Long-term stability of dental adhesive incorporated by boron nitride nanotubes

Publication date: Available online 6 December 2017
Source:Dental Materials
Author(s): Felipe Weidenbach Degrazia, Vicente Castelo Branco Leitune, Fernanda Visioli, Susana Maria Werner Samuel, Fabrício Mezzomo Collares
ObjectiveThe aim of this study was to evaluate physicochemical properties, long-term microtensile bond strength and cytotoxicity of methacrylate-based adhesive containing boron nitride nanotubes (BNNTs) as fillers.MethodsA dental adhesive was formulated using BisGMA/HEMA, 66/33wt% (control). Inorganic BNNT fillers were incorporated into the adhesive at different concentrations (0.05, 0.075, 0.1 and 0.15wt%). Analyses of degree of conversion (DC), polymerization rate [Rp.(s⁻¹)], contact angle (CA) on dentin, after 24h and 6 months microtensile bond strength (μTBS-24h and 6 months) were assessed. Cytotoxicity was performed through viability of fibroblast cells (%) by sulforhodamine B (SRB) colorimetry.ResultsDC and max. polymerization rate increased (p<0.05) after incorporating 0.075 and 0.1wt% BNNT. The contact angle on dentin increased (p<0.05) after incorporating 0.15wt% BNNT. The μTBS-24h showed no changes (p>0.05) after incorporating up to 0.15wt% BNNT comparing to control. After 6 months, μTBS decreased (p<0.05) for control and 0.15wt% BNNT and BNNT groups up to 0.15wt% showed higher μTBS than control (p<0.05). No difference of fibroblast growth was found among adhesives (p>0.05) and up to 19% of cell viability was found comparing 0.05wt% BNNT to positive control group (100%).SignificanceIncorporating boron nitride nanotubes up to 0.1wt% into dental adhesive increased the long-term stability to dentin without decreasing viability of fibroblast cell growth. Thus, the use of BNNTs as filler may decrease failure rate of current dentinal adhesives.



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Varicella pseudo-Koebner phenomenon associated with vascular access opening

http://ift.tt/2AirVX2

Circadian and endocrine rhythms

Publication date: October 2017
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 31, Issue 5
Author(s): Andries Kalsbeek, Eric Fliers




http://ift.tt/2j26amL

Dislocation network in additive manufactured steel breaks strength–ductility trade-off

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Leifeng Liu, Qingqing Ding, Yuan Zhong, Ji Zou, Jing Wu, Yu-Lung Chiu, Jixue Li, Ze Zhang, Qian Yu, Zhijian Shen
Most mechanisms used for strengthening crystalline materials, e.g. introducing crystalline interfaces, lead to the reduction of ductility. An additive manufacturing process – selective laser melting breaks this trade-off by introducing dislocation network, which produces a stainless steel with both significantly enhanced strength and ductility. Systematic electron microscopy characterization reveals that the pre-existing dislocation network, which maintains its configuration during the entire plastic deformation, is an ideal "modulator" that is able to slow down but not entirely block the dislocation motion. It also promotes the formation of a high density of nano-twins during plastic deformation. This finding paves the way for developing high performance metals by tailoring the microstructure through additive manufacturing processes.

Graphical abstract

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Improving solar cells with light and humidity

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Laurie Donaldson




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Microbots that use magnetism to capture cells

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Laurie Donaldson




http://ift.tt/2ABbjZE

Polymer-coated gold nanocages control cells’ fate

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Cordelia Sealy




http://ift.tt/2jlV5tV

European team tunes LEDs

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): David Bradley




http://ift.tt/2AA2r6f

Full-thickness human skin-on-chip with enhanced epidermal morphogenesis and barrier function

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Gopu Sriram, Massimo Alberti, Yuri Dancik, Bo Wu, Ruige Wu, Zhaoxu Feng, Srinivas Ramasamy, Paul Lorenz Bigliardi, Mei Bigliardi-Qi, Zhiping Wang
Reconstruction of full-thickness skin equivalents with physiologically relevant cellular and matrix architecture is gaining importance as an in vitro tool for basic research, and for the pharmaceutical, toxicological, and cosmetic industries. However, human skin equivalents reconstructed on traditional culture systems are limited by a weak skin barrier function compared to normal human skin. Probable reasons include the lack of mechanical forces and dynamic flow system that provide necessary mechanistic signals and continuous supply and/or drainage of nutrients and metabolites. Here, we combine a fibrin-based dermal matrix with a biomimetic 'organ-on-chip' system for the development of human skin equivalents that better recapitulate the structure and functionalities of human skin, compared to conventional static culture systems. We demonstrate that dynamic perfusion and a fine control of the microenvironment enable improved epidermal morphogenesis and differentiation, and enhanced barrier function. It is also shown that integrated 3D culturing and integrity/permeability testing can be conducted directly on the organ-on-chip device owing to the non-contracting properties of the fibrin-based dermal matrix, thus overcoming the limitations of collagen-based skin equivalents used in conventional cell culture inserts and diffusion cells. With this scalable system, it is possible to achieve higher throughput and automation of culture and testing protocols, and deliver low-cost alternatives to animal and clinical studies for drug screening and toxicological applications.

Graphical abstract

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Automotive Weight Reduction Expo 2018

Publication date: Available online 6 December 2017
Source:Materials Today





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New diode displays purest green light

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Laurie Donaldson




http://ift.tt/2jot0Sw

Massless magnets

Publication date: Available online 6 December 2017
Source:Materials Today





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Useful hybrid photoactive materials produced

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Laurie Donaldson




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Nanomanufacturing made quicker

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Laurie Donaldson




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Recent advances in emerging 2D nanomaterials for biosensing and bioimaging applications

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Wei Wen, Yang Song, Xu Yan, Chengzhou Zhu, Dan Du, Shengfu Wang, Abdullah M. Asiri, Yuehe Lin
The great success of graphene throws new light on discovering more two-dimensional (2D) layered nanomaterials that stem from atomically thin 2D sheets. Compared with a single element of graphene, emerging graphene-like 2D materials composed of multiple elements that possess more versatility, greater flexibility and better functionality with a wide range of potential applications. In this review, we provide insights into the rapidly emerging 2D materials and their biosensing and bioimaging applications in recent three years, including 2D transition metal nanomaterials, graphitic nitride materials, black phosphorus, and emerging 2D organic polymers. We first briefly highlight their unique 2D morphology and physicochemical properties and then focus on their recent applications in electrochemical biosensing, optical biosensing and bioimaging. The challenges and some thoughts on future perspectives in this field are also addressed.

Graphical abstract

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ZnO tetrapod materials for functional applications

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Yogendra Kumar Mishra, Rainer Adelung
In the last 15 years, more than 50,000 papers with zinc oxide (ZnO) in the title are listed within ISI database. The outstanding popularity of ZnO has many reasons; the most important one appears to be its multi-functionality, resulting in applications in physics, chemistry, electrical engineering, material science, energy, textile, rubber, additive manufacturing, cosmetics, and pharmaceutical or medicine, as well as the ease to grow all kinds of nano- and microstructures. A key structure is the tetrapod-shaped ZnO (T-ZnO), which we want to focus on in this mini-review to demonstrate the remarkable properties and multifunctionality of ZnO and motivate why even much more research and applications are likely to come in near future. As T-ZnO came into focus again mainly during the last 10 years, the big data problem in T-ZnO is not as severe as in ZnO; nevertheless, a complete overview is impossible. However, this brief T-ZnO overview attempts to cover the scopes toward advanced technologies; nanoelectronics/optoelectronics sensing devices; multifunctional composites/coatings; novel biomedical engineering materials; versatile energy harvesting candidates; and unique structures for applications in chemistry, cosmetics, pharmaceuticals, food, agriculture, engineering technologies, and many others. The 3D nanotechnology is a current mainstream in materials science/nanotechnology research, and T-ZnO contributes to this field by its simple synthesis of porous networks as sacrificial templates for any desired new cellular materials.

Graphical abstract

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Chameleon materials

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): David Bradley




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Bioactive origami with “tissue” paper

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): David Bradley




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Nanoparticles trick immune system into action

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Cordelia Sealy




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Polymer composite combines novel properties

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Cordelia Sealy




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Tunable materials that can change between mirror and window

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): Laurie Donaldson




http://ift.tt/2jogF0B

Is modern diesel cleaner than cold-start gasoline?

Publication date: Available online 6 December 2017
Source:Materials Today
Author(s): David Bradley




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Dengue re-emergence in Delhi: Lessons to learn

Publication date: Available online 6 December 2017
Source:Medical Journal Armed Forces India
Author(s): Ram Kumar Mishra




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Do Resident Case Logs Meet ACGME Requirements? A Comparison Between Acute Care and Elective Cases

Publication date: Available online 6 December 2017
Source:Journal of Surgical Education
Author(s): Kathryn R. Wolf, Zachary A. Taylor, Sarah B. Placek, Michael W. Tsai, Brenton R. Franklin, E. Matthew Ritter
PurposeOperative experience is at the core of general surgery residency, and recently operative volume requirements for graduating residents were increased. The ACGME has outlined 4 areas of required resident participation and documentation in order for a surgical case to be logged: determination or confirmation of the diagnosis, provision of preoperative care, selection and accomplishment of the operative procedure, and direction of the postoperative care. The purpose of this study was to examine whether general surgery residents are currently meeting the required care participation documentation standard and to examine the effect of acute care vs. elective cases on documentation.MethodsThe operative case logs of 7 PGY-3 and 7 PGY-5 general surgery residents from March 2016 were retrospectively reviewed and compared to the electronic medical record (EMR) to verify documentation of resident participation in each of the 4 required areas. Chart review was also utilized to classify cases as either acute care or elective.ResultsA total of 339 cases were reviewed (159 PGY-3 and 180 PGY-5). Of these, 251 cases were classified as elective and 88 were classified as acute care. Overall, documentation of comprehensive care (participation in all four required areas) was found for 44% of cases, with residents reporting participation in a higher percentage of comprehensive care (all 4 domains completed) than was actually documented in the EMR (71.9% vs. 44.4%, t[13] = 2.57, p = 0.023, d = 1.13). Comprehensive care was documented more frequently in elective cases than acute care cases (49.7% vs. 38.3%), and there was less discrepancy between perceived and documented comprehensive care within elective cases (67% vs. 49.7%, t[13] = 1.17, p = 0.27) than acute care cases (80.9% vs. 38.3%, t[13] = 4.40, p = 0.001).ConclusionsDespite ACGME requirements, the majority of cases logged by general surgery residents do not have documentation by the operating resident in the EMR verifying provision of comprehensive care. Elective cases were more likely to meet documentation requirements than acute care cases, and we purport that this is possibly secondary to restricted work hours. We expect that other programs would find similar compliance in the documentation of comprehensive care. These results question whether the requirement for documenting comprehensive care to log a surgical case is practical in surgical residency training, particularly with an increasing demand for operative volume in the setting of limited work hours.



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Primary sinonasal tuberculosis: Our experiences in a tertiary care hospital of eastern India

Publication date: Available online 6 December 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Santosh Kumar Swain, Ishwar Chandra Behera, Mahesh Chandra Sahu
BackgroundPrimary sinonasal tuberculosis is an extremely rare clinical entity. Often the clinician fail to diagnose the primary sinonasal tuberculosis, so treatment is frequently delayed and leading to complications.ObjectiveTo evaluate the clinical profile, diagnostic tools, treatment and outcome of primary sinonasal tuberculosis.Materials and MethodsRetrospective studies of six cases of primary sinonasal tuberculosis were done over period of five years. The detail clinical profile, diagnosis, treatment and outcome were studied in these patients.ResultsOut of the six cases of primary sinonasal tuberculosis, four cases were female and two were male. The mean age during the time of diagnosis was 35 years (16–67 years). The most common clinical presentations were chronic nasal obstruction, epistaxis and ulcerations at the nasal vestibule and nasal cavity. Diagnosis was confirmed by Histopathological diagnosis in all six cases. All cases received antitubercular therapy for 6–9 months. All six patients successfully responded to antitubercular therapy. Two year follow up showed no relapse, dissemination and death.ConclusionPrimary sinonasal tuberculosis is a rare clinical entity. It is always suspected among the patients with nasal obstruction, epistaxis and ulcerations at nasal vestibule and nasal cavity in the region with high prevalence of Tuberculosis.



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The role of Mannose-binding lectin 2 (MBL2) gene polymorphisms in adenoid hypertrophy among young children

Publication date: Available online 6 December 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Husam Majeed Hameed, Ali S. Dawood
ObjectiveIs to determine the role of Mannose binding lectin (MBL) 2 (SNP 49 C/T rs#5030737) gene polymorphism among patients with adenoidal hypertrophy in Iraqi population.MethodsFrom July through December 2015, a total of 60 adenoid hypertrophy (study group) young child patients (35 males and 25 females) with an age between (4 and 12) years old, were enrolled in this study according to selection criteria. A second group of otherwise healthy young child who did not have any symptoms or signs of adenoid hypertrophy were considered to be a control group. Confirmation of adenoid hypertrophy was achieved by: clinical examination, radiological assessment of postnasal space and an endoscopic nasopharyngoscopy. Blood samples were collected from both groups and genotyping of MBL-2 gene polymorphism was performed using traditional PCR and allele-specific technique.ResultsMBL2 gene polymorphism and allele frequencies among adenoid hypertrophy patients and their control were studied and the results showed that CC = 40 (66.7%), TT = 13(21.7%), and CT = 7 (11.6) in study group, while in control group CC = 5(8.3), TT = 9 (15%).CT = 46 (67.7%). The P-value of genotypes (CC, TT and CT) in study groups versus the control group were P < 0.001 (highly significant), P = 0.435 (non-significant) and P < 0.001 (highly significant) respectively.ConclusionThe difference between the MBL2 (SNP 49 C/T rs#5030737) gene polymorphism among adenoid hypertrophy patients and healthy people may indicate it could be used as an early predictive factor for children whom will be prone to adenoid hypertrophy. The genotype CC could be considered as a risk factor while CT genotype could be considered a protective factor against adenoid hypertrophy in the current study. A further study needed to evaluate the use of the above mentioned polymorphism as a prognostic value foradenoid hypertrophy.



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Surgical strategy for frontal sinus inverted papilloma

Publication date: Available online 6 December 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): A.A. Ibrahim, Haitham Morsi, Mohamed Hassab, Mohamed Eid, Samy Elwany
Inverted papilloma (IP) is a benign tumor with a local aggressive nature and has a tendency to recur after excision. Despite the evolution of endoscopic techniques in the management of IP, external approaches still play a crucial role in frontal sinus involvement.ObjectiveThe present study aimed at planning a strategy for managing IP arising in or involving the frontal recess and/or frontal sinus.Patients and methodsTen patients with frontal sinus IP were enrolled in the present study. The type of surgical procedure was tailored according to the site of origin and extent of the tumor.ResultsFive combined surgeries and five extended endoscopic surgeries were performed in 1 year and 4 months with a follow up period of 2 years. Complete resection of the tumor was achieved in all the cases and no recurrences were reported at the end of the follow up period.ConclusionsThe exact approach to frontal sinus IP differ from one case to the other. Endoscopic frontal surgery is the mainstay in treatment of frontal sinus IP. External or combined approaches still remain a valid option for lesions affecting the mucosa of the frontal sinus extensively or extending far lateral.



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Intracranial metastasis of follicular thyroid carcinoma mimicking cerebellopontine angle tumour

Publication date: Available online 6 December 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Li Yun Lim, Jamuneswary Selvarajoo, Norhafiza Mat Lazim, Ing Ping Tang
Cerebellopontine angle (CPA) tumour is most commonly associated acoustic neuroma. The occurrence of metastatic brain tumour at CPA is rare. Follicular thyroid carcinoma is second most common well differentiated thyroid malignancy and brain metastasis is unusual. We would like to report an unusual presentation of follicular thyroid carcinoma with brain metastasis at the CPA region. A 60 year old gentleman presented with occipital headache, slurred speech with positive cerebellar signs and multiple cranial nerve palsies with no neurological deficit to upper and lower limbs. No other significant findings noted on examination. Imaging investigations revealed a CPA tumour. Transnasal transphenoidal tumour debulking was done and biopsy revealed a metastasis of follicular thyroid carcinoma. After total thyroidectomy, the patient was scheduled for radioactive iodine ablation. Metastasis brain tumour with high vascular supply can contribute to difficult tumour debulking. Embolisation and stereotactic therapy are the supporting and alternative method of treatment.



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Atypical multiple metastasis of recurrent pleomorphic adenoma

Publication date: Available online 6 December 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Darshini Nagarajah, Irfan Mohamad, Norhafiza Mat Lazim, Sharifah Emilia Tuan Sharif, Nur Hidayati Mohamad Pakarul Razy
Pleomorphic adenoma is the commonest benign neoplasm of the parotid gland and minor salivary glands. It is composed of epithelial and myoepithelial cells arranged in various morphological patterns. The concrete reasons contributing to a recurrent disease are obvious or attempts of accidental tumor spillage, enucleation with rupture and incomplete excision during operation. The other solid reasons that could contribute to recurrence are known incomplete pseudocapsule, extracapsular extensions, pseudopods of pleomorphic adenoma tissue, and satellite pleomorphic beyond the pseudocapsule matrix. Most recurrent pleomorphic adenoma are multinodular with different recurrent sites and time duration. We describe a case of 55-year-old lady who underwent left superficial parotidectomy for pleomorphic adenoma 14 years prior to current presentation. After 8 years, she presented with ipsilateral level II lymph node, in which excision showed pleomorphic adenoma. Within 2 years after excision, she experienced another multiple small neck swellings at the level II-III, in which histopathology examination of the excised masses were consistent with pleomorphic adenoma, without evidence of lymph node background to suggest metastasis.



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Wrist accelerometry for physical activity measurement in individuals with spinal cord injury – a need for individually calibrated cut-points

Publication date: Available online 6 December 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Laura A. McCracken, Jasmin K. Ma, Christine Voss, Franco H.N. Chan, Kathleen A. Martin Ginis, Christopher R. West
ObjectiveTo create and compare individual and group-based cut-points for wrist-accelerometry that corresponds to moderate-to-vigorous physical activity (MVPA) in people with spinal cord injury (SCI).DesignParticipants completed a graded treadmill-wheeling test while being assessed for oxygen consumption, wrist-acceleration vector magnitude, and spoke acceleration. Oxygen consumption was converted to SCI metabolic equivalents (SCI METS) and linear regression was applied to determine an individualized vector magnitude cut-point (counts per minute, VM-CPM) corresponding with MVPA (≥3 SCI METS). Multilevel linear regression was applied to determine a group MVPA cut-point. Participants then completed a 6-day monitoring period while wearing the accelerometers.SettingA local SCI research centre.ParticipantsTwenty manual wheelchair users (30-64yrs, C5-L1) with chronic (>1 year) SCI.InterventionsNot applicable.Main outcome measuresMean total daily MVPA, wheeled MVPA, and non-wheeled MVPA were calculated using both the individual and group cut-points. Agreement on measures of min/day of MVPA between the individual and group mean cut-point method was compared using Bland-Altman plots.ResultsIndividual cut-points for MVPA ranged from 6040 to 21540 VM-CPM, with a group cut-point of 11652 (CI 7395 – 15909). For total daily MVPA, Bland-Altman analysis revealed a bias of 0.22 ± 33.0 minutes, with 95% limits of agreement from -64.5 to 64.9 minutes, suggesting a large discrepancy between total MVPA calculated from individual and group-mean cut-points.ConclusionsIndividual calibration of wrist-worn accelerometry is recommended for effective habitual PA monitoring in this population.



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Role of Dopamine Receptors in the Anticancer Activity of ONC201

Publication date: January 2018
Source:Neoplasia, Volume 20, Issue 1
Author(s): Christina Leah B. Kline, Marie B. Ralff, Amriti R. Lulla, Jessica M. Wagner, Phillip H. Abbosh, David T. Dicker, Joshua E. Allen, Wafik S. El-Deiry
ONC201/TIC10 is a first-in-class small molecule inducer of TRAIL that causes early activation of the integrated stress response. Its promising safety profile and broad-spectrum efficacy in vitro have been confirmed in Phase I/II trials in several advanced malignancies. Binding and reporter assays have shown that ONC201 is a selective antagonist of the dopamine D2-like receptors, specifically, DRD2 and DRD3. We hypothesized that ONC201's interaction with DRD2 plays a role in ONC201's anticancer effects. Using cBioportal and quantitative reverse-transcription polymerase chain reaction analyses, we confirmed that DRD2 is expressed in different cancer cell types in a cell type–specific manner. On the other hand, DRD3 was generally not detectable. Overexpressing DRD2 in cells with low DRD2 levels increased ONC201-induced PARP cleavage, which was preceded and correlated with an increase in ONC201-induced CHOP mRNA expression. On the other hand, knocking out DRD2 using CRISPR/Cas9 in three cancer cell lines was not sufficient to abrogate ONC201's anticancer effects. Although ONC201's anticancer activity was not dependent on DRD2 expression in the cancer cell types tested, we assessed the cytotoxic potential of DRD2 blockade. Transient DRD2 knockdown in HCT116 cells activated the integrated stress response and reduced cell number. Pharmacological antagonism of DRD2 significantly reduced cell viability. Thus, we demonstrate in this study that disrupting dopamine receptor expression and activity can have cytotoxic effects that may at least be in part due to the activation of the integrated stress response. On the other hand, ONC201's anticancer activity goes beyond its ability to antagonize DRD2, potentially due to ONC201's ability to activate other pathways that are independent of DRD2. Nevertheless, blocking the dopamine D1-like receptor DRD5 via siRNA or the use of a pharmacological antagonist promoted ONC201-induced anticancer activity.



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Limitations in learning: How treatment verifications fail and what to do about it?

Publication date: Available online 6 December 2017
Source:Brachytherapy
Author(s): Susan Richardson, Bruce Thomadsen
PurposeThe purposes of this study were: to provide dialog on why classic incident learning systems have been insufficient for patient safety improvements, discuss failures in treatment verification, and to provide context to the reasons and lessons that can be learned from these failures.Methods and MaterialsHistorically, incident learning in brachytherapy is performed via database mining which might include reading of event reports and incidents followed by incorporating verification procedures to prevent similar incidents. A description of both classic event reporting databases and current incident learning and reporting systems is given. Real examples of treatment failures based on firsthand knowledge are presented to evaluate the effectiveness of verification. These failures will be described and analyzed by outlining potential pitfalls and problems based on firsthand knowledge.ResultsDatabases and incident learning systems can be limited in value and fail to provide enough detail for physicists seeking process improvement. Four examples of treatment verification failures experienced firsthand by experienced brachytherapy physicists are described. These include both underverification and oververification of various treatment processes.ConclusionsDatabase mining is an insufficient method to affect substantial improvements in the practice of brachytherapy. New incident learning systems are still immature and being tested. Instead, a new method of shared learning and implementation of changes must be created.



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Treatment planning considerations for permanent breast seed implant

Publication date: Available online 6 December 2017
Source:Brachytherapy
Author(s): Amy Frederick, Tyler Meyer, Michael Roumeliotis
PurposeTo determine an optimal planning strategy for permanent breast seed implant that minimizes dose heterogeneity without degrading coverage and conformity.Methods and MaterialsA simple model was developed to investigate planning strategies incorporating a range of ¹⁰³Pd seed activities, needle and seed spacings, and implants in which seed positions are either restricted to or permitted outside of spherical planning target volumes (PTVs). To address more realistic target geometries, model parameters were used to retrospectively replan a 10-patient cohort in MIM Symphony.ResultsWe confirm that the current clinical modified uniform implantation pattern provides the most favorable dose distributions, given the resolution of the template grid and spacer length. We show that needle and seed counts for replans with seed placement permitted 0.3 cm outside of the PTV are most comparable to clinical preplans, but offer a 13 ± 11% average reduction in the VPTV150%. Replans produced with seed placement 0.5 cm outside of the PTV provide the largest improvement in dose homogeneity, at the cost of a slight increase in irradiated volume and an increase in the number of needles and seeds.ConclusionsImplanting seeds beyond the PTV within a 0.3–0.5 cm margin, and optimizing seed activity on a per patient basis, allows for improvement in dose homogeneity. However, these plans require higher needle and seed counts and result in a small increase in irradiated volume. Before planning recommendations can be made, the implications of these changes must be investigated in the context of clinical outcome for permanent breast seed implant.



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Asymmetrical Arterial Diameters

Publication date: Available online 6 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Wolfgang G. Mouton, André Wyss




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Re: “Management of Atherosclerotic Carotid and Vertebral Disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS)”

Publication date: Available online 6 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Karl Sörelius




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Floating Aortic Thrombus in a Non-aneurysmal and Non-atherosclerotic Aorta

Publication date: Available online 6 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): C. Sosa, F. Zuccarino




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Response to “Re. Management of Atherosclerotic Carotid and Vertebral Disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS)”

Publication date: Available online 6 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): A Ross Naylor, Jean-Baptiste Ricco




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Double Banana Technique: A Fruity Solution for Treating Iliac Aneurysms After Aortic Surgery

Publication date: Available online 6 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Lucie Salomon du Mont, Simon Rinckenbach




http://ift.tt/2B8QZQq

Efficient Differentiation of Bone Marrow Mesenchymal Stem Cells into Endothelial Cells in Vitro

Publication date: Available online 6 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Chengen Wang, Yuan Li, Min Yang, Yinghua Zou, Huihui Liu, Zeyin Liang, Yue Yin, Guochen Niu, Ziguang Yan, Bihui Zhang
ObjectiveEndothelial cells (ECs) play an important role in neovascularisation, but are too limited in number for adequate therapeutic applications. Mesenchymal stem cells (MSCs) have the potential to differentiate into endothelial lineage cells, which makes them attractive candidates for therapeutic angiogenesis. The aim of this study was to investigate efficient differentiation of MSCs into ECs by inducing medium in vitro.MethodsMSCs were isolated from bone marrow by density gradient centrifugation. The characterisation of the MSCs was determined by their cluster of differentiation (CD) marker profile. Inducing medium containing vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), insulin like growth factor (IGF), epidermal growth factor (EGF), ascorbic acid, and heparin was applied to differentiate the MSCs into ECs. Endothelial differentiation was quantitatively evaluated using flow cytometry. Real time quantitative PCR (qRT-PCR) was used to analyse mRNA expression of endothelial markers. Tube formation assay was further performed to examine the functional status of the differentiated MSCs.ResultsFlow cytometry analysis demonstrated that CD31⁺ and CD34⁺ cells increased steadily from 12% at 3 days, to 40% at 7 days, and to 60% at 14 days. Immunofluorescence staining further confirmed the expression of CD31 and CD34. qRT-PCR showed that expression of von Willebrand factor (vWF), vascular endothelial cadherin (VE-cadherin) and vascular endothelial growth factor receptor-2 (VEGFR-2) were significantly higher in the induced MSCs group compared with the uninduced MSCs group. The functional behavior of the differentiated cells was tested by tube formation assay in vitro on matrigel. Induced MSCs were capable of developing capillary networks, and progressive formation of vessel like structures was associated with increased EC population.ConclusionsThese results provide a method to efficiently promote differentiation of MSCs into ECs in vitro for potential application in the treatment of peripheral arterial disease.



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Radiosensitization with an inhibitor of poly(ADP-ribose) glycohydrolase: A comparison with the PARP1/2/3 inhibitor olaparib

Publication date: January 2018
Source:DNA Repair, Volume 61
Author(s): Polly Gravells, James Neale, Emma Grant, Amit Nathubhai, Kate M. Smith, Dominic I. James, Helen E. Bryant
Upon DNA binding the poly(ADP-ribose) polymerase family of enzymes (PARPs) add multiple ADP-ribose subunits to themselves and other acceptor proteins. Inhibitors of PARPs have become an exciting and real prospect for monotherapy and as sensitizers to ionising radiation (IR). The action of PARPs are reversed by poly(ADP-ribose) glycohydrolase (PARG). Until recently studies of PARG have been limited by the lack of an inhibitor. Here, a first in class, specific, and cell permeable PARG inhibitor, PDD00017273, is shown to radiosensitize. Further, PDD00017273 is compared with the PARP1/2/3 inhibitor olaparib. Both olaparib and PDD00017273 altered the repair of IR-induced DNA damage, resulting in delayed resolution of RAD51 foci compared with control cells. However, only PARG inhibition induced a rapid increase in IR-induced activation of PRKDC (DNA-PK) and perturbed mitotic progression. This suggests that PARG has additional functions in the cell compared with inhibition of PARP1/2/3, likely via reversal of tankyrase activity and/or that inhibiting the removal of poly(ADP-ribose) (PAR) has a different consequence to inhibiting PAR addition. Overall, our data are consistent with previous genetic findings, reveal new insights into the function of PAR metabolism following IR and demonstrate for the first time the therapeutic potential of PARG inhibitors as radiosensitizing agents.

Graphical abstract

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Constitutive MAP-kinase activation suppresses germline apoptosis in NTH-1 DNA glycosylase deficient C. elegans

Publication date: January 2018
Source:DNA Repair, Volume 61
Author(s): Henok Kassahun, Tanima SenGupta, Alfonso Schiavi, Silvia Maglioni, Hanne K. Skjeldam, Katarzyna Arczewska, Nicole L. Brockway, Suzanne Estes, Lars Eide, Natascia Ventura, Hilde Nilsen
Oxidation of DNA bases, an inevitable consequence of oxidative stress, requires the base excision repair (BER) pathway for repair. Caenorhabditis elegans is a well-established model to study phenotypic consequences and cellular responses to oxidative stress. To better understand how BER affects phenotypes associated with oxidative stress, we characterised the C. elegans nth-1 mutant, which lack the only DNA glycosylase dedicated to repair of oxidative DNA base damage, the NTH-1 DNA glycosylase.We show that nth-1 mutants have mitochondrial dysfunction characterised by lower mitochondrial DNA copy number, reduced mitochondrial membrane potential, and increased steady-state levels of reactive oxygen species. Consistently, nth-1 mutants express markers of chronic oxidative stress with high basal phosphorylation of MAP-kinases (MAPK) but further activation of MAPK in response to the superoxide generator paraquat is attenuated. Surprisingly, nth-1 mutants also failed to induce apoptosis in response to paraquat. The ability to induce apoptosis in response to paraquat was regained when basal MAPK activation was restored to wild type levels. In conclusion, the failure of nth-1 mutants to induce apoptosis in response to paraquat is not a direct effect of the DNA repair deficiency but an indirect consequence of the compensatory cellular stress response that includes MAPK activation.

Graphical abstract

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8-oxoguanine DNA glycosylase (Ogg1) controls hepatic gluconeogenesis

Publication date: January 2018
Source:DNA Repair, Volume 61
Author(s): Katja Scheffler, Lyudmila Rachek, Panpan You, Alexander D. Rowe, Wei Wang, Anna Kuśnierczyk, Lene Kittelsen, Magnar Bjørås, Lars Eide
Mitochondrial DNA (mtDNA) resides in close proximity to metabolic reactions, and is maintained by the 8-oxoguanine DNA glycosylase (Ogg1) and other members of the base excision repair pathway. Here, we tested the hypothesis that changes in liver metabolism as under fasting/feeding conditions would be sensed by liver mtDNA, and that Ogg1 deficient mice might unravel a metabolic phenotype. Wild type (WT) and ogg1^−/− mice were either fed ad libitum or subjected to fasting for 24h, and the corresponding effects on liver gene expression, DNA damage, as well as serum values were analyzed. Ogg1 deficient mice fed ad libitum exhibited hyperglycemia, elevated insulin levels and higher liver glycogen content as well as increased accumulation of 8oxoG in mtDNA compared to age- and gender matched WT mice. Interestingly, these phenotypes were absent in ogg1^−/− mice during fasting. Gene expression and functional analyses suggest that the diabetogenic phenotype in the ogg1^−/− mice is due to a failure to suppress gluconeogensis in the fed state. The ogg1^−/− mice exhibited reduced mitochondrial electron transport chain (ETC) capacity and a combined low activity of the pyruvate dehydrogenase (PDH), alluding to inefficient channeling of glycolytic products into the citric acid cycle. Our data demonstrate a physiological role of base excision repair that goes beyond DNA maintenance, and implies that DNA repair is involved in regulating metabolism.



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Application of Single Nucleotide Extension and MALDI-TOF Mass Spectrometry in Proofreading and DNA Repair Assay

Publication date: Available online 2 December 2017
Source:DNA Repair
Author(s): Kang-Yi Su, Hung-Ming Lai, Steven D. Goodman, Wei-Yao Hu, Wern-Cherng Cheng, Liang-In Lin, Ya-Chien Yang, Woei-horng Fang
Proofreading and DNA Repair are important factors in maintaining the high fidelity of genetic information during DNA replication. Herein, we designed a non-labeled and non-radio-isotopic simple method to measure proofreading. An oligonucleotide primer is annealed to a template DNA forming a mismatched site and is proofread by Klenow fragment of Escherichia coli DNA polymerase I (pol I) in the presence of all four dideoxyribonucleotide triphosphates. The proofreading excision products and re-synthesis products of single nucleotide extension are subjected to MALDI-TOF mass spectrometry (MS). The proofreading at the mismatched site is identified by the mass change of the primer. We examined proofreading of Klenow fragment with DNAs containing various base mismatches. Single mismatches at the primer terminus can be proofread efficiently. Internal single mismatches can also be proofread at different efficiencies, with the best correction for mismatches located 2-4-nucleotides from the primer terminus. For mismatches located 5-nucleotides from the primer terminus there was partial correction and extension. No significant proofreading was observed for mismatches located 6-9-nucleotides from the primer terminus. We also subjected primers containing 3′ penultimate deoxyinosine (dI) lesions, which mimic endo V nicked repair intermediates, to pol I repair assay. The results showed that T-I was a better substrate than G-I and A-I, however C-I was refractory to repair. The high resolution of MS results clearly demonstrated that all the penultimate T-I, G-I and A-I substrates had been excised last 2 dI-containing nucleotides by pol I before adding a correct ddNMP, however, pol I proofreading exonuclease tolerated the penultimate C-I mismatch allowing the primer to be extended by polymerase activity.



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The global role for Cdc13 and Yku70 in preventing telomere resection across the genome

Publication date: Available online 29 November 2017
Source:DNA Repair
Author(s): James W. Westmoreland, Michael J. Mihalevic, Kara A. Bernstein, Michael A. Resnick
Yeast Cdc13 protein (related to human CTC1) maintains telomere stability by preventing 5′-3′ end resection. While Cdc13 and Yku70/Yku80 proteins appear to prevent excessive resection, their combined contribution to maintenance of telomere ends across the genome and their relative roles at specific ends of different chromosomes have not been addressable because Cdc13 and Yku70/Yku80 double mutants are sickly. Using our PFGE-shift approach where large resected molecules have slower pulse field gel electrophoresis mobilities, along with methods for maintaining viable double mutants, we address end-resection on most chromosomes as well as telomere end differences. In this global approach to looking at ends of most chromosomes, we identify chromosomes with 1-end resections and end-preferences. We also identify chromosomes with resection at both ends, previously not possible. 10-20% of chromosomes exhibit PFGE-shift when cdc13-1 cells are switched to restrictive temperature (37°C). In yku70Δ cdc13-1 mutants, there is a telomere resection "storm" with approximately half the chromosomes experiencing at least 1-end resection, ∼10kb/telomere, due to exonuclease1 and many exhibiting 2-end resection. Unlike for random internal chromosome breaks, resection of telomere ends is not coordinated. Telomere restitution at permissive temperature is rapid (<1h) in yku70Δ cdc13-1 cells. Surprisingly, survival can be high although strain background dependent. Given large amount of resected telomeres, we examined associated proteins. Up to 90% of cells have ≥1 Rfa1 (RPA) focus and 60% have multiple foci when ∼30-40 telomeres/cell are resected. The ends are dispersed in the nucleus suggesting wide distribution of resected telomeres across nuclear space. The previously reported Rad52 nuclear centers of repair for random DSBs also appear in cells with many resected telomere ends, suggesting a Rad52 commonality to the organization of single strand ends and/or limitation on interactions of single-strand ends with Rad52.



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The mechanisms of K. lactis Cdc13 in telomere DNA-binding and telomerase regulation

Publication date: Available online 28 November 2017
Source:DNA Repair
Author(s): Min Hsu, Neal F. Lue
Eukaryotic chromosome ends, or telomeres, are essential for genome stability and are protected by an intricate nucleoprotein assembly. Cdc13, the major single-strand telomere-binding protein in budding yeasts, mediates critical functions in both telomere protection and telomere elongation by telomerase. In particular, the interaction between S. cerevisiae Cdc13 and telomerase subunit Est1 has long served as a paradigm for telomerase regulation. However, despite extensive investigations, the role of this interaction in regulating telomerase recruitment or activation remains controversial. In addition, budding yeast telomere repeat sequences are extraordinarily variable and how Cdc13 orthologs recognize diverse repeats is not well understood. In this report, we examined these issues using an alternative model, K. lactis. We reconstituted a direct physical interaction between purified K. lactis Cdc13 and Est1, and by analyzing point mutations, we demonstrated a close correspondence between telomere maintenance defects in vivo and Cdc13-Est1 binding defects in vitro, thus supporting a purely recruitment function for this interaction in K. lactis. Because mutations in well aligned residues of Cdc13 and Est1 in S. cerevisiae and K. lactis do not cause identical defects, our results also point to significant evolutionary divergence in the Cdc13-Est1 interface. In addition, we found that K. lactic Cdc13, unlike previously characterized orthologs, recognizes an unusually long and non-G-rich target sequence, underscoring the flexibility of the Cdc13 DNA-binding domain. Analysis of K. lactis Cdc13 and Est1 thus broadens understanding of telomere and telomerase regulation in budding yeast.

Graphical abstract

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Hypersensitivity of mouse embryonic fibroblast cells defective for DNA polymerases η, ι and κ to various genotoxic compounds: Its potential for application in chemical genotoxic screening

Publication date: Available online 26 November 2017
Source:DNA Repair
Author(s): Jun-ichi Akagi, Masayuki Yokoi, Young-Man Cho, Takeshi Toyoda, Haruo Ohmori, Fumio Hanaoka, Kumiko Ogawa
Genotoxic agents cause modifications of genomic DNA, such as alkylation, oxidation, bulky adduct formation, and strand breaks, which potentially induce mutations and changes to the structure or number of genes. Majority of point mutations are generated during error-prone bypass of modified nucleotides (translesion DNA synthesis, TLS); however, when TLS fails, replication forks stalled at lesions eventually result in more lethal effects, formation of double-stranded breaks (DSBs). Here we compared sensitivities to various compounds among mouse embryonic fibroblasts derived from wild-type and knock-out mice lacking one of the three Y-family TLS DNA polymerases (Polη, Polι, and Polκ) or all of them (TKO). The compounds tested in this study include genotoxins such as methyl methanesulfonate (MMS) and nongenotoxins such as ammonium chloride. We found that TKO cells exhibited the highest sensitivities to most of the tested genotoxins, but not to the non-genotoxins. In order to quantitatively evaluate the hypersensitivity of TKO cells to different chemicals, we calculated ratios of half-maximal inhibitory concentration for WT and TKO cells. The ratios for 9 out of 10 genotoxins ranged from 2.29 to 5.73, while those for 5 nongenotoxins ranged from 0.81 to 1.63. Additionally, the two markers for DNA damage, ubiquitylated proliferating cell nuclear antigen and γ-H2AX after MMS treatment, were accumulated in TKO cells more greatly than in WT cells. Furthermore, following MMS treatment, TKO cells exhibited increased frequency of sister chromatid exchange compared with WT cells. These results indicated that the hypersensitivity of TKO cells to genotoxins resulted from replication fork stalling and subsequent DNA double-strand breaks, thus demonstrating that TKO cells should be useful for evaluating chemical genotoxicity.

Graphical abstract

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DNA Replication and associated repair pathways are involved in the mutagenesis of methylated cytosine

Publication date: Available online 24 November 2017
Source:DNA Repair
Author(s): Marketa Tomkova, Michael McClellan, Skirmantas Kriaucionis, Benjamin Schuster-Böckler
Transitions of cytosine to thymine in CpG dinucleotides are the most frequent type of mutations observed in cancer. This increased mutability is commonly explained by the presence of 5-methylcytosine (5mC) and its spontaneous hydrolytic deamination into thymine. Here, we describe observations that question whether spontaneous deamination alone causes the elevated mutagenicity of 5mC. Tumours with somatic mutations in DNA mismatch-repair genes or in the proofreading domain of DNA polymerase ε (Pol ε) exhibit more 5mC to T transitions than would be expected, given the kinetics of hydrolytic deamination. This enrichment is asymmetrical around replication origins with a preference for the leading strand template, in particular in methylated cytosines flanked by guanines (GCG). Notably, GCG to GTG mutations also exhibit strand asymmetry in mismatch-repair and Pol ε wild-type tumours. Together, these findings suggest that mis-incorporation of A opposite 5mC during replication of the leading strand might be a contributing factor in the mutagenesis of methylated cytosine.



http://ift.tt/2AZD5zg

The underlying physiological basis of the desert rodent Meriones shawi's survival to prolonged water deprivation: Central vasopressin regulation on peripheral kidney water channels AQPs-2

Publication date: Available online 6 December 2017
Source:Acta Histochemica
Author(s): A. Elgot, O. El Hiba, M. Belkouch, H. Gamrani
Meriones shawi (M. shawi) is a particular semi-desert rodent known by its resistance to long periods of thirst. The aim of the present investigation is to clarify the underlying mechanisms allowing M. shawi to resist to hard conditions of dehydration. For this reason we used two different approaches: i) a morphometric study, which consists in measuring the effect of dehydration on body and kidneys weights as well as the report kidney weight/body weight, ii) By immunohistochemistry, we proceed to study the effect of dehydration on the immunoreactivity of central vasopressin (AVP) and the kidney aquaporin-2 (AQP-2) which is a channel protein that allows water to permeate across cell membranes. Our results showed both a body mass decrease accompanied by a remarkable kidneys hypertrophy. The immunohistochemical study showed a significant increase of AQP-2 immunoreactivity in the medullar part of Meriones kidneys allowing probably to Meriones a great ability to water retention. Consistently, we demonstrate that the increased AQP-2 expression occurred together with an increase in vasopressin (AVP) expression in both hypothalamic supraoptic (SON) and paraventricular nucleus (PVN), which are a major hub in the osmotic control circuitry.These various changes seen either in body weight and kidneys or at the cellular level might be the basis of peripheral control of body water homeostasis, providing to M. shawia strong resistance against chronic dehydration.



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Environmental levels of triclosan and male fertility

Abstract

Triclosan is a synthetic chemical with broad antimicrobial activity that has been used extensively in consumer products, including personal care products, textiles, and plastic kitchenware, although the exposure which is widespread evidence from human studies is scarce. Our study aims to investigate the relationship between triclosan exposure and male fertility. Triclosan (TCS) urinary concentrations were measured using gas chromatography coupled with tandem mass spectrometry in 315 men recruited from a male reproductive health clinic with normal sperm concentration (≥ 15 mln/ml) (WHO 2010) under 45 years of age. Participants were interviewed and provided a semen sample. TCS was detected in 84.13% of urine samples, with a median concentration of 2.83 μg/l (2.57 μg/g creatinine). A multiple linear regression analysis showed a positive association between the urinary concentrations of triclosan 50th–75th percentile and ≥ 50 percentile and percentage of sperm with abnormal morphology (p = 0.016 and p = 0.002, respectively). The study provides evidence that exposure to triclosan is associated with poorer semen quality. Future studies are needed to confirm these findings.

http://ift.tt/2jmMcjJ

Characteristics of different molecular weight EPS fractions from mixed culture dominated by AnAOB and their role in binding metal ions

Abstract

Ultraviolet-visible (UV-Vis) absorbance spectra were adopted to quantify the binding of metal ions (e.g., Fe(III), Cu(II), Pb(II), and Cd(II)) on three MW fractions (> 100, 10~100, and < 10 k Da) of extracellular polymeric substances (EPS) extracted from mixed cultures dominated by anaerobic ammonium-oxidizing bacteria (AnAOB). The results showed that the AnAOB EPS with different MW size ranges all had strongest binding capability of Fe(III), and the lowest binding capability of Cd(II). The complexation ability of metal ions for the EPS of AnAOB with molecular weight < 10 kDa was stronger than EPS with >100 and 10~100 kDa, very likely because of the contribution of the tyrosine-, tryptophan-, and aromatic protein-like components. It was obvious that the different size fractions of EPS affect the metal binding ability. Essentially, the content of proteins, polysaccharides, TOC, and UVA₂₅₄ distributed within various MW fractions of EPS from AnAOB were different, as well as the different fluorescent components and total functional groups.

http://ift.tt/2BFWTV3

Amicarbazone degradation promoted by ZVI-activated persulfate: study of relevant variables for practical application

Abstract

Alarming amounts of organic pollutants are being detected in waterbodies due to their ineffective removal by conventional treatment techniques, which warn of the urgent need of developing new technologies for their remediation. In this context, advanced oxidation processes (AOPs), especially those based on Fenton reactions, have proved to be suitable alternatives, due to their efficacy of removing persistent organic compounds. However, the use of ferrous iron in these processes has several operational constraints; to avoid this, an alternative iron source was here investigated: zero-valent-iron (ZVI). A Fenton-like process based on the activation of a recently explored oxidant-persulfate (PS)—with ZVI was applied to degrade an emerging contaminant: Amicarbazone (AMZ). The influence of ZVI size and source, PS/ZVI ratio, pH, UVA radiation, dissolved O₂, and inorganic ions was evaluated in terms of AMZ removal efficiency. So far, this is the first time these parameters are simultaneously investigated, in the same study, to evaluate a ZVI-activated PS process. The radical mechanism was also explored and two radical scavengers were used to determine the identity of major active species taking part in the degradation of AMZ. The degradation efficiency was found to be strongly affected by the ZVI dosage, while positively affected by the PS concentration. The PS/ZVI system enabled AMZ degradation in a wide range of pH, although with a lower efficiency under slightly alkaline conditions. Dissolved O₂ revealed to play an important role in reaction kinetics as well as the presence of inorganic ions. UVA radiation seems to improve the degradation kinetics only in the presence of extra O₂ content. Radicals quenching experiments indicated that both sulfate (SO₄^•−) and hydroxyl (^•OH) radicals contributed to the overall oxidation performance, but SO₄^•− was the dominant oxidative species.

http://ift.tt/2jnVLij

Cutometric assessment of elasticity of skin with striae distensae following carboxytherapy

Summary

Objective

The aim of the study was to evaluate the effectiveness of carboxytherapy in the treatment of striae distensae. Additionally, discomfort and side effects associated with the treatment were assessed.

Materials and methods

This study involved 15 women aged 22-40 years. They underwent 3 sessions of carboxytherapy at one-week intervals. Treatment was performed in skin area within stretch marks located on stomach, buttocks, and thighs. Cutometric probe was used to evaluate skin elasticity. Four measurements were performed—immediately before each treatment and one month after the last session. Photographic documentation was made before and after a series of treatment to perform clinical evaluation of changes in skin condition.

Results

Statistical analysis of results obtained with the use of Cutometer (R2 and R8 parameters) demonstrated that carboxytherapy significantly improved skin elasticity within stretch marks (P < .05). The analysis of photographic documentation revealed 58% improvement in stretch mark visibility. The width and length of stretch marks decreased, and their color became more like the natural color of the skin. Carboxytherapy is associated with moderate pain/discomfort. The occurrence of hematoma is the main side effect of this procedure.

Conclusions

Carboxytherapy seems to be an effective method of reducing stretch marks. This procedure is safe, and it can be performed without the risk of complications. Moreover, it does not require special postoperative convalescence. Photographic documentation is a method of assessment of aesthetic procedures effectiveness, which is complementary to other objective methods (eg, the use of MPA probes).

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HER2 copy number of circulating tumour DNA functions as a biomarker to predict and monitor trastuzumab efficacy in advanced gastric cancer

Publication date: January 2018
Source:European Journal of Cancer, Volume 88
Author(s): Haixing Wang, Beifang Li, Zhentao Liu, Jifang Gong, Lin Shao, Jun Ren, Yunyun Niu, Shiping Bo, Zhongwu Li, Yumei Lai, Sijia Lu, Jing Gao, Lin Shen
BackgroundHER2 status is significant to trastuzumab therapy; however, it is difficult to determine HER2 status accurately with few pieces of biopsies from advanced gastric cancer (AGC) due to highly heterogeneity and invasive behaviour, which will be investigated in this study.MethodsFifty-six patients with AGC were included in this study. Primary tumour tissues and matched plasmas before medication from 36 patients were retrospectively collected, and the other 20 patients with primary tumour tissues and paired plasmas were prospectively collected. HER2 expression and amplification in 56 tumour tissues were determined by immunohistochemistry (IHC) and dual in situ hybridisation (DISH), and HER2 copy number in 135 circulating tumour DNAs (ctDNAs) was judged by next-generation sequencing.ResultsFor tumour tissues, HER2 amplification by DISH was most commonly found in patients with HER2 score 3+by IHC. For plasmas, HER2 amplification defined as HER2 copy number >2.22 was identified in 26 of 56 patients. There was a high concordance of HER2 amplification between ctDNA and tumour tissues, suggesting that ctDNA could function as an alternative to screen HER2-targeted population. Moreover, the changes of HER2 copy number in ctDNA could efficiently monitor trastuzumab efficacy, the power of which was superior to commonly used markers carcinoembryonic antigen (CEA) and CA199, suggesting its potential role in clinical practice.ConclusionctDNA for HER2 analysis was strongly recommended to serve as a surrogate to screen trastuzumab-suitable population and monitor trastuzumab efficacy.



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The use of palliative medications before death from prostate cancer: Swedish population-based study with a comparative overview of European data

Publication date: January 2018
Source:European Journal of Cancer, Volume 88
Author(s): Magdalena Lycken, Linda Drevin, Hans Garmo, Pär Stattin, Jan Adolfsson, Ingela Franck Lissbrant, Lars Holmberg, Anna Bill-Axelson
BackgroundSymptoms of terminal cancer have previously been reported as undertreated. The aim of this study was to assess the use of palliative medications before death from prostate cancer.MethodsThis Swedish register study included men who died from 2009 to 2012 with prostate cancer as the underlying cause of death. We assessed the proportion who collected a prescription of androgen deprivation therapy, non-steroidal anti-inflammatory drugs, paracetamol, opioids, glucocorticoids, antidepressants, anxiolytics and sedative-hypnotics and the differences in treatment related to age, time since diagnosis, educational level, close relatives and comorbidities. Data were collected from 3 years before death from prostate cancer.ResultsWe included 8326 men. The proportion who received opioids increased from 30% to 72% during the last year of life, and 67% received a strong opioid at the time of death. Antidepressants increased from 13% to 22%, anxiolytics from 9% to 27% and sedative-hypnotics from 21% to 33%. Men without close relatives and older men had lower probability to receive opioids (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.47–0.66 for >85 years versus <70 years) and (OR 0.78, 95% CI: 0.66–0.92 for unmarried without children versus married with children).ConclusionOur results represent robust epidemiological data from Sweden for comparison of palliative care quality between countries. The findings indicate that men without close relatives and older men are disadvantaged with respect to the treatment of cancer pain and need closer attention from health care providers and highlight the importance to identify psychological distress in terminal prostate cancer.



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Improved stratification of pT1 melanoma according to the 8th American Joint Committee on Cancer staging edition criteria: A Dutch population-based study

Publication date: Available online 5 December 2017
Source:European Journal of Cancer
Author(s): D. Verver, W.J. Louwman, S. Koljenović, C. Verhoef, D.J. Grünhagen, A.C.J. van Akkooi
IntroductionThe 8th American Joint Committee on Cancer (AJCC) staging edition includes revisions regarding pT1 melanomas. We aimed to evaluate the expected impact of this edition on staging and survival in the Dutch pT1 melanoma population.MethodsIn total, 32,935 pT1 melanoma patients, whose data were retrieved from the Netherlands Cancer Registry between 2003 and 2015, were included in the study. Patients were stratified by the 6th AJCC edition (cohort 1: 2003–2009) and 7th edition (cohort 2: 2010–2015) and all reclassified according to the 8th edition. Stage migration, sentinel lymph node biopsy (SLNB) positivity rates and relative survival were analysed. Agreement between staging systems was calculated by Cohen's kappa coefficient.ResultsIn cohort 2, restaging according to the 8th edition led to an increase of 7% in the total number of patients staged pT1b. The kappa score for agreement between the 6th and 8th edition was 0.15 and 0.25 for agreement between 7th and 8th edition. Restaging according to the 8th edition resulted in a higher SLNB positivity rate for pT1b patients than pT1a patients (8% versus 5%, p = 0.08). Relative survival curves were predominantly similar between the staging editions.ConclusionsImplementation of the 8th AJCC staging edition will presumably not have major impact on the total number of Dutch pT1b patients. Consequently, the number of patients eligible for SLNB would roughly remain similar. In terms of SLNB positivity, the selection of high-risk pT1 melanoma patients is likely to improve. In addition, the 8th edition criteria for pT1 melanoma seem more workable for pathologists.



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C-statistic: A brief explanation of its construction, interpretation and limitations

Publication date: Available online 5 December 2017
Source:European Journal of Cancer
Author(s): S.J. Caetano, G. Sonpavde, G.R. Pond




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Lipoid proteinosis: towards predictive clinical clues

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Predictors of Response and Survival in Locally Advanced Adenocarcinoma of the Pancreas Following Neoadjuvant GTX with or Without Radiation Therapy

AbstractLessons Learned. There is no presenting parameter that predicts the success of neoadjuvant therapy for pancreatic cancer.Despite the images on scans following neoadjuvant therapy, all patients should be evaluated, because inflammation following radiation therapy (RT) may overstate the extent of tumor and vascular involvement.Background.In patients presenting with locally advanced pancreatic adenocarcinoma deemed unresectable by two pancreatic cancer surgeons, we analyzed presenting tumor size, extent of vascular involvement, tumor markers, response to neoadjuvant gemcitabine (G), docetaxel (T), and capecitabine (X) with or without additional chemoradiotherapy with GX on R0 resection rates (≥2 mm margins), and survival.Methods.All patients had baseline magnetic resonance imaging (MRI) and/or computed tomography (CT) scans and endoscopic ultrasound. A baseline positron emission tomography‐computed tomography (PET‐CT) was performed in 39 patients. The scans were reviewed by two radiologists.GTX (gemcitabine 750 mg/m2 and docetaxel 30 mg/m2 on days 4 and 11 with capecitabine 1,500 mg/m2 days 1–14) was administered on a 3‐week schedule for 6 cycles to patients with both arterial and venous‐only involvement. Patients in the arterial arm received GX/RT before surgery, and those in the venous arm received GX/RT after R1 resection. Standard‐dose RT was delivered by intensity‐modulated radiation therapy (IMRT) or conformal fields to 5040 cGy along with capecitabine for 5 days and gemcitabine on day 5 of weeks 1, 2, 4, and 5 of RT, starting with the first full week of RT.A cancer antigen test 19‐9 (CA 19‐9) was obtained at baseline and days 4 and 11 of each cycle. The rate of change in CA 19‐9 was calculated using the formula: (Log10 CA 19‐9 time 0) − (Log10 CA 19‐9 at 9 weeks)/9 weeks. This was derived based on the observation that the fall in CA 19‐9 following effective chemotherapy is a second‐order function.Results.Of the 34 patients with arterial involvement and 11 with extensive venous involvement who met the eligibility criteria and began GTX, only 5 patients in the arterial arm did not undergo subsequent resection. The remaining 40 patients were included in this analysis of presenting parameters with respect to R0 resection, disease‐free survival (DFS), and overall survival (OS). R0 resection was achieved in 28 of 40 patients (70%), and R1 resection in the remaining 12 (30%). The OS after R0 resection was a median 37 months (95% confidence interval [CI]: 29.3–44.7) compared with 29 months (95% CI: 28.5–41.5) for those with R1 resection.Excluding four postoperative deaths, median DFS for the 25 (71%) with R0 resection was 31 months (95% CI: 11.3–51.1), and the median DFS for R1 resection was only 14 months (95% CI: 11.1–17). Eleven of the twenty‐eight (39%) patients achieving R0 resection have not relapsed (median = 45 months, range = 25–71 months).Conclusion.R0 resection, the goal of neoadjuvant treatment, can be achieved in 70% of patients presenting with locally advanced pancreatic cancer. The median DFS was 31 months (95% CI: 11. 3–51.1). No relationship was found with tumor size, degree of vascular involvement, carcinoembryonic antigen test (CEA), CA 19‐9, degree of tumor regression on scan, fall in CA 19‐9, or SUV on PET scan and subsequent survival.

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Decision‐Making Capacity for Chemotherapy and Associated Factors in Newly Diagnosed Patients with Lung Cancer

AbstractBackground.The objective of this study was to assess decision‐making capacity in patients newly diagnosed with lung cancer, clinical factors associated with impaired capacity, and physicians' perceptions of patients' decision‐making capacity.Materials and Methods.We recruited 122 patients newly diagnosed with lung cancer. One hundred fourteen completed the assessment. All patients were receiving a combination of treatments (e.g., chemotherapy, chemo‐radiotherapy, or targeted therapy). Decision‐making capacity was assessed using the MacArthur Competence Tool for Treatment. Cognitive impairment, depressive symptoms, and frailty were also evaluated. Physicians' perceptions were compared with the ascertainments.Results.Twenty‐seven (24%, 95% confidence interval [CI], 16–31) patients were judged to have incapacity. Clinical teams had difficulty in judging six (22.2%) patients for incapacity. Logistic regression identified frailty (odds ratio, 3.51; 95% CI, 1.13–10.8) and cognitive impairment (odds ratio, 5.45; 95% CI, 1.26–23.6) as the factors associated with decision‐making incapacity. Brain metastasis, emphysema, and depression were not associated with decision‐making incapacity.Conclusion.A substantial proportion of patients diagnosed with lung cancer show impairments in their capacity to make a medical decision. Assessment of cognitive impairment and frailty may provide appropriate decision‐making frameworks to act in the best interest of patients.Implications for Practice.Decision‐making capacity is the cornerstone of clinical practice. A substantial proportion of patients with cancer show impairments in their capacity to make a medical decision. Assessment of cognitive impairment and frailty may provide appropriate decision‐making frameworks to act in the best interest of patients.

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Successful Ovarian Stimulation for Fertility Preservation in a Patient with Chronic Myeloid Leukemia: Switch from Nilotinib to Interferon‐α

AbstractThe development of tyrosine‐kinase inhibitors (TKIs) has improved survival of patients with chronic myeloid leukemia (CML). Some patients may become resistant to TKIs and require hematopoietic stem cell transplant (HSCT) that is highly gonadotoxic. Fertility preservation with ovarian stimulation might be indicated but is challenging if patients need to remain on TKIs until HSCT because TKIs may compromise follicular development and response to ovarian stimulation. We report the case of a patient with CML resistant to TKI and planned for an HSCT, in which treatment by TKI was replaced by interferon‐α before and during ovarian stimulation for fertility preservation. Successful ovarian stimulation was performed, allowing cryopreservation of nine zygotes. Hematopoietic stem cell transplantation was performed, and at present, 3 years later, the patient presents a sustained major molecular response.

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The Role of Rituximab in Chronic Lymphocytic Leukemia Treatment and the Potential Utility of Biosimilars

AbstractChronic lymphocytic leukemia (CLL) is managed with observation for asymptomatic or clinically silent disease; pharmacologic intervention is generally required for symptomatic patients with clinically significant adenopathy or cytopenia. In the front‐line treatment of CLL, the current standard‐of‐care includes chemotherapy in combination with an anti‐CD20 monoclonal antibody (e.g., rituximab, ofatumumab, or obinutuzumab) or ibrutinib as single agent. Despite the evolving treatment paradigm toward targeted therapy, it is likely that rituximab (plus chemotherapy), with or without targeted agents, will retain a significant role in CLL treatment. However, patents for many biologics, including rituximab, have expired or will expire in the near future. Furthermore, access to rituximab has remained challenging, particularly in countries with restricted resources. Together, these concerns have prompted the development of safe and effective rituximab biosimilars. The term "biosimilar" refers to a biologic that is highly similar to an approved reference (originator) product, notwithstanding minor differences in clinically inactive components, and for which there are no clinically meaningful differences in purity, potency, or safety. Biosimilars are developed to treat the same condition(s) using the same treatment regimens as an approved reference biologic and have the potential to increase access to more affordable treatments. We review the importance of rituximab in the current treatment of CLL, the scientific basis of its future role in combination with chemotherapy, and the role of new and emerging agents in the treatment of CLL, which could potentially be used in combination with rituximab biosimilars. We also discuss rituximab biosimilars currently in development.Implications for Practice.Front‐line treatments for chronic lymphocytic leukemia (CLL) include chemotherapy in combination with an anti‐CD20 monoclonal antibody (e.g., rituximab, ofatumumab, or obinutuzumab) or ibrutinib as single agent. Despite the evolving treatment paradigm, it is likely rituximab (plus chemotherapy) and targeted agents undergoing clinical evaluation will retain a significant role in CLL treatment. However, patents for many biologics, including rituximab, have expired or will expire in the near future and, in many regions, access to rituximab remains challenging. Together, these concerns have prompted the development of safe and effective rituximab biosimilars, with the potential to increase access to more affordable treatments.

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Clinical Activity of Pazopanib in Patients with Advanced Desmoplastic Small Round Cell Tumor

AbstractBackground.Desmoplastic small round cell tumor (DSRCT) is an aggressive, often fatal soft tissue sarcoma that lacks an optimal salvage regimen. We retrospectively reviewed data from 29 pretreated DSRCT patients who received pazopanib at MD Anderson Cancer Center after failure of standard chemotherapies.Subjects, Materials, and Methods.Medical records of patients treated from January 2012 to December 2016 were reviewed and regression analyses were performed. Median progression‐free survival (PFS) and overall survival (OS) were estimated using the Kaplan‐Meier method and differences in survival were assessed by a log‐rank test. A landmark statistical analysis was used to assess OS at a predefined 12‐week time point following pazopanib initiation.Results.The mean age at pazopanib treatment was 27.5 years (range, 6.3–50.1 years). According to RECIST 1.1 criteria, 16 patients (55%) had stable disease, 1 patient (3%) had partial response, 1 patient (3%) had complete response, and 11 patients (38%) had progressive disease. Estimated median PFS was 5.63 months (95% confidence interval [CI]: 3.23–7.47). Median OS was 15.7 months (95% CI: 10.3–32.4). As of December 2016, 11 patients (38%) were still alive, with a median follow‐up time of 16.8 (range 3.8–30.1) months. Doses between 400 and 800 mg were included. Pazopanib was well tolerated and 23 (79%) of the patients continued it until progression or death, 4 discontinued because of side effects, and 2 were still on pazopanib at the time of data analysis.Conclusion.In the largest study conducted to date in DSRCT, pazopanib was well tolerated and clinically active in heavily pretreated patients who otherwise lack good treatment options.Implications for Practice.Desmoplastic small round cell tumor (DSRCT) is a rare, extremely aggressive soft tissue sarcoma subtype that most commonly occurs in adolescent and young adult males. No DSRCT‐specific therapies exist, and for lack of a better treatment approach, current therapies have relied upon U.S. Food and Drug Administration‐approved drugs like pazopanib that exhibit clinical activity in other sarcoma subtypes. Herein, we describe the largest experience to date using pazopanib as salvage treatment in heavily pretreated DSRCT patients. Pazopanib was well tolerated and clinically active, surpassing predefined metrics proposed by the European Organization for Research and Treatment of Cancer indicative of "active" sarcoma drugs (5.63 months progression‐free survival [PSF], with 62% of the study population achieving progression‐free survival at 12 weeks).

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Cities of the future—bionic systems of new urban environment

Abstract

The concepts of the cities we know nowadays, and which we are accustomed to, change at a very rapid pace. The philosophy of their design is also changing. It will base on new standards, entering a completely different, futuristic dimension. This stage is related to changes in the perception of space, location and lack of belonging to definite, national or cultural structures. Cities of the future are cities primarily intelligent, zero-energetic, zero-waste, environmentally sustainable, self-sufficient in terms of both organic food production and symbiosis between the environment and industry. New cities will be able to have new organisational structures—either city states, or, apolitical, jigsaw-like structures that can change their position—like in the case of the city of Artisanopolis, designed as a floating city, close to the land, reminiscent of the legendary Atlantis. This paper is focused on the main issues connected with problems of the contemporary city planning. The purpose of the research was to identify existing technological solutions, whose aim is to use solar energy and urban greenery. The studies were based on literature related to future city development issues and futuristic projects of the architects and city planners. In the paper, the following issues have been verified: futuristic cities and districts, and original bionic buildings, both residential and industrial. The results of the analysis have been presented in a tabular form.

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Cigarette butts abundance and association of mercury and lead along the Persian Gulf beach: an initial investigation

Abstract

The toxic metal contents of cigarette butts and distribution of cigarette butts have not been studied well in maritime environment. In the present study, cigarette butts distribution and the associations of Hg and Pb from cigarette butts were monitored along the Persian Gulf with 10 days interval sampling time. The number of cigarette butts, and Hg and Pb associations of butts were found to vary widely between 2 and 38 items per square meter, 2.5 and 86.32 ng/g cigarette butt (CB), as well as 650 and 8630 ng/g CB, respectively. Wilcoxon signed-rank test showed that there were no significant differences between the number of butts, and Hg and Pb contents of the butts at different sampling times. Considering amount of cigarette butts littered yearly, this study demonstrates that remarkable toxic metals of Hg and Pb may enter maritime environment each year and may introduce critical hazards to aquatic organisms, enter food chain, and finally human body.

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Case of Bilateral Sequential Nonarteritic Ischemic Optic Neuropathy After Rechallenge With Sildenafil

No abstract available

http://ift.tt/2BEBOdC

Horizontal Gaze Palsy With Progressive Scoliosis: Two Novel ROBO3 Mutations in a Compound Heterozygous Sporadic Case

No abstract available

http://ift.tt/2iy3xFF

Retinal Ganglion Cell Topography in Patients With Visual Pathway Pathology

Background: To investigate and quantify the impact of intracranial lesions at different locations within the visual pathway on the ganglion cell layer–inner plexiform layer (GCL–IPL) complex and the retinal nerve fiber layer (RNFL). Methods: Patients with intracranial lesions affecting the optic chiasm (Group I) or the optic tract and/or lateral geniculate nucleus (Group II) were included. All patients received kinetic visual field assessment and underwent spectral domain optical coherence tomography. Peripapillary and papillomacular bundle (PMB) RNFL and macular GCL–IPL thickness in 4 perifoveal areas were measured and compared with normal values derived from 52 age-matched healthy control subjects. Z-scores for each parameter of every patient were calculated and compared with the normative data. Z-scores less than −2.0 (e.g., −2.5) were considered as being statistically significant. Results: Twenty-two patients (Group I and II: 13 and 9, respectively) were included. Ten of 13 patients in Group I showed significant binasal GCL–IPL thinning, with associated temporal sector thinning in 8 patients. In Group II, all 9 patients showed significant reduction of the GCL–IPL corresponding to the homonymous visual field defect, but only 4 demonstrated RNFL thinning. Contralateral RNFL thinning within the PMB clinically similar to bow-tie atrophy was evident in all patients in Group II. GCL–IPL and RNFL thinning varied in severity from mild (isolated PMB RNFL thickness reduction) to severe (bilateral asymmetrical reduction of PMB RNFL associated with asymmetric, predominantly nasal reduction of GCL–IPL) in Group I. Conclusion: Clinical abnormalities in patients with visual pathway lesions are more likely to demonstrate abnormalities of GCL–IPL than global peripapillary RNFL thickness. However, PMB thickness measurement appears to be a valuable tool to detect abnormalities of the anterior visual pathways. If peripapillary RNFL measurements are performed in such patients, PMB thickness should be considered the most useful quantitative parameter. Address correspondence to Christina Gerth-Kahlert, MD, Department of Ophthalmology, University Hospital Zurich, Frauenklinikstrasse 24, CH-8091 Zurich, Switzerland; E-mail: christina.gerth-kahlert@usz.ch J. V. M. Hanson is partially funded by the Clinical Research Priority Program of the University of Zurich and has received speaker fees and travel support from Biogen. S. Lukas is currently employed by Heidelberg Engineering but was employed by the University of Zurich during the study. The remaining authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the full text and PDF versions of this article on the journal's Web site (http://ift.tt/2BFTkP1). © 2017 by North American Neuro-Ophthalmology Society

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Optic Disc Edema in Glial Fibrillary Acidic Protein Autoantibody–Positive Meningoencephalitis

Background: Glial fibrillary acidic protein (GFAP) autoantibody–positive meningoencephalitis is a newly described entity characterized by a corticosteroid-responsive meningoencephalomyelitis. Some patients with GFAP autoantibody–positive meningoencephalitis have been found to have optic disc edema, which has previously not been well characterized. Methods: We performed a retrospective, observational case series of Mayo Clinic patients found to have GFAP-IgG and optic disc edema from January 1, 2000, to December 31, 2016. We identified 40 patients with GFAP-IgG seropositivity by tissue-based immunofluorescence and cell-based assay. Patients were screened for the following inclusion criteria: 1) serum, cerebrospinal fluid, or both that yielded a characteristic astrocytic pattern of mouse tissue immunostaining with confirmation of IgG reactive with specific GFAPα isoform by cell-based assay; 2) meningoencephalitis or encephalitis; and 3) optic disc edema. We excluded those with coexisting aquaporin-4-IgG or insufficient clinical information. Results: Ten patients had optic disc edema and met inclusion criteria. The median age was 39.5 years and 60% were men. Visual acuity was unaffected and disc edema was bilateral in all cases. Mild vitreous cell was noted in 3 patients. The optic disc edema resolved with corticosteroid treatment but resulted in mild optic atrophy in 2 patients. The median lumbar puncture opening pressure was 144 mm H2O (range, 84–298 mm H2O). Brain MRI revealed radial perivascular enhancement in all except 1 patient. Fluorescein angiography was available for 1 patient with optic disc edema, which showed leakage from the venules. Conclusions: Patients with GFAP autoantibody–positive meningoencephalitis can have optic disc edema that can mimic papilledema. The cause of the optic disc edema remains uncertain, but most patients did not have raised intracranial pressure. Address correspondence to John J. Chen, MD, PhD, Departments of Ophthalmology and Neurology, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905; E-mail: chen.john@mayo.edu Supported in part by an unrestricted grant to the Department of Ophthalmology by Research to Prevent Blindness, Inc, New York, NY; the Mayo Clinic Center for Individualized Medicine; Department of Laboratory Medicine and Pathology; and the Center of MS and Autoimmune Neurology. Dr. A. McKeon is a named inventor on a patent application filed by the Mayo Foundation relating to the GFAP antibody. The remaining authors report no conflicts of interest. © 2017 by North American Neuro-Ophthalmology Society

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Leber Hereditary Optic Neuropathy Caused by a Mitochondrial DNA 10663T>C Point Mutation and Its Response to Idebenone Treatment

No abstract available

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Historical Trends in the Diagnosis of Peduncular Hallucinosis

Background: Peduncular hallucinosis (PH) describes the clinical syndrome of vivid, dream-like visual hallucinations that intrude on normal wakefulness. Additional clinical deficits, especially ophthalmoparesis, have historically been an important part of the diagnosis and localization of this syndrome. We examined how modern neuroimaging has impacted the diagnosis of PH. Methods: We reviewed all available cases of PH, including 3 of ours and all previously reported in the literature. We determined whether other eye movement abnormalities were part of the clinical presentation and whether a neuroimaging study was performed to make the diagnosis. Results: A total of 85 cases were identified and evaluated. Eye movement abnormalities were present in 12/15 (80%) without a neuroimaging study but in only 24/70 (34%) of cases in which a neuroimaging study was performed (P = 0.001). Conclusions: Although eye movement abnormalities historically have been considered a key localizing clinical feature supporting the diagnosis of PH, we found that in the era of modern neuroimaging, co-occurring eye movement abnormalities are far less frequent and are not a requisite feature of the diagnosis. Address correspondence to Sashank Prasad, MD, Department of Neurology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02215; E-mail: sprasad2@partners.org The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the full text and PDF versions of this article on the journal's Web site (http://ift.tt/2BFTkP1). © 2017 by North American Neuro-Ophthalmology Society

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Photodynamic therapy in fibrosarcoma BALB/c animal model: Observation of the rebound effect

Publication date: March 2018
Source:Photodiagnosis and Photodynamic Therapy, Volume 21
Author(s): Etcheverry María Eugenia, Pasquale Miguel Ángel, Gutiérrez Anabella, Bibé Solange, Ponzinibbio Carlos, Poteca Horacio, Garavaglia Mario
In vivo spectrofluorometric analysis during photodynamic therapy (PDT) is a fundamental tool to obtain information about drug bleaching kinetics. Using a portable spectrofluorometer with an excitation source emitting at 400nm wavelength and a spectral analyzer ranging from 500nm to 800nm, the evolution of the meta-tetra(hydroxyphenyl) chlorin (m-THPC) photosensitizer fluorescence spectrum at the tumoral tissue of BALB/c murines with fibrosarcoma located at their flank was followed up. Ex vivo fluorescence measurements of the tumor and skin were also performed with the aim of better characterizing the in vivo signal at different parts of the tumor. PDT was performed employing a LED 637nm light source. Fluorescence at different parts of the tumor and at the tail and armpit of mice was measured immediately after injection and followed daily. The average fluorescence intensity in the tumor reached a maximum after 24–72h. Subsequently, illuminations 24, 48, 72 and 96h post-injection were performed, and the fluorescence was measured immediately before and after each illumination. Eventually, 24h post-illumination, the fluorescence at certain parts of the tumor increased in comparison with that measured immediately after illumination. This effect, named "rebound effect", was due to the new local accumulation of the drug, and was used to perform a second illumination on some mice to increase the amount of photodynamic reaction and significantly improve the PDT outcome. These results are encouraging to optimize PDT in the proposed animal model, thinking about the possible translation to humans.



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Evaluation of photosensitizer penetration into sound and decayed dentin: A photoacoustic spectroscopy study

Publication date: March 2018
Source:Photodiagnosis and Photodynamic Therapy, Volume 21
Author(s): Ingrid Gomes Perez Occhi-Alexandre, Mauro Luciano Baesso, Francielle Sato, Lidiane Vizioli de Castro-Hoshino, Pedro Luiz Rosalen, Raquel Sano Suga Terada, Antonio Medina Neto, Mitsue Fujimaki
BackgroundPhotodynamic therapy (PDT) may have topical indications. In those cases it is important for a topical photosensitizer to penetrate into the tissue to which it has been applied. This study aimed to compare the penetration of two different concentrations of erythrosine into intact and in vitro decayed dentin samples.MethodsThis in vitro study evaluated erythrosine (0.3 and 5%) penetration into sound (intact) and decayed dentin. A total of 11 dentin discs were prepared and divided into two equal halves, in order to keep one half sound while the other half was submitted to sterilization and an in vitro demineralization model for 5 days. Before erythrosine application, the organic and inorganic composition of all samples was evaluated by Fourier Transform Raman spectroscopy, and after erythrosine application for 30min, the penetration depth was determined by Photoacoustic spectroscopy technique.ResultsThe results indicated that 0.3% erythrosine showed a higher penetration depth into sound dentin (p=0.002); and 5% erythrosine higher penetration into decayed dentin (p<0.001). However considering clinical parameters, no statistically significant difference was found between any of the conditions tested.ConclusionsErythrosine demonstrated ability to penetrate into dentin, irrespective of sound or decayed condition. Photoacoustic spectroscopy can be considered a method for estimating the penetration into hard tissues, and in conjunction with Raman spectroscopy, these are effective methods for evaluating the spectral response of dentin. Considering that erythrosine is capable of penetrating into decayed dentin, clinical trials are needed to test the effectiveness of this photosensitizer in Photodynamic therapy and Antimicrobial Photodynamic therapy.



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Photochemical Internalization Enhanced Macrophage Delivered Chemotherapy

Publication date: Available online 6 December 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Diane Shin, Catherine Christie, David Ju, Rohit Kumar Nair, Stephanie Molina, Kristian Berg, Tatiana B. Krasieva, Steen J. Madsen, Henry Hirschberg
BACKGROUNDMacrophage (Ma) vectorization of chemotherapeutic drugs has the advantage for cancer therapy in that it can actively target and maintain an elevated concentration of drugs at the tumor site, preventing their spread into healthy tissue. A potential drawback is the inability to deliver a sufficient number of drug-loaded Ma into the tumor, thus limiting the amount of active drug delivered. This study examined the ability of photochemical internalization (PCI) to enhance the efficacy of released drug by Ma transport.METHODSTumor spheroids consisting of either F98 rat glioma cells or F98 cells combined with a subpopulation of empty or doxorubicin (DOX)-loaded mouse Ma (RAW264.7) were used as in vitro tumor models. PCI was performed with the photosensitizer AlPcS2a and laser irradiation at 670nm.RESULTSRAW264.7 Ma pulsed with DOX released the majority of the incorporated DOX within two hours of incubation. PCI significantly increased the toxicity of DOX either as pure drug or derived from monolayers of DOX-loaded Ma. Significant growth inhibition of hybrid spheroids was also observed with PCI even at subpopulations of DOX-loaded Ma as low as 11% of the total initial hybrid spheroid cell number.CONCLUSIONResults show that RAW264.7 Ma, pulsed with DOX, could effectively incorporate and release DOX. PCI significantly increased the ability of both free and Ma-released DOX to inhibit the growth of tumor spheroids in vitro. The growth of F98+DOX loaded Ma hybrid spheroids were synergistically reduced by PCI, compared to either photodynamic therapy or released DOX acting alone.



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Photodynamic Antimicrobial Chemotherapy (PACT), using Toluidine blue O inhibits the viability of biofilm produced by Candida albicans at different stages of development

Publication date: Available online 6 December 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Ana Paula Pinto, Isabela Bueno Rosseti, Moisés Lopes Carvalho, Bruna Graziele Marques da Silva, Carlos Alberto-Silva, Maricilia Silva Costa
BackgroundCandida albicans is an opportunistic fungus producing both superficial and systemic infections, especially in immunocompromised individuals. It has been demonstrated that C. albicans ability to form biofilms is a crucial process for colonization and virulence. Furthermore, a correlation between the development of drug resistance and biofilm maturation at Candida biofilms has been shown. Photodynamic Antimicrobial Chemotherapy (PACT) is a potential antimicrobial therapy that combines visible light and a non-toxic dye, known as a photosensitizer, producing reactive oxygen species (ROS) that can kill the treated cells. The objective of this study was to investigate the effects of PACT, using Toluidine Blue O (TBO) on the viability of biofilms produced by C. albicans at different stages of development.MethodsIn this study, the effects of PACT on both biofilm formation and viability of the biofilm produced by C. albicans were studied. Biofilm formation and viability were determined by a metabolic assay based on the reduction of XTT assay. In addition, the morphology of the biofilm was observed using light microscopy.ResultsPACT inhibited both biofilm formation and viability of the biofilm produced by C. albicans. Furthermore, PACT was able to decrease the number of both cells and filamentous form present in the biofilm structure. This inhibitory effect was observed in both early and mature biofilms.ConclusionsThe results obtained in this study demonstrated the potential of PACT (using TBO) as an effective antifungal therapy, including against infections associated with biofilms at different stages of development.



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The applicability fluorescence guided detection of epithelial dysplasia and oral cancer

Publication date: Available online 6 December 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Saygo Tomo, Luciana Estevam Simonato




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Synthesis and Characterization of Small-Sized Gold Nanoparticles Coated By Bovine Serum Albumin (BSA) For Cancer Photothermal Therapy

Publication date: Available online 6 December 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Selma M.H. AL-Jawad, Ali A. Taha, Mohammad M.F. Al-Habosiy, Lamyaa F.A. AL-Barram
In the present study, small gold nanoparticles <5nm coated with natural protein Bovine Serum Albumin (BSA) was synthesized and characterized using UV–Vis spectrophotometer, Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM), zeta potential and scanning electron microscopy (SEM). Three types of cancer cell lines; Rhabdomyosarcoma (RD), Murine fibroblast (L20B) and RAW 264.7 monocyte-macrophage (MQ) were tested and treated by photothermal strategy, in vitro, by conjugating BSA-AuNPs complex of (0.125, 0.25, 0.5 and 1mg/ml) concentrations with continuous low power laser irradiation, green (532nm) and near-infrared (NIR) (800nm) at 0.5, 1, 2 and 3min, separately. Cytotoxicity effect was determined by MTT assay. The vital impact of photothermal technique has investigated at 1mg/ml and 3min irradiation period as identified in RD cell line in comparison with other types; where cytotoxicity more than 74% was reached. Prominent results were demonstrated in the green and NIR region by PH-induced aggregation effect of small nanoparticles inside the cancer cells, which make the small-sized BSA-AuNPs are promising agents for cancer photothermal therapy.



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Muscle thickness and echo intensity measurements of the rectus femoris muscle of healthy subjects: Intra and interrater reliability of transducer tilt during ultrasound

Publication date: Available online 6 December 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Hiroshi Ishida, Tadanobu Suehiro, Keita Suzuki, Susumu Watanabe
This study aimed to assess the intra and interrater reliability of transducer tilt during the ultrasound (US) measurements of the muscle thickness and the echo intensity of the rectus femoris muscle (RF). Fourteen healthy male subjects (20.8 ± 0.8 years) participated in this study. The transducer tilt was measured using a digital angle gauge (°) during US. Two experimenters took two images to measure the muscle thickness (mm) and the echo intensity (a.u.: arbitrary unit). The intra and interclass correlation coefficient (ICC), standard error of measurement (SEM), and minimal detectable change (MDC) were also calculated. These measurements were immediately repeated. The ICC for the intrarater reliability for the transducer tilt, muscle thickness, and echo intensity were 0.96 (SEM: 0.9°, MDC: 2.6°), 0.99 (SEM: 0.4 mm, MDC: 0.1 mm), and 0.97 (SEM: 0.6 a.u., MDC: 1.7 a.u.), respectively. The ICC for the interrater reliability for the transducer tilt, muscle thickness, and echo intensity were 0.40 (SEM: 4.0°, MDC: 11.1°), 0.96 (SEM: 0.7 mm, MDC: 2.0 mm), and 0.95 (SEM: 0.9 a.u., MDC: 2.4 a.u.), respectively. The intrarater reliability of the transducer tilt was reliable, but the interrater reliability was questionable. Meanwhile, both the intra- and interrater reliability of the muscle thickness and the echo intensity were reliable.



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Integration of a neurodynamic approach into the treatment of dysarthria for patients with idiopathic Parkinson's disease: A pilot study

Publication date: Available online 6 December 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Barbara Ateras, Harry von Piekartz
PurposeDifferences between standard dysarthria treatment and the same treatment with the integration of neurodynamic techniques tailored to the severity of dysarthria in patients with Parkinson's disease were examined.MethodIn total, 10 subjects with idiopathic Parkinson's disease and rigid–hypokinetic dysarthria were enrolled in this quasi-randomized, controlled, single-blind, pre–post study. In each of 12 therapy sessions the control group (n = 5) received standard dysarthria treatment (usual care), while the intervention group (n = 5) received the same treatment with the addition of integrated neurodynamic treatment (special care).ResultsThere was no significant difference between the two groups for either the pre-test (p = 0.739) or the post-test (p = 0.156) results. However, significant differences between the pre-test and post-test results within each group (intervention group p = 0.001; control group p = 0.003) were found.ConclusionsThe significant differences in the pre–post comparison within the groups may indicate a high probability of a positive effect of standard dysarthria treatment on the severity of dysarthria. In between-group comparisons, the study results indicated no evidence of a significant difference between standard dysarthria treatment with or without neurodynamics. Due to the small sample size, the effectiveness of the integration of neurodynamics into speech therapy cannot be definitively concluded for now. In order to be able to have generalized applicability, future studies with larger numbers of participants are required.



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