Third EU-US workshop on “Nucleotide excision repair and crosslink repair—From molecules to mankind”, Smolenice Castle, Slovak Republic, May 7th–11th 2017

Publication date: Available online 30 August 2017
Source:DNA Repair
Author(s): Peter J. McHugh, Caroline Kisker, Miroslav Chovanec, Bennett Van Houten
The purpose of this workshop was to bring together scientists from the EU and US to discuss our current understanding of how protein machines assemble and sort through genomic DNA to identify specific damaged sites which are repaired through the two critical repair pathways: nucleotide excision repair or interstrand crosslink repair. Several of the enzymes perform dual functions in both pathways, thus combining these two topics in one meeting provided tremendous synergy and was a unique feature of this workshop. Many endogenous agents, environmental toxicants and chemotherapeutic agents cause a spectrum of DNA lesions that are repaired through these two mechanisms. The importance of the repair pathways acting on these forms of DNA damage is underscored by the fact that their loss or dysregulation is associated with a variety of devastating heritable human conditions including cancer, neurodegeneration, premature aging and severe developmental abnormalities. The workshop covered research conducted on molecules to mankind, and included discussions of disease syndromes associated with poor repair of these forms of damage. The meeting also provided an unparalleled opportunity to interact with scientists from the EU, US, and throughout the world, who are driving the field.



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Increased oxytocin-monomeric red fluorescent protein 1 fluorescent intensity with urocortin-like immunoreactivity in the hypothalamo-neurohypophysial system of aged transgenic rats

Publication date: Available online 30 August 2017
Source:Neuroscience Research
Author(s): Shigeo Ohno, Hirofumi Hashimoto, Hiroaki Fujihara, Nobuhiro Fujiki, Mitsuhiro Yoshimura, Takashi Maruyama, Yasuhito Motojima, Reiko Saito, Hiromichi Ueno, Satomi Sonoda, Motoko Ohno, Yuichi Umezu, Akinori Hamamura, Satoru Saeki, Yoichi Ueta
To visualize oxytocin in the hypothalamo-neurohypophysial system, we generated a transgenic rat that expresses the oxytocin-monomeric red fluorescent protein 1 (mRFP1) fusion gene. In the present study, we examined the age-related changes of oxytocin-mRFP1 fluorescent intensity in the posterior pituitary (PP), the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) of transgenic rats. The mRFP1 fluorescent intensities were significantly increased in the PP, the SON and the PVN of 12-, 18- and 24-month-old transgenic rats in comparison with 3-month-old transgenic rats. Immunohistochemical staining for urocortin, which belongs to the family of corticotropin-releasing factor family, revealed that the numbers of urocortin-like immunoreactive (LI) cells in the SON and the PVN were significantly increased in 12-, 18- and 24-month-old transgenic rats in comparison with 3-month-old transgenic rats. Almost all of urocortin-LI cells co-exist mRFP1-expressing cells in the SON and the PVN of aged transgenic rats. These results suggest that oxytocin content of the hypothalamo-neurohypophysial system may be modulated by age-related regulation. The physiological role of the co-existence of oxytocin and urocortin in the SON and PVN of aged rats remains unclear.



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Blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) during transcranial near-infrared laser irradiation

Publication date: Available online 30 August 2017
Source:Brain Stimulation
Author(s): Hiroshi Nawashiro, Shunichi Sato, Satoko Kawauchi, Satoru Takeuchi, Kimihiro Nagatani, Nobuyuki Yoshihara, Hiroshi Shinmoto




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Comparison of the effect of aerosolized fibrin sealant and biodegradable synthetic polyurethane foam on hemostasis and wound healing after endoscopic sinus surgery: a prospective randomized study

Background

Use of absorbable packing materials after functional endoscopic sinus surgery (FESS) is associated with increased patient comfort and a lack of need for packing removal. Different materials may induce different patterns of mucosal healing and hemostasis. This study investigated the effect of fibrin sealant (FS; Tisseel) or biodegradable synthetic polyurethane foam (Nasopore^®) packing on hemostasis and wound healing after FESS.

Methods

This prospective randomized controlled trial included 35 consecutive patients who underwent bilateral FESS for chronic rhinosinusitis. The patients were randomized to receive FS through aerosol spraying on 1 side and Nasopore packing on the opposite side. They were followed at 1, 2, 4, 8, and 12 weeks after surgery. Endoscopically visible packing material, crusting, adhesion, bleeding, granulation tissue formation, frontal sinus patency, and adverse effects were assessed. Subjective symptoms related to nasal packing were evaluated by using questionnaires quantified with a visual analogue scale.

Results

No significant differences were found between the FS-treated side and the Nasopore-packed side with respect to postoperative bleeding, adhesion, or frontal sinus patency. However, crusting and granulation were significantly lower in FS-treated nostrils (p < 0.01). The patients' satisfaction and willingness to reuse the material were not significantly different between FS and Nasopore. There were no allergic reactions to either material.

Conclusion

FS and Nasopore were equally successful in achieving hemostasis and patient satisfaction after FESS. However, our results suggest that differential mucosal healing patterns may be induced by alternative absorbable hemostatic materials. FS-treated sides showed more optimal healing patterns than Nasopore-packed sides.

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Significance of human papillomavirus positivity in sinonasal squamous cell carcinoma

Background

The role of human papillomavirus (HPV) in sinonasal squamous cell carcinoma (SNSCC) is not well understood.

Methods

The National Cancer Database was queried for cases of SNSCC with known HPV status. Demographics, socioeconomic variables, TNM stage, histology, grade, treatment modalities, and overall survival (OS) through 5 years were compared between HPV-positive and HPV-negative tumors. Cox proportional hazard regression analyses were performed.

Results

Seven hundred seventy (770) cases were identified; 526 were HPV-negative (68.3%) and 244 (31.7%) were HPV-positive. Patients with HPV-positive tumors were younger (58.0 vs 63.7 years, p < 0.0001). Nasal cavity (49.4%) tumors were more likely to be HPV-positive (p < 0.05) than maxillary (18.8%), ethmoid (18.8%), and frontal (18.2%) sinus tumors. Large cell nonkeratinizing (42.4%), papillary (42.1%), and basaloid (56.5%) tumors were more likely than keratinizing (25.2%) tumors to be HPV-positive (p < 0.05). Well-differentiated (grade I) tumors (9.0%) were less likely than higher grade tumors to be HPV-positive (p < 0.05). Gender, race, facility type, insurance type, median income, education level, Charlson-Deyo comorbidity score, overall stage, T stage, N stage, M stage, tumor size, treatment modality, surgical approach, and surgical margins did not vary by HPV status (p ≥ 0.05). HPV-positive tumors had higher OS than HPV-negative tumors (p < 0.0001). At 5 years, OS was 68.1% and 51.5% for HPV-positive and HPV-negative tumors, respectively. On multivariate analyses, HPV positivity remained a favorable prognostic factor (hazard ratio, 0.49; 95% confidence interval, 0.34-0.70).

Conclusion

HPV positivity is more common in nasal cavity SCC and nonkeratinizing SNSCC. It is also a favorable prognostic factor in SNSCC. Future studies on SNSCC should take HPV positivity into consideration.

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Paths to Open Access: An update from Acta Materialia, Inc.

Publication date: 15 September 2017
Source:Acta Biomaterialia, Volume 60
Author(s): Christopher A. Schuh, Kazuhiro Hono, William R. Wagner, Baptiste Gault, Joseph D'Angelo, George T. Gray




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Rheological characterization of human brain tissue

Publication date: 15 September 2017
Source:Acta Biomaterialia, Volume 60
Author(s): S. Budday, G. Sommer, J. Haybaeck, P. Steinmann, G.A. Holzapfel, E. Kuhl
The rheology of ultrasoft materials like the human brain is highly sensitive to regional and temporal variations and to the type of loading. While recent experiments have shaped our understanding of the time-independent, hyperelastic response of human brain tissue, its time-dependent behavior under various loading conditions remains insufficiently understood. Here we combine cyclic and relaxation testing under multiple loading conditions, shear, compression, and tension, to understand the rheology of four different regions of the human brain, the cortex, the basal ganglia, the corona radiata, and the corpus callosum. We establish a family of finite viscoelastic Ogden-type models and calibrate their parameters simultaneously for all loading conditions. We show that the model with only one viscoelastic mode and a constant viscosity captures the essential features of brain tissue: nonlinearity, pre-conditioning, hysteresis, and tension-compression asymmetry. With stiffnesses and time constants of μ∞=0.7kPa, μ1=2.0kPa, and τ1=9.7s in the gray matter cortex and μ∞=0.3kPa, μ1=0.9kPa and τ1=14.9s in the white matter corona radiata combined with negative parameters α∞ and α1, this five-parameter model naturally accounts for pre-conditioning and tissue softening. Increasing the number of viscoelastic modes improves the agreement between model and experiment, especially across the entire relaxation regime. Strikingly, two cycles of pre-conditioning decrease the gray matter stiffness by up to a factor three, while the white matter stiffness remains almost identical. These new insights allow us to better understand the rheology of different brain regions under mixed loading conditions. Our family of finite viscoelastic Ogden-type models for human brain tissue is simple to integrate into standard nonlinear finite element packages. Our simultaneous parameter identification of multiple loading modes can inform computational simulations under physiological conditions, especially at low to moderate strain rates. Understanding the rheology of the human brain will allow us to more accurately model the behavior of the brain during development and disease and predict outcomes of neurosurgical procedures.Statement of SignificanceWhile recent experiments have shaped our understanding of the time-independent, hyperelastic response of human brain tissue, its time-dependent behavior at finite strains and under various loading conditions remains insufficiently understood. In this manuscript, we characterize the rheology of human brain tissue through a family of finite viscoelastic Ogdentype models and identify their parameters for multiple loading modes in four different regions of the brain. We show that even the simplest model of this family, with only one viscoelastic mode and five material parameters, naturally captures the essential features of brain tissue: its characteristic nonlinearity, pre-conditioning, hysteresis, and tension-compression asymmetry. For the first time, we simultaneously identify a single parameter set for shear, compression, tension, shear relaxation, and compression relaxation loading. This parameter set is significant for computational simulations under physiological conditions, where loading is naturally of mixed mode nature. Understanding the rheology of the human brain will help us predict neurosurgical procedures, inform brain injury criteria, and improve the design of protective devices.

Graphical abstract

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