Moore, Ilya Shpitser, Wei Jiang, Pranav Lakshminarayanan, Zhi Cheng, Peijin Han, Xuan Hui, Minoru Nakatsugawa, Junghoon Lee, Joseph A. Moore, Scott P. Robertson, Veeraj Shah, Russ Taylor, Harry Quon, John Wong, Theodore DeWeese
Big Clinical Data Analytics as a primary component of precision medicine is discussed, ] identifying where these emerging tools fit in the spectrum of genomic and radiomic research. A learning health system (LHS) is conceptualized that utilizes clinically acquired data with machine learning to advance the initiatives of precision medicine. The LHS is comprehensive and can be used for clinical decision support, discovery, and hypothesis derivation. These developing uses can positively impact the ultimate management and therapeutic course for patients. The conceptual model for each use of clinical data, is however different, and an overview of the implications is discussed. With advancement in technologies and culture to improve the efficiency, accuracy and breadth of measurements of the patient condition, the concept of a LHS may be realized in precision radiotherapy.



http://ift.tt/2teHU5a

Esophagus toxicity after stereotactic and hypofractionated radiotherapy for central lung tumors: Normal tissue complication probability modeling

Publication date: Available online 2 March 2018
Source:Radiotherapy and Oncology
Author(s): M. Duijm, H. Tekatli, E. Oomen-de Hoop, W. Verbakel, W. Schillemans, B.J. Slotman, S. Senan, J.J. Nuyttens
PurposeTo correlate esophagus toxicity and dose-volume histogram (DVH) parameters in order to assess risks, and derive a Normal Tissue Complication Probability (NTCP) model.Methods and materialsPatients with a central lung tumor from 2 centers, who underwent stereotactic or hypofractionated radiotherapy (≤12 fractions), were analyzed. Doses were recalculated to an equivalent dose of 2 Gy with an α/β ratio of 10 (EQD2¹⁰). The esophagus was manually delineated and DVH-parameters (Dmax,EQD2, D1cc,EQD2, D2cc,EQD2, D5cc,EQD2) were analyzed and used for NTCP modeling based on logistic regression analysis.ResultsTwo-hundred-and-thirty-one patients with 252 tumors were eligible. No acute or late grade 3–5 esophageal toxicity was reported. Acute grade 1–2 esophagus toxicity was recorded in 38 patients (17%). All DVH-parameters were significantly higher in patients with toxicity. NTCP models showed a 50% probability of acute grade 1–2 toxicity at a Dmax of 67 Gy EQD2¹⁰ and D1cc of 42 Gy EQD2¹⁰. No difference in overall survival was observed between patients with and without toxicity (p = 0.428).ConclusionAs no grade 3–5 esophageal toxicity was observed in our cohort, a Dmax of 56 Gy EQD2¹⁰ and a D5cc of 35.5 Gy EQD2¹⁰ could be delivered without high risks of severe toxicity. The NTCP models of this study might be used as practical guidelines for the treatment of central lung tumors with stereotactic radiotherapy.



http://ift.tt/2F8nyvW

Imaging biomarkers of outcome after radiotherapy for pediatric ependymoma

Publication date: Available online 2 March 2018
Source:Radiotherapy and Oncology
Author(s): Fatima Tensaouti, Anne Ducassou, Léonor Chaltiel, Annick Sevely, Stéphanie Bolle, Laetitia Padovani, Anais Jouin, Claire Alapetite, Stéphane Supiot, Aymeri Huchet, Valérie Bernier, Line Claude, Christine Kerr, Elisabeth Le Prisé, Anne-Isabelle Bertozzi-Salamon, Samuel Liceaga, Jean Albert Lotterie, Patrice Péran, Anne Laprie
Background and purposeEpendymoma is the third most common brain tumor in children. Radiation therapy (RT) is systematically administered after maximum surgical resection, utilizing recent advances in radiation delivery. Imaging can make a significant contribution to improving treatment outcome. This prompted us to look for significant preoperative and postoperative imaging markers for survival.Material and methodsWe undertook a national retrospective review of 121 patients who had undergone resection followed by RT. Preoperative tumor volumes on T1 and FLAIR images were delineated, together with postoperative hyperintense volumes on FLAIR images. Overall survival (OS) and disease-free survival (DFS) analyses included clinical data and volumes extracted from images.ResultsAfter a median follow-up of 38.5 months, 80.2% of patients were alive, but 39.7% had experienced at least one event. Statistically significant differences between patients with and without postoperative FLAIR abnormalities were found for both DFS (71.9% vs. 40.3%; p = 0.006) and OS (93.7% vs. 72.4%; p = 0.023) in the univariate analyses, and for OS (p = 0.049) in the multivariate analyses.ConclusionsPostoperative FLAIR hyperintensities are a negative prognostic factor for intracranial ependymoma and may be a surrogate for residual disease. They could therefore prove helpful in patients' surgical and radiotherapeutic management.



http://ift.tt/2FQ4jbS

Optimal image guided radiation therapy strategy for organs at risk sparing in radiotherapy of the prostate including pelvic lymph nodes

Publication date: Available online 2 March 2018
Source:Radiotherapy and Oncology
Author(s): A. van Nunen, P.P.G. van der Toorn, T.C.G. Budiharto, D. Schuring
Background and purposePurpose of this study was to quantify the OAR dose for different position correction strategies, and to determine which strategy is most optimal for treating patients on the prostate and pelvic lymph nodes.Materials and methodsFor 30 patients, four different treatment plans were made reflecting different correction strategies: online correction on bony anatomy; offline correction on bony anatomy; online correction on the prostate fiducials; using 1 cm margins around both CTVs. The dose to the PTVs and OARs was quantified and a pairwise statistical analysis was performed.ResultsNo statistically significant differences were observed in the dose to the PTVs, ensuring that any OAR sparing is not caused by differences in PTV coverage. Dose to the rectum and anal canal was lowest when applying an online correction on prostate fiducials, although the total PTV volume was higher. Dose to the small bowel bag and femoral heads was slightly higher compared to online correction on bony structures, but well within clinically acceptable limits.ConclusionAlthough the total PTV volume is higher when applying an online correction on the prostate, this strategy leads to the most optimal sparing of relevant OARs, at the cost of a slightly higher dose to the femoral heads and small bowel bag.



http://ift.tt/2FMLuWJ

Correction to: Multi-sensor temporal assessment of tropospheric nitrogen dioxide column densities over Pakistan

Abstract

The present address of Rabbia Murtaza is shown in this paper. (please tag the affiliation below, this is only for Rabbia Murtaza)

http://ift.tt/2HYsci3

[Pyroptosis and stroke].

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[Pyroptosis and stroke].

Sheng Li Xue Bao. 2018 Feb 25;70(1):93-98

Authors: Tang B, Deng CQ

Abstract
Pyroptosis is a form of inflammatory programmed cell death activated by caspase-1 and caspase-4/5/11, and involves in the pathogenesis of infectious diseases and nervous system diseases. Pyroptosis is mediated by canonical inflammasome pathway and non-canonical inflammasome pathway. The canonical inflammasome pathway is activated in stroke and aggravates brain injury. Inhibition of inflammasome, caspase-1, IL-1β and IL-18 ameliorates brain injury. These studies indicate that canonical inflammasome pathway contributes to post-stroke brain injury, therefore, pyroptosis has become a potential therapeutic target for preventing excessive cell death during stroke. We reviewed the relationship between pyroptosis and stroke to provide some perspectives on future researches in this field.

PMID: 29492520 [PubMed - in process]

http://ift.tt/2HV4ItY

[Superior colliculus-pulvinar-amygdala subcortical visual pathway and its biological significance].

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[Superior colliculus-pulvinar-amygdala subcortical visual pathway and its biological significance].

Sheng Li Xue Bao. 2018 Feb 25;70(1):79-84

Authors: Wang L, Yang LC, Meng QL, Ma YY

Abstract
Superior colliculus-pulvinar-amygdala pathway is one of the subcortical visual pathways in mammalian brain. Some recent studies suggest that this pathway is involved in processing emotion-related visual information. This review discusses the possibility that this pathway is more related to visual alert rather than simply the early visual information processing. The biological significance of this pathway is also discussed. Instead of detecting "where" or "what" the visual target is, the task of this early visual stage is to send out a warning signal, i.e., "something appears", so that the brain can be set up in a state of alert, which is important for the survival of animals. Thus, in the early visual information process, detection of new object "emerging" or "disappearing" takes priority over the acquisition of its feature information of "texture" and "shape", etc. The subcortical pathway may provide the neural basis of early visual warning in topological perception, a biological significance critical for animal survival.

PMID: 29492518 [PubMed - in process]

http://ift.tt/2tcLfBL

[Advances in neurobiological mechanisms of comorbid depression and gastrointestinal disease].

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[Advances in neurobiological mechanisms of comorbid depression and gastrointestinal disease].

Sheng Li Xue Bao. 2018 Feb 25;70(1):71-78

Authors: Zhang T, Linghu T, Zhang X, Tian JS, Qin XM

Abstract
Depression is a common mood disorder, which is harmful to public health critically. Gastrointestinal diseases are a series of diseases with both dynamic changes and organic disease, including functional gastrointestinal disease, gastroesophageal reflux disease, gastritis, and gastric ulcer. In recent years, the phenomena of comorbid depression and gastrointestinal disease have become common, however, most patients were diagnosed as unilateral depression or gastrointestinal disease in the clinical treatment process, resulting in delayed treatment or even invalid. The present review focuses on some of the clinical symptoms of comorbid depression and gastrointestinal disease, and begins to explore the possible pathogenesis, so as to find out the potential neurobiological pathways of comorbidity. Consequently, the more attention on comorbid depression and gastrointestinal disease will be paid, and the clinical and basic research of comorbidity and the drug development will be provided.

PMID: 29492517 [PubMed - in process]

http://ift.tt/2oAVDyD

[Insulin and cardiovascular protection: from bench to bedside].

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[Insulin and cardiovascular protection: from bench to bedside].

Sheng Li Xue Bao. 2018 Feb 25;70(1):61-70

Authors: Zhang HF, Zhang X, Gao F

Abstract
Insulin resistance is "common soil" of many major cardiovascular diseases, such as diabetes, coronary heart disease, hypertension and heart failure. Recent studies have revealed that, in addition to metabolic modulation, insulin exerts direct cardiovascular protective effects. This article reviews the current progresses in the pathogenesis and cardiovascular protection strategies of metabolic cardiovascular diseases, and highlights the mechanism of actions of insulin in cardiovascular protection.

PMID: 29492516 [PubMed - in process]

http://ift.tt/2H1rPBN

[The glymphatic system: concept, function and research progresses].

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[The glymphatic system: concept, function and research progresses].

Sheng Li Xue Bao. 2018 Feb 25;70(1):52-60

Authors: Wang LH, Wang ZL, Chen WY, Chen MJ, Xu GY

Abstract
The glymphatic system is a cerebrospinal fluid-interstitial fluid exchange system dependent on the water channel aquaporin-4 polarized on astrocyte endfeet, which is proposed to account for the clearance of abnormal proteins (e.g. β-amyloid) and metabolites (e.g. lactate) from the brain. Accumulating studies have revealed that glymphatic activity during sleep and general anesthesia is dramatically enhanced, while its function is significantly damaged during aging, traumatic brain injury, Alzheimer's disease, stroke, and diabetes. The glymphatic hypothesis is a breakthrough in the field of neuroscience recently, which would considerably enhance our comprehension on the cerebrospinal fluid circulation and its role in the maintenance of brain homeostasis. In this review, we briefly introduced the conceptualization of glymphatic system, summarized the recent progresses, and prospected its future investigation and potential clinical application.

PMID: 29492515 [PubMed - in process]

http://ift.tt/2GXmn3d

[An improved method for in vivo electroporation of morpholinos into the adult zebrafish retina].

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[An improved method for in vivo electroporation of morpholinos into the adult zebrafish retina].

Sheng Li Xue Bao. 2018 Feb 25;70(1):47-51

Authors: Hou HT, Lv JY, Zhang ZQ, Lu Y, Zhou CP, Zhou TQ, Zhang SQ, Xu H

Abstract
In vivo electroporation of morpholinos (MOs) into the retina of adult zebrafish is an efficient method to study gene function related to retinal disease and regeneration. However, the currently reported methods are complicated with low MO transfer efficiency and high probability to cause collateral damage. The present study was aimed to optimize the existing MO electroporation methods. Two major changes were made to MO electroporation procedure in zebrafish retina. One was to coat the inner side of the electrode with ultrasonic gel. The other was to replace the commonly used round electrode with novel rectangular one. The results showed that the use of ultrasonic gel reduced collateral damage caused by retinal electroporation and simplified the experimental procedure. The rectangular electrode significantly increased transfection efficiency of MO electroporation. In particular, knocking down the expression of Ascl1a in the retina by using our method significantly inhibited the generation of retinal progenitor cells. These results suggest our method is the optimization of the current MO electroporation methods and may be a better alternative for relevant researchers.

PMID: 29492514 [PubMed - in process]

http://ift.tt/2oDFLLF

[Hirsutine induces apoptosis of human breast cancer MDA-MB-231 cells through mitochondrial pathway].

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[Hirsutine induces apoptosis of human breast cancer MDA-MB-231 cells through mitochondrial pathway].

Sheng Li Xue Bao. 2018 Feb 25;70(1):40-46

Authors: Huang QW, Zhai NN, Huang T, Li DM

Abstract
The aim of this study was to investigate the effects of hirsutine on apoptosis of breast cancer cells and its possible mechanism. The MCF-10A, MCF-7 and MDA-MB-231 cells were treated with hirsutine at different concentrations for 48 h or incubated with 160 μmol/L hirsutine for 24, 48, and 72 h. The MCF-10A cell line is a non-tumorigenic epithelial cell line, and the MCF-7 and MDA-MB-231 are human breast adenocarcinoma cell lines. CCK-8 assay was employed to detect the cell viability. Flow cytometry was used to assay the apoptosis and mitochondrial membrane potential (MMP). The protein expressions of Bcl-2, Bax, cleaved-caspase 9, cleaved-caspase 3 and cytochrome C (Cyt C) in the MDA-MB-231 cells were detected by Western blotting. The results showed that hirsutine remarkably reduced the viability of MCF-7 and MDA-MB-231 cells in a time- and dose-dependent manner (P < 0.05) with IC50 values of 447.79 and 179.06 μmol/L, respectively. In the MDA-MB-231 cells, hirsutine induced apoptosis and depolarization of MMP (P < 0.05), released Cyt C from mitochondria (P < 0.05), and activated caspase 9 and caspase 3 (P < 0.05). However, these effects induced by hirsutine were all inhibited by cyclosporin A (CsA) (P < 0.05), a specific inhibitor of mitochondrial permeability transition pore (MPTP). In addition, hirsutine down-regulated the protein level of Bcl-2 and up-regulated the protein level of Bax (P < 0.05). These results suggest that hirsutine may induce apoptosis of human breast cancer MDA-MB-231 cells through decreasing the ratio of Bcl-2 to Bax, opening MPTP, releasing Cyt C from mitochondria, and activating caspase 9 and caspase 3.

PMID: 29492513 [PubMed - in process]

http://ift.tt/2t9Vvef

[Acetylcholine suppresses microglial inflammatory response in rats via acting on microglial α7nAChR].

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[Acetylcholine suppresses microglial inflammatory response in rats via acting on microglial α7nAChR].

Sheng Li Xue Bao. 2018 Feb 25;70(1):33-39

Authors: Jiang YY, Li L, Shen WX, Qiu YH, Peng YP

Abstract
Microglia are the main immune cells in the central nervous system. In the present study, the mechanism for acetylcholine (ACh) inhibiting microglial inflammatory response was investigated. Primary culture of microglia was isolated from cerebral cortex of Sprague-Dawley (SD) rats. Lipopolysaccharide (LPS) was used to activate the microglia to induce inflammatory response, and then the microglia were treated with ACh for 24 h. Protein expressions of several inflammatory factors, insulin-like growth factor 1 (IGF-1) and α7 nicotinic acetylcholine receptor (α7nAChR) were detected by Western blot. Release of inflammatory factors and IGF-1 into media was detected by ELISA. After α7nAChR gene silence was achieved by lentivirus-transfection of α7nAChR-shRNA, the change of ACh effect was observed. The results showed that LPS induced microglial activation, up-regulated inducible nitric oxide synthase (iNOS) protein expression, increased the expressions and release of IL-1β and TNF-α, and decreased the expression and release of the neurotrophic factor, IGF-1. ACh could reverse these effects of LPS. Meanwhile, LPS reduced the protein expression of α7nAChR on the microglial cells, whereas ACh could reverse the effect. Silencing of α7nAChR gene in microglia abolished the ability of ACh to inhibit LPS-induced inflammatory responses. These results suggest that ACh exerts its protection against LPS-induced microglial inflammation via acting on α7nAChR on microglia, which may provide a novel target for the treatment of neuro-inflammatory diseases.

PMID: 29492512 [PubMed - in process]

http://ift.tt/2F89qH3

[Macrophages depletion impairs skeletal muscle regeneration by regulating inflammation and oxidative stress levels].

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[Macrophages depletion impairs skeletal muscle regeneration by regulating inflammation and oxidative stress levels].

Sheng Li Xue Bao. 2018 Feb 25;70(1):23-32

Authors: Liu XG, Chen PJ, Zhao LL, Zeng ZG, Xiao WH

Abstract
The objective of this study was to explore the roles of macrophages in the regeneration of injured skeletal muscle and the mechanisms involved. Mice were randomly divided into the following groups: muscle contusion (S), muscle contusion control (SCon), macrophages depleted (T) and macrophages depleted control (TCon) groups. Muscle contusion model was created by high-energy blunt injury. Macrophages depletion model was constructed by injection of clodronate-liposomes. Their gastrocnemius muscles were harvested at the time points of 1, 3, 7 and 14 d post-injury. The changes in skeletal muscle morphology were assessed by hematoxylin-eosin (HE) staining and Masson's trichrome staining. The mRNA and protein levels of inflammatory cytokines, chemokines and oxidative stress factors were analyzed by real-time polymerase chain reaction (RCR) and Western blotting, respectively. HE staining results showed that a small amount of regenerating myofibers were observed in the S group (14 d post-injury), whereas a large number of regenerating muscle fibers were observed in the T group. Quantitative analyses showed that the sizes of regenerating myofibers were significantly smaller in the T group as compared with the S group at 14 d post-injury (P < 0.05). At the same time, Masson staining results showed that macrophage depletion significantly increased the area of fibrosis as compared with the S group at 14 d post-injury (P < 0.01). The expression levels of inflammatory cytokines, chemokines, and oxidative stress factors were increased significantly after muscle injury. Moreover, macrophage depletion increased the expressions of inflammatory cytokines, chemokines and oxidative stress factors as compared with the S group during the later stage of injury (7-14 d post-injury). These results suggest that macrophages depletion can aggravate fibrosis and impair muscle regeneration, and inflammatory cytokines, chemokines and oxidative stress factors may be involved in this process.

PMID: 29492511 [PubMed - in process]

http://ift.tt/2FLxRai

[Effect of different concentrations of calcitonin gene-related peptide on the long-term potentiation in hippocampus of mice].

Related Articles

[Effect of different concentrations of calcitonin gene-related peptide on the long-term potentiation in hippocampus of mice].

Sheng Li Xue Bao. 2018 Feb 25;70(1):17-22

Authors: Wu X, Zheng WJ, Lv MH, Su SH, Zhang SJ, Gao JF

Abstract
The purpose of this study was to explore the effects of different concentrations of calcitonin gene-related peptide (CGRP) on long-term potentiation (LTP) in the hippocampus of mice. C57BL/6J mice (30 days old) were randomly divided into control group, three CGRP groups, and CGRP + CGRP8-37 group (10 mice for each group). Different concentrations of CGRP (50, 100 and 200 nmol/L) were given to the hippocampal slices of mice. The presynaptic release of neurotransmitters and the induction of LTP were measured by extracellular field recording techniques. The result showed that different concentrations of CGRP did not affect the presynaptic release of neurotransmitters, but 100 and 200 nmol/L CGRP increased the amplitude of LTP induced in the hippocampus of mice. This facilitation effect of CGRP was blocked by its specific antagonist CGRP8-37. These results suggest that CGRP dose-dependently facilitates the induction of LTP in the hippocampus of mice through its specific receptor.

PMID: 29492510 [PubMed - in process]

http://ift.tt/2GVnyzZ

[Functional plasticity of trigeminal motor nucleus in unilateral mastication model rats].

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[Functional plasticity of trigeminal motor nucleus in unilateral mastication model rats].

Sheng Li Xue Bao. 2018 Feb 25;70(1):9-16

Authors: Wang Y, Yu LF, Wang MY

Abstract
To observe the plasticity changes of trigeminal motor nucleus (Mo5) and masseter H-reflex in unilateral mastication model rats and explore the possible mechanism of functional plasticity in motor center involved in unilateral mastication, 54 adult male Wistar rats were randomly divided into 1-month (n = 10), 3-month (n = 10), and 16-month (n = 7) model groups and their corresponding control groups, respectively. Unilateral mastication model rats were prepared by intermittent removal of clinical crowns of left teeth (model side). Rats were anesthetized (20% urethane, i.p.), and bilateral Mo5 were chosen to conduct extracellular recordings, while bilateral electromyography (EMG) of masseter muscle and its H-reflex were simultaneously recorded by a polygraph. It was observed that the firing rate of Mo5 neurons in model sides was significantly lower than that of right sides in 3 model groups, and that of left sides in their control groups. The response latency of Mo5, which was evoked by electrical stimulation of masseter nerve in model sides of 1-month and 3-month model groups, was significantly longer than that of left sides in their control groups. Moreover, the amplitude of H-wave in model sides of 3-month and 16-month model groups was lower than that of left sides in their control groups when H-reflex was evoked by electrical stimulation of left masseter nerve. These results suggest that unilateral mastication in model rats decreases the Mo5 neuron excitability, and this may be one of the functional plasticity mechanisms in motor center involved in unilateral mastication.

PMID: 29492509 [PubMed - in process]

http://ift.tt/2F89eaN

RNA-binding protein HuR regulates hsa-let-7c expression by its RNA recognition motif.

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RNA-binding protein HuR regulates hsa-let-7c expression by its RNA recognition motif.

Sheng Li Xue Bao. 2018 Feb 25;70(1):1-8

Authors: Song Y, Feng W, Shi GM, Chen C, Zhang YY

Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that control diverse cellular and developmental events through repression of large sets of target mRNAs. miRNAs expressions were mainly regulated at two levels: transcriptional and post-transcriptional. Transcriptional regulation of miRNA-encoding genes produce specific expression patterns of individual miRNA. However, the mechanism of post-transcriptional regulation of miRNAs remains largely unknown. The present study was aimed to clarify whether HuR, an evolutionary conserved AU-rich binding protein, could regulate miRNAs expressions. By means of a computational screen for AUUUA motifs within pri-miRNAs, we found that the downstream of hsa-let-7c but not hsa-miR-21 was enriched of AUUUA motifs. Then we transfected HuR and mutant HuR lacking RNA recognition motif 3 (RRM3) respectively into HEK293T cells. And HuR protein and miRNAs expressions were detected by Western blot and real-time PCR, respectively. The results showed that the overexpression of HuR promoted mature hsa-let-7c expression but not hsa-miR-21 expression. Furthermore, overexpression of HuR deletion mutant lacking RRM3 did not promote hsa-let-7c expression. These results suggest that RRM3 is crucial for HuR mediating mature hsa-let-7c expression. Collectively, these findings proposed a novel role of HuR in biogenesis of miRNAs, possibly by way of post-transcriptional regulation of miRNAs.

PMID: 29492508 [PubMed - in process]

http://ift.tt/2teTJbL

Radial nerve injury following dry needling

Robin McManus<br />Jan 26, 2018; 2018:bcr-2017-221302-bcr-2017-221302<br />Case report

http://ift.tt/2oNOha7

Integration of reward with cost anticipation during performance monitoring revealed by ERPs and EEG spectral perturbations

Publication date: June 2018
Source:NeuroImage, Volume 173
Author(s): Davide Gheza, Rudi De Raedt, Chris Baeken, Gilles Pourtois
Effort expenditure has an aversive connotation and it can lower hedonic feelings. In this study, we explored the electrophysiological correlates of the complex interplay of reward processing with cost anticipation. To this aim, healthy adult participants performed a gambling task where the outcome (monetary reward vs. no-reward) and its expectancy were manipulated on a trial by trial basis while 64-channel EEG was recorded. Crucially, on some trials, the no-reward outcome could be transformed to a rewarding one, pending effort expenditure by means of an orthogonal dot clicking task, enabling us to compare at the electrophysiological level reward processing when cost was anticipated or not. We extracted and compared different markers of reward processing at the feedback level using both classical ERPs and EEG spectral perturbations in specific bands (theta, delta and beta-gamma). At the behavioral level, participants reported enhanced pleasure and relief when the outcome was rewarding but effort expenditure could be avoided, relative to a control condition where the outcome was rewarding but no extra effort was anticipated. In this condition, EEG results showed a larger Reward Positivity ERP component and increased power in the Delta and Beta-gamma bands. By comparison, cost anticipation did not influence the processing of the no-reward outcome at the FRN and frontal midline theta levels. All together, these neurophysiological results suggest that effort avoidance is associated with increased reward processing.



http://ift.tt/2HVR2z7

Effects of resting state condition on reliability, trait specificity, and network connectivity of brain function measured with arterial spin labeled perfusion MRI

Publication date: June 2018
Source:NeuroImage, Volume 173
Author(s): Zhengjun Li, Marta Vidorreta, Natalie Katchmar, David C. Alsop, Daniel H. Wolf, John A. Detre
Resting state fMRI (rs-fMRI) provides imaging biomarkers of task-independent brain function that can be associated with clinical variables or modulated by interventions such as behavioral training or pharmacological manipulations. These biomarkers include time-averaged regional brain function as manifested by regional cerebral blood flow (CBF) measured using arterial spin labeled (ASL) perfusion MRI and correlated temporal fluctuations of function across brain networks with either ASL or blood oxygenation level dependent (BOLD) fMRI. Resting-state studies are typically carried out using just one of several prescribed state conditions such as eyes closed (EC), eyes open (EO), or visual fixation on a cross-hair (FIX), which may affect the reliability and specificity of rs-fMRI. In this study, we collected test-retest ASL MRI data during 4 resting-state task conditions: EC, EO, FIX and PVT (low-frequency psychomotor vigilance task), and examined the effects of these task conditions on reliability and reproducibility as well as trait specificity of regional brain function. We also acquired resting-state BOLD fMRI under FIX and compared the network connectivity reliabilities between the four ASL conditions and the BOLD FIX condition. For resting-state ASL data, EC provided the highest CBF reliability, reproducibility, trait specificity, and network connectivity reliability, followed by EO, while FIX was lowest on all of these measures. PVT demonstrated lower CBF reliability, reproducibility and trait specificity than EO and EC. Overall network connectivity reliability was comparable between ASL and BOLD. Our findings confirm ASL CBF as a reliable, stable, and consistent measure of resting-state regional brain function and support the use of EC or EO over FIX and PVT as the resting-state condition.



http://ift.tt/2oIn0WG

Stress affects the neural ensemble for integrating new information and prior knowledge

Publication date: June 2018
Source:NeuroImage, Volume 173
Author(s): Susanne Vogel, Lisa Marieke Kluen, Guillén Fernández, Lars Schwabe
Prior knowledge, represented as a schema, facilitates memory encoding. This schema-related learning is assumed to rely on the medial prefrontal cortex (mPFC) that rapidly integrates new information into the schema, whereas schema-incongruent or novel information is encoded by the hippocampus. Stress is a powerful modulator of prefrontal and hippocampal functioning and first studies suggest a stress-induced deficit of schema-related learning. However, the underlying neural mechanism is currently unknown. To investigate the neural basis of a stress-induced schema-related learning impairment, participants first acquired a schema. One day later, they underwent a stress induction or a control procedure before learning schema-related and novel information in the MRI scanner. In line with previous studies, learning schema-related compared to novel information activated the mPFC, angular gyrus, and precuneus. Stress, however, affected the neural ensemble activated during learning. Whereas the control group distinguished between sets of brain regions for related and novel information, stressed individuals engaged the hippocampus even when a relevant schema was present. Additionally, stressed participants displayed aberrant functional connectivity between brain regions involved in schema processing when encoding novel information. The failure to segregate functional connectivity patterns depending on the presence of prior knowledge was linked to impaired performance after stress. Our results show that stress affects the neural ensemble underlying the efficient use of schemas during learning. These findings may have relevant implications for clinical and educational settings.



http://ift.tt/2I2776s

Exploring the origins of EEG motion artefacts during simultaneous fMRI acquisition: Implications for motion artefact correction

Publication date: June 2018
Source:NeuroImage, Volume 173
Author(s): Glyn S. Spencer, James A. Smith, Muhammad E.H. Chowdhury, Richard Bowtell, Karen J. Mullinger
Motion artefacts (MAs) are induced within EEG data collected simultaneously with fMRI when the subject's head rotates relative to the magnetic field. The effects of these artefacts have generally been ameliorated by removing periods of data during which large artefact voltages appear in the EEG traces. However, even when combined with other standard post-processing methods, this strategy does not remove smaller MAs which can dominate the neuronal signals of interest. A number of methods are therefore being developed to characterise the MA by measuring reference signals and then using these in artefact correction. These methods generally assume that the head and EEG cap, plus any attached sensors, form a rigid body which can be characterised by a standard set of six motion parameters. Here we investigate the motion of the head/EEG cap system to provide a better understanding of MAs. We focus on the reference layer artefact subtraction (RLAS) approach, as this allows measurement of a separate reference signal for each electrode that is being used to measure brain activity.Through a series of experiments on phantoms and subjects, we find that movement of the EEG cap relative to the phantom and skin on the forehead is relatively small and that this non-rigid body movement does not appear to cause considerable discrepancy in artefacts between the scalp and reference signals. However, differences in the amplitude of these signals is observed which may be due to differences in geometry of the system from which the reference signals are measured compared with the brain signals. In addition, we find that there is non-rigid body movement of the skull and skin which produces an additional MA component for a head shake, which is not present for a head nod. This results in a large discrepancy in the amplitude and temporal profile of the MA measured on the scalp and reference layer, reducing the efficacy of MA correction based on the reference signals.Together our data suggest that the efficacy of the correction of MA using any reference-based system is likely to differ for different types of head movement with head shake being the hardest to correct. This provides new information to inform the development of hardware and post-processing methods for removing MAs from EEG data acquired simultaneously with fMRI data.



http://ift.tt/2oMLw93

"Ear Nose Throat J"[jour]; +22 new citations

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Ear Nose Throat J"[jour]

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http://ift.tt/2oL2d4F

Recovery of low volumes of wear debris from rat stifle joint tissues using a novel particle isolation method

Publication date: Available online 2 March 2018
Source:Acta Biomaterialia
Author(s): J. Patel, S. Lal, K. Nuss, S.P. Wilshaw, B. von Rechenberg, R.M. Hall, J.L. Tipper
Less than optimal particle isolation techniques have impeded analysis of orthopaedic wear debris in vivo. The purpose of this research was to develop and test an improved method for particle isolation from tissue. A volume of 0.018 mm³ of clinically relevant CoCrMo, Ti-6Al-4V or Si3N4 particles was injected into rat stifle joints for seven days of in vivo exposure. Following sacrifice, particles were located within tissues using histology. The particles were recovered by enzymatic digestion of periarticular tissue with papain and proteinase K, followed by ultracentrifugation using a sodium polytungstate density gradient. Particles were recovered from all samples, observed using SEM and the particle composition was verified using EDX, which demonstrated that all isolated particles were free from contamination. Particle size, aspect ratio and circularity were measured using image analysis software. There were no significant changes to the measured parameters of CoCrMo or Si3N4 particles before and after the recovery process (KS tests, p>0.05). Titanium particles were too few before and after isolation to analyse statistically, though size and morphologies were similar. Overall the method demonstrated a significant improvement to current particle isolation methods from tissue in terms of sensitivity and efficacy at removal of protein, and has the potential to be used for the isolation of ultra-low wearing total joint replacement materials from periprosthetic tissues.Statement of SignificanceThis research presents a novel method for the isolation of wear particles from tissue. Methodology outlined in this work would be a valuable resource for future researchers wishing to isolate particles from tissues, either as part of preclinical testing, or from explants from patients for diagnostic purposes. It is increasingly recognised that analysis of wear particles is critical to evaluating the safety of an orthopaedic device.

Graphical abstract

http://ift.tt/2F7qFbr

Puncturing of lyophilized tissue engineered vascular matrices enhances the efficiency of their recellularization

Publication date: Available online 2 March 2018
Source:Acta Biomaterialia
Author(s): Agnieszka A. Ksiazek, Laura Frese, Petra E. Dijkman, Bart Sanders, Sarah E. Motta, Benedikt Weber, Simon P. Hoerstrup
Data on in vitro engineered "off the shelf" matrices support the concept of endogenous cellular repopulation driving the graft's remodeling via immune-mediated response. This seems important to further accelerate the cell reconstitution and may play a crucial role when mononuclear cells are used. Nevertheless, studies on decellularized xenogeneic grafts showed only limited host cell repopulation post-implantation.This study aims at a systematic comparison of reseeding methods (dripping, injection, bathing in a cell suspension and combined puncturing-dripping method) to define the most efficient technique enhancing recellularization of tissue engineered vascular matrices (patches, vessels, small diameter and standard size valves) prior implantation. The constructs were analyzed histologically, biochemically and biomechanically. Various preconditioning treatments (wet, lyophilized and air-dried) combined with reseeding methods demonstrated the highest cell loading efficiency, despite applied crimping and flow stress, of lyophilization followed by puncturing-dripping technique.This novel seeding method allows for an efficient, time saving graft reseeding that can be used within a one-step cardiovascular clinical intervention.Statement of significanceThe concept of living tissue engineered, self-repairing, autologous cardiovascular replacements, was proposed alternatively to existing synthetic/xenogeneic prostheses. Recent studies in animal models demonstrate faster in vivo recellularization after grafts pre-seeding with cells prior implantation. Pre-seeded cells hold either, the ability to differentiate directionally or attract host cells, crucial for graft integration and remodeling. It is unclear, however, how efficient the pre-loading is and how well cells withstand the flow. The study presents a systematic overview on cell loading techniques of different cardiovascular constructs, tested under static and dynamic conditions. Comparison illustrates a significantly higher efficiency of cells loading in lyophilized tissues punctured before their standard seeding. This technique may beneficially accelerate remodeling of cardiovascular grafts in further in vivo studies.

Graphical abstract

http://ift.tt/2FhPJMh

Electrofabrication of Functional Materials: Chloramine-based Antimicrobial Film for Infectious Wound Treatment

Publication date: Available online 2 March 2018
Source:Acta Biomaterialia
Author(s): Xue Qu, Huan Liu, Chuchu Zhang, Yu Lei, Miao Lei, Miao Xu, Dawei Jin, Peng Li, Meng Yin, Gregory F. Payne, Changsheng Liu
Electrical signals can be imposed with exquisite spatiotemporal control and provide exciting opportunities to create structure and confer function. Here, we report the use of electrical signals to program the fabrication of a chloramine wound dressing with high antimicrobial activity. This method involves two electrofabrication steps: (i) a cathodic electrodeposition of an aminopolysaccharide chitosan triggered by a localized region of high pH; and (ii) an anodic chlorination of the deposited film in the presence of chloride. This electrofabrication process is completed within several minutes and the chlorinated chitosan can be peeled from the electrode to yield a free-standing film. The presence of active N-Cl species in this electrofabricated film was confirmed with chlorination occurring first on the amine groups and then on the amide groups when large anodic charges were used. Electrofabrication is quantitatively controllable as the cathodic input controls film growth during deposition and the anodic input controls film chlorination.In vitro studies demonstrate that the chlorinated chitosan film has antimicrobial activities that depend on the chlorination degree. In vivostudies with a MRSA infected wound healing model indicate that the chlorinated chitosan film inhibited bacterial growth, induced less inflammation, developed reorganized epithelial and dermis structures, and thus promoted wound healing compared to a bare wound or wound treated with unmodified chitosan. These results demonstrate the fabrication of advanced functional materials (i.e., antimicrobial wound dressings) using controllable electrical signals to both organize structure through non-covalent interactions (i.e., induce chitosan's reversible self-assembly) and to initiate function-conferring covalent modifications (i.e., generate chloramine bonds). Potentially, electrofabrication may provide a simple, low cost and sustainable alternative for materials fabrication.Statement of SignificanceWe believe this work is novel because this is the first report (to our knowledge) that electronic signals enable the fabrication of advanced antimicrobial dressings with controlled structure and biological performance.We believe this work is significant because electrofabrication enables rapid, controllable and sustainable materials construction with reduced adverse environmental impacts while generating high performance materials for healthcare applications. More specifically, we report an electrofbrication of antimicrobial film that can promote wound healing.

Graphical abstract

http://ift.tt/2CWpSnL

Histone-Targeted Gene Transfer of Bone Morphogenetic Protein-2 Enhances Mesenchymal Stem Cell Chondrogenic Differentiation

Publication date: Available online 2 March 2018
Source:Acta Biomaterialia
Author(s): Erik V. Munsell, Deepa S. Kurpad, Theresa A. Freeman, Millicent O. Sullivan
Skeletal tissue regeneration following traumatic injury involves a complex cascade of growth factor signals that direct the differentiation of mesenchymal stem cells (MSCs) within the fracture. The necessity for controlled and localized expression of these factors has highlighted the role gene therapy may play as a promising treatment option for bone repair. However, the design of nanocarrier systems that negotiate efficient intracellular trafficking and nuclear delivery represents a significant challenge. Recent investigations have highlighted the roles histone tail sequences play in directing nuclear delivery and activating DNA transcription. We previously established the ability to recapitulate these natural histone tail activities within non-viral nanocarriers, improving gene transfer and expression by enabling effective navigation to the nucleus via retrograde vesicular trafficking. Herein, we demonstrate that histone-targeting leads to ∼4-fold enhancements in osteogenic bone morphogenetic protein-2 (BMP-2) expression by MSCs over 6 days, as compared with standard polymeric transfection reagents. This improved expression augmented chondrogenesis, an essential first step in fracture healing. Importantly, significant enhancements of cartilage-specific protein expression were triggered by histone-targeted gene transfer, as compared with the response to treatment with equivalent amounts of recombinant BMP-2 protein. In fact, a 100-fold increase in recombinant BMP-2 was required to achieve similar levels of chondrogenic gene and protein expression. The enhancements in differentiation achieved using histone-targeting were in part enabled by an increase in transcription factor expression, which functioned to drive MSC chondrogenesis. These novel findings demonstrate the utility of histone-targeted gene transfer strategies to enable substantial reductions in BMP-2 dosing for bone regenerative applications.Statement of SignificanceThis contribution addresses significant limitations in non-viral gene transfer for bone regenerative applications by exploiting a novel histone-targeting approach for cell-triggered delivery that induces osteogenic BMP-2 expression coincident with the initiation of bone repair. During repair, proliferating mesenchymal stem cells (MSCs) respond to a complex series of growth factor signals that direct their differentiation along cellular lineages essential to mature bone formation. Although these MSCs are ideal targets for enhanced transfection during cellular mitosis, few non-viral delivery approaches exist to enable maximization of this effect. Accordingly, this contribution seeks to utilize our histone-targeted nanocarrier design strategy to stimulate BMP-2 gene transfer in dividing MSCs. This gene-based approach leads to significantly augmented MSC chondrogenesis, an essential first step in bone tissue repair.

Graphical abstract

http://ift.tt/2FlS2y9

Corrigendum to “NF-κB signaling is key in the wound healing processes of silk fibroin” [Acta Biomater. 67 (2018), 183–195]

Publication date: Available online 2 March 2018
Source:Acta Biomaterialia
Author(s): Ye Ri Park, Md. Tipu Sultan, Hyun Jung Park, Jung Min Lee, Hyung Woo Ju, Ok Joo Lee, Dong Jin Lee, David L. Kaplan, Chan Hum Park




http://ift.tt/2CUtpmD

The in vitro effects of macrophages on the osteogenic capabilities of MC3T3-E1 cells encapsulated in a biomimetic poly(ethylene glycol) hydrogel

Publication date: Available online 2 March 2018
Source:Acta Biomaterialia
Author(s): Leila S. Saleh, Maria Carles-Carner, Stephanie J. Bryant
Poly(ethylene glycol) PEG-based hydrogels are promising for cell encapsulation and tissue engineering, but are known to elicit a foreign body response (FBR) in vivo. The goal of this study was to investigate the impact of the FBR, and specifically the presence of inflammatory macrophages, on encapsulated cells and their ability to synthesize new extracellular matrix. This study employed an in vitro co-culture system with murine macrophages and MC3T3-E1 pre-osteoblasts encapsulated in a bone-mimetic hydrogel, which were cultured in transwell inserts, and exposed to an inflammatory stimulant, lipopolysaccharide (LPS). The co-culture was compared to mono-cultures of the cell-laden hydrogels alone and with LPS over 28 days. Two macrophage cell sources, RAW 264.7 and primary derived, were investigated. The presence of LPS-stimulated primary macrophages led to significant changes in the cell-laden hydrogel by a 5.3-fold increase in percent apoptotic osteoblasts at day 28, 4.2-fold decrease in alkaline phosphatase activity at day 10, and 7-fold decrease in collagen deposition. The presence of LPS-stimulated RAW macrophages led to significance changes in the cell-laden hydrogel by 5-fold decrease in alkaline phosphatase activity at day 10 and 4-fold decrease in collagen deposition. Mineralization, as measured by von Kossa stain or quantified by calcium content, was not sensitive to macrophages or LPS. Elevated interleukin-6 and tumor necrosis factor-α secretion were detected in mono-cultures with LPS and co-cultures. Overall, primary macrophages had a more severe inhibitory effect on osteoblast differentiation than the macrophage cell line, with greater apoptosis and collagen I reduction. In summary, this study highlights the detrimental effects of macrophages on encapsulated cells for bone tissue engineering.Statement of SignificancePoly(ethylene glycol) (PEG)-based hydrogels are promising for cell encapsulation and tissue engineering, but are known to elicit a foreign body response (FBR)in vivo. The impact of the FBR on encapsulated cells and their ability to synthesize tissue has not been well studied. This study utilizes thiol-ene click chemistry to create a biomimetic, enzymatically degradable hydrogel system with which to encapsulate MC3T3-E1 pre-osteoblasts. The osteogenic capabilities and differentiation of these cellswerestudied in co-culture with macrophages, known drivers of the FBR.This study demonstrates that macrophages reduce osteogenic capabilities of encapsulated cellsin vitroand suggestthat the FBR should be considered for in vivo tissue engineering.

Graphical abstract

http://ift.tt/2F9SEri

Crystallinity of Hydroxyapatite Drives Myofibroblastic Activation and Calcification in Aortic Valves

Publication date: Available online 2 March 2018
Source:Acta Biomaterialia
Author(s): Jennifer M. Richards, Jennie A.M.R. Kunitake, Heather B. Hunt, Alexa N. Wnorowski, Debra W. Lin, Adele L. Boskey, Eve Donnelly, Lara A. Estroff, Jonathan T. Butcher
Calcific aortic valve disease (CAVD) is an inexorably degenerative pathology characterized by progressive calcific lesion formation on the valve leaflets. The interaction of valvular cells in advanced lesion environments is not well understood yet highly relevant as clinically detectable CAVD exhibits calcifications composed of non-stoichiometric hydroxyapatite (HA). In this study, Fourier transform infrared spectroscopic imaging was used to spatially analyze mineral properties as a function of disease progression. Crystallinity (size and perfection) increased with increased valve calcification. To study the relationship between crystallinity and cellular behavior in CAVD, valve cells were seeded into 3D mineral-rich collagen gels containing synthetic HA particles, which had varying crystallinities. Lower crystallinity HA drove myofibroblastic activation in both valve interstitial and endothelial cells, as well as osteoblastic differentiation in interstitial cells. Additionally, calcium accumulation within gels depended on crystallinity, and apoptosis was insufficient to explain differences in HA-driven cellular activity. The protective nature of endothelial cells against interstitial cell activation and calcium accumulation was completely inhibited in the presence of less crystalline HA particles. Elucidating valve cellular behavior post-calcification is of vital importance to better predict and treat clinical pathogenesis, and mineral-containing hydrogel models provide a unique 3D platform to evaluate valve cell responses to a later stage of valve disease.Statement of significanceWe implement a 3D in vitro platform with embedded hydroxyapatite (HA) nanoparticles to investigate the interaction between valve interstitial cells, valve endothelial cells, and a mineral-rich extracellular environment. HA nanoparticles were synthesized based on analysis of the mineral properties of calcific regions of diseased human aortic valves. Our findings indicate that crystallinity of HA drives activation and differentiation in interstitial and endothelial cells. We also show that a mineralized environment blocks endothelial protection against interstitial cell calcification. Our HA-containing hydrogel model provides a unique 3D platform to evaluate valve cell responses to a mineralized ECM. This study additionally lays the groundwork to capture the diversity of mineral properties in calcified valves, and link these properties to progression of the disease.

Graphical abstract

http://ift.tt/2CTSfmI

Human iPSC-derived mesenchymal stem cells matured into valve interstitial-like cells using PEGDA hydrogels

Publication date: Available online 2 March 2018
Source:Acta Biomaterialia
Author(s): Aline L.Y. Nachlas, Siyi Li, Rajneesh Jha, Monalisa Singh, Chunhui Xu, Michael E. Davis
Despite recent advances in tissue engineered heart valves (TEHV), a major challenge is identifying a cell source for seeding TEHV scaffolds. Native heart valves are durable because valve interstitial cells (VICs) maintain tissue homeostasis by synthesizing and remodeling the extracellular matrix. In this study, the goal is to demonstrate that induced pluripotent stem cells (iPSC)-derived mesenchymal stem cells (iMSCs) can be derived from iPSCs using a feeder-free protocol and then further matured into VICs by encapsulation within 3D hydrogels. The differentiation efficiency was characterized using flow cytometry, immunohistochemistry staining, and trilineage differentiation. Using our feeder-free differentiation protocol, iMSCs were differentiated from iPSCs and had CD90⁺, CD44⁺, CD71⁺, αSMA⁺, and CD45^- expression. iMSCs underwent trilineage differentiation when cultured in induction media for 21 days. iMSCs were encapsulated in poly(ethylene glycol) diacrylate (PEGDA) hydrogels, grafted with adhesion peptide (RGDS), to promote remodeling and further maturation into VIC-like cells. VIC phenotype was assessed by the expression of alpha-smooth muscle actin (αSMA), vimentin, and the collagen production after 28 days. When MSC-derived cells were encapsulated in PEGDA hydrogels that mimic the leaflet modulus, we observed a decrease in αSMA expression and increase in vimentin. In addition, iMSCs synthesized collagen type I after 28 days in 3D hydrogel culture. Thus, the results from this study suggest that iMSCs may be a promising cell source for TEHV.Statement of SignificanceDeveloping a suitable cell source is a critical component for the success and durability of tissue engineered heart valves. The significance of this study is the generation of iPSCs-derived mesenchymal stem cells (iMSCs) that have the capacity to mature into valve interstitial-like cells when introduced into a 3D cell culture designed to mimic the layers of the valve leaflet. iMSCs were generated using a feeder-free protocol, which is one of the major advantage over other methods, as it is more clinically relevant. In addition to generating a potential new cell source for heart valve tissue engineering, this study also highlights the importance of a 3D culture environment to influence cell phenotype and function.

Graphical abstract

http://ift.tt/2FlCtWS

Fine-Tuning Limited Proteolysis: A Major Role for Regulated Site-Specific O-Glycosylation

Publication date: Available online 2 March 2018
Source:Trends in Biochemical Sciences
Author(s): Christoffer K. Goth, Sergey Y. Vakhrushev, Hiren J. Joshi, Henrik Clausen, Katrine T. Schjoldager
Limited proteolytic processing is an essential and ubiquitous post-translational modification (PTM) affecting secreted proteins; failure to regulate the process is often associated with disease. Glycosylation is also a ubiquitous protein PTM and site-specific O-glycosylation in close proximity to sites of proteolysis can regulate and direct the activity of proprotein convertases, a disintegrin and metalloproteinases (ADAMs), and metalloproteinases affecting the activation or inactivation of many classes of proteins, including G-protein-coupled receptors (GPCRs). Here, we summarize the emerging data that suggest O-glycosylation to be a key regulator of limited proteolysis, and highlight the potential for crosstalk between multiple PTMs.



http://ift.tt/2oGmAAX

Uvulopalatopharyngoplasty vs CN XII stimulation for treatment of obstructive sleep apnea: A single institution experience

Hypoglossal nerve stimulation (HNS) therapy is an emerging surgical treatment for select patients with obstructive sleep apnea (OSA). This study aims to compare outcomes in patients with moderate to severe OSA who underwent HNS surgery (Inspire Medical Systems) and those who underwent traditional airway reconstructive surgery, specifically uvulopalatopharyngoplasty (UPPP).

http://ift.tt/2Febrkv

Victim-focussed studies of intimate partner femicide: A critique of methodological challenges and limitations in current research

Publication date: March–April 2018
Source:Aggression and Violent Behavior, Volume 39
Author(s): S. McPhedran, L. Eriksson, P. Mazerolle, H. Johnson
Developing strategies to prevent intimate partner femicide (IPF) remains a pressing policy challenge across nations. However, most research to date focuses on perpetrators of IPF rather than victims, which creates gaps in understanding of IPF. A contributor to the limited amount of victim-focussed knowledge is that – for sadly obvious reasons – IPF victims cannot directly provide information about their own experiences and circumstances. This challenge, and methodological approaches researchers have used in an attempt to overcome it, has not been given consideration in its own right. The current study examines dominant approaches used in the study of IPF, and discusses strengths and limitations of each approach. Implications and potential ways forward for enhancing methodological approaches to the study of IPF victimisation are identified, such as adapting 'psychological autopsy' methods commonly used in suicide research to the study of IPF.



http://ift.tt/2F9cEpY

Out of place: Sexualities, sexual violence, and heteronormativity

Publication date: March–April 2018
Source:Aggression and Violent Behavior, Volume 39
Author(s): Aliraza Javaid
In this paper, I offer a platform in which to theorise sexual violence against men. In doing so, I critically interrogate the ways in which male sexual victimisation is socially and culturally constructed in the public space of compulsory heterosexuality. Drawing on male rape as a case study and focus, I explore how rape against men is constructed and socially defined in public territory where homosexuality is often marginal, excluded, and stigmatised. The interactional, social and cultural contexts wherein rape against men is constructed are considered, with the adoption of the theoretical framework of heteronormativity to make sense of the connection between male rape and 'heterosexual spaces'. In respect of the binary distinction between the public and private, whereby homosexuality is deemed 'private' and heterosexuality 'public', and drawing on ideas of male sexual victimisation and victim blameworthy, I provide an improved understanding of the different ways in which rape against men is constructed within a heterosexual landscape that always surrounds us all.



http://ift.tt/2FMbamq

The time for causal designs: Review and evaluation of empirical support for mechanisms of political radicalisation

Publication date: March–April 2018
Source:Aggression and Violent Behavior, Volume 39
Author(s): Oluf Gøtzsche-Astrup
This paper evaluates the most influential current approaches to the mechanisms of radicalisation on the basis of their empirical evidence and calls for a focus on research designs capable of arbitrating on matters of causality, not just correlation. It shows how the existing evidence converges on a handful of factors involved in radicalisation, including negative life experiences leading to fundamental uncertainty or loss of significance, which spur on the search for and identity shift towards groups with strong norms and ideals, including sacred values that enable extreme ingroup defences (e.g. acts of terrorism). The cumulative empirical data indicates support for some, but not all, kinds of interventions. Finally, because both theoretical approaches and current interventions propose cause-and-effect relationships, the paper argues that it is imperative that the field shifts its focus to experimental research designs capable of making causal inferences.



http://ift.tt/2telyAM

Shame and a Theory of war and violence

Publication date: March–April 2018
Source:Aggression and Violent Behavior, Volume 39
Author(s): Thomas Scheff, G. Reginald Daniel, Joseph Sterphone
It is possible that war in modern societies is largely driven by emotions, but in a manner that is almost completely hidden. Modernity rationalizes the self and tends to ignore emotions, which can result in the total hiding of humiliation leads to vengeance. This essay outlines a theory of the social-emotional world implied in the work of C. H. Cooley, whose concept of the "looking-glass self" can be used as antidote to the assumptions of modernity: the self is based on "living in the mind" of others, resulting in feeling either pride or shame. This essay proposes that the complete hiding of shame can lead to feedback loops with no natural limit. These ideas may help explain the role of France in causing WWI, and Hitler's rise to power in Germany.



http://ift.tt/2FNBsET

Treatment effect on psychosocial functioning of juveniles with harmful sexual behavior: A multilevel meta-analysis

Publication date: March–April 2018
Source:Aggression and Violent Behavior, Volume 39
Author(s): Ellis ter Beek, Chris H.Z. Kuiper, Rachel E.A. van der Rijken, Anouk Spruit, Geert Jan J.M. Stams, Jan Hendriks
This multilevel meta-analysis examined the effects of treatment for juveniles with harmful sexual behavior on psychosocial functioning, and the potential moderating effects of outcome, treatment, participant, and study characteristics. In total, 23 studies, comprising 31 independent samples and 1342 participants, yielded 362 effect sizes (Cohen's d). A moderate overall effect size was found of d = 0.60, indicating that groups receiving treatment achieved an estimated relative improvement in psychosocial functioning of 33%. Type of outcome did moderate the effect of treatment, indicating that effects on atypical sexual arousal and empathy (a trend) were smaller, compared to effects on other outcomes. Most prominently, studies of weak quality produced larger effect sizes. Unexpectedly, non-established treatments had more effect than did established treatments, which may be explained by the use of less rigorous study designs. Treatment groups with a higher percentage of juveniles with similar age victims or mixed type problem behavior also yielded larger effect sizes. Lastly, evaluation of treatment effects by professionals produced higher effect sizes, compared to other sources of information (e.g., adolescent self-report). Although only a marginal to no indication was found for publication bias by means of funnel plot analysis of the distribution of effect sizes, articles published in peer reviewed journals showed relatively large effect sizes. Implications for future research and clinical practice are discussed.



http://ift.tt/2tdykiX