Source apportionment of soil-contamination in Baotou City (North China) based on a combined magnetic and geochemical approach

Publication date: 15 November 2018
Source:Science of The Total Environment, Volume 642
Author(s): Bo Wang, Dunsheng Xia, Ye Yu, Hong Chen, Jia Jia
We studied the magnetic properties and trace element concentrations (Cr, Cu, Fe, Mn, Pb, Ti, V, Zn) of urban topsoils from 111 urban sites in a large REE-Nb-Fe mining and smelting city, Baotou, Inner Mongolia, China. The results show that pseudo-single domain and multi-domain magnetite dominates the magnetic properties of the soil samples, and the magnetic concentration parameters show a large positive anomaly near the Baotou iron and steel works. The average contents of all trace metals exceeded their background level in soils in Inner Mongolia, except for Pb. The spatial distribution and correlation analysis show that magnetic parameters related to the magnetite concentration and Cr, Fe, Mn, Ti, V and Zn show similar trends of variation. In addition, the results of PCA show that Fe, Ti, and V are highly correlated with the magnetic particles derived from the Baotou iron and steel works, tailing dam, chromium plant, and cement plant. In contrast, Cr, Mn, Pb and Zn are derived from both the steel plant and traffic pollution. Using a PMF model, three potential pollution sources are identified: industrial pollution, including the steel works, tailing dam, cement plant and chromium plant, are reflected by χlf, χARM, SIRM and SOFT, and they account for 71.2%; traffic pollution is reflected by Pb and Zn and accounts for 9.0%; and natural sources, reflected by χfd%, χARM/χ, χARM/SIRM, HARD%, S−300, S−100 and Ti, contribute 19.8%. The results are potentially useful for developing control measures for reducing trace metal contamination in soils in Baotou city, and in addition we conclude that a combined magnetic approach and geochemical approach is an effective means for qualitative and quantitative sources apportionment of urban surface soil pollution.

Graphical abstract

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The association between autologous breast reconstruction and body mass index in breast oncology

No abstract available

https://ift.tt/2sKmgmG

Reply to Letter to the Editor by Dr. Innocenti et al. on our paper the Extended Transconjunctival Lower Eyelid Blepharoplasty with Release of the Tear Trough Ligament and Fat Redistribution

No abstract available

https://ift.tt/2HzHjgw

Reply: The association between autologous breast reconstruction and body mass index in breast oncology

No abstract available

https://ift.tt/2sKYRl5

Extended Transconjunctival Lower Eyelid Blepharoplasty with Release of the Tear Trough Ligament and Fat Redistribution

No abstract available

https://ift.tt/2HzHg4k

Prepectoral Breast Reconstruction

No abstract available

https://ift.tt/2sLVcU0

The Differential Use of Bilobed and Trilobed Transposition Flaps in Cutaneous Nasal Reconstructive Surgery

Background: Bilobed and trilobed transposition flaps are versatile random pattern transposition flaps which reliably restore nasal symmetry, topography, light reflex, contour and are frequently used in cutaneous nasal reconstructive surgery. We wish to compare the characteristics of bilobed and trilobed flaps in cutaneous reconstructive surgery and to identify scenarios for their differential use. Methods: A retrospective chart review over 7 years of consecutive patients reconstructed with a bilobed or trilobed flap after Mohs micrographic surgery was performed. Statistical analysis of patient and surgery characteristics, anatomic distribution, postprocedural events and need for revisions after both flap types was conducted. Results: One hundred eleven patients with bilobed flaps and 74 patients with trilobed flaps were identified. Bilobed flaps are significantly more frequently used on the inferior nasal dorsum and on the sidewall whereas trilobed flaps are significantly more frequently used on the nasal tip and infratip. No significant difference in postprocedural events (complications, erythema, trapdoor, etc) was noted between the two flap types. Conclusion: Bilobed and trilobed transposition flaps are versatile repairs for nasal reconstruction. Trilobed flaps may be used to repair defects in a more distal nasal location than bilobed flaps. Regardless of flap type, complications are rare. Conflicts of interest: none declared Funding sources: none Presented at: American College of Mohs Surgeons Annual Meeting 2017 in San Francisco, CA Corresponding author/Reprint requests: Nathaniel J. Jellinek, MD, 1672 South County Trail, Suite 101, East Greenwich, RI, 02818, (401)-885-6647 (phone), (401)-885-6639 (fax), email: winenut15@yahoo.com ©2018American Society of Plastic Surgeons

https://ift.tt/2LF2r7v

A simple dynamic strategy to deliver stem cells to decellularized nerve allografts

Background: The addition of adipose-derived Mesenchymal Stromal Cells (MSCs) to decellularized nerve allografts may improve outcomes of nerve reconstruction. Prior techniques used for cell seeding are traumatic to both the MSCs and nerve graft. An adequate, reliable and validated cell seeding technique is an essential step for evaluating the translational utility of MSC-enhanced decellularized nerve grafts. The purpose of this study was to develop a simple seeding strategy with an optimal seeding duration. Methods: A dynamic bioreactor was used to seed rat and human MSCs separately onto rat and human decellularized nerve allografts. Cell viability was evaluated by MTS assays and cellular topology after seeding was determined by SEM microscopy. Cell density and distribution were determined by LIVE/DEAD assays and Hoechst staining at 4 different time points (6, 12, 24 and 72 hours). The validity and reliability of the seeding method were calculated. Results: Cells remained viable at all time points, and MSCs exhibited exponential growth in the first 12 hours of seeding. Seeding efficiency increased significantly from 79.5% at 6 hours to 89.2% after 12 hours of seeding (p = 0.004). Both intra-rater (r = 0.97) and inter-rater reliability (r = 0.92) of the technique were high. Conclusions: This study describes and validates a new method to effectively seed decellularized nerve allografts with MSCs. This method is reproducible, distributes cells homogenously over the graft and does not traumatize the intra-neural architecture of the allograft. Utilization of this validated seeding technique will permit critical comparison of graft outcomes. Financial Disclosure Statement: Funding for this study was received from the Mayo Clinic Center for Regenerative Medicine Acknowledgements: We thank the American Donor Services for providing fresh human cadaveric motor nerves. We also thank Drs. Anthony Windebank, Allan Dietz, Amel Dudakovic and Roman Thaler for their expertise and guidance. Presentations: Part of this work was presented at the Annual Meeting of the American Society for Peripheral Nerve, Hawaii, United States, January 13th, 2017. Author Contributions: Nadia Rbia: contributed to the conception, analysis, interpretation of the data, as well as drafting of the manuscript for submission.Liselotte F. Bulstra: contributed to the conception, analysis, interpretation of the data, as well as the drafting of the manuscript for submission. Allen T. Bishop: contributed to the conception and interpretation of data, as well as edited the manuscript. Andre J. van Wijnen: contributed to the conception and interpretation of data, as well as edited the manuscript. Alexander Y. Shin: contributed to the conception and interpretation of data, as well as the acquisition of funding and editing of this manuscript. Corresponding Author: Alexander Y. Shin, M.D., Professor of Orthopedic Surgery, Professor of Neurosurgery, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, Phone: 507-284-0475, Email: shin.alexander@mayo.edu. ©2018American Society of Plastic Surgeons

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Comparison of the microstructures and properties of different microcannulas for HA injection

BACKGROUND: Microcannulas are used for hyaluronic acid and other fillers injection and reduce the side effects and complications. There are several microcannulas manufactured by different manufacturers but the differences between microcannulas haven't been carefully investigated. OBJECTIVE: To compare the microstructures and properties of different microcannulas by several trials and provide guidance for clinical application. METHODS: In this study, 9 kinds of microcannulas, from different manufacturers were chose. Scanning electron microscope(SEM) was used to obtain high-definition image of microstructures, chemical composition analyzers were used to test the chemical composition for the microcannulas' tips and universal testing machine was used to measure mechanical properties. Injection speed test recorded the time spent for the weight pushed hyaluronic acid out during different microcannulas. Vessel piercing force test was conducted to simulate the process of puncturing the vessels in vitro. RESULTS: The SEM images showed the differences in the tips and inner surfaces which may relate to the characteristics. Most microcannulas' chemical composition met the American Society for Testing Material(ASTM) standards basically. For mechanical properties, the elastic modulus and the yield strength were obviously different. The injection speed test showed the speed of difference microcannulas through same force was discrepant more than 7 times. The vessel piercing test showed which microcannula was most difficult to puncture the aorta and which was the easiest. CONCLUSION: The results indicated there are significant differences between different microcannulas. The differences are instructive to physician to select suitable microcannulas to improve the injection effect and reduce discomfort and complications. Financial disclosure: The authors have no financial interest to declare in relation to the content of this article. Acknowledgement: none Corresponding author: Wang Hang, Sichuan Univ, West China Sch Stomatol, Dept Oral & Maxillofacial Surg, 14,3rd Sect,RenMin Nan Rd, Chengdu 610041, Peoples R China. Tel: +86 13980888813, E-mail:dr.hangwang@hotmail.com ©2018American Society of Plastic Surgeons

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“Oncological Resection and Reconstruction of the Chest Wall –19 year experience in a single center”

OBJECTIVE: The study aim was to analyse chest wall reconstruction following oncological resection by a single surgeon over an 19 year period. METHODS: A retrospective review was performed for 135 patients who underwent oncological chest wall resection during 1997-2015. RESULTS: Average patient age was 57.8 years. Indications for resection were: advanced breast cancer n=44, soft tissue sarcoma n=38, bone or chondrosarcoma n=28, desmoid tumour n=11, metastasis from other cancers n=7, and other primary tumours n=7. There were 72 full-thickness and 63 partial-thickness resections (34 soft tissue resections only and 29 skeletal bone resections only). Resection margins were wide n=29, marginal n=82 and intralesional n=24. Reconstruction was warranted in 118 cases: chest wall stabilization and flap coverage n=57, chest wall stabilization only n=36 and soft tissue flap coverage only n=25. In total, 82 flaps were performed (17 free flaps and 65 pedicled/local flaps). There were no perioperative mortalities nor flap losses. Complications occurred in 29 operations (Clavien-Dindo classifications grII 12, grIIIa 4, grIIIb 10, grIVa 3) and 19 re-operations were necessary. Median follow-up was 49 months. Survival was calculated by the Kaplan and Meier Method. One- year, 2-year and 5-year survival rates were 84%, 82% and 70%, respectively. CONCLUSION: With careful patient selection, appropriate peri- and postoperative care and accurate surgical technique, even extensive chest wall resections and reconstructions are safe. Financial Disclosure Statement: Dr. Salo and Dr. Tukiainen had nothing to disclose. No funding was received for this article. Presented at (if applicable): EURAPS 2017 meeting, in Pisa, Italy Corresponding author: Juho T.K. Salo M.D., Department of Plastic Surgery, Töölö Hospital, PO Box 266, FIN 0029 HUS, Finland, email: juho.salo@hus.fi tel: + 358 50 428 4681 fax: + 358 9 471 87 217 ©2018American Society of Plastic Surgeons

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Anatomical Understanding of Target Subcutaneous Tissue Layer for Thinning Procedures in TDAP, SCIP and ALT Perforator Flaps

Background: Thinned perforator flaps, reported techniques and degree of thinning differ by study. This study investigated the anatomy of subcutaneous tissue according to the varying fattiness and identified which component and how much of the subcutaneous tissue layer needed to be excluded to meet target flap thickness using computed tomography(CT). Methods: Three stratified fattiness groups consisting of 30 donors were made for TDAP, SCIP and ALT flaps. The thickness of the superficial fat layer (SFL) and the deep fat layer (DFL) were measured at 3 points in TDAP, 2 points in SCIP and 3 points in ALT flaps, and the proportion of SFL and DFL to exclude to reach target flap thickness (4, 6, and 8mm) was calculated. Result: The median proportion for SFL ranged from 54.8% to 75.2% for TDAP, 62.1% to 72.7% for SCIP and 48.7% to 69.1% for ALT depending on donor fattiness. The estimated % reduction of thickness after thin flap elevation along superficial fascia was approximately one third of the whole layer. A variable proportion of SFL and DFL needs to be excluded to obtain required thinness and in very thick groups, part of the SFL must be removed to reach any of the target thicknesses for three flaps. Conclusion: The present study demonstrated the frequent need for SFL manipulation when obtaining a thin perforator flap. To cope with various combinations of donor site fattiness and different required thicknesses effectively, an appropriate thinning method should have increased adaptability, including the ability to control SFL thickness. Financial Disclosure: None of the authors have a financial interest in any of the products, devices, or drugs mentioned in this manuscript. Corresponding Author Contact Information: Dr. Goo-Hyun Mun, M.D., Ph.D. Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, S. Korea, 06351 Tel.: 82-2-3410-2233/Fax: 82-2-3410-0036/E-mail: supramicro@gmail.com ©2018American Society of Plastic Surgeons

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SIMULTANEOUS LOWER BODY LIFT AND GLUTEAL IMPLANTS: SEVERE COMPLICATIONS RELATED TO THE SAME INCISIONAL APPROACH

No abstract available

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Prepectoral Breast Reconstruction.

No abstract available

https://ift.tt/2LERKBL

Editorial Board

Publication date: July 2018
Source:Acta Histochemica, Volume 120, Issue 5





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Changes in mucins and matrix metalloproteases in the endometrium of early pregnant alpacas (Vicugna pacos)

Publication date: July 2018
Source:Acta Histochemica, Volume 120, Issue 5
Author(s): Daniela E. Barraza, Renato Zampini, Silvana A. Apichela, Joel I. Pacheco, Martin E. Argañaraz
South American Camelids (SAC) have unique reproductive features, one of which is that 98% of the pregnancies develop in the left uterine horn. Furthermore, early pregnancy is an uncharacterized process in these species, especially in regard to the ultrastructural, biochemical and genetic changes that the uterine epithelial surface undergoes to allow embryo implantation. The present study describes the uterine horn luminal surface and the characteristics of the mucinous glycocalyx in non-pregnant and early pregnant (15 days) female alpacas. In addition, the relative abundance of Mucin 1 and 16 genes (MUC1 and MUC16) was determined, as well as the relative mRNA abundance of matrix metalloproteinases (MMPs) that could be involved in MUC shedding during early pregnancy. Noticeable changes were detected in the uterine luminal epithelium and glycocalyx of pregnant alpacas in comparison to non-pregnant ones, as well as presence of MUCs and MMPs in the endometrial environment. The decrease in glycocalyx staining and in the relative abundance of MUC 1 and MUC 16 transcripts in pregnant females would allow embryo attachment to the luminal epithelium and its subsequent implantation, as has been described in other mammals. These results suggest a crucial role of MUC1 and MUC16 and a possible role of MMPs in successful embryo implantation and survival in alpacas.



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Anatomical, histological and immunohistochemical study of testicular development in Columba livia (Aves: Columbiformes)

Publication date: July 2018
Source:Acta Histochemica, Volume 120, Issue 5
Author(s): G.B. Olea, M.V. Aguirre, D.M. Lombardo
In this work, testicular ontogeny is analyzed at the anatomical, histological and immunohistochemical levels; the latter through the detection of GnRHR and PCNA in the testicles of embryos, neonates and juveniles of Columba livia. We analyzed 150 embryos, 25 neonates and 5 juveniles by means of observations under a stereoscopic magnifying glass and scanning electron microscope (SEM). The histological analysis was performed using hematoxylin-eosin staining techniques and the PAS reaction. For the immunohistochemical analysis, the expression of GnRHR and PCNA in embryos corresponding to stages 41, 43 and in neonates of 2, 5, 7 and 75 days post-hatch was revealed in testicular histological preparations. That gonadal outline is evident in stage 18. In stage 29, the testes are constituted of a medulla in which the PGCs are surrounded by the Sertoli cells, constituting the seminiferous tubules. From stage 37 a greater organization of the tubules is visualized and at the time of hatching the testicle is constituted of the closed seminiferous tubules, formed of the PGCs and Sertoli cells. The Leydig cells are evident outside the tubules. In the juvenile stages, the differentiation of germline cells and the organization of small vessels that irrigate the developing testicle begin to be visible. In the analyzed stages, the immunodetection of the GnRHR receptor and PCNA revealed specific marking in the plasma membrane and in the perinuclear zone for GnRHR and in the nucleus of the germline cells in juvenile testicles for PCNA. These results can be used as a basis for further study of endocrine regulation events during testicular ontogeny in avian species.



https://ift.tt/2JD4X0y

Second primary malignancies after high-dose-rate 60Co photon or 252Cf neutron brachytherapy in conjunction with external-beam radiotherapy for endometrial cancer

Publication date: Available online 9 June 2018
Source:Brachytherapy
Author(s): Ernestas Janulionis, Vitalija Samerdokiene, Konstantinas Povilas Valuckas, Vydmantas Atkocius, Mark J. Rivard
PurposeSecond primary malignancies (SPMs) may occur in organs after radiotherapy (RT). This study aimed to determine the rate and distribution of SPMs for photon- or neutron-emitting radiotherapy sources for patients treated for primary endometrial cancer.Methods and MaterialsThe cohort comprised 426 patients with 5334 patient-years of observation. Patients were treated by different methods of RT from 1990 to 2000. Patients received postoperative ⁶⁰Co external-beam radiotherapy (43.4%), external-beam radiotherapy + high-dose-rate (HDR) intracavitary brachytherapy with ⁶⁰Co or ²⁵²Cf (42.3%), or HDR intracavitary brachytherapy alone with ⁶⁰Co or ²⁵²Cf (14.3%).ResultsOver a 25-year period, 47 SPMs were observed (21 for HDR ⁶⁰Co and 26 for HDR ²⁵²Cf). SPMs were observed for 13 patients in the high-intermediate risk group for each radiation source. Patients treated with ⁶⁰Co developed SPMs in the urinary tract (1.2%) and in lymphoid/hematopoietic tissues (1.2%). Only three SPM cases (0.7%) were observed in digestive tract. In comparison, the patient group treated with ²⁵²Cf developed SPMs in the digestive tract (1.4%) with the majority in the colon (1.2%), urinary tract (0.9%) primarily the kidneys, and vulva (0.7%). All other SPMs (4.9%) were in the low-risk group. Of these, SPMs in the skin were most prevalent (1.6%) for ⁶⁰Co, and breast (1.6%) for ²⁵²Cf, but believed to be caused by factors other than treatment. SPM incidence in the digestive and urinary tracts were similar (2.1%), regardless of radiation source.ConclusionsFor followup at 25 years, 47 SPMs were observed with no differences in the high-intermediate risk group depending on the RT source.



https://ift.tt/2JGWSYB

The detection of brucellosis antibody in whole serum based on the low-fouling electrochemical immunosensor fabricated with magnetic Fe3O4@Au@PEG@HA nanoparticles

Publication date: 15 October 2018
Source:Biosensors and Bioelectronics, Volume 117
Author(s): Shuli Lv, Jinliang Sheng, Shiyi Zhao, Mingchao Liu, Lihua Chen
It is a novel competitive challenge for electrochemical biosensor to directly, rapidly and ultrasensitively detect the disease markers in the whole serum due to biofouling caused by the complexity of actual samples. In this paper, poly (ethylene glycol) (PEG) and hyaluronic acid (HA) were utilized to modify Fe3O4 @Au nanoparticles (NPs). Based on the successfully preparation and characterization of Fe3O4 @Au@PEG@HA NPs with TEM, SEM, XRD, FTIR and EDS, respectively, a novel immunosensor of brucellosis with high selectivity, sensitivity and almost perfect protein-resistant properties in various external environments, especially, in complex biological systems was fabricated. More importantly, this immunosensor is capable of assaying brucellosis antibody in 100% serum without suffering from any significant biological interference. In addition, a wide linear response range from 10^–15 g mL⁻¹ to 10^–11 g mL⁻¹ towards antibody in 100% serum and a low limit of detection (LOD) of 0.36 fg mL⁻¹ (3σ, n = 13) are demonstrated, which indicates that this immunosensor has a promising potential in clinical diagnosis.



https://ift.tt/2MfGI75

KRAS: Reasons for optimism in lung cancer

Publication date: August 2018
Source:European Journal of Cancer, Volume 99
Author(s): C.R. Lindsay, M. Jamal-Hanjani, M. Forster, F. Blackhall
Despite being the most frequent gain-of-function genetic alteration in human cancer, KRAS mutation has to date offered only limited potential as a prognostic and predictive biomarker. Results from the phase III SELECT-1 trial in non-small cell lung cancer (NSCLC) recently added to a number of historical and more contemporary disappointments in targeting KRAS mutant disease, including farnesyl transferase inhibition and synthetic lethality partners such as STK33. This narrative review uses the context of these previous failures to demonstrate how the knowledge gained from these experiences can be used as a platform for exciting advances in NSCLC on the horizon. It now seems clear that mutational subtype (most commonly G12C) of individual mutations is of greater relevance than the categorical evaluation of KRAS mutation presence or otherwise. A number of direct small molecules targeted to these subtypes are in development and have shown promising biological activity, with some in the late stages of preclinical validation.



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Independent effects of age and levodopa on reversal learning in healthy volunteers

Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Andrew Vo, Ken N. Seergobin, Penny A. MacDonald
The dopamine overdose hypothesis has provided an important theoretical framework for understanding cognition in Parkinson's disease. It posits that effects of dopaminergic therapy on cognition in Parkinson's disease depend on baseline dopamine levels in brain regions that support different functions. Although functions performed by more severely dopamine-depleted brain regions improve with medication, those associated with less dopamine deficient areas are actually worsened. It is presumed that medication-related worsening of cognition owes to dopamine overdose. We investigated whether age-related changes in baseline dopamine levels would modulate effects of dopaminergic therapy on reward learning in healthy volunteers. In a double-blind, crossover design, healthy younger and older adults completed a probabilistic reversal learning task after treatment with 100/25 mg of levodopa/carbidopa versus placebo. Older adults learned more poorly than younger adults at baseline, being more likely to shift responses after misleading punishment. Levodopa worsened stimulus-reward learning relative to placebo to the same extent in both groups, irrespective of differences in baseline performance and expected dopamine levels. When order effects were eliminated, levodopa induced response shifts after reward more often than placebo. Our results reveal independent deleterious effects of age group and exogenous dopamine on reward learning, suggesting a more complex scenario than predicted by the dopamine overdose hypothesis.



https://ift.tt/2JtVqtp

Functional networks underlying item and source memory: shared and distinct network components and age-related differences

Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Zachary A. Monge, Matthew L. Stanley, Benjamin R. Geib, Simon W. Davis, Roberto Cabeza
Although the medial temporal lobes (MTLs) are critical for both item memory (IM) and source memory (SM), the lateral prefrontal cortex and posterior parietal cortex play a greater role during SM than IM. It is unclear, however, how these differences translate into shared and distinct IM versus SM network components and how these network components vary with age. Within a sample of younger adults (YAs; n = 15, Mage = 19.5 years) and older adults (OAs; n = 40, Mage = 68.6 years), we investigated the functional networks underlying IM and SM. Before functional MRI scanning, participants encoded nouns while making either pleasantness or size judgments. During functional MRI scanning, participants completed IM and SM retrieval tasks. We found that MTL nodes were similarly interconnected among each other during both IM and SM (shared network components) but maintained more intermodule connections during SM (distinct network components). Also, during SM, OAs (compared to YAs) had MTL nodes with more widespread connections. These findings provide a novel viewpoint on neural mechanism differences underlying IM versus SM in YAs and OAs.

Graphical abstract

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Data on modeling of nexus between entrepreneurs׳ commitment and business performance in a developing country

Publication date: August 2018
Source:Data in Brief, Volume 19
Author(s): Ayoade Omisade, Ogunnaike Olaleke, Adegbuyi Omotayo, Kehinde Oladele, Iyiola Oluwole, Lawal Fatai, Onakoya Femi
This article presents data that examined the modeling of nexus between entrepreneurs׳ commitment and business performance in a developing country. 315 copies of questionnaire were retrieved from 400 copies that were administered to Nigerian Association of Small Scale Industrialists (NASSI) Southwest chapters which comprised of six states. In addition to descriptive analysis of part of the data, correlation and regression analysis were used to present the data through structural equation model (SEM). The SEM path analysis shows the estimates of the interconnectedness of the major constructs in the data.



https://ift.tt/2Jsk7Xa

Data regarding talent management practices and innovation performance of academic staff in a technology-driven private university

Publication date: August 2018
Source:Data in Brief, Volume 19
Author(s): Odunayo Salau, Adewale Osibanjo, Anthonia Adeniji, Olumuyiwa Oludayo, Hezekiah Falola, Ebeguki Igbinoba, Opeyemi Ogueyungbo
The article presented an integrated data on talent management practices and innovation performance of academic staff in a technology-driven private university in Nigeria. The study adopted a quantitative approach with a survey research design to establish the major determinants of talent management practices. The population of this study included academic staff and the use of questionnaire was adopted to elicit from the study population. Data was analysed with the use of structural equation modelling and the field data set is made widely accessible to enable critical or a more comprehensive investigation. The findings identified talent development and retention strategies as predictors for facilitating innovation performance in the sample University. It was recommended that management of the sampled university will consistently need to adopt reliable range of strategies to attract and retain people for excellence performance.



https://ift.tt/2LAFq5u

Targeted inhibition of Axl receptor tyrosine kinase ameliorates anti-GBM-induced lupus-like nephritis

Publication date: Available online 9 June 2018
Source:Journal of Autoimmunity
Author(s): Yuxuan Zhen, Iris J. Lee, Fred D. Finkelman, Wen-Hai Shao
Glomerulonephritis (GN) is a typical lesion in autoantibody and immune complex disorders, including SLE. Because the Gas6/Axl pathway has been implicated in the pathogenesis of many types of GN, targeting this pathway might ameliorate GN. Consequently, we have studied the efficacy and mechanism of R428, a potent selective Axl inhibitor, in the prevention of experimental anti-GBM nephritis. Axl upregulation was investigated with Sp1/3 siRNA in the SV40-transformed mesangial cells. For Axl inhibition, a daily dose of R428 (125 mg/kg) or vehicle was administered orally. GN was induced with anti-GBM sera. Renal disease development was followed by serial blood urine nitrogen (BUN) determinations and by evaluation of kidney histology at the time of sacrifice. Axl-associated signaling proteins were analyzed by Western blotting and inflammatory cytokine secretion was analyzed by Proteome array. SiRNA data revealed the transcription factor Sp1 to be an important regulator of mesangial Axl expression. Anti-GBM serum induced severe nephritis with azotemia, protein casts and necrotic cell death. R428 treatment diminished renal Axl expression and improved kidney function, with significantly decreased BUN and glomerular proliferation. R428 treatment inhibited Axl and significantly decreased Akt phosphorylation and renal inflammatory cytokine and chemokine expression; similar effects were observed in anti-GBM antiserum-treated Axl-KO mice. These studies support a role for Axl inhibition in glomerulonephritis.



https://ift.tt/2LAUyju

Frequent HPV-independent p16/INK4A overexpression in head and neck cancer

Publication date: August 2018
Source:Oral Oncology, Volume 83
Author(s): Matt Lechner, Ankur R. Chakravarthy, Vonn Walter, Liam Masterson, Andrew Feber, Amrita Jay, Paul M. Weinberger, Richard A. McIndoe, Cillian T. Forde, Kerry Chester, Nicholas Kalavrezos, Paul O'Flynn, Martin Forster, Terry M. Jones, Francis M. Vaz, D. Neil Hayes, Tim R. Fenton
Objectivesp16^INK4A (p16) is the most widely used clinical biomarker for Human Papillomavirus (HPV) in head and neck squamous cell cancer (HNSCC). HPV is a favourable prognostic marker in HNSCC and is used for patient stratification. While p16 is a relatively accurate marker for HPV within the oropharynx, recent reports suggest it may be unsuitable for use in other HNSCC subsites, where a smaller proportion of tumors are HPV-driven.Materials and methodsWe integrated reverse phase protein array (RPPA) data for p16 with HPV status based on detection of viral transcripts by RNA-seq in a set of 210 HNSCCs profiled by The Cancer Genome Atlas project. Samples were queried for alterations in CDKN2A, and other pathway genes to investigate possible drivers of p16 expression.ResultsWhile p16 levels as measured by RPPA were significantly different by HPV status, there were multiple HPV (−) samples with similar expression levels of p16 to HPV (+) samples, particularly at non-oropharyngeal subsites. In many cases, p16 overexpression in HPV (−) tumors could not be explained by mutation or amplification of CDKN2A or by RB1 mutation. Instead, we observed enrichment for inactivating mutations in the histone H3 lysine 36 methyltransferase, NSD1 in HPV (−)/p16-high tumors.ConclusionsRPPA data suggest high p16 protein expression in many HPV (−) non-oropharyngeal HNSCCs, limiting its potential utility as an HPV biomarker outside of the oropharynx. HPV-independent overexpression of wild-type p16 in non-oropharyngeal HNSCC may be linked to global deregulation of chromatin state by inactivating mutations in NSD1.



https://ift.tt/2sU3fNV

Transcriptional control of long-range cortical projections

Publication date: December 2018
Source:Current Opinion in Neurobiology, Volume 53
Author(s): Annalisa Paolino, Laura R Fenlon, Rodrigo Suárez, Linda J Richards
Long-range projection neurons of the neocortex form the major tracts of the mammalian brain and are crucial for sensory-motor, associative and executive functions. Development of such circuits involves neuronal proliferation, specification and migration, as well as axonal elongation, navigation and targeting, where growing axons encounter multiple guidance cues and integrate these signals to execute guidance decisions. The complexity of axon guidance mechanisms in the formation of long-range neuronal projections has suggested that they might be under control of transcription factors, which are DNA-binding proteins that regulate the expression of downstream genes. Here we discuss recent advances in our understanding of the control of axon guidance by transcriptional regulation, as well as future directions for the elucidation of the mechanisms and pathological relevance of this process.



https://ift.tt/2JwbmY7

Does Virtual Reality Increase Emotional Engagement During Exposure for PTSD? Subjective Distress During Prolonged and Virtual Reality Exposure Therapy

Publication date: Available online 8 June 2018
Source:Journal of Anxiety Disorders
Author(s): Greg M. Reger, Derek Smolenski, Aaron Norr, Andrea Katz, Benjamin Buck, Barbara O. Rothbaum
Prolonged exposure (PE) is a treatment for posttraumatic stress disorder (PTSD) based on emotional processing theory. According to this theory, emotional engagement during imaginal exposure is critical to clinical outcome. One rationale for virtual reality exposure therapy (VRE) is the ability of trauma-relevant, multi-sensory stimuli to increase emotional engagement. This study compared the subjective distress of active duty soldiers (N = 108) during exposure via PE or VRE. Soldiers with higher mean or peak distress during the first imaginal exposure had higher baseline PTSD symptom severity. There was no difference between groups on average or peak distress during imaginal exposure at the first or final exposure session. There were no significant differences in between-session habituation observed between VRE and PE groups. However, each ten-point decrease in SUDS scores, either mean or peak, from the initiation of imaginal exposure to the end of treatment, was associated with a greater decrease in CAPS-W scores for both groups. There were no group differences in these trajectories or the magnitude of the association between distress/habituation, and PTSD symptoms. Future research on VRE should measure patient ratings of engagement during exposure to better understand which patients are aided by this innovative approach to treatment.



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Editorial Board

Publication date: July–August 2018
Source:Journal of Communication Disorders, Volume 74





https://ift.tt/2Jw4EkT

Feasibility of using computer simulation to predict the postoperative outcome of the minimally invasive Nuss procedure: Simulation prediction vs. postoperative clinical observation

The Nuss procedure is the most minimally invasive and commonly used surgical correction for pectus excavatum (PE) by using a pre-bent pectus bar to elevate the deformed chest wall. However, there exist some complications such as postoperative pain as well as surgical uncertainties due to human judgement. It is therefore important to understand the biomechanical effect of the pectus bar on PE thoraces undergoing an operation to alleviate the postoperative pain as well as to improve surgical outcome.

https://ift.tt/2JoZs6y

Should Planned/Desired Pregnancy be Considered an Absolute Contraindication to Breast Reconstruction with Free Abdominal Flaps? A Retrospective Case Series and Systematic Review

Autologous breast reconstruction is considered by many to be the gold standard reconstructive modality following mastectomy. Despite the advantages of autologous reconstruction, however, surgeons have been cautious in recommending this approach to patients who desire to becoming pregnant postoperatively due to concerns related to abdominal wall morbidity. While intuitive, this approach does not appear to be based on robust data. Hence, the authors examined the clinical outcome in patients who became pregnant following autologous breast reconstruction.

https://ift.tt/2HAZYbx

Long-Distance Care of Face Transplant Recipients in the United States

Promising aesthetic and functional outcomes in facial transplantation have fueled the interest of patients and providers alike. However, there are currently only 11 active face transplant centers in the United States, and only five have accumulated operative experience to date, resulting in an extremely unbalanced geographical distribution of providers. Since face transplant recipients must receive life-long follow-up, this presents unique challenges for face transplant candidates and provider teams, as long-distance travel may add considerable difficulty to pre- and post-transplant care.

https://ift.tt/2JoZnzM

“Immediate breast reconstruction with a Wise pattern mastectomy and NAC-sparing McKissock vertical bipedicle dermal flap”

Preservation of the nipple-areola complex (NAC) in immediate reconstruction of ptotic and large breasts is surgically challenging. This article presents a modification of the inferior dermal flap ("dermal sling") to a vertical bipedicle flap with NAC preservation. The flap is well described in breast reductions, but has never been described in a mastectomy setting. The study reviews data for a case series of 17 breasts in 11 women who were reconstructed with the new technique. The complication rate was 12 percent and the vertical bipedicle NAC-sparing flap has to be considered a feasible option in women with ptotic and/or large breasts.

https://ift.tt/2LE5Y5I

Risk factors for developing capsular contracture in women after breast implant surgery A systematic review of the literature

Capsular contracture is the most frequent complication in breast augmentation or reconstruction with breast implants. The exact mechanism for this complication is not completely understood. Yet, it is most likely to be a multifactorial condition. Several patient-, as well as surgery-, and implant-specific risk factors have been related to cause capsular contracture. This review aims to provide a clear overview of all risk factors for capsular contracture.

https://ift.tt/2JoZhbo

DONOR SKIN ALLOGRAFT SURVIVAL AFTER BONE MARROW TRANSPLANTATION: CASE REPORT AND SYSTEMATIC REVIEW OF THE LITERATURE

we present a case of skin allograft survival in a patient who previously received a bone marrow transplant from the same HLA-matched donor. DNA fingerprinting of skin biopsies showed mixed cellularity originating from the donor and recipient (68% and 32% donor DNA in the allograft skin and the native recipient's skin, respectively). Histologic sections demonstrated both grade 3/4 rejection and graft-versus-host- disease. We have conducted a systematic review in search for other cases of donor skin allograft survival after a bone marrow or hematopoietic stem cell transplantation.

https://ift.tt/2Hxx24p

Are facial injuries really different?

The article by Rahtz and colleagues concludes that appearance concern after facial injury may not lead either to stigma or to psychosocial burden.1 This is the conclusion that I reached this conclusion in an uncontrolled follow-up study of facial casualties of the First World War treated at the Cambridge Military Hospital, Aldershot and the Queen's Hospital, Sidcup (now Queen Mary's Hospital).

https://ift.tt/2JoZco6

Validation of the revised Food Neophobia Scale (FNS-R) in the Italian context

Publication date: 1 September 2018
Source:Appetite, Volume 128
Author(s): Margherita Guidetti, Luciana Carraro, Nicoletta Cavazza, Michele Roccato
Measuring individuals' level of food neophobia, i.e., the reluctance to eat novel food, is a critical task since it negatively affects diet variety and quality. Using structural equations models, the revised Food Neophobia Scale (FNS-R) was validated with a sample of 711 Italian adults. After deleting 4 items characterized by both low face validity and a suboptimal association with the other items, and after correcting statistically for the acquiescent response-set, the resulting 6-item, fully balanced FNS-R showed a good construct validity. Moreover, it showed the expected positive correlations with General Neophobia and with Disgust Sensitivity. Finally, it resulted invariant across participants' genders, age classes, and levels of education, and across methods of administration (paper-and-pencil and on-line). Strong points and possible developments of the study are discussed.



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Pain and modifiable risk factors among weight loss seeking Veterans with overweight

Publication date: 1 September 2018
Source:Appetite, Volume 128
Author(s): Kathryn M. Godfrey, Anastasia J. Bullock, Lindsey M. Dorflinger, Kathryn M. Min, Christopher B. Ruser, Robin M. Masheb
ObjectiveOverweight/obesity and chronic pain frequently co-occur and demonstrate a bidirectional relationship. Modifiable risk factors, such as eating behaviors and mental health symptoms, may be important to understand this relationship and improve interventions in Veterans.DesignCross-sectional.SettingVeterans Health Administration Medical Center outpatient clinic.SubjectsThe sample of Veterans (N = 126) was mostly male (89.7%), White (76%), and non-Hispanic (94%) with average age of 61.9 years (SD = 8.5) and average body mass index (BMI) of 38.5 (SD = 7.5).MethodsVeterans referred for weight loss treatment (MOVE!) at VA Connecticut completed self-report questionnaires, and electronic medical records were reviewed.ResultsMean self-reported pain rating was 4.5 out of 10 (SD = 2.3). Moderate to severe pain was endorsed by 60% of the sample. Veterans with higher pain intensity and interference reported higher global eating disorder symptoms, emotional overeating, night eating, insomnia severity, and mental health symptoms (all p's < 0.01). However, pain intensity and interference were not associated with BMI.ConclusionsFor Veterans seeking behavioral weight loss treatment, higher pain intensity and interference were associated with more severe eating disorder, sleep, and mental health symptoms. A better description of the clinical characteristics of Veterans with pain who participate in MOVE! highlights their unique needs and may improve treatments to address pain in the context of weight loss treatment.



https://ift.tt/2xXXV1O

Experimental scarcity increases the relative reinforcing value of food in food insecure adults

Publication date: 1 September 2018
Source:Appetite, Volume 128
Author(s): Amanda K. Crandall, Jennifer L. Temple
People with fewer financial resources are at greater risk for obesity, but the mechanisms of this relationship are not fully understood. One factor that is related, both cross-sectionally and prospectively, to obesity is the relative reinforcing value of food. It is possible that the experience of scarcity increases this reinforcing value. To date, no studies have examined this potential relationship experimentally in humans. The purpose of the studies presented here was to test the hypothesis that experimental manipulations of perceived scarcity would impact the relative reinforcing value of food. A secondary hypothesis was that individuals who report experiencing food insecurity would be more sensitive to these experimental manipulations. In order to test these hypotheses, we investigated the effects of experimentally manipulated scarcity on the relative reinforcing value of food in a laboratory setting. Study 1 had a within-subjects design and included 25 adults. Scarcity was manipulated by placing time and resource limits on the relative reinforcing value task and examining responding for a high calorie snack food versus that of an alternative reinforcer. Study 1 showed a tendency for food insecure participants to respond more for all reinforcers across conditions and have a higher proportional response for food when resources were limited. Study 2 also made use of a within-subjects design with 30 adults and primed scarcity by creating financial gains and losses on the Iowa Gambling Task. We observed higher relative reinforcing values of food among food insecure participants in the control condition, which decreased in the financial gain condition. When taken together, these two studies suggest that individuals who report experiencing food insecurity respond to acute manipulations of scarcity by increasing their reinforcing value of snack food.



https://ift.tt/2kX7kNE

Usefulness of EEG-EMG coherence analysis to confirm epileptic nature of spells mimicking hemifacial spasms

Publication date: Available online 8 June 2018
Source:Clinical Neurophysiology
Author(s): Edoardo Ferlazzo, Sara Gasparini, Chiara Sueri, Vittoria Cianci, Damiano Branca, Silvana Franceschetti, Ferruccio Panzica, Laura Canafoglia, Umberto Aguglia




https://ift.tt/2xWZrBl

Atypical Auditory Language Processing in Adolescents with Autism Spectrum Disorders

Publication date: Available online 8 June 2018
Source:Clinical Neurophysiology
Author(s): Junpei Tanigawa, Kuriko Kagitani-Shimono, Junko Matsuzaki, Rei Ogawa, Ryuzo Hanaie, Tomoka Yamamoto, Koji Tominaga, Shin Nabatame, Ikuko Mohri, Masako Taniike, Keiichi Ozono
ObjectiveIndividuals with autism spectrum disorder (ASD) often show characteristic differences in auditory processing. To clarify the mechanisms underlying communication impairment in ASD, we examined auditory language processing with both anatomical and functional methods.MethodsWe assessed the language abilities of adolescents with ASD and typically developing (TD) adolescents, and analyzed the surface-based morphometric structure between the groups using magnetic resonance imaging. Furthermore, we measured cortical responses to an auditory word comprehension task with magnetoencephalography and performed network-based statistics using the phase locking values.ResultsWe observed no structural differences between the groups. However, the volume of the left ventral central sulcus (vCS) showed a significant correlation with linguistic scores in ASD. Moreover, adolescents with ASD showed weaker cortical activation in the left vCS and superior temporal sulcus. Furthermore, these regions showed differential correlations with linguistic scores between the groups. Moreover, the ASD group had an atypical gamma band (25–40 Hz) network centered on the left vCS.ConclusionsAdolescents with ASD showed atypical responses on the auditory word comprehension task and functional brain differences.SignificanceOur results suggest that phonological processing and gamma band cortical activity play a critical role in auditory language processing-related pathophysiology in adolescents with ASD.



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Small fibre neuropathy in mitochondrial diseases explored with sudoscan

Publication date: August 2018
Source:Clinical Neurophysiology, Volume 129, Issue 8
Author(s): Marco Luigetti, Guido Primiano, Cristina Cuccagna, Daniela Bernardo, Donato Sauchelli, Catello Vollono, Serenella Servidei
ObjectivePolyneuropathy in mitochondrial diseases (MDs) is relatively common and widely investigated, but few data are instead reported about small fibres involvement.MethodsIn order to investigate the involvement of small fibres in MDs we performed extensive neurophysiological test (nerve conduction studies; sympathetic skin response; sudoscan) in 27 patients with genetic diagnosis of MD (7 m.3243A > G; 4 m.8344A > G; 9 single mtDNA deletion; 7 multiple mtDNA deletions).ResultsNCS showed a polyneuropathy in 11/27 cases (41%). The incidence was very high in POLG1 (100%), m.8344A > G (75%) and m.3243A > G (43%), while only 11% of patients with single deletion had evidence of large fibres involvement. Sympathetic skin response was abnormal only in three patients (one progressive external ophthalmoplegia with single mtDNA deletion; one patient with m.3243A > G mutation; one patient with POLG1 mutation). Sudoscan revealed the presence of an autonomic small fibres dysfunction in 9/27 cases (33%), most of them (7/9) carrying a single mtDNA deletion. Sudoscan data were also confirmed in a sub-group of patients by laser evoked potentials study. Considering only patients with single mtDNA deletion 7/9 (78%) showed abnormal results at sudoscan.ConclusionsSmall fibre neuropathy is another feature to investigate in mitochondrial diseases and seems specifically associated with the presence of single mtDNA deletion.SignificanceThe correct identification through specific neurophysiological tests of small fibres involvement in MDs represents another tile in this challenging diagnosis.



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Incidence of epileptiform discharges in children during induction of anaesthesia using Propofol versus Sevoflurane

Publication date: Available online 8 June 2018
Source:Clinical Neurophysiology
Author(s): Susanne Koch, Leopold Rupp, Christine Prager, Rudolf Mörgeli, Sylvia Kramer, Klaus Dieter Wernecke, Astrid Fahlenkamp, Claudia Spies
ObjectiveIn pediatric patients, anaesthesia induction is often performed with intravenous Propofol or Sevoflurane inhalation. Although epileptiform discharges have been observed during inductions with Sevoflurane, their occurrence has not been investigated for i.v. Propofol inductions. The aim of this study is to compare the incidence of epileptiform discharges in children during anaesthesia induction using Propofol versus Sevoflurane.MethodsProspective, observational cohort study in children aged 0.5 to 8 years undergoing elective surgery. Children were anaesthetized with either Propofol or Sevoflurane. Bi-frontal electroencephalograms electrodes were placed before start of anaesthesia. Visual electroencephalogram analysis was performed from start of anesthetic agent administration until Intubation with regard to identify epileptiform patterns, i.e. delta with spikes; rhythmic polyspikes; periodic, epileptiform discharges; or suppression with spikes.Results39 children were anaesthetized with Propofol, and 18 children with Sevoflurane. Epileptiform discharges were seen in 36% of the children in the Propofol group, versus 67% in the Sevoflurane group (p=0.03). Incidence of the distinct types of epileptiform discharge differed for periodic, epileptiform discharges (Sevoflurane group 39% vs. Propofol group 3%; p<0.001). Higher concentration of Remifentanil (≥ 0.15µg/kg/min) was associated with less frequent epileptiform discharges (Exp 5.8; CI 95% 1.6 / 21.2; p=0.008).ConclusionsPropofol i.v. induction of anaesthesia in children triggers epileptiform discharges, whereas to a lesser extent than Sevoflurane does.SignificancePresuming that epileptiform discharges have an impact on postoperative brain function, it is advisable to use Propofol rather than Sevoflurane and higher level of Remifentanil for anaesthesia induction in children.



https://ift.tt/2kXT87b

Survival benefit of adjuvant brachytherapy after hysterectomy with positive surgical margins in cervical cancer

Publication date: Available online 8 June 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Richard Li, Ashwin Shinde, Yi-Jen Chen, Arya Amini, Stephen Lee, Thanh Dellinger, Ernest Han, Mark Wakabayashi, Rebecca Nelson, Sushil Beriwal, Scott Glaser
PurposeWe evaluated the utilization of brachytherapy (BT) in addition to external beam radiation therapy (EBRT) and the resulting impact on survival in patients with cervical cancer after hysterectomy with positive surgical margins.Methods and MaterialsPatients with cervical cancer diagnosed from 2004 to 2015 who underwent hysterectomy followed by adjuvant EBRT were identified using the National Cancer Data Base. Only patients with positive surgical margins were included for analysis. Logistic regression was used to evaluate predictors of BT utilization and for propensity score matching. Survival was compared between patients receiving EBRT alone and EBRT combined with BT for adjuvant treatment. Survival analysis using log-rank test and Cox proportional hazards modeling was performed in the overall and propensity score-matched cohorts.ResultsWe identified 1,719 patients who received hysterectomy with positive surgical margins followed by adjuvant radiation therapy, of which 778 patients (45.3%) received additional BT. Predictors of increased receipt of BT included age > 55 years, private rather than government insurance, radiation treatment duration ≥7 weeks, external beam radiation dose ≥4500 cGy, and time between radiation and surgery ≤9 weeks. With a median follow-up of 3.8 years, 3-year overall survival was 79.4% in patients receiving BT compared to 71.9% in patients receiving EBRT alone (log-rank p<0.001). On multivariate analysis, EBRT and BT was associated with significantly improved survival (hazard ratio 0.77; 95% confidence interval 0.64-0.92; p=0.003) compared to EBRT alone. The survival benefit of combining EBRT and BT persisted on propensity score-matched analysis (log-rank p=0.005).ConclusionsIn women with positive margins after hysterectomy for cervical cancer, the combination of EBRT and BT showed significantly improved overall survival compared to EBRT alone. However, only 45.3% of patients in our cohort received BT.

Teaser

We analyzed a cohort of patients from the National Cancer Database who underwent hysterectomy for cervical cancer with positive surgical margins followed by adjuvant radiation therapy. We found that the addition of brachytherapy to external beam radiation therapy was associated with improved overall survival compared to external beam radiation therapy alone. However, only 45% of patients in this cohort received brachytherapy.


https://ift.tt/2kXS7vO

Analyzing Circulating Tumor Cells One at a Time

Publication date: Available online 8 June 2018
Source:Trends in Cell Biology
Author(s): Veronica Ortiz, Min Yu
Whole-genome sequencing has made a significant impact on cancer research, but traditional bulk methods fail to detect information from rare cells. Recently developed single-cell sequencing methods have provided new insights and unprecedented details about cancer progression and diversity. These advancements also enable the investigation of rare cells, such as circulating tumor cells (CTCs) derived from cancer patients. In this review, we outline various single-cell sequencing techniques that can elucidate the molecular properties of CTCs. In addition, we explain the drawbacks that need to be overcome for each method.



https://ift.tt/2HAEEmA

A novel punch biopsy technique without scissors or forceps

Publication date: Available online 9 June 2018
Source:Journal of the American Academy of Dermatology
Author(s): Ali Moiin, Brett C. Neill




https://ift.tt/2LBCgP7

Feasibility of a play-based intervention set for toddlers with autism

Publication date: September 2018
Source:Research in Developmental Disabilities, Volume 80
Author(s): Cooper R. Woodard, Jin Chung
The Meta-play Method is a play-based, naturalistic set of interventions designed to decrease the symptoms associated with autism in toddlers. The purpose of the present study was to explore the feasibility of using this intervention set with a small group of toddlers and their parents. We selected seven toddlers diagnosed with autism and tested these children for autism severity and severity of repetitive behaviors. Parents were trained on the basic concepts of DBTA and the Meta-play activities. Researchers reviewed the integrity of interventions at once- or twice-monthly home visits for a six-month period, and recorded progress as rated by the parent. Activities were adapted at each visit to the interests and progress of the participating toddler. At the end of six months, autism symptoms and repetitive behavior decreased and parents reported high levels of social validity. Additional aspects of data collection and outcome measures, and suitability of interventions and procedures are discussed. While some outcomes were encouraging, a number of changes are recommended for future research.



https://ift.tt/2kZcith

Evolutionary Perspective on Sex Differences in the Expression of Neurological Diseases

Publication date: Available online 8 June 2018
Source:Progress in Neurobiology
Author(s): David C. Geary
Sex-specific brain and cognitive deficits emerge with malnutrition, some infectious and neurodegenerative diseases, and often with prenatal or postnatal toxin exposure. These deficits are described in disparate literatures and are generally not linked to one another. Sexual selection may provide a unifying framework that integrates our understanding of these deficits and provides direction for future studies of sex-specific vulnerabilities. Sexually selected traits are those that have evolved to facilitate competition for reproductive resources or that influence mate choices, and are often larger and more complex than other traits. Critically, malnutrition, disease, chronic social stress, and exposure to man-made toxins compromise the development and expression of sexually selected traits more strongly than that of other traits. The fundamental mechanism underlying vulnerability might be the efficiency of mitochondrial energy capture and control of oxidative stress that in turn links these traits to current advances in neuroenergetics, stress endocrinology, and toxicology. The key idea is that the elaboration of these cognitive abilities, with more underlying gray matter or more extensive inter-modular white matter connections, makes them particularly sensitive to disruptions in mitochondrial functioning and oxidative stress. A framework of human sexually selected cognitive abilities and underlying brain systems is proposed and used to organize what is currently known about sex-specific vulnerabilities.



https://ift.tt/2sNTm4m

Pathologic role of nitrergic neurotransmission in mood disorders

Publication date: Available online 8 June 2018
Source:Progress in Neurobiology
Author(s): Mehdi Ghasemi, Joshua Claunch, Kathy Niu
Mood disorders are chronic, recurrent mental diseases that affect millions of individuals worldwide. Although over the past 40 years the biogenic amine models have provided meaningful links with the clinical phenomena of, and the pharmacological treatments currently employed in, mood disorders, there is still a need to examine the contribution of other systems to the neurobiology and treatment of mood disorders. This article reviews the current literature describing the potential role of nitric oxide (NO) signaling in the pathophysiology and thereby the treatment of mood disorders. The hypothesis has arisen from several observations including (i) altered NO levels in patients with mood disorders; (ii) antidepressant effects of NO signaling blockers in both clinical and pre-clinical studies; (iii) interaction between conventional antidepressants/mood stabilizers and NO signaling modulators in several biochemical and behavioral studies; (iv) biochemical and physiological evidence of interaction between monoaminergic (serotonin, noradrenaline, and dopamine) system and NO signaling; (v) interaction between neurotrophic factors and NO signaling in mood regulation and neuroprotection; and finally (vi) a crucial role for NO signaling in the inflammatory processes involved in pathophysiology of mood disorders. These accumulating lines of evidence have provided a new insight into novel approaches for the treatment of mood disorders.



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Editorial board

Publication date: May 2018
Source:Revue des Maladies Respiratoires, Volume 35, Issue 5





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Maladies respiratoires chroniques : être psychologue en milieu hospitalier

Publication date: May 2018
Source:Revue des Maladies Respiratoires, Volume 35, Issue 5
Author(s): J. Vanneste, S. Flament, A. Bourjot, E. Leclercq, A. Prevotat




https://ift.tt/2sLthne

Prise en charge des pneumothorax chez les fumeurs de cannabis : à propos de trois cas

Publication date: May 2018
Source:Revue des Maladies Respiratoires, Volume 35, Issue 5
Author(s): M.-L. Chardon, J.-C. Dalphin, B. Degano
IntroductionLa consommation de cannabis est fréquente chez les adolescents et les jeunes adultes français. En plus de ses effets neurologiques, le cannabis est susceptible d'induire un emphysème pulmonaire parfois sévère chez des patients jeunes. Lorsqu'un pneumothorax spontané survient chez un fumeur de cannabis, l'hypothèse d'un pneumothorax secondaire mérite probablement d'être évoquée car la prise en charge thérapeutique peut être différente de celle, bien codifiée, des pneumothorax spontanés primaires.ObservationLes données cliniques et radiologiques de trois jeunes patients fumeurs de cannabis ayant présenté des pneumothorax spontanés ont été recueillies. Compte tenu de l'importance de l'emphysème, on a considéré qu'il s'agissait de pneumothorax spontanés secondaires. Deux patients ont bénéficié d'un traitement chirurgical, avec des suites simples dans un cas et un bullage prolongé dans un autre cas. La prise en charge du troisième patient, exclusivement médicale, a été longue et compliquée.ConclusionL'importance de l'emphysème chez des patients pourtant jeunes, fumeurs de cannabis, complique la prise en charge d'un pneumothorax spontané. Dans ce contexte, il semble donc légitime de se poser la question d'un traitement chirurgical de première intention.IntroductionCannabis consumption is common among adolescents and young adults in France. In addition to its neurological effect, cannabis smoking can induce severe pulmonary emphysema, even in young patients. When a spontaneous pneumothorax occurs in a cannabis smoker, the possibility of a secondary spontaneous pneumothorax should be considered. This may be of importance as management of secondary spontaneous pneumothorax may differ from the well-codified handling of primary spontaneous pneumothorax.ObservationClinical and radiological data from three young cannabis-using patients with spontaneous pneumothorax were collected. Given the presence of emphysema, they were all considered secondary spontaneous pneumothorax. Two patients underwent surgical treatment, with simple postoperative follow-up in one case and prolonged air leak in the other case. The management of the third patient, exclusively medical, was prolonged and complicated.ConclusionThe presence of emphysema in young cannabis smokers complicates the management of spontaneous pneumothorax. In this context, a first-line surgical intervention may be an option to be considered.



https://ift.tt/2sNT2CG

Le syndrome d’apnées obstructives du sommeil n’est pas mauvais que pour le cœur !

Publication date: May 2018
Source:Revue des Maladies Respiratoires, Volume 35, Issue 5
Author(s): J. Rajaoarifetra, A. Palot, D. Tissier Ducamp, C. Tummino, M. Gouitaa, P. Chanez
Le syndrome d'apnées-hypopnées obstructives du sommeil (SAHOS) est une pathologie fréquente surtout chez les sujets âgés. Ses complications cardiovasculaires sont fréquentes et graves. Cependant, l'indication de son traitement chez les sujets âgés reste discutée. Nous rapportons le cas d'un homme de 79 ans qui a inhalé son bridge dentaire au cours du sommeil. Le corps étranger inhalé s'est arrêté au niveau de la bronche souche gauche. Un état d'obésité avec un indice de masse corporelle à 30kg/m² associé à des ronflements, une nycturie, des céphalées matinales et un score d'Epworth à 11 ont conduit à la réalisation d'une polygraphie ventilatoire qui a confirmé le SAHOS avec un index d'apnée-hypopnée à 53 par heure. Cette observation souligne que le SAHOS peut constituer un facteur de risque d'inhalation de corps étranger chez les sujets âgés par la force du mouvement ventilatoire post-éveil cortical.Obstructive sleep apnoea (OSA) is common in the general population, particularly in the elderly. This syndrome is frequently responsible for severe cardiovascular complications. However, the indications for its treatment in the elderly remain controversial. We report the case of a 79-year-old man with severe, undiagnosed OSA who inhaled his fixed dental bridge during sleep. The inhaled foreign body came to rest in the lumen of the left main stem bronchus. The association of obesity with a body mass index of 30kg/m², snoring with breathing pauses reported by his partner, nocturia, morning headache and an Epworth score of 11 led to polysomnography which confirmed OSA with an apnoea/hypopnoea index of 53 per hour. This case report emphasises that OSA may constitute a risk fact for foreign body inhalation in elderly subjects due to arousal-induced hyperventilation following the apnoeic event.



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ABCT-IMMUNOBZH : évaluation de l’efficacité du nivolumab dans la vraie vie chez 259 patients porteurs d’un cancer bronchique non à petites cellules de stade avancé

Publication date: May 2018
Source:Revue des Maladies Respiratoires, Volume 35, Issue 5
Author(s): M. Geier, R. Descourt, R. Corre, G. Leveiller, G. Le Garff, E. Briens, R. Lamy, E. Goarant, J.L. Bizec, C. Bernier, G. Quéré, E. Gaye, F. Montestruc, F. Couturaud, G. Robinet
IntroductionL'immunothérapie s'est récemment imposée comme standard en 2^e ligne thérapeutique des cancers bronchiques non à petites cellules (CBNPC) de stade avancé. Cependant, les données concernant son efficacité sont basées sur des populations sélectionnées ne reflétant pas toujours la pratique clinique quotidienne. Cette étude avait pour but d'évaluer l'efficacité du nivolumab dans la vraie vie et de déterminer un sous-type de patients plus à même d'en bénéficier.MéthodesÉtaient éligibles à l'inclusion les patients porteurs d'un CBNPC de stade avancé (IIIB-IV) traités par nivolumab entre le 01/09/2015 et le 30/09/2016 après échec d'au moins une ligne de chimiothérapie. Le nivolumab était administré à une dose de 3mg/kg tous les 15jours jusqu'à progression ou toxicité majeure. Le critère de jugement principal était le taux de réponse objective (TRO) selon RECIST 1.1. Les critères secondaires étaient la survie sans progression (SSP), la survie globale (SG) et la recherche de facteurs prédictifs d'efficacité.RésultatsAu total, 259 patients ont été inclus dans neuf centres bretons. Les caractéristiques au diagnostic étaient : âge médian de 62 ans [29–85], 72,2 % d'hommes, 73 % avec un performance status ≤ 1, histoire tabagique dans 85,8 % des cas, avec une majorité de stades IV (85,3 %) et d'adénocarcinomes (63,7 %). La mutation KRAS était la plus fréquente et retrouvée chez 55 patients. Dans 61,4 % des cas, le nivolumab était administré en 2^e ligne. Le TRO était de 22,4 % (58 patients). La SSP médiane et la SG médiane étaient de 2,3 et 11 mois, respectivement. L'histologie épidermoïde était associée à une meilleure réponse (HR=1,98, IC95 % [1,08-3,61], p=0,03). La survenue d'effets secondaires d'ordre immunitaire était associée à une meilleure réponse et à une amélioration de la SG (HR=0,42, IC95 % [0,26–0,70], p<0,01).ConclusionAvec un TRO de 22,4 %, similaire aux essais cliniques, et une SG de 11 mois, le nivolumab semble tenir ses promesses dans la vraie vie. Dans cette étude, l'histologie épidermoïde et la survenue d'effets secondaires d'ordre immunitaire sont des facteurs prédictifs d'efficacité.



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Cardiopathie fulminante après traitement par pembrolizumab et revue de la littérature

Publication date: May 2018
Source:Revue des Maladies Respiratoires, Volume 35, Issue 5
Author(s): G. Justeau, G. de Chabot, S. Delépine, T. Urban
Nous rapportons le cas d'une patiente de 67 ans prise en charge pour un carcinome épidermoïde bronchopulmonaire métastatique PDL-1 positif>50 %. Cette patiente a bénéficié en deuxième ligne thérapeutique d'un traitement par pembrolizumab. Six jours après l'administration de la première cure d'immunothérapie, la patiente a présenté une altération de l'état général rapidement progressive au domicile et elle a été hospitalisée à j10. Les explorations ont mis en évidence une atteinte de sa fonction cardiaque possiblement iatrogène. Malgré une prise en charge dans l'unité de soins intensifs de cardiologie, la patiente a présenté une défaillance myocardique et est décédée le jour même.Plusieurs cas de toxicité cardiaque sous immunothérapie ont été rapportés dans la littérature. L'originalité de ce cas est la gravité du tableau et la précocité de la survenue de cette toxicité, entraînant le décès de la patiente seulement dix jours après l'administration du traitement. De telles toxicités aiguës et vitales doivent être connues des cliniciens afin d'initier précocement une corticothérapie.



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Toxicité immunologique sévère du nivolumab et réponse tumorale prolongée dans le cancer bronchique non à petites cellules

Publication date: May 2018
Source:Revue des Maladies Respiratoires, Volume 35, Issue 5
Author(s): H. Gendreau, L. Lagarce, L. Savary, T. Urban, J. Hureaux
IntroductionLe nivolumab est un nouveau traitement pour le cancer bronchique non à petites cellules (CBNPC) en 2^e ligne après une chimiothérapie cytotoxique. Des effets indésirables nouveaux sont apparus et sont de type immunologique. Il semblerait que ces toxicités soient associées à une meilleure survie du patient.MéthodesL'objectif de cette étude était de recenser les cas de patients traités par nivolumab pour un CBPNC qui ont dû interrompre ce traitement pour une toxicité immunologique sévère entre juin 2015 et juin 2017, afin de décrire cette population, d'analyser la réponse tumorale et d'évaluer la survie. Il s'agissait d'une étude rétrospective menée avec l'aide du centre régional de pharmacovigilance d'Angers.RésultatsOnze patients ont été recensés, dont 54,5 % d'hommes ; 45,5 % des types histologiques étaient des carcinomes épidermoïdes. L'âge moyen à l'initiation du nivolumab était de 68,8 ans. La médiane de durée de réponse était de 5 mois, la médiane de survie sans progression de 9 mois et la médiane de survie globale de 17 mois.ConclusionLa présence d'une toxicité immunologique limitante au nivolumab serait associée à une meilleure survie, mais ces résultats restent à confirmer sur une étude comparative.



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Une complication rare de leptospirose pulmonaire

Publication date: May 2018
Source:Revue des Maladies Respiratoires, Volume 35, Issue 5
Author(s): A. Delgoulet, M.C. Roger, J.C. Meurice
La leptospirose est une zoonose ubiquitaire endémique dans les régions tropicales où le réservoir animal naturel est abondant et où le climat chaud et humide constitue la condition propice pour la transmission à l'Homme. Nous rapportons le cas d'une jeune éducatrice spécialisée de 31 ans, exerçant en Guyane française, prise en charge dans le service de pneumologie du CHU de Poitiers pour toux fébrile.Cette patiente, fréquemment en contact avec des eaux stagnantes, présente ces symptômes quelques jours seulement après son retour en France métropolitaine pour ses vacances. L'examen clinique initial ne retrouve pas de signe de gravité, une SpO2 à 94 % et une fièvre à 39°C. Le murmure vésiculaire est aboli dans la partie supérieure de l'hémichamp pulmonaire gauche et la toux ne s'accompagne d'aucune expectoration. Le bilan radiologique met en évidence une pneumonie compliquée d'une pleurésie enkystée lobaire supérieure gauche. La biologie retrouve une hyperleucocytose à 12 500 éléments/mm³ dont 65 % de polynucléaires neutrophiles et un syndrome inflammatoire biologique avec une CRP à 154mg/L. Les fonctions hépatiques et rénales sont conservées.Après avoir éliminé une infection tuberculeuse pulmonaire, l'évolution est rapidement favorable après l'introduction d'une antibiothérapie probabiliste par amoxicilline/acide clavulanique et le drainage de la pleurésie. Le bilan étiologique infectieux nous permet d'évoquer le diagnostic de leptospirose pulmonaire grâce à une sérologie positive à IgM.La leptospirose pulmonaire est habituellement décrite dans les atteintes sévères de la maladie. Cette infection est néanmoins sous-estimée et doit être évoquée devant toute manifestation pulmonaire en retour de voyage. Les complications pleurales de la leptospirose sont rares mais d'évolution favorable sous antibiothérapie adaptée.



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Une microangiopathie révélatrice d’une néoplasie pulmonaire

Publication date: May 2018
Source:Revue des Maladies Respiratoires, Volume 35, Issue 5
Author(s): M. Deudon, B. Martignac, C. Robin, C. Marty-Enguehard, L. Du Couedic, A. Trehony, J. Graveleau, C. L'Heveder
La microangiopathie thrombotique (MAT) correspond à l'association d'une anémie hémolytique mécanique et d'une thrombopénie périphérique. Elle rentre parfois dans le cadre d'un syndrome paranéoplasique, notamment dans certains cas de cancer pulmonaire.Nous présentons le cas d'un patient de 61 ans hospitalisé pour une altération de l'état général et une dyspnée, qui font découvrir une MAT. L'origine paranéoplasique a été suspectée devant la révélation d'une tumeur pulmonaire au scanner, dont l'analyse anatomopathologique confirmera ensuite la présence d'un carcinome épidermoïde. Le myélogramme était normal. Des échanges plasmatiques au PFC et une corticothérapie ont été débutés en urgence, permettant d'obtenir une amélioration partielle de la numération sanguine. Dans un second temps, le patient a reçu un traitement par chimiothérapie et radiothérapie, ce qui a fait régresser la MAT.Bien qu'il n'existe pas de données épidémiologiques précises, cette pathologie a été décrite de nombreuses fois dans la littérature. Elle est difficile à différencier du purpura thrombotique thrombocytopénique, qui est le principal diagnostic différentiel à évoquer chez un adulte. Il existe des signes clinico-biologiques évocateurs de l'origine néoplasique, qu'il faut savoir reconnaître afin de débuter rapidement une prise en charge adaptée. Les examens à réaliser en urgence sont, d'une part, le myélogramme à la recherche d'un envahissement par des cellules cancéreuses, et d'autre part, le dosage sanguin de l'activité ADAMST13. Une fois l'étiologie néoplasique confirmée, le seul traitement efficace est le traitement du cancer sous jacent. Les données rapportent une efficacité décevante des échanges plasmatiques, probablement du fait d'un mécanisme physiopathologique propre au cancer. La particularité de notre patient a été d'y répondre favorablement. On peut ainsi se poser la question d'un lien entre l'absence d'envahissement médullaire et l'efficacité des échanges plasmatiques.



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La fièvre des métaux

Publication date: May 2018
Source:Revue des Maladies Respiratoires, Volume 35, Issue 5
Author(s): M. Veillard, G. Lasnier, M. Jouvenot, F. Goupil
Nous rapportons le cas d'un patient de 56 ans ayant consulté en 2017 pour des symptômes stéréotypés évoluant depuis de nombreuses années et devenant mensuels, associant fièvre brutale jusqu'à 40°C, sueurs nocturnes et douleurs thoraciques à caractéristiques pleurales. La radiographie thoracique était normale. Les symptômes étaient spontanément résolutifs ou sous l'effet de traitements symptomatiques en 3 à 5 jours. Il s'agissait d'un patient sans antécédent de maladie respiratoire familiale ou personnelle, sans comorbidité, non tabagique, exerçant la profession de métallier soudeur depuis plus de 20 ans. Le scanner thoracique retrouvait des images de bronchectasies modérées et de bronchiolite aux niveaux des 2 bases. Le lavage bronchoalvéolaire était normal, sans germe, sans argument pour une pneumopathie d'hypersensibilité. Il n'y avait pas d'éléments biologiques en faveur d'un déficit immunitaire ou d'une pathologie auto-immune. L'hypothèse d'une pathologie environnementale professionnelle était confirmée par l'intervention du médecin du travail. Les symptômes disparaissaient après la mise en place d'un masque de protection lors des activités de soudure.La pneumopathie des soudeurs, aussi appelée « fièvre des soudeurs » ou « fièvre des métaux », résulte de l'inhalation de nanoparticules de métaux lourds responsable d'une inflammation des bronches. Elle dépend du type de procédé de soudage et du niveau d'empoussiérage. Il s'agit d'une pathologie mal connue du milieu pneumologique, sous diagnostiquée, efficacement contrôlable par des méthodes de prévention simples.



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Complications des anti-PD-1 dans le cancer bronchopulmonaire : trois cas d’infections thoraciques bactériennes graves

Publication date: May 2018
Source:Revue des Maladies Respiratoires, Volume 35, Issue 5
Author(s): F. Lisée, E. Pichon, T. Flament, M. Campana, D. Carmier, P. Diot, S. Marchand-Adam
IntroductionLes inhibiteurs des check-points de l'immunité font aujourd'hui partie intégrante du traitement des carcinomes bronchiques non à petites cellules (CBNPC). Alors que leurs effets indésirables dysimmunitaires sont connus, leurs complications infectieuses sont plus rarement décrites.Cas cliniquesNous rapportons les cas de trois patients suivis pour un CBNPC évolué exprimant le PD-L1 entre 0 et 75 %. Ces trois patients ont présenté après les 4^e, 3^e et 2^e cycles de nivolumab des infections thoraciques graves caractérisées respectivement par un abcès pulmonaire sans germe identifié développé à distance de la tumeur, une pleurésie purulente droite à S. pneumoniae compliquée d'un choc septique et une récidive à 5 ans d'un abcès étendu des parties molles à S. aureus méticilline-S en regard d'une cicatrice de lobectomie. En se basant sur les critères de Naranjo, l'imputabilité du nivolumab dans la survenue de ces infections était retenue comme possible dans un cas et probable dans les deux autres cas. L'évolution de l'infection était toujours favorable après suspension du nivolumab et traitement adapté mais précipitait probablement les patients vers une prise en charge palliative.ConclusionPar le blocage de l'interaction PD-1/PD-L1, l'anti-PD-1 pourrait exacerber l'immunité antibactérienne et participer à la gravité des infections observées. La banalisation des infections thoraciques au cours du CBNPC pourrait favoriser la sous-estimation de l'incrimination de l'immunothérapie dans leur survenue. La gravité et les conséquences directes et indirectes de ces infections sur le pronostic des patients incitent à une déclaration large de ces cas aux centres de pharmacovigilance.



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Adénocarcinome pancréatique métastatique aux poumons : un train peut en cacher un autre !

Publication date: May 2018
Source:Revue des Maladies Respiratoires, Volume 35, Issue 5
Author(s): C. Ropars, M. Kerjouan, C. Larible, F. Llamas Gutierrez ou Dan, M. Léderlin, B. De Latour, B. Desrues, S. Jouneau
Les métastases pulmonaires révélatrices d'un cancer du pancréas posent le problème principal de retard diagnostic. Nous rapportons le cas d'une jeune patiente de 37 ans adressée pour un bilan de pneumopathie infiltrante diffuse présentant de multiples nodules excavés pulmonaires (Fig. 1–2). Le diagnostic différentiel est celui de la maladie kystique multiple pulmonaire. La biopsie pulmonaire chirurgicale a permis de poser le diagnostic de lésions secondaires de cancer d'origine digestive notamment pancréatique (Fig. 3).La dégradation clinique est rapide dans cette pathologie de pronostic effroyable. Il est indispensable de rechercher la surinfection des lésions, notamment l'aspergillose pulmonaire chronique.



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Asthme et aptitude militaire en France et dans les pays étrangers

Publication date: May 2018
Source:Revue des Maladies Respiratoires, Volume 35, Issue 5
Author(s): E. Rivière
L'asthme est une pathologie chronique alliant une obstruction des voies respiratoires, une inflammation et une hyperréactivité bronchique. Il est admis que le milieu militaire concentre de nombreux facteurs favorisant l'aggravation d'une maladie asthmatique. L'asthme est d'ailleurs une cause majeure d'inaptitude à l'engagement dans l'armée française.L'aptitude militaire est une évaluation de l'adéquation entre l'état de santé d'un candidat et le poste qu'il devra occuper au sein de l'armée. Chaque pays dispose d'une réglementation propre, plus ou moins complexe et souvent évolutive dans le temps.Ce travail a pour but de faire un état des lieux de la problématique d'aptitude à l'engagement vis-à-vis de la pathologie asthmatique dans différents pays selon les données disponibles de la littérature. Cela permet de comprendre la construction de ces normes dans le temps et d'entrevoir les pistes futures de leur évolution. Enfin, la connaissance de ces normes permet une meilleure information des futurs candidats qui cherchent souvent une première information auprès de leur praticien civil.



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Does CoolSculpting work?

CoolSculpting is a noninvasive cosmetic procedure to reduce stubborn areas of fat using cold temperatures. Plastic surgeons make bold claims about its benefits, but does it really work? In this article, we take a close look at what the research says about how effective and safe CoolSculpting is for removing body fat.

https://ift.tt/2sPRKHj

What are the side effects of laser hair removal?

Removing unwanted hair from the body and face is usually done safely and effectively using laser hair removal therapy. Some people may experience mild redness, swelling, and irritation of the treated area. Here, we look at how safe laser hair removal is, possible side effects, and some of the myths about the process.

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Regulation of decellularized tissue remodeling via scaffold-mediated lentiviral delivery in anatomically-shaped osteochondral constructs

Publication date: September 2018
Source:Biomaterials, Volume 177
Author(s): Christopher R. Rowland, Katherine A. Glass, Adarsh R. Ettyreddy, Catherine C. Gloss, Jared R.L. Matthews, Nguyen P.T. Huynh, Farshid Guilak
Cartilage-derived matrix (CDM) has emerged as a promising scaffold material for tissue engineering of cartilage and bone due to its native chondroinductive capacity and its ability to support endochondral ossification. Because it consists of native tissue, CDM can undergo cellular remodeling, which can promote integration with host tissue and enables it to be degraded and replaced by neotissue over time. However, enzymatic degradation of decellularized tissues can occur unpredictably and may not allow sufficient time for mechanically competent tissue to form, especially in the harsh inflammatory environment of a diseased joint. The goal of the current study was to engineer cartilage and bone constructs with the ability to inhibit aberrant inflammatory processes caused by the cytokine interleukin-1 (IL-1), through scaffold-mediated delivery of lentiviral particles containing a doxycycline-inducible IL-1 receptor antagonist (IL-1Ra) transgene on anatomically-shaped CDM constructs. Additionally, scaffold-mediated lentiviral gene delivery was used to facilitate spatial organization of simultaneous chondrogenic and osteogenic differentiation via site-specific transduction of a single mesenchymal stem cell (MSC) population to overexpress either chondrogenic, transforming growth factor-beta 3 (TGF-β3), or osteogenic, bone morphogenetic protein-2 (BMP-2), transgenes. Controlled induction of IL-1Ra expression protected CDM hemispheres from inflammation-mediated degradation, and supported robust bone and cartilage tissue formation even in the presence of IL-1. In the absence of inflammatory stimuli, controlled cellular remodeling was exploited as a mechanism for fusing concentric CDM hemispheres overexpressing BMP-2 and TGF-β3 into a single bi-layered osteochondral construct. Our findings demonstrate that site-specific delivery of inducible and tunable transgenes confers spatial and temporal control over both CDM scaffold remodeling and neotissue composition. Furthermore, these constructs provide a microphysiological in vitro joint organoid model with site-specific, tunable, and inducible protein delivery systems for examining the spatiotemporal response to pro-anabolic and/or inflammatory signaling across the osteochondral interface.



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Development and MPI tracking of novel hypoxia-targeted theranostic exosomes

Publication date: September 2018
Source:Biomaterials, Volume 177
Author(s): Kyung Oh Jung, Hunho Jo, Jung Ho Yu, Sanjiv Sam Gambhir, Guillem Pratx
Treating the hypoxic region of the tumor remains a significant challenge. The goals of this study are to develop an exosome platform that can target regions of tumor hypoxia and that can be monitored in vivo using magnetic particle imaging (MPI). Four types of exosomes (generated under hypoxic or normoxic conditions, and with or without exposure to X-ray radiation) were isolated from MDA-MB-231 human breast cancer cells. Exosomes were labeled by DiO, a fluorescent lipophilic tracer, to quantify their uptake by hypoxic cancer cells. Subsequently, the exosomes were modified to carry SPIO (superparamagnetic iron oxide) nanoparticles and Olaparib (PARP inhibitor). FACS and fluorescence microscopy showed that hypoxic cells preferentially take up exosomes released by hypoxic cells, compared with other exosome formulations. In addition, the distribution of SPIO-labeled exosomes was successively imaged in vivo using MPI. Finally, the therapeutic efficacy of Olaparib-loaded exosomes was demonstrated by increased apoptosis and slower tumor growth in vivo. Our novel theranostic platform could be used as an effective strategy to monitor exosomes in vivo and deliver therapeutics to hypoxic tumors.



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Oxygen-boosted immunogenic photodynamic therapy with gold nanocages@manganese dioxide to inhibit tumor growth and metastases

Publication date: September 2018
Source:Biomaterials, Volume 177
Author(s): Ruijing Liang, Lanlan Liu, Huamei He, Zhikuan Chen, Zhiqun Han, Zhenyu Luo, Zhihao Wu, Mingbing Zheng, Yifan Ma, Lintao Cai
Metastatic triple-negative breast cancer (mTNBC) is an aggressive disease among women worldwide, characterized by high mortality and poor prognosis despite systemic therapy with radiation and chemotherapies. Photodynamic therapy (PDT) is an important strategy to eliminate the primary tumor, however its therapeutic efficacy against metastases and recurrence is still limited. Here, we employed a template method to develop the core-shell gold nanocage@manganese dioxide (AuNC@MnO2, AM) nanoparticles as tumor microenvironment responsive oxygen producers and near-infrared (NIR)-triggered reactive oxygen species (ROS) generators for oxygen-boosted immunogenic PDT against mTNBC. In this platform, MnO2 shell degrades in acidic tumor microenvironment pH/H2O2 conditions and generates massive oxygen to boost PDT effect of AM nanoparticles under laser irradiation. Fluorescence (FL)/photoacoustic (PA)/magnetic resonance (MR) multimodal imaging confirms the effective accumulation of AM nanoparticles with sufficient oxygenation in tumor site to ameliorate local hypoxia. Moreover, the oxygen-boosted PDT effect of AM not only destroys primary tumor effectively but also elicits immunogenic cell death (ICD) with damage-associated molecular patterns (DAMPs) release, which subsequently induces DC maturation and effector cells activation, thereby robustly evoking systematic antitumor immune responses against mTNBC. Hence, this oxygen-boosted immunogenic PDT nanosystem offers a promising approach to ablate primary tumor and simultaneously prevent tumor metastases via immunogenic abscopal effects.

Graphical abstract

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Hyaluronic acid formulation of near infrared fluorophores optimizes surgical imaging in a prostate tumor xenograft

Publication date: Available online 8 June 2018
Source:Acta Biomaterialia
Author(s): Joshua J. Souchek, Nicholas E. Wojtynek, William M. Payne, Megan B. Holmes, Samikshan Dutta, Bowen Qi, Kaustubh Datta, Chad A. LaGrange, Aaron M. Mohs
The presence of positive surgical margins confers an increased risk of biochemical relapse and need for salvage therapy in men undergoing radical prostatectomy. Image-guided surgery using near-infrared (NIR) fluorescent contrast agents is a potential method to detect remaining cancerous tissue. The objective of this study was to evaluate three hyaluronic acid (HA) nanoparticle (NP) formulations loaded with NIR fluorophore for their ability to contrast-enhance prostate cancer. HA was modified by conjugation with the hydrophobic ligand, aminopropyl-1-pyrenebutanamide to drive nanoparticle self-assembly. Indocyanine green (ICG) was physicochemically entrapped in the HA-NP, termed NanoICG. Alternatively, Cy7.5 was directly conjugated to amphiphilic HA, termed NanoCy7.5. NanoCy7.5 was synthesized with two HA molecular weights to determine the HA size contribution to delivery to PC3 prostate tumor xenografts. Contrast-enhancement of the tumors and relative biodistribution were assessed by a series of fluorescence imaging, image-guided surgery with spectroscopy, and microscopic techniques. Intravenously administered NanoICG improved tumor signal-to-noise ratio (SNR) at 24 h over ICG by 2.9-fold. NanoCy7.5 with 10 kDa and 100kDa HA improved tumor SNR by 6.6- and 3.1-fold over Cy7.5 alone, respectively. The PC3 xenograft was clearly identified with the image-guided system providing increased contrast enhancement compared to surrounding tissue for NanoICG and NanoCy7.5 with 10 kDa HA. NIR fluorescence microscopy showed that Cy7.5 in NPs with 10 kDa HA were distributed throughout the tumor, while NanoCy7.5 with 100 kDa HA or NanoICG delivered dye mainly to the edge of the tumor. CD31 staining suggested that PC3 tumors are poorly vascularized. These studies demonstrate the efficacy of a panel of HA-derived NPs in identifying prostate tumors in vivo, and suggest that by tuning the structural properties of these NPs, optimized delivery can be achieved to poorly vascularized tumors.Statement of SignificanceWe have demonstrated the potential of a panel of near-infrared fluorescent (NIRF) nanoparticles (NPs) for image-guided surgery in a prostate cancer xenograft model. Image-guided surgery and imaging of organsex vivoshowed greater tumor signal and contrast when mice were administered NIRF dyes that were covalently conjugated to (NanoCy7.510k-PBA) or physicochemically entrapped in (NanoICGPBA) hyaluronic acid (HA) NPs, compared to free dyes. These results show the potential to use these NPs as tools to detect the margins of tumors and to differentiate healthy and tumor tissue intraoperatively. Moreover, this project provides insight into selecting optimal formulation strategies for poorly vascularized tumors.

Graphical abstract

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Scholar : Philosophical Magazine, Volume 98, Issue 19, July 2018 is now available online on Taylor & Francis Online

The online platform for Taylor & Francis Online content Philosophical Magazine, Volume 98, Issue 19, July 2018 is now available online on Taylor & Francis Online. This new issue contains the following articles: Part A: Materials Science Surface stress mediated image force and torque on an edge dislocation R. M. Raghavendra, Divya, Ganesh Iyer, Arun Kumar & Anandh Subramaniam Pages: 1731-1743 | DOI: 10.1080/14786435.2018.1456688 Dual self-organised shear banding behaviours and enhanced ductility in phase separating Zr-based bulk metallic glasses Z. Q. Zhang, K. K. Song, B. A. Sun, L. Wang, W. C. Cui, Y. S. Qin, X. L. Han, Q. S. Xue, C. X. Peng, B. Sarac, F. Spieckermann, I. Kaban & J. Eckert Pages: 1744-1764 | DOI: 10.1080/14786435.2018.1456690 Periodic cracks and temperature-dependent stress in Mo/Si multilayers on Si substrates Grygoriy Kravchenko, Hai T. Tran & Alex A. Volinsky Pages: 1765-1779 | DOI: 10.1080/14786435.2018.1459055 Exact solution of two collinear cracks normal to the boundaries of a 1D layered hexagonal piezoelectric quasicrystal Y.-B. Zhou & X.-F. Li Pages: 1780-1798 | DOI: 10.1080/14786435.2018.1459057 Part B:Condensed Matter Physics Conductivity of disordered 2d binodal Dirac electron gas: effect of internode scattering Andreas Sinner & Klaus Ziegler Pages: 1799-1822 | DOI: 10.1080/14786435.2018.1447703 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.