Covalent Growth Factor Tethering to Direct Neural Stem Cell Differentiation and Self-Organization

Publication date: Available online 2 February 2017
Source:Acta Biomaterialia
Author(s): Trevor R. Ham, Mahmoud Farrag, Nic D. Leipzig
Tethered growth factors offer exciting new possibilities for guiding stem cell behavior. However, many of the current methods present substantial drawbacks which can limit their application and confound results. In this work, we developed a new method for the site-specific covalent immobilization of azide-tagged growth factors and investigated its utility in a model system for guiding neural stem cell (NSC) behavior. An engineered interferon-γ (IFN-γ) fusion protein was tagged with an N-terminal azide group, and immobilized to two different dibenzocyclooctyne-functionalized biomimetic polysaccharides (chitosan and hyaluronan). We successfully immobilized azide-tagged IFN-γ under a wide variety of reaction conditions, both in solution and to bulk hydrogels. To understand the interplay between surface chemistry and protein immobilization, we cultured primary rat NSCs on both materials and showed pronounced biological effects. Expectedly, immobilized IFN-γ increased neuronal differentiation on both materials. Expression of other lineage markers varied depending on the material, suggesting that the interplay of surface chemistry and protein immobilization plays a large role in nuanced cell behavior. We also investigated the bioactivity of immobilized IFN-γ in a 3D environment in vivo and found that it sparked the robust formation of neural tube-like structures from encapsulated NSCs. These findings support a wide range of potential uses for this approach and provide further evidence that adult NSCs are capable of self-organization when exposed to the proper microenvironment.Statement of SignificanceFor stem cells to be used effectively in regenerative medicine applications, they must be provided with the appropriate cues and microenvironment so that they integrate with existing tissue. This study explores a new method for guiding stem cell behavior: covalent growth factor tethering. We found that adding an N-terminal azide-tag to interferon-γ enabled stable and robust Cu-free 'click' immobilization under a variety of physiologic conditions. We showed that the tagged growth factors retained their bioactivity when immobilized and were able to guide neural stem cell lineage commitment in vitro. We also showed self-organization and neurulation from neural stem cells in vivo. This approach will provide another tool for the orchestration of the complex signaling events required to guide stem cell integration.

Graphical abstract

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Study of efficacy of esthetic High-Intensity Focused Ultrasound system on Iranian skin for reducing the laxity and wrinkles of aging

Summary

Background

Ultrasound is a mechanical wave that transmitted in a straight line and it can be focused at frequencies of 1-7 MHz with a high degree of precision. An important aspect of HIFU is that damaging focal point is located several millimeters below the surface of the skin and tissue above and below the focal point remains unaffected. Due to absorption of this energy, temperature of tissue rises to more than 60°C and this stimulates the cells for collagen production and tissue rejuvenation.

Objective

To evaluate the clinical efficacy and safety of High-Intensity Focused Ultrasound on Skin Laxity and wrinkles.

Material and Method

The study involved 22 women aged 35-62 with skin type II-IV. HIFU device with three transducers was employed. Various focal depths with different energies were used in accordance with skin thickness. Improvement for seven regions of face and whole face were evaluated by two dermatologists and patients 3 months after treatment.

Results

All of the patients completed the study. Three months after treatment, there was a highly statistical improvement in skin laxity for all of the patients. Also, the average percentage of improvement by doctor's opinion and patients was 58% and 60%, respectively.

Conclusion

The experimental data obtained from dermatologists and patients showed that HIFU appears to be a safe and effective modality for skin laxity treatment.

http://ift.tt/2kYLl7d

The efficacy study of the combination of tripeptide-10-citrulline and acetyl hexapeptide-3. A prospective, randomized controlled study

Summary

Background

Bioactive peptides have beneficial effects on the skin.

Objective

We investigated to evaluate the effect of acetyl hexapeptide-3 and tripeptide-10 citrulline and the possible synergism between these two peptides.

Methods

Twenty-four healthy volunteers were randomized to receive combination of acetyl hexapeptide-3 with tripeptide-10 citrulline (Group G1), tripeptide-10 citrulline (Group, G2), acetyl hexapeptide-3 (Group G3), or neither peptide (Group G4) for 60 days. Skin properties evaluated included skin microtopography, parameters cR2 and cR3, and transepidermal water loss (TEWL) using a skin visioscan and a tewameter, respectively.

Results

After 20 days, the measurements between G1 and G2 groups (cR2 P=.045, cR3 P=.044), G2 and G3 groups (cR2 P=.017, cR3 P=.017), G3 and G4 groups (CR2 P=.022), and G2 and G4 groups (cR3 P=.028) from baseline were significant. After 60 days, measurements between groups G1 and G3 (cR2 P=.016, cR3 P=.025), groups G2 and G3 (cR2 P=.044, cR3= P=.044), and groups G1 and G4 (cR2 P=.025) were significant. After 20 days, changes in TEWL between groups G1 and G3 (P=.03), groups G2 and G3 (P=.045), and groups G3 and G4 (P=.025) were significant. After 40 days, changes between groups G2 and G3 (P=.028) and groups G3 and G4 (P=.01) from baseline were significant.

Conclusion

Our results confirm the antiwrinkle activity of acetyl hexapeptide-3. A significant decrease in TEWL with acetyl hexapeptide-3 treatment is observed. We provided clinical evidence for the antiwrinkle efficacy of tripeptide-10 citrulline and possibly TEWL. The underlying mechanism by which these two peptides can act synergistically was not clear in this study.

http://ift.tt/2ksSAYe

Chemotherapy-induced alopecia management: Clinical experience and practical advice

Summary

Background

Chemotherapy-induced alopecia (CIA) is probably one of the most shocking aspects for oncological patients and underestimated by physicians. Among hair loss risk factors, there are treatment-related aspects such as drug dose, administration regimen, and exposure to X-rays, but also patient-related characteristics. To the best of our knowledge, no guidelines are available about CIA management.

Aims and methods

With this study, based on literature background and our clinical experience, we would like to propose a list of actions in order to estimate the risk of hair loss before starting chemotherapy and to manage this condition before, during, and after drug administration and to create a sort of practical guide for dermatologists and oncologists.

Results and conclusion

There is an urgent need for prospective studies to clarify the mechanistic basis of alopecia associated with these drugs and consequently to design evidence-based management strategies.

http://ift.tt/2kYT0Cs

Characterizing the detectability of emission signals from a North Korean nuclear detonation

Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): David Werth, Robert Buckley
The detectability of emission sources, defined by a low-level of mixing with other sources, was estimated for various locations surrounding the Sea of Japan, including a site within North Korea. A high-resolution meteorological model coupled to a dispersion model was used to simulate plume dynamics for four periods, and two metrics of airborne plume mixing were calculated for each source. While emissions from several known sources in this area tended to blend with others while dispersing downwind, the North Korean plume often remained relatively distinct, thereby making it potentially easier to unambiguously 'backtrack' it to its source.



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Public member dose assessment of Bushehr Nuclear Power Plant under normal operation by modeling the fallout from stack using the HYSPLIT atmospheric dispersion model

Publication date: May 2017
Source:Journal of Environmental Radioactivity, Volume 171
Author(s): A. Zali, M. Shamsaei Zafarghandi, S.A. Feghhi, A.M. Taherian
In this work, public dose resulting from fission products released from Bushehr Nuclear Power Plant (BNPP) under normal operation is assessed. Due to the long range transport of radionuclides in this work (80 km) and considering terrain and meteorological data, HYbrid Single-Particle Lagrangian Integrated Trajectory (HYsplit) model, which uses three dimensional long-range numerical models, has been employed to calculate atmospheric dispersion. Annual effective dose calculation is carried out for inhalation, ingestion, and external exposure pathways in 16directions and within 80 km around the site for representative person. The results showed the maximum dose of inhalation and external exposure for adults is 3.8 × 10⁻⁸Sv/y in the SE direction and distance of 600 m from the BNPP site which is less than ICRP 103 recommended dose limit (1 mSv). Children and infants' doses are higher in comparison with adults, although they are less than 1 mSv. Ingestion dose percentage in the total dose is less than 0.1%. The results of this study underestimate the Final Safety Analysis Report ofBNPP-1 (FSAR)data.



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Radioactivity levels in the mostly local foodstuff consumed by residents of the high level natural radiation areas of Ramsar, Iran

Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): Nasrin Fathabadi, Ali Akbar Salehi, Kazem Naddafi, Mohammad Reza Kardan, Masud Yunesian, Ramin Nabizadeh Nodehi, Mohammad Reza Deevband, Molood Gooniband Shooshtari, Saeedeh Sadat Hosseini, Mahtab Karimi
Among High Level Natural Radiation Areas (HLNRAs) all over the world, the northern coastal city of Ramsar has been considered enormously important. Many studies have measured environmental radioactivity in Ramsar, however, no survey has been undertaken to measure concentrations in the diets of residents. This study determined the ²²⁶Ra activity concentration in the daily diet of people of Ramsar. The samples were chosen from both normal and high level natural radiation areas and based on the daily consumption patterns of residents. About 150 different samples, which all are local and have the highest consumption, were collected during the four seasons. In these samples, after washing and drying and pretreatment, the radionuclide was determined by α-spectrometry. The mean radioactivity concentration of ²²⁶Ra ranged between 5 ± 1 mBq kg⁻¹ wet weight (chino and meat) to 725 ± 480 mBq kg⁻¹ for tea dry leaves. The ²²⁶Ra activity concentrations compared with the reference values of UNSCEAR appear to be higher in leafy vegetables, milk and meat product. Of the total daily dietary ²²⁶Ra exposure for adults in Ramsar, the largest percentage was from eggs. The residents consuming eggs from household chickens may receive an elevated dose in the diet.



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Treatment pattern and frequency of serum TSH measurement in users of different levothyroxine formulations: a population-based study during the years 2009–2015

Abstract

Background

Several conditions can modify the intestinal absorption of levothyroxine tablets, with potential consequences on their therapeutic effect. Pre-dosed ampoules and oral drops have been recently made available to overcome this limitation.

Aims

To describe the pattern of use of different formulations of levothyroxine in a general population of Southern Italy and to perform an exploratory analysis investigating the effect of switching from levothyroxine tablets to oral liquid formulations.

Methods

Data were extracted from the Caserta Local Health Unit database. All patients receiving at least one levothyroxine prescription during the years 2009–2015 were identified. 1-year incidence of use of formulation-specific levothyroxine was calculated. Switchers between levothyroxine tablets and oral liquid formulations were identified and the frequency of thyroid-stimulating hormone measurement within 2 years prior and after the switch date was explored.

Results

Overall, 56,354 levothyroxine users were included in the study. Of these, 55,147 patients received at least one prescription for tablets (97.9%), 1867 pre-dosed ampoules (3.3%) and 1550 oral drops (2.8%). The proportion of levothyroxine users receiving oral liquid formulations slightly increased over time. Patients switching from tablets to oral liquid formulations showed a statistically significant reduction in the number of thyroid-stimulating hormone measurements after switching from tablets, especially in presence of drugs interacting with levothyroxine potentially altering its absorption.

Conclusions

Use of levothyroxine oral liquid formulations is increasing over time even though their use is still limited in a general population of Southern Italy. Our exploratory analysis showed that the frequency of thyroid-stimulating hormone measurement was reduced in patients switching from levothyroxine tablet to new formulations.

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Quantifying 125I placement accuracy in prostate brachytherapy using postimplant transrectal ultrasound images

Publication date: Available online 1 February 2017
Source:Brachytherapy
Author(s): Muhammad F. Jamaluddin, Sunita Ghosh, Michael P. Waine, Ronald S. Sloboda, Mahdi Tavakoli, John Amanie, Albert D. Murtha, Don Yee, Nawaid Usmani
PurposeThe quality of a prostate brachytherapy implant depends on the accurate placement of sources. This study quantifies the misplacement of ¹²⁵I sources from the intended location using intraoperative ultrasound images.Methods and Materials¹²⁵I sources were manually identified in the postimplant ultrasound images and compared to the preoperative plan. Due to the subjective nature of the identifying sources, only sources identified with high confidence were included in the analysis. Misplacements from the original intended coordinate were measured along the X, Y, and Z axes and were stratified between overall misplacements and regions of the prostate gland.ResultsA total of 1619 ¹²⁵I sources using 357 strands were implanted in 15 patients' prostate glands, with 1197 (74%) confidently identified for misplacement analysis. The overall mean displacement was 0.49 cm and in the X, Y, and Z direction was 0.13, 0.15, and 0.38 cm, respectively. Greater source misplacement occurred in the anterior part of the prostate gland than the posterior part of the prostate gland by a factor 1.33 (p < 0.0001). Comparing sources in the lateral vs. medial regions of the prostate, no statistically significant differences on source misplacement were observed. Comparing misplacement in the base vs. midgland vs. apex identified the greatest difference between the base and midgland by a factor of 1.29 (p < 0.0001).ConclusionsThis study has identified significant misplacement of ¹²⁵I sources from their intended locations with the greatest error misplacement occurring in the Z direction. Source misplacement tends to occur more commonly in the anterior gland and in the base of the prostate.



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MRI in prostate brachytherapy: Evidence, clinical end points to data, and direction forward

Publication date: Available online 1 February 2017
Source:Brachytherapy
Author(s): Thomas J. Pugh, Sajal S. Pokharel
The integration of multiparametric MRI into prostate brachytherapy has become a subject of interest over the past 2 decades. MRI directed high-dose-rate and low-dose-rate prostate brachytherapy offers the potential to improve treatment accuracy and standardize postprocedure quality. This article reviews the evidence to date on MRI utilization in prostate brachytherapy and postulates future pathways for MRI integration.



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Dosimetric and radiobiologic comparison of 103Pd COMS plaque brachytherapy and Gamma Knife radiosurgery for choroidal melanoma

Publication date: Available online 1 February 2017
Source:Brachytherapy
Author(s): Daniel Gorovets, Nolan L. Gagne, Christopher S. Melhus
PurposePlaque brachytherapy (BT) and Gamma Knife radiosurgery (GKRS) are highly conformal treatment options for choroidal melanoma. This study objectively compares physical dose and biologically effective dose (BED) distributions for these two modalities.Methods and MaterialsTumor and organ-at-risk (OAR) dose distributions from a CT-defined reference right eye were compared between ¹⁰³Pd COMS (Collaborative Ocular Melanoma Study Group) plaques delivering 70 Gy (plaque heterogeneity corrected) over 120 h to the tumor apex and GKRS plans delivering 22 Gy to the 40% isodose line for a representative sample of clinically relevant choroidal melanoma locations and sizes. Tumor and OAR biologically effective dose-volume histograms were generated using consensus radiobiologic parameters and modality-specific BED equations.ResultsPublished institutional prescriptive practices generally lead to larger tumor and OAR physical doses from COMS BT vs. GKRS. Radiobiologic dose conversions, however, revealed variable BEDs. Medium and large tumors receive >1.3 times higher BEDs with COMS BT vs. GKRS. OAR BEDs have even greater dependence on tumor size, location, and treatment modality. For example, COMS BT maximum BEDs to the optic nerve are lower than from GKRS for large anterior and all posterior tumors but are higher for anterior small and medium tumors.ConclusionsBT and GKRS for choroidal melanoma have different physical dose and BED distributions with potentially unique clinical consequences. Using published institutional prescriptive practices, neither modality is uniformly favored, although COMS BT delivers higher physical doses and BEDs to tumors. These results suggest that lowering the physical prescription dose for COMS BT to more closely match the BED of GKRS might maintain equivalent tumor control with less potential morbidity.



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Deformable image registration for cervical cancer brachytherapy dose accumulation: Organ at risk dose–volume histogram parameter reproducibility and anatomic position stability

Publication date: Available online 1 February 2017
Source:Brachytherapy
Author(s): E. Flower, V. Do, J. Sykes, C. Dempsey, L. Holloway, K. Summerhayes, D.I. Thwaites
PurposeThe purpose of this study was to determine the effect of deformable image registration (DIR) on cumulative organ at risk dose–volume histogram (DVH) parameter summation for more than three brachytherapy fractions. The reproducibility of different methods of DIR was tested. DIR was then used to assess the stability of the anatomic position of the DVH parameters within the bladder and rectum.Methods and MaterialsDIR was completed for 39 consecutive cervical cancer brachytherapy patients' planning CTs. Accumulated DVH parameters (D2cc and D0.1cc) for bladder and rectum were compared with dose summation without DIR. Reproducibility of DIR results was assessed for different methods of implementation based on adding contour biases added to the DIR algorithm. VolD2cc and VolD0.1cc structures were created from the overlap of the D2cc and D0.1cc isodose and the bladder or rectum, respectively. The overlap of VolD2cc and VolD0.1cc structures was calculated using the Dice similarity coefficient.ResultsDIR accumulated D2cc and D0.1cc decreased by an average of 2.9% and 4.2% for bladder and 5.08% and 2.8% for rectum compared with no DIR. DIR was most reproducible when the bladder or rectum contour was masked. The average Dice similarity coefficient was 0.78 and 0.61 for the bladder D2cc and D0.1cc as well as 0.83 and 0.62 for rectal D2cc and D0.1cc, respectively.ConclusionsDose decreases were observed for accumulated DVH parameters using DIR. Adding contour-based biases to the algorithm increases the reproducibility of D2cc and D0.1cc accumulation. The anatomic position of VolD2cc was more stable than VolD0.1cc.



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Brachytherapy boost for prostate cancer: Trends in care and survival outcomes

Publication date: Available online 1 February 2017
Source:Brachytherapy
Author(s): S.M. Glaser, M.J. Dohopolski, G.K. Balasubramani, R.M. Benoit, R.P. Smith, S. Beriwal
PurposeAndrogen suppression combined with elective nodal and dose-escalated radiation therapy recently demonstrated an improved biochemical failure–free survival in men who received external beam radiation therapy (EBRT) plus a brachytherapy boost (BB) compared with dose-escalated external beam radiotherapy (DE-EBRT). We sought to analyze the factors predictive for use of EBRT + BB as compared with DE-EBRT and report resulting survival outcomes on a national level using a hospital-based registry.Methods and MaterialsWe identified 113,719 men from the National Cancer Database from 2004 to 2013 with intermediate- or high-risk prostate cancer who were treated with EBRT + BB or DE-EBRT. We performed univariate and multivariate analyses of all available factors potentially predictive of receipt of treatment selection. Survival was evaluated in a multivariable model with propensity adjustment.ResultsFor intermediate-risk patients, utilization of BB decreased from 33.1% (n = 1742) in 2004 to 12.5% (n = 766) in 2013 and for high-risk patients, utilization dropped from 27.6% (n = 879) to 10.8% (n = 479). Numerous factors predictive for use of BB were identified. Cox proportional hazards analysis was performed—adjusting for age, Charlson–Deyo comorbidity score, T stage, prostate-specific antigen, Gleason score, and sociodemographic factors—and demonstrated BB use was associated with a hazard ratio of 0.71 (95% confidence interval, 0.67–0.75; p < 0.0005) and 0.73 (95% confidence interval, 0.68–0.78; p < 0.0005) for intermediate- and high-risk patients, respectively.ConclusionsThere has been a concerning decline in the utilization of BB for intermediate- and high-risk prostate cancer patients despite an association with improved on overall survival. Numerous factors predictive for use of BB have been identified.



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Target volume and artifact evaluation of a new data driven 4D CT

Publication date: Available online 2 February 2017
Source:Practical Radiation Oncology
Author(s): Rachael Martin, Tinsu Pan
Purpose4D CT is often used to define the internal gross target volume (IGTV) for radiation therapy of lung cancer. Traditionally, this technique requires the use of an external motion surrogate, however, a new image data driven 4D CT has become available. This study aims to describe this data driven 4D CT and compare target contours created with it to those created using standard 4D CT.MethodsCine CT data of 35 patients undergoing SBRT were collected and sorted into phases using standard and data driven 4D CT. IGTV contours were drawn using a semi-automated method on maximum intensity projection (MIP) images of both 4D CT methods. Errors due to reproducibility of the method were characterized. A comparison of phase image artifacts was made using a normalized cross correlation method which assigned a score from +1 (data driven "better") to −1 (standard "better").ResultsThe volume difference between the data driven and standard IGTVs was not significant (data driven was 2.1±1.0% smaller, p=0.08). The Dice similarity coefficient (DSC) showed good similarity between the contours (0.949±0.006). The mean surface separation was 0.4±0.1mm and the Hausdorff distance was 3.1±0.4mm. An average artifact score of +0.37 indicated the data driven method had significantly fewer and/or less severe artifacts than the standard method (p=1.5e-5 for difference from 0).ConclusionOn average, the difference between IGTVs derived from data driven and standard was not clinically relevant or statistically significant, suggesting data driven 4D CT can be used in place of standard 4D CT without adjustments to IGTVs. The relatively large differences in some patients were usually attributed to limitations in automatic contouring or differences in artifacts. Artifact reduction and setup simplicity suggest a clinical advantage to data driven 4D CT.



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Improving patient safety and workflow efficiency with standardized pre-treatment radiation therapist chart reviews

Publication date: Available online 2 February 2017
Source:Practical Radiation Oncology
Author(s): Kelly Cooper Younge, Katherine Woch Naheedy, Joel Wilkinson, Joumana Dekmak, Elizabeth Covington, Bonnie Durbin, Eric Nelson, Stephanie Filpansick, Jean M Moran
PurposeTherapists play a critical role in ensuring patient safety, however, they are sometimes given insufficient time to perform quality assurance of a patient's treatment chart and documentation prior to the start of treatment. In this work, we show the benefits of introducing a formal therapist pre-start QA checklist, completed in a quiet space well in advance of treatment, into our workflow.Materials and MethodsA therapist pre-start QA checklist was created by analyzing in-house variance reports and treatment unit delays over a period of six months. Therapists were then given dedicated time and a workspace to perform their checks within the dosimetry office of our department. The effectiveness of the checklist was quantified by recording the percentage of charts QA'ed prior to treatment, the percentage of charts with errors needing intervention, and treatment unit delays over a nearly two year time period. The frequency and types of errors found by the pre-start QA were also recorded.ResultsThrough the use of therapist pre-start QA, instances of treatment unit delays were reduced by up to a factor of nine over the first year of the program. At the outset of this new initiative, nearly 40% of charts had errors requiring intervention, with the majority being scheduling-related. With upstream workflow changes and automation, this was reduced over the period of a year to about 10%.ConclusionThe number of treatment unit delays was dramatically reduced through the use of a formal therapist pre-start QA checklist completed well in advance of treatment. The data collected via the checklist continues to be used for further quality improvement efforts.



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MEG and EEG demonstrate similar test-retest reliability of the 40Hz auditory steady-state response

Publication date: Available online 1 February 2017
Source:International Journal of Psychophysiology
Author(s): Kristina T. Legget, Allison K. Hild, Sarah E. Steinmetz, Steven T. Simon, Donald C. Rojas
The auditory steady-state response (ASSR) is increasingly being used as a biomarker in neuropsychiatric disorders, but research investigating the test-retest reliability of this measure is needed. We previously reported ASSR reliability, measured by electroencephalography (EEG), to 40Hz amplitude-modulated white noise and click train stimuli. The purpose of the current study was to (a) assess the reliability of the MEG-measured ASSR to 40Hz amplitude-modulated white noise and click train stimuli, and (b) compare test-retest reliability between MEG and EEG measures of ASSR, which has not previously been investigated. Additionally, impact of stimulus parameter choice on reliability was assessed, by comparing responses to white noise and click train stimuli. Test-retest reliability, across sessions approximately one week apart, was assessed in 17 healthy adults. On each study day, participants completed two passive listening tasks (white noise and click train stimuli) during separate MEG and EEG recordings. Between-session correlations for evoked power and inter-trial phase coherence (ITPC) were assessed following source-space projection. Overall, the MEG-measured ASSR was significantly correlated between sessions (p<0.05, FDR corrected), suggesting acceptable test-retest reliability. Results suggest greater response reproducibility for ITPC compared to evoked responses and for click train compared to white noise stimuli, although further study is warranted. No significant differences in reliability were observed between MEG and EEG measures, suggesting they are similarly reliable. This work supports use of the ASSR as a biomarker in clinical interventions with repeated measures.



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Thermoplastic polyurethanes from β-methyl-δ-valerolactone-derived amidodiol chain extenders

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): David M. Guptill, Jacob P. Brutman, Thomas R. Hoye
Here we describe the synthesis of thermoplastic polyurethanes (TPUs) from polyols and amidodiol chain extenders, each of which is prepared from glucose-derived β-methyl-δ-valerolactone (MVL). Utilizing these novel chain extenders, we prepared TPUs with ca. 42–44 wt% hard segment content, comprising 72–75 wt% MVL-derived atoms. This compares favorably with an analogous sample prepared using 1,4-butanediol as the chain extender having 57 wt%. These TPUs are ductile (600–900% strain at break) and have high tensile strength (14–33 MPa stress at break). By virtue of the nature of the diamidodiol used as chain extenders, the hard segments contain a greater density of hydrogen bonding –NHC(=O)– functional groups relative to those prepared using traditional short chain 1,n-alkanediols.

Graphical abstract

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A processing method with high efficiency for low density polyethylene nanofibers reinforced by aligned carbon nanotubes via nanolayer coextrusion

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Junfeng Cheng, Hongting Pu, Jiang Du
A method for large-scale processing of low density polyethylene (LDPE) nanofibers reinforced by aligned multi-walled carbon nanotubes (MWCNTs) is achieved via nanolayer coextrusion. The morphology and nano-sized diameter of the nanofibers are observed on scanning electron microscope. The prioritized alignment and dispersion of MWCNTs along the fiber axis are determined by transmission electron microscopy, polarized Raman spectra, and high resolution optical microscopy. The dispersion of MWCNTs in nanofibers is better than that in homologous micron-fibers. In addition, MWCNTs can promote the crystallization of LDPE in varying degrees which depend on the fiber diameter and MWCNTs content. As a result of the alignment of MWCNTs, the nanofibers exhibit enhanced mechanical properties. The tensile strength of LDPE(1 wt% MWCNTs) nanofibers is more than twice of pure nanofibers (without MWCNTs). The volume resistivity of the LDPE(MWCNTs) nanofiber mats containing 9 wt% MWCNTs can be reduced to 100 Ω cm.

Graphical abstract

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Size control of aromatic polyamide hollow spheres prepared by reaction-induced phase separation

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Hirofumi Nakayama, Naoto Adachi, Hironori Atarashi, Tetsuya Uchida, Shinichi Yamazaki, Kunio Kimura
Size control of the poly (1,4-phenylene-5-hydroxyisophthalamide) hollow spheres was examined by tuning the polymerization condition, focusing on concentration, temperature and solvent. Higher concentration lowered the diameter owing to the higher degree of super-saturation for nucleation. Temperature drop during the polymerization just before the nucleation was so effective to make the diameter smaller. Moreover, the diameter was susceptive to the solubility of oligomers in the solvent, and higher content of liquid paraffin in the aromatic solvent lowered the solubility, resulting in the decrease in the diameter. Based on these results, the combination of the temperature drop and the solvent effect was the most desirable to prepare the smallest hollow spheres, and the diameter of hollow spheres could be controlled from 4.4 to 0.7 μm.

Graphical abstract

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Modeling the formation of layered, amphiphilic gels

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Santidan Biswas, Awaneesh Singh, Antoine Beziau, Tomasz Kowalewski, Krzysztof Matyjaszewski, Anna C. Balazs
The efficient formulation of layered gels that encompass both hydrophilic and hydrophobic domains could lead to novel materials with a range of vital functionalities. To facilitate the fabrication of these materials, we perform dissipative particle dynamics (DPD) simulations to model the formation of two-layered stackable gels where the gels are incompatible and their respective solvents are immiscible. The bottom layer of the gel is created first and then a solution of new initiators, monomers and cross-linkers is introduced on top of this first layer. These components then undergo living copolymerization to form the second gel layer. We investigate all possible combinations using free radical polymerization (FRP) and controlled/living atom transfer radical polymerization (ATRP) to form the two-layered material. When the lower gel is formed via ATRP, the system forms connected, stacked gel layers. If, however, the lower gel is formed via FRP, the gels do not form interconnected layers. The presence of active radical chain ends in the lower gel grown by ATRP enables the formation of covalent bonds with the upper gel layer. On the other hand, the lack of active radicals in the lower FRP gel leads to a sharp interfacial region, with negligible inter-gel bonds connecting the two layers. Our simulations provide insight into the nanoscale nature of the interface between the gel layers and yield guidelines for forming mechanically robust, "stackable" amphiphilic gels.

Graphical abstract

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Microspheres of polyurethanes functionalized with push-pull type azo chromophores and their photoinduced deformation behavior

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Yuqi Zhou, Bingyang Liu, Xiaogong Wang
A series of azo polyurethanes bearing push-pull type azo chromophores was synthesized by post-polymerization azo-coupling reactions between a polyurethane precursor and diazonium salts of different aniline derivatives, respectively. Colloidal spheres with narrow size distributions were obtained by aggregation of these azo polyurethanes in DMF-H2O mixed solvents, which were induced by slowly increasing the water content. The self-assembling processes and formed structures were investigated by laser light scattering and transmission electron microscopy. When irradiated with linearly polarized light from Ar⁺ laser (488 nm) and diode solid state laser (532 nm), the azo polyurethane microspheres showed significant deformations elongated in the light polarization direction. The electron-withdrawing groups on the azo chromophores show a significant effect on the photoinduced deformation degree. These microspheres composed of the azo polyurethanes bearing carboxylic acid and trifluoromethyl groups as the electron-withdrawing substituents shows the largest deformation degrees when irradiated with 488 and 532 nm light, respectively.

Graphical abstract

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Investigation of the biocompatibility and cytotoxicity associated with ROP initiator and its role in bulk polymerization of l-lactide

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Sharad P. Parwe, Shrikant D. Warkad, Manoj V. Mane, Pranita S. Shedage, Baijayantimala Garnaik
Poly (l-lactide) (PLLA) is one of the most attractive polymers for use in biomedical applications. In such applications it is necessary to reduce the use of toxic chemicals and catalysts used in PLLA synthesis, to minimize any adverse effects. In view of this, we have performed ring opening polymerization (ROP) of l-lactide (LA) using biocompatible initiator, namely, Zinc l-Proline (ZnP) in bulk. High molecular weight PLLA (Mw up to 1.45 × 10⁵ Da) was obtained using the ZnP complex. The ZnP complex is safe, easy to prepare, store and handle. ¹H and ¹³C NMR spectra of PLLA were used to determine the extent of monomer conversion and stereo sequence respectively. Differential Scanning Calorimetry (DSC) and Size Exclusion Chromatography (SEC) were used to determine thermal properties, Mn, Mw and polydispersity index respectively. The mechanism of ROP of LA in the presence of ZnP was studied using Density Functional Theory (DFT) which was in good agreement with results from ¹H NMR and Matrix-Assisted Laser Desorption/Ionization Spectrometry (MALDI-TOF). Biocompatibility/non toxicity of PLLA prepared using ZnP was studied in-vitro using MTT assay by examining the proliferation rate of mouse myoblast C2C12 cell line. Escherichia coli and Staphylococcus aureus were used for the study of antibacterial activity of PLLA.

Graphical abstract

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Preparation and properties of positively charged mesoglobules based on poly(2-isopropyl-2-oxazoline) and evaluation of their potential as carriers of polynucleotides

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Natalia Toncheva-Moncheva, Emilia Veleva-Kostadinova, Christo Tsvetanov, Denitsa Momekova, Stanislav Rangelov
A series of random copolymers of 2-isopropyl-2-oxazoline and ethylenimine (PiPOX-ran-PEI) with PEI contents 5–84% were prepared by partial acidic hydrolysis of poly(2-isopropyl-2-oxazoline) (PiPOX). Dynamic and electrophoretic light scattering were utilized to investigate aqueous solution properties of the copolymers. Above the phase transition temperature of PiPOX, well-defined nanoparticles (mesoglobules) typically ranging in size 200–500 nm, depending on the heating protocol, and surface potential reaching +35 mV, were formed. The mesoglobules consisted of a core dominated by PiPOX and a thin positively charged shell from PEI moieties which mediated formation of polyplexes with DNA. Upon complexation with DNA, performed at 65 °C and at varying N/P (amine-to-phosphate groups) ratios, well-defined polyplex particles with dimensions ranging between 110 and 250 nm and typically negative ζ potential were formed. Cooling down to the physiologically relevant temperature of 37 °C resulted in a slight-to-moderate increase of the size due to swelling of the polyplex particles and reduction of the negative ζ potential. The copolymers with PEI contents ≥15% can be considered perspective for delivery of polynucleotides.

Graphical abstract

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Facile preparation of hydrogen-bonded supramolecular polyvinyl alcohol-glycerol gels with excellent thermoplasticity and mechanical properties

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Shengjie Shi, Xin Peng, Tianqi Liu, Ya-Nan Chen, Changcheng He, Huiliang Wang
Facile preparation of tough hydrogels with excellent processability is of great practical importance, but it remains a great challenge. A novel type of hydrogen-bonded supramolecular PVA-glycerol gels is prepared with a very simple physical mixing method, in which glycerol molecules connect PVA chains into bundles by forming many H-bonds. The PVA-glycerol gels show much higher transparency than common PVA gels, due to their lower crystallinities and nanosized microstructures. The physical crosslinking nature and easy gelation at room temperature endow the gels with excellent moldability and thermoplasticity. The easy breaking of the H-bonding provides an effective energy-dissipating mechanism, leading to the high tensile strengths (up to more than 2 MPa), moduli, toughness and fracture energies of the gels. The PVA-glycerol gels also exhibit weaker temperature-dependent mechanical behaviors and excellent cold-resistance. The easy preparation and excellent properties of these gels should facilitate the practical applications of tough gels in many fields.

Graphical abstract

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Rheological behavior of polyacrylonitrile and polyacrylonitrile/lignin blends

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): H. Clive Liu, Chia-Chi Tuan, Amir A. Bakhtiary Davijani, Po-Hsiang Wang, Huibin Chang, Ching-Ping Wong, Satish Kumar
Dynamic shear rheology study is conducted on the polyacrylonitirile (PAN) solution and composite solutions of PAN with up to 37.5 wt% annual plant lignin (APL) to address current barriers of PAN/lignin blend development as carbon fiber precursor. PAN/APL blends exhibit lower yield stresses, lower relaxation times, and lower viscosities than to PAN solution according to the dynamic frequency sweep measurements from −7 °C to 56 °C. Yet an increase of solution activation energy of flow is observed with the increasing lignin content in solution. This is attributed to the potential interactions of PAN and lignin. Solution loss tangents obtained from dynamic frequency sweeps between −7 °C and 56 °C at an oscillatory frequency of 100 rad/s is used to envision the effect of lignin on solution structure during fiber processing.

Graphical abstract

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An abnormal melting behavior of isotactic polypropylene spherulites grown at low temperatures

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Zhenzhen Zhou, Le Ma, Weiwei Zhen, Xiaoli Sun, Zhongjie Ren, Huihui Li, Shouke Yan
In this work, an abnormal melting behavior of isotactic polypropylene (iPP) was investigated by polarized optical microscopy (POM), temperature-modulated differential scanning calorimetry (TMDSC), scanning electron microscopy (SEM), wide-angle X-ray diffraction (WAXD) and small-angle X-ray scattering (SAXS). It can be found by POM that the melting of α-iPP spherulites isothermally crystallized at 135 °C could occur prior to that of α-iPP spherulites crystallized at 125 °C when heated by 2 °C min⁻¹, but the case is opposite if the heating rates are 10, 20 or 50 °C min⁻¹. Meanwhile, the occurrence of lamellar thickening could be revealed by in-situ synchrotron SAXS, it can be revealed that the initial lamellar thickness of α-iPP spherulites grown at 135 °C is over that of spherulites grown at 125 °C, whereas the latter exceeds the former by means of lamellar thickening after heating. After a series of experiments, the lamellar thickening mechanism could be described as the following, i.e., the tangential lamellae in the spherulite melt and recrystallize on the radial lamellae during heating process, yielding much thicker radial lamellae with higher perfection.

Graphical abstract

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Dynamic, ultra-pH-sensitive graft copolymer micelles mediated rapid, complete destruction of 3-D tumor spheroids in vitro

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Guoqing Yan, Qian Zha, Jun Wang, Xin Wang, Xu Cheng, Weijing Yao, Rupei Tang
PEGylated poly(ortho ester amides) copolymer micelles (POEAd-g-MPEG micelles) with ultra-pH-sensitivity, which exhibited a dynamic change in size under mildly acidic conditions, were constructed by facile method, therefore achieving: (i) remaining stealthy and long-circulating in the blood; (ii) small NPs once in the tumor extracellular space for enhancing penetration; (iii) bigger NPs after penetration into the core of tumor for improving retention; (iv) rapid and complete dissolution to release drug at intracellular pH for improving toxicity to tumor cells upon being internalized by tumor cells. The enhanced tumor penetration and inhibition are closely related to these dynamic characteristics, resulting in unprecedentedly rapid, complete destruction of 3-D tumor spheroids in vitro.

Graphical abstract

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Impact of carbon nanotube prelocalization on the ultra-low electrical percolation threshold and on the mechanical behavior of sintered UHMWPE-based nanocomposites

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Tiana Deplancke, Olivier Lame, Sophie Barrau, Kesavan Ravi, Florent Dalmas
Nascent powder particles of Ultra High Molecular Weight Polyethylene have been covered by multi-walled carbon nanotubes and then processed by means of sintering. The prelocalization of carbon nanotubes in the interfacial region between powder particles of UHMWPE allowed reaching an electrical percolation threshold as low as 0.04 wt%. It is also a possible way to reinforce specifically the interfacial regions with a very small amount of fillers. Indeed, the nucleation effect of the nanotubes is very strong on the strain-induced crystallization in the melting state of the composite. The tensile experiments above the melting point allowed by the extremely broad rubbery plateau of the UHMWPE show a significant increase in strain-hardening due to the addition of CNTs from 0.02 wt%. In the solid state the elastic properties, such as yield stress, and the crystallinity can also be increased for higher CNT concentrations despite the presence of aggregates which reduce the elongation at break.

Graphical abstract

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A Characterization of Cancer Patients in Inpatient Rehabilitation Facilities: A Retrospective Cohort Study

Publication date: Available online 1 February 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Jacqueline M. Mix, Carl V. Granger, Michael J. LaMonte, Paulette Niewczyk, Margaret DiVita, Richard Goldstein, Jerome Yates, Jo L. Freudenheim
ObjectiveTo identify the types of cancer patients admitted to inpatient medical rehabilitation and to describe their rehabilitation outcomes.DesignRetrospective cohort study;SettingU.S. inpatient rehabilitation facilities (IRFs)ParticipantsAdult patients diagnosed with malignant cancer for a cancer related impairment admitted to an IRF between October 2010 and September 2012 were identified from the Uniform Data System for Medical Rehabilitation (UDSMR) database (n = 27,952).InterventionsnoneMain Outcome Measure(s)Demographic, medical and rehabilitation characteristics for patients with various cancer tumor types were summarized using data collected from the Inpatient Rehabilitation Patient Assessment Instrument (IRF-PAI). Rehabilitation outcomes included the percentage of patients discharged to community and acute care settings and functional change from admission to discharge. Functional status was measured using the FIM® instrument.ResultsCancer patients constituted about 2.4% of the total IRF patient population. Cancer types included brain and nervous system (52.9%), digestive (12.0%), bone and joint (8.7%), blood and lymphatic (7.6%), respiratory (7.1%) and other (11.7%). Overall, 72% were discharged to a community setting and 16.5% were discharged back to acute care. Patients with blood and lymphatic cancers had the highest frequency of discharge back to acute care (28%). On average, all cancer patient groups made significant functional gain during their IRF stay (FIM total change: 23.5 ± 16.2).ConclusionsIn a database representing approximately 70% of all US patients in IRFs, we found that a variety of cancer types are admitted to inpatient rehabilitation. The majority of cancer patients admitted to IRFs were discharged to a community setting and on average, improved their function. Future research is warranted to understand the referral patterns of admission to post-acute care rehabilitation and to identify factors that are associated with rehabilitation benefit in order to inform the establishment of appropriate care protocols.



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Letter from the Guest Editor: Pelvic MR Imaging

Publication date: Available online 31 January 2017
Source:Seminars in Ultrasound, CT and MRI
Author(s): Tarun Pandey




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Editorial Board

Publication date: January–February 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 1





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Tell me how pleased you are with your workplace, and I will tell you how often you wash your hands

Publication date: Available online 1 February 2017
Source:American Journal of Infection Control
Author(s): Liana Sholomovich, Racheli Magnezi
Hospital-acquired infections are the most common complication of treatment and the primary patient safety hazard. Hand hygiene (HH) is the most important tool for preventing these infections. Although thousands of research projects have been conducted, many articles written, and numerous therapeutic recommendations made, the goal has not yet been reached. The professional literature emphasizes that the reasons HH strategies fail are still only partially understood. The aim of this study was to examine the correlation between the psychological safety of an organization's nursing staff and its sense of personal responsibility for avoiding transmission of infections. Questionnaires were distributed to the 400 nurses in a children's hospital. Nurses' psychological safety and sense of responsibility for transmitting infections were positively correlated (r = 0.425; P < .001). In addition, 209 respondents (95.7%) believe that transmission of resistant infections between patients is preventable and 74% agree that transmission of infections is the responsibility of the care staff, but only 40% were willing to take personal responsibility in the department in which they were employed. There is a correlation between nurses' psychological safety and sense of responsibility for transmitting infections. To increase workers' sense of personal responsibility regarding infections as a way to increase the response to HH, hospital management must work toward increasing workers' psychological safety.



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Murine models of germinal center derived-lymphomas

Publication date: April 2017
Source:Current Opinion in Immunology, Volume 45
Author(s): Parham Ramezani-Rad, Robert C Rickert
The germinal center (GC) reaction is an adaptive immune response to select B cells bearing high-affinity B cell receptors (BCRs) to undergo further differentiation into antibody-producing cells or memory B cells. To drive affinity maturation, (GC) B cells undergo rounds of hypermutation and rapid proliferation, which can enhance susceptibility to malignant transformation. Lymphomas frequently originate from GC B cells, but the etiology for most lymphoma subtypes is unknown. Work in the past decade has more fully documented the mutational landscape in lymphomas, but the impact of these genomic lesions is often difficult to ascertain. In addition, while mutations affecting BCR signaling are well studied, the impact of extrinsic microenvironmental factors has not been widely addressed. Murine models are useful tools to study lymphomagenesis and disease progression, as well as potential treatment in a pre-clinical setting. Herein we discuss advances in murine models of lymphoma and how they inform on key characteristics of human lymphomas.

Graphical abstract

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Making Mouse Models That Reflect Human Immune Responses

Publication date: Available online 1 February 2017
Source:Trends in Immunology
Author(s): Lili Tao, Tiffany A. Reese
Humans are infected with a variety of acute and chronic pathogens over the course of their lives, and pathogen-driven selection has shaped the immune system of humans. The same is likely true for mice. However, laboratory mice we use for most biomedical studies are bred in ultra-hygienic environments, and are kept free of specific pathogens. We review recent studies that indicate that pathogen infections are important for the basal level of activation and the function of the immune system. Consideration of these environmental exposures of both humans and mice can potentially improve mouse models of human disease.



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Messages from the first International Conference on Clinical Metagenomics (ICCMg)

Publication date: Available online 1 February 2017
Source:Microbes and Infection
Author(s): Etienne Ruppé, Gilbert Greub, Jacques Schrenzel
Metagenomics is recently entering in the clinical microbiology and an increasing number of diagnostic laboratories are now proposing the sequencing & annotation of bacterial genomes and/or the analysis of clinical samples by direct or PCR-based metagenomics with short time to results. In this context, the first International Conference on Clinical Metagenomics (ICCMg) was held in Geneva in October 2016 and several key aspects have been discussed including: (i) the need for improved resolution, (ii) the importance of interpretation given the common occurrence of sequence contaminants, iii) the need for improved bioinformatic pipelines, iv) the bottleneck of DNA extraction, v) the importance of gold standards, vi) the need to further reduce time to results, vii) how to improve data sharing, viii) the applications of bacterial genomics and clinical metagenomics in better adapting therapeutics and ix) the impact of metagenomics and new sequencing technologies in discovering new microbes. Further efforts in term of reduced turnaround time, improved quality and lower costs are however warranted to fully translate metagenomics in clinical applications.



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Patient blood management and perioperative anaemia

<span class="paragraphSection"><div class="boxedTextSection">Key points<ul><li class="bullet">Perioperative anaemia and allogenic blood transfusion are independent risk factors for poor postoperative outcomes: morbidity and mortality.</li><li class="bullet">Approximately one-third of patients are found to be anaemic on pre-assessment.</li><li class="bullet">Patient Blood Management (PBM) is a clinical concept with the goal of avoiding unnecessary blood transfusions to improve patient outcomes and safety.</li><li class="bullet">PBM involves early detection and treatment of preoperative anaemia, minimization of perioperative blood loss and improving tolerance to anaemia in the postoperative setting.</li><li class="bullet">Iron deficiency can be absolute or functional and requires iron supplementation to improve body reserves and utilization.</li><li class="bullet">PBM is a multimodal, multidisciplinary strategy requiring surgical and medical speciality input.</li></ul></div>Perioperative anaemia is an independent risk factor for increased length of hospital and intensive care stay, postoperative complications, and increased mortality.<a href="#mkw061-B1" class="reflinks">¹</a> It is a strong predictor for perioperative blood transfusion requirements. In general, approximately one-third of patients are found to be anaemic at pre-assessment. Perioperative anaemia and allogenic blood transfusion are both, preventable surgical risks. Administration of blood in the perioperative setting is a risk factor which contributes to poor outcomes.<a href="#mkw061-B1" class="reflinks">¹</a> Patient Blood Management (PBM) is a clinical concept, which when implemented, has the primary goal of avoiding unnecessary blood transfusions and improving patient outcome and safety. This article summarizes PBM and the strategies involved in identifying and managing perioperative anaemia and blood transfusion.</span>

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Corrigendum

<span class="paragraphSection"><strong>Principles of total intravenous anaesthesia: practical aspects of using total intravenous anaesthesia <span style="font-style:italic;">BJA Education</span>, 2016, 16(8): <strong><a href="article.aspx?volume=&page=">276–280<span></span></a></strong>, DOI 10.1093/bjaed/mkv074</strong> </span>

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Hypothalamic–pituitary–adrenal function during health, major surgery, and critical illness

<span class="paragraphSection">1A011A022C012C04</span>

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Mitral valve and mitral valve disease

<span class="paragraphSection">1A012A033G00</span>

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Pain management programmes

<span class="paragraphSection">2E033E00</span>

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Disaster management in a low-resource setting: the role of anaesthetists in international emergency medical teams

<span class="paragraphSection">1I022A072A123A103I00</span>

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Anaesthesia for liver transplantation

<span class="paragraphSection">2A033A04</span>

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Optimal vitamin D supplementation strategies

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Measuring youth beliefs about the harms of e-cigarettes and smokeless tobacco compared to cigarettes

Publication date: July 2017
Source:Addictive Behaviors, Volume 70
Author(s): Alexander Persoskie, Erin Keely O'Brien, Anh B. Nguyen, Cindy Tworek
This study examined validity of direct and indirect measures of perceived harm of e-cigarettes and smokeless tobacco (SLT) compared to cigarettes. On direct measures, people compare one product to another, whereas on indirect measures, people rate each product separately and the researcher compares these ratings. Data from youth in Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study (2013–2014) were analyzed (N=13,651 youth aged 12–17years). The study included direct measures of perceived harm of e-cigarettes and SLT compared to cigarettes, and indirect measures were created by comparing ratings of the products. Weighted multinomial logistic regressions tested criterion validity by assessing whether direct and indirect measures were associated with criterion variables, including use of e-cigarettes and SLT. Youth were more likely to rate e-cigarettes as less harmful than cigarettes on the indirect measure (67.3%) than the direct measure (50.2%). The same pattern held for ratings of SLT as less harmful than cigarettes (indirect: 29.7%; direct: 11.7%). Direct measures explained unique variance in product use criterion variables even after adjusting for indirect measures, as did indirect measures after adjusting for direct measures. However, the criterion variables were more often associated with the direct measures than the indirect measures. Results offer preliminary support for using both direct and indirect measures when assessing youth's perceived relative harm of various types of products. However, if researchers cannot include both direct and indirect measures in a study, associations with product use criterion variables support prioritizing direct measures.



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Altered default mode, fronto-parietal and salience networks in adolescents with Internet addiction

Publication date: July 2017
Source:Addictive Behaviors, Volume 70
Author(s): Lubin Wang, Hui Shen, Yu Lei, Ling-Li Zeng, Fenglin Cao, Linyan Su, Zheng Yang, Shuqiao Yao, Dewen Hu
Internet addiction (IA) is a condition characterized by loss of control over Internet use, leading to a variety of negative psychosocial consequences. Recent neuroimaging studies have begun to identify IA-related changes in specific brain regions and connections. However, whether and how the interactions within and between the large-scale brain networks are disrupted in individuals with IA remain largely unexplored. Using group independent component analysis, we extracted five intrinsic connectivity networks (ICNs) from the resting-state fMRI data of 26 adolescents with IA and 43 controls, including the anterior and posterior default mode network (DMN), left and right fronto-parietal network (FPN), and salience network (SN). We then examined the possible group differences in the functional connectivity within each ICN and between the ICNs. We found that, compared with controls, IA subjects showed: (1) reduced inter-hemispheric functional connectivity of the right FPN, whereas increased intra-hemispheric functional connectivity of the left FPN; (2) reduced functional connectivity in the dorsal medial prefrontal cortex (mPFC) of the anterior DMN; (3) reduced functional connectivity between the SN and anterior DMN. Our findings suggest that IA is associated with imbalanced interactions among the DMN, FPN and SN, which may serve as system-level neural underpinnings for the uncontrollable Internet-using behaviors.



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The effect of pre-operative topical anaesthetic cream on the ablative width and coagulative depth of ablative fractional resurfacing laser

Abstract

Topical anaesthetic cream (TAC) is commonly used as a pre-treatment of ablative fractional resurfacing (AFR) laser. Most of anaesthetic cream contains distilled water as major component. Therefore, pre-operative TAC may interfere the photothermal reaction in the skin treated with fractional carbon-dioxide (FCO₂) laser and fractional erbium-doped yttrium aluminium garnet (FEr:YAG) laser. The objective of the study was to compare the ablative width (AW) and coagulative depth (CD) of AFR laser with and without pre-treatment with TAC. Four Thai females who underwent abdominoplasty were included in the study. The excised skin of each subject was divided into four areas. TAC (eutectic mixture of local anaesthesia; EMLA) with 1-h occlusion was applied only on the first and second areas. The first and third areas were treated with FCO₂ at 15 mj and 5% density. The second and fourth areas were treated with FEr:YAG at 28 J/cm² and 5% density. Six biopsied specimens were obtained from each area. A total of 96 specimens (24 specimens from each area) were collected from four patients and examined randomly by two dermatopathologists. The ablative width and coagulative depth from each specimen were determined. In FCO₂-treated specimens, the mean AW of the specimens that were pre-treated with TAC and control was 174.86 ± 24.57 and 188.52 ± 41.32 μm. The mean CD of the specimens that were pre-treated with TAC and control was 594.96 ± 111.72 and 520.03 ± 147.40 μm. There were no significant differences in AW and CD between both groups (p = 0.53 and p = 0.15). In FEr:YAG-treated specimens, the mean AW of the specimens that were pre-treated with TAC and control was 381.11 ± 48.02 and 423.65 ± 60.16 μm. The mean CD of the specimens that were pre-treated with TAC and control was 86.03 ± 29.44 and 71.59 ± 18.99 μm. There were no significant differences in AW and CD between both groups (p = 0.16 and p = 0.24). The pre-treatment with TAC provided no statistically difference from the control group on AW and CD of both FCO₂ and FEr:YAG laser irradiation. However, there was a tendency to have narrower AW and deeper CD of the areas that were pre-treated with TAC when comparing to that of the control.

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A review of the mechanism of action of lasers and photodynamic therapy for onychomycosis

Abstract

Onychomycosis is one of the most common diseases in the field of dermatology. It refers to the fungal infection of the nail plate or nail bed with high incidence in the general population. The available treatment options for onychomycosis have limited use due to side effects, drug interactions, and contraindications, which necessitates the application of an alternative treatment for onychomycosis. In the recent years, lasers and photodynamic therapy (PDT) have been recognized as alternative treatment options. Most of the previous studies have found them to be safe and effective treatment modalities in this indication; however, the results varied greatly and the in vitro and in vivo outcomes are contradictory. In the present review, studies related to the mechanism of action of lasers and PDT for the treatment of onychomycosis will be discussed, with a focus on to find explanation to the contradictory results.

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Application of reflectance confocal microscopy to evaluate skin damage after irradiation with an yttrium-scandium-gallium-garnet (YSGG) laser

Abstract

The objective of this study was to observe the characteristics of the skin after irradiation with a 2790-nm yttrium-scandium-gallium-garnet (YSGG) laser using reflectance confocal microscopy (RCM). A 2790-nm YSGG laser was used to irradiate fresh foreskin (four doses, at spot density 3) in vitro. The characteristics of microscopic ablative columns (MAC), thermal coagulation zone (TCZ), and microscopic treatment zones (MTZ) were observed immediately after irradiation using digital microscope and RCM. The characteristics of MAC, TCZ, and MTZ with variations in pulse energy were comparatively analyzed. After irradiation, MAC, TCZ, and MTZ characteristics and undamaged skin between MTZs can be observed by RCM. The depth and width of MTZ obviously increased with the increase in pulse energy. At 80, 120, and 160 mJ/microbeam (MB), the MTZ actual area and proportion were about two times that of the theoretical value and three times at 200 mJ/MB. With increases in depth, the single MAC gradually decreased in a fingertip-shaped model, with TCZ slowly increasing, and MTZ slightly decreasing in a columnar shape. RCM was able to determine the characteristics of thermal injury on the skin after the 2790-nm YSGG laser irradiation with different pulse energies. Pulse energy higher than 200 mJ/MB may have much larger thermal injury and side effect. RCM could be used in the clinic in future.

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Laser and LED phototherapy on midpalatal suture after rapid maxilla expansion: Raman and histological analysis

Abstract

The aim of this study was to analyze the effect of laser or LED phototherapy on the acceleration of bone formation at the midpalatal suture after rapid maxilla expansion. Forty-five rats were divided into groups at 7 days (control, expansion, expansion and laser irradiation, and expansion and LED irradiation) and into 14 days (expansion, expansion and laser in the 1st week, expansion and LED in the 1st week, expansion and laser in the 1st and 2nd weeks, expansion and LED in the 1st and 2nd weeks). Laser/LED irradiation occurred every 48 h. Expansion was accomplished with a spatula and maintained with a triple helicoid of 0.020-in stainless steel orthodontic wire. A diode laser (λ780 nm, 70 mW, spot of 0.04 cm², t = 257 s, SAEF of 18 J/cm²) or a LED (λ850 ± 10 nm, 150 ± 10 mW, spot of 0.5 cm², t = 120 s, SAEF of 18 J/cm²) was applied in one point in the midpalatal suture immediately behind the upper incisors. Raman spectroscopy and histological analyses of the suture region were carried and data was submitted to statistical analyses (p ≤ 0.05). Raman spectrum analysis demonstrated that irradiation increases hydroxyapatite in the midpalatal suture after expansion. In the histological analysis of various inflammation, there was a higher production of collagen and osteoblastic activity and less osteoclastic activity. The results showed that LED irradiation associated to rapid maxillary expansion improves bone repair and could be an alternative to the use of laser in accelerating bone formation in the midpalatal suture.

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Low-level laser therapy as an adjunct to conventional therapy in the treatment of diabetic foot ulcers

Abstract

Foot ulcers are serious complications of diabetes mellitus (DM) and are known to be resistant to conventional treatment. This study was conducted to evaluate the efficacy of low-level laser therapy (LLLT) for the treatment of diabetic foot ulcers in a tertiary care centre (Department of Surgery, Mahatma Gandhi Memorial Medical College and Maharaja Yashwantrao Hospital, A.B. Road, Indore). A total of 30 patients with type 2 DM having Meggitt-Wagner grade I foot ulcers of more than 6 weeks duration with negative culture were studied. Patients were randomized into two groups of 15 each. Patients in study group received LLLT (660 ± 20 nm, 3 J/cm²) along with conventional therapy and those in control group were treated with conventional therapy alone. The primary outcome measure was the absolute and relative wound size reduction at 2 weeks compared to the baseline parameter. Percentage ulcer area reduction was 37 ± 9% in the LLLT group and 15 ± 5.4% in the control group (p < 0.001). For ∼75% of wounds of the treatment group, wound area reduction of 30–50% was observed. In contrast, for the control group, ∼80% of wounds showed a wound area reduction of <20% on day 15. Further, the wounds with initial wound area 1000–2000 mm² seems to have better final outcome than the groups with larger areas. The treated groups showed higher amount of granulation than the control group. The results suggest that LLLT is beneficial as an adjunct to conventional therapy in the treatment of diabetic foot ulcers.

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Recent Coating Developments for Combination Devices in Orthopedic and Dental Applications: A Literature Review

Publication date: Available online 1 February 2017
Source:Advanced Drug Delivery Reviews
Author(s): Eric J. Tobin
Orthopedic and dental implants have been used successfully for decades to replace or repair missing or damaged bones, joints, and teeth, thereby restoring patient function subsequent to disease or injury. However, although device success rates are generally high, patient outcomes are sometimes compromised due to device-related problems such as insufficient integration, local tissue inflammation, and infection. Many different types of surface coatings have been developed to address these shortcomings, including those that incorporate therapeutic agents to provide localized delivery to the surgical site. While these coatings hold enormous potential for improving device function, the list of requirements that an ideal combination coating must fulfill is extensive, and no single coating system today simultaneously addresses all of the criteria. Some of the primary challenges related to current coatings are non-optimal release kinetics, which most often are too rapid, the potential for inducing antibiotic resistance in target organisms, high susceptibility to mechanical abrasion and delamination, toxicity, difficult and expensive regulatory approval pathways, and high manufacturing costs. This review provides a survey of the most recent developments in the field, i.e., those published in the last 2-3 years, with a particular focus on technologies that have potential for overcoming the most significant challenges facing therapeutically-loaded coatings. It is concluded that the ideal coating remains an unrealized target, but that advances in the field and emerging technologies are bringing it closer to reality. The significant amount of research currently being conducted in the field provides a level of optimism that many functional combination coatings will ultimately transition into clinical practice, significantly improving patient outcomes.

Graphical abstract

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A Novel Modified Tracheo-Esophageal Voice Prosthesis for Total Laryngectomy Patients

Conditions:   Laryngeal Cancer;   Hypopharynx Cancer
Intervention:   Device: Modified Trans-Esophageal Prosthesis
Sponsor:   HealthCare Global Enterprise Ltd.
Recruiting - verified January 2017

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Effect of a Combination of Local Steroid Injection With Oral Steroid Administration for the Prevention on Esophageal Stricture After Endoscopic Submucosal Dissection for Early Esophageal Neoplasm

Condition:   Esophageal Stricture
Interventions:   Drug: combination of local steroid injection（triamcinolone ）with oral steroid administration（prednisone）;   Drug: oral steroid administration（prednisone）
Sponsor:   Shanghai Zhongshan Hospital
Not yet recruiting - verified January 2017

http://ift.tt/2jE6lPE

A Trial of Intratumoral Injections of SD-101 in Combination With Pembrolizumab in Patients With Metastatic Melanoma or Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Conditions:   Metastatic Melanoma;   Head Neck Cancer
Interventions:   Drug: SD-101;   Biological: Pembrolizumab;   Drug: SD-101;   Biological: Pembrolizumab
Sponsors:   Dynavax Technologies Corporation;   Merck Sharp & Dohme Corp.
Recruiting - verified January 2017

http://ift.tt/2kWtMo7

Substantieller Vorteil durch CT-geplante HDR-Brachytherapie bei Zervixkarzinompatientinnen im Vergleich zu historischen Serien bezüglich lokaler Kontrolle und Toxizität?

http://ift.tt/2kR0oE1

Commentary on “Robotic Arch Catheter Placement Reduces Cerebral Embolisation During Thoracic Endovascular Aortic Repair (TEVAR)”

Publication date: Available online 1 February 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): H.H. Dosluoglu




http://ift.tt/2jWcFml

Re. “Contrast Enhanced Ultrasound Can Replace Computed Tomography Angiography for Surveillance After Endovascular Aortic Aneurysm Repair”

Publication date: Available online 31 January 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): K. Bashar, T. Jaipersad, J. Asquith, S. Rajagopalan




http://ift.tt/2jYJlhI

Nanotechnology in Drug Discovery and Development

Publication date: 2017
Source:Reference Module in Chemistry, Molecular Sciences and Chemical Engineering
Author(s): L. Gutiérrez, G. Stepien, L. Gutiérrez, M. Pérez-Hernández, J. Pardo, J. Pardo, V. Grazú, J.M. de la Fuente
Nanotechnology is a promising tool expected to have a strong impact in the health sector in the future years, especially related to the development of nanomaterials with new properties. In this work we have focused on the use of nanomaterials in the frame of drug development. These materials aim at overcoming present challenges from conventional medicine by modifying the properties of the final products in comparison with already existing drugs. We will provide a general overview of the different nanomaterials being studied in health treatments and a discussion on the current challenges that these compounds face in order to reach the clinical practice. Given the importance of the knowledge on the biodistribution and toxicity of new nanomaterials for their subsequent approval for regulatory agencies, the last two sections of this work focus on the methodology used to evaluate these parameters in new nanomaterials for health treatment.



http://ift.tt/2jYIf5w

Characteristics of Pelargonium radula as a mercury bioindicator for safety assessment of drinking water

Abstract

Identification of Pelargonium radula as bioindicator for mercury (Hg) detection confers a new hope for monitoring the safety of drinking water consumption. Hg, like other non-essential metals, inflicts the deterioration of biological functions in human and other creatures. In the present study, effects of Hg on the physiology and biochemical content of P. radula were undertaken to understand the occurrence of the morphological changes observed. Young leaves of P. radula were treated with different concentrations of Hg-containing solution (0.5, 1.0 and 2.0 ppb) along with controls for 4 h, prior to further analysis. Elevated Hg concentration in treatment solution significantly prompted an increased accumulation of Hg in the leaf tissues. Meanwhile, total protein, chlorophyll and low molecular mass thiol contents (cysteine, glutathione and oxidized glutathione) decreased as Hg accumulation increased. However, phytochelatin 2 productions were induced in the treated leaves, in comparison to the control. Based on these findings, it is postulated that as low as 0.5 ppb of Hg interferes with the metabolic processes of plant cells, which was reflected from the morphological changes exhibited on P. radula leaves—the colour of the Hg-treated leaves changed from green to yellowish-brown, became chlorosis and wilted. Changes in the tested characteristics of plant are closely related to the Hg-induced morphological changes on P. radula leaves, a potential bioindicator for detecting Hg in drinking water.

http://ift.tt/2kstmZE

Phytosterols as a natural anticancer agent: Current status and future perspective

Publication date: April 2017
Source:Biomedicine & Pharmacotherapy, Volume 88
Author(s): Naiyer Shahzad, Wajahatullah Khan, Shadab MD, Asgar Ali, Sundeep Singh Saluja, Sadhana Sharma, Faisal A. Al-Allaf, Zainularifeen Abduljaleel, Ibrahim Abdel Aziz Ibrahim, Ali Fathi Abdel-Wahab, Mohamed Abdelaziz Afify, Saeed Saeed Al-Ghamdi
Phytosterols are naturally occurring compounds in plants, structurally similar to cholesterol. The human diet is quite abundant in sitosterol and campesterol. Phytosterols are known to have various bioactive properties including reducing intestinal cholesterol absorption which alleviates blood LDL-cholesterol and cardiovascular problems. It is indicated that phytosterol rich diets may reduce cancer risk by 20%. Phytosterols may also affect host systems, enabling antitumor responses by improving immune response recognition of cancer, affecting the hormone dependent endocrine tumor growth, and by sterol biosynthesis modulation. Moreover, phytosterols have also exhibited properties that directly inhibit tumor growth, including reduced cell cycle progression, apoptosis induction, and tumor metastasis inhibition. The objective of this review is to summarize the current knowledge on occurrences, chemistry, pharmacokinetics and potential anticancer properties of phytosterols in vitro and in vivo. In conclusion, anticancer effects of phytosterols have strongly been suggested and support their dietary inclusion to prevent and treat cancers.



http://ift.tt/2jYlXk5

The vector-related influences of autophagic microRNA delivery by Lipofectamine 2000 and polyethylenimine 25K on mouse embryonic fibroblast cells

Publication date: 1 April 2017
Source:European Journal of Pharmaceutical Sciences, Volume 101
Author(s): Chia-Wei Lin, Ming-Shiou Jan, Jung-Hua Steven Kuo
Despite the greater potential for clinical applications of autophagic microRNA (miRNA) delivery, the vector-related effects of such delivery on cells have not been fully explored. In this study, autophagic mmu-miR-494-3p (miR-494) in mouse embryonic fibroblast (MEF) cells was selected as a cargo miRNA, and two commonly used non-viral carriers (Lipofectamine 2000 (Lipo) and polyethylenimine 25K (PEI)), were used as delivery vectors to mechanistically elucidate its vector-related effects. The cellular uptake, nuclear localization, and quantitative miR-494 levels of the complexes of miR-494 with Lipo (miR-494 lipoplexes) were lower than those of the complexes of miR-494 with PEI (miR-494 polyplexes) in MEF cells. The indicator of autophagic activity (LC3 (microtubule-associated protein 1 light chain 3)-II/LC3-I ratio) in cells treated with miR-494 lipoplexes was higher than that in cells treated with miR-494 polyplexes. Lipo alone and PEI alone induced slight increases in the quantitative levels of miR-494 in cells, but Lipo resulted in higher gene and protein expressions of target Igf1, higher LC3-II/LC3-I ratios, and higher autophagosome formation than PEI. We also demonstrated that the delivery of miR-494 by Lipo was more involved in apoptotic caspase-3 pathways than such delivery by PEI. By applying knock-out atg5 gene in MEF cells, we found that autophagy played a protective role in cell survival and also affected cellular uptake, the quantitative level of miR-494, and target gene Igf1 regulation of delivery systems. Taken together, these results indicate that there are different degrees of responses in MEF cells for autophagic miR-494 delivery through the use of Lipo or PEI vectors that also induce autophagy in cells. Therefore, Lipo and PEI vectors cannot be treated as inert molecules, and their effects must be known and evaluated when they are used in autophagic miRNA delivery systems. Most importantly, understanding these vector-related effects on cells will be helpful in achieving optimal delivery of autophagic miRNAs.

Graphical abstract

http://ift.tt/2jYdu0l

Preparation and characterisation of vandetanib-eluting radiopaque beads for locoregional treatment of hepatic malignancies

Publication date: 1 April 2017
Source:European Journal of Pharmaceutical Sciences, Volume 101
Author(s): Alice Hagan, Gary J. Phillips, Wendy M. Macfarlane, Andrew W. Lloyd, Peter Czuczman, Andrew L. Lewis
Since their introduction around a decade ago, embolic drug-eluting beads (DEBs) have become a well-established treatment option for the locoregional transarterial treatment of hepatic malignancies. Despite this success, the therapy is seen to be limited by the choice of drug and more effective options are therefore being sought. These include the small molecule multi-tyrosine kinase inhibitors (MTKi), which exert an anti-angiogenic and anti-proliferative effect that could be highly beneficial in combating some of the unwanted downstream consequences of embolization. Vandetanib is an MTKi which acts against such targets as vascular endothelial growth factor receptor (VEGFR) and epithelial growth factor receptor (EGFR) and has demonstrated modest activity against hepatocellular carcinoma (HCC), albeit with some dose-limiting cardiac toxicity. This makes this compound an interesting candidate for DEB-based locoregional delivery. In this study we describe the preparation and characterisation of vandetanib DEBs made from DC Bead™ and its radiopaque counterpart, DC Bead LUMI™. Drug loading was shown to be dependent upon the pH of the drug loading solution, as vandetanib has multiple sites for protonation, with the bead platform also having a fundamental influence due to differences in binding capacities and bead shrinkage effects. Fourier transform infrared (FTIR) spectroscopy and energy dispersive X-ray (EDX) Spectroscopy confirmed drug interaction is by ionic interaction, and in the case of the radiopaque DEB, the drug is distributed uniformly inside the bead and contributes slightly to the overall radiopacity by virtue of a bromine atom on the vandetanib structure. Drug release from both bead platforms is controlled and sustained, with a slightly slower rate of release from the radiopaque bead due to its more hydrophobic nature. Vandetanib DEBs therefore have suitable characteristics for intra-arterial delivery and site-specific sustained release of drug into liver tumours.

Graphical abstract

http://ift.tt/2jY4CYx

Combined CoMFA and CoMSIA 3D-QSAR study of benzimidazole and benzothiophene derivatives with selective affinity for the CB2 cannabinoid receptor

Publication date: 1 April 2017
Source:European Journal of Pharmaceutical Sciences, Volume 101
Author(s): Javier Romero-Parra, Hery Chung, Ricardo A. Tapia, Mario Faúndez, Cesar Morales-Verdejo, Marcos Lorca, Carlos F. Lagos, Vincenzo Di Marzo, C. David Pessoa-Mahana, Jaime Mella
The preceding years have brought an exponential increase in our understanding of the endocannabinoid system (ECS), including the knowledge of CB1 and CB2 cannabinoid receptors, endocannabinoids, and the enzymes that synthesize and degrade endocannabinoids. Among these ECS components CB2 receptors have been the subject of considerable attention, primarily due to their promising therapeutic potential to treat numerous pathologies while avoiding the adverse psychotropic effects that can accompany CB1 receptor–based therapies. Recently, our research group has reported a new series of non-cytotoxic benzo[d]imidazoles and benzo[b]thiophenes displaying high CB2/CB1 selectivity index. In order to investigate the structural requirements for CB2 ligands and to derive a predictive model that can be used for the design of novel selective CB2 ligands, a three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed on the above mentioned chemical series employing comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) techniques. The CoMFA and CoMSIA models displayed high external predictability (rpred² 0.919 and 0.908) and good statistical robustness. Valuable information regarding the steric, electrostatic and hydrophobic properties of the molecules was obtained, and several modifications around both heterocycles were evaluated with the aim to generate new promising series of benzo[d]imidazoles and benzo[b]thiophenes derivatives displaying high CB2 selectivity and low toxicity.

Graphical abstract

http://ift.tt/2jY7SmO

Stability of an ophthalmic micellar formulation of cyclosporine A in unopened multidose eyedroppers and in simulated use conditions

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): P. Chennell, L. Delaborde, M. Wasiak, M. Jouannet, E. Feschet-Chassot, F. Chiambaretta, V. Sautou
Cyclosporine A eye drops are used at concentrations ranging from 0.5 to 20mg/mL to treat a variety of ophthalmic diseases. Cyclosporine A formulations at high concentrations are difficult to manufacture because of cyclosporine's lipophilicity, and generally require an oil based vector. In this study, we investigated the physicochemical and microbiological stability of two high concentrations (10mg/mL and 20mg/mL) of an ophthalmic cyclosporine A micellar solution in a low density polyethylene multidose eyedropper, at two conservation conditions (5°C and 25°C), before and with simulated use. Analyses used were the following: visual inspection, cyclosporine quantification by a stability-indicating liquid chromatography method, osmolality and pH measurements and turbidity. A complementary analysis by dynamic light scattering was implemented to evaluate potential particle formation or micelle size change. In the in-use study, cyclosporine quantification was also performed on the drops emitted from the multidose eyedroppers. Our results show that the cyclosporine micellar formulation retains good physicochemical and microbiological stability, as all parameters stayed within acceptable range limits, however a higher variability in cyclosporine concentrations was observed for 20mg/mL units stored at 25°C. The in-use study showed that cyclosporine concentrations in the emitted drops were also within acceptable range limits. The micellar formulation presented in this study can therefore be stored at 5°C or at ≤25°C for up to 6months.

Graphical abstract

http://ift.tt/2jYdqxD

The release kinetics, antimicrobial activity and cytocompatibility of differently prepared collagen/hydroxyapatite/vancomycin layers: Microstructure vs. nanostructure

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): Tomáš Suchý, Monika Šupová, Eva Klapková, Václava Adamková, Jan Závora, Margit Žaloudková, Šárka Rýglová, Rastislav Ballay, František Denk, Marek Pokorný, Pavla Sauerová, Marie Hubálek Kalbáčová, Lukáš Horný, Jan Veselý, Tereza Voňavková, Richard Průša
The aim of this study was to develop an osteo-inductive resorbable layer allowing the controlled elution of antibiotics to be used as a bone/implant bioactive interface particularly in the case of prosthetic joint infections, or as a preventative procedure with respect to primary joint replacement at a potentially infected site. An evaluation was performed of the vancomycin release kinetics, antimicrobial efficiency and cytocompatibility of collagen/hydroxyapatite layers containing vancomycin prepared employing different hydroxyapatite concentrations. Collagen layers with various levels of porosity and structure were prepared using three different methods: by means of the lyophilisation and electrospinning of dispersions with 0, 5 and 15wt% of hydroxyapatite and 10wt% of vancomycin, and by means of the electrospinning of dispersions with 0, 5 and 15wt% of hydroxyapatite followed by impregnation with 10wt% of vancomycin.The maximum concentration of the released active form of vancomycin characterised by means of HPLC was achieved via the vancomycin impregnation of the electrospun layers, whereas the lowest concentration was determined for those layers electrospun directly from a collagen solution containing vancomycin. Agar diffusion testing revealed that the electrospun impregnated layers exhibited the highest level of activity. It was determined that modification using hydroxyapatite exerts no strong effect on vancomycin evolution. All the tested samples exhibited sufficient cytocompatibility with no indication of cytotoxic effects using human osteoblastic cells in direct contact with the layers or in 24-hour infusions thereof. The results herein suggest that nano-structured collagen-hydroxyapatite layers impregnated with vancomycin following cross-linking provide suitable candidates for use as local drug delivery carriers.

Graphical abstract

http://ift.tt/2jY8NUp

Hydrophobin-nanofibrillated cellulose stabilized emulsions for encapsulation and release of BCS class II drugs

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): Heli Paukkonen, Anni Ukkonen, Geza Szilvay, Marjo Yliperttula, Timo Laaksonen
The purpose of this study was to construct biopolymer-based oil-in-water emulsion formulations for encapsulation and release of poorly water soluble model compounds naproxen and ibuprofen. Class II hydrophobin protein HFBII from Trichoderma reesei was used as a surfactant to stabilize the oil/water interfaces of the emulsion droplets in the continuous aqueous phase. Nanofibrillated cellulose (NFC) was used as a viscosity modifier to further stabilize the emulsions and encapsulate protein coated oil droplets in NFC fiber network. The potential of both native and oxidized NFC were studied for this purpose. Various emulsion formulations were prepared and the abilities of different formulations to control the drug release rate of naproxen and ibuprofen, used as model compounds, were evaluated. The optimal formulation for sustained drug release consisted of 0.01% of drug, 0.1% HFBII, 0.15% oxidized NFC, 10% soybean oil and 90% water phase. By comparison, the use of native NFC in combination with HFBII resulted in an immediate drug release for both of the compounds. The results indicate that these NFC originated biopolymers are suitable for pharmaceutical emulsion formulations. The native and oxidized NFC grades can be used as emulsion stabilizers in sustained and immediate drug release applications. Furthermore, stabilization of the emulsions was achieved with low concentrations of both HFBII and NFC, which may be an advantage when compared to surfactant concentrations of conventional excipients traditionally used in pharmaceutical emulsion formulations.

Graphical abstract

http://ift.tt/2jY7QLI

Synthetic Analogs of Rhamnolipids Modulate Structured Biofilms Formed by Rhamnolipid-Nonproducing Mutant of Pseudomonas aeruginosa

Publication date: Available online 1 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Hewen Zheng, Nischal Singh, Gauri S. Shetye, Yucheng Jin, Diana Li, Yan-Yeung Luk
Rhamnolipids secreted by Pseudomonas aeruginosa are required for the bacteria to form biofilm efficiently and form biofilm with internal structures including pores and channels. In this work, we explore the effect of a class of synthetic analogs of rhamnolipids at controlling (promoting and inhibiting) the biofilm formation activities of a non-rhamnolipid-producing strain – rhlA – of P. aeruginosa. This class of rhamnolipid analogs is known to modulate the swarming motilities of wild-type PAO1 and rhlA mutant, but its effect on biofilm formation of rhlA mutant is unknown. We show that small structural details of these molecules are important for the bioactivities, but do not affect the general physical properties of the molecules. The bioactive synthetic analogs of rhamnolipids promote biofilm formation by rhlA mutant at low concentrations, but inhibit the biofilm formation at high concentrations. To explore the internal structures formed by the biofilms, we first demonstrate that wild-type biofilms are formed with substantial topography (hills and valleys) when the sample is under shaking conditions. Using this observation as a comparison, we found that synthetic analogs of rhamnolipids promoted structured (porous) biofilm of rhlA mutant, at intermediate concentrations between the low ones that promoted biofilm formation and the high ones that inhibited biofilm formation. This study suggests a potential chemical signaling approach to control multiple bacterial activities.

Graphical abstract

http://ift.tt/2kslpDK

Nodular fasciitis causing progressive limitation of knee flexion in a marathon runner: Imaging with ultrasound and magnetic resonance

Publication date: Available online 1 February 2017
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Chen-Yu Hung, Ke-Vin Chang, Levent Özçakar




http://ift.tt/2kRIxMY

Subthalamic nucleus Deep Brain Stimulation on motor-symptoms of Parkinson’s disease: focus on neurochemistry

Publication date: Available online 31 January 2017
Source:Progress in Neurobiology
Author(s): A. Stefani, V. Trendavilof, C. Liguori, E. Fedele, S. Galati
Deep brain stimulation (DBS) has become a standard therapy for Parkinson's disease (PD) and it is also currently under investigation for other neurological and psychiatric disorders. Although many scientific, clinical and ethical issues are still unresolved, DBS delivered into the subthalamic nucleus (STN) has improved the quality of life of several thousands of patients.The mechanisms underlying STN-DBS have been debated extensively in several reviews; less investigated are the biochemical consequences, which are still under scrutiny. Crucial and only partially understood, for instance, are the complex interplays occurring between STN-DBS and levodopa (LD)-centred therapy in the post-surgery follow-up.The main goal of this review is to address the question of whether an improved motor control, based on STN-DBS therapy, is also achieved through the additional modulation of other neurotransmitters, such as noradrenaline (NA) and serotonin (5-HT). A critical issue is to understand not only acute DBS-mediated effects, but also chronic changes, such as those involving cyclic nucleotides, capable of modulating circuit plasticity.The present article will discuss the neurochemical changes promoted by STN-DBS and will document the main results obtained in microdialysis studies. Furthermore, we will also examine the preliminary achievements of voltammetry applied to humans, and discuss new hypothetical investigational routes, taking into account novel players such as glia, or subcortical regions such as the pedunculopontine (PPN) area.Our further understanding of specific changes in brain chemistry promoted by STN-DBS would further disseminate its utilisation, at any stage of disease, avoiding an irreversible lesioning approach.



http://ift.tt/2kh19D3

Effects of targeted therapies on the bone in arthritides

Publication date: Available online 31 January 2017
Source:Autoimmunity Reviews
Author(s): Ágnes Szentpétery, Ágnes Horváth, Katalin Gulyás, Zsófia Pethö, Harjit Pal Bhattoa, Sándor Szántó, Gabriella Szücs, Oliver FitzGerald, Georg Schett, Zoltán Szekanecz
Inflammatory arthritides, such as rheumatoid arthritis (RA) and spondyloarthritides (SpA) have been associated with both localized bone resorption and/or formation, and generalized osteoporosis. Systemic inflammation may be the major driver for bone loss in arthritis. In RA and peripheral SpA the RANK-RANKL-OPG network is involved in bone resorption, while in axial SpA the Wnt-β-catenin axis and its inhibitors (DKK-1, sclerostin) are the most relevant. Targeted therapies including biologics and small molecule tyrosine kinase inhibitors may interfere with inflammatory bone metabolism. Most of these compounds are able to slow down radiographic progression and osteoporosis in arthritides. In very early cases of non-radiological SpA, there may be a window of opportunity allowing to prevent syndesmophyte formation. The inability of targeted therapies to increase the production of DKK-1 and sclerostin may explain the lack of efficacy of TNF inhibitors to halt syndesmophyte formation in SpA. Further clinical trials are needed to better understand the bone effects of targeted therapies.



http://ift.tt/2jw3RHL

Demyelinating syndrome in SLE encompasses different subtypes: Do we need new classification criteria? Pooled results from systematic literature review and monocentric cohort analysis

Publication date: Available online 31 January 2017
Source:Autoimmunity Reviews
Author(s): Matteo Piga, Elisabetta Chessa, Maria Teresa Peltz, Alberto Floris, Alessandro Mathieu, Alberto Cauli
ObjectiveTo describe features of demyelinating syndrome (DS) in systemic lupus erythematosus (SLE).MethodsA systematic review using a combination of Mesh terms in PubMed and a retrospective analysis of 343 adult patients with SLE were carried out to identify patients with DS. Retrieved cases were classified as affected with DS according to 1999 ACR nomenclature and attributed to SLE by applying the 2015 algorithm. DS defined according to the clinical but not temporal 1999 ACR criteria was classified as clinically isolated syndrome (CIS).ResultsEstimated prevalence of DS (including CIS) in the SLE cohort was 1.3% and incidence rate was 1.5 cases per 1000 patient-years. Overall, 100 cases from literature review and 4 from SLE cohort were identified and are presented as a whole: 49 (47.1%) were classified as neuromyelitis optica spectrum disorders (NMOSD), 29 (27.9%) as CIS, 14 (13.5%) as NMO, 7 (6.7%) as DS prominently involving the brainstem and 5 (4.8%) as DS prominently involving the brain. DS was the SLE onset manifestation in 41 (39.4%) patients. Longitudinally extensive transverse myelitis was the most frequent manifestations being present in 73 (70.2%) patients (37 NMOSD, 21 CIS, 14 NMO, 1 DSB). Methylprednisolone pulses (79.8%) and cyclophosphamide (55.8%), but also plasma-exchange (16.3%) and rituximab (7.6%) in relapsing-refractory cases, were mostly prescribed. Complete recovery rate ranged between 62% in CIS to 7% in NMO.ConclusionDS in SLE is rare (1%) and encompasses different subtypes including CIS. Timely diagnosis and early treatment are recommended to minimize complications.



http://ift.tt/2jwapGv

Balloon cell change in common blue nevus

http://ift.tt/2kS3sfR

Do the European Medicines Agency Decisions Hurt Pediatric Melanoma Patients?

Publication date: Available online 31 January 2017
Source:Clinical Therapeutics
Author(s): Klaus Rose, Philip D. Walson
PurposeUS pediatric legislation was introduced in 1997 and was followed by European Union pediatric legislation that, since 2007, requires a European Medicines Agency (EMA)–approved pediatric investigation plan (PIP) for registration of new medicines unless they are PIP exempted. In 2008, the EMA decided that enough adolescent patients with melanoma existed and removed melanoma from the list of PIP-exempted diseases (class waiver list). We examined the logic and the results of this decision.MethodsWe analyzed the EMA class waiver decision, the melanoma PIP decisions, the wording of the European Union pediatric legislation, and melanoma trials listed in http://ift.tt/PmpYKN and http://ift.tt/PmpZP1 that recruit adults and minors or only minors.FindingsThere are 12 melanoma PIP decisions. Two apparently PIP-triggered melanoma trials were terminated in 2016 because of slow recruitment, and 4 are ongoing. Numerous non–PIP-driven trials are recruiting both adults and minors with melanoma worldwide, thus competing with PIP-triggered melanoma trials.ImplicationsRevoking the melanoma class waiver was not based on science but on flawed logic. It resulted in PIP-demanded pediatric trials that do not make medical sense, fail to recruit adequately, and prevent participants from more promising off-label treatment or treatment in clinically, scientifically, and ethically superior non–PIP-triggered studies. Institutional review boards and ethics committees should consult both http://ift.tt/PmpYKN and http://ift.tt/PmpZP1 for competing trials in the same population and reject or withdraw approval for questionable trials. A major revision or replacement of the European Union pediatric legislation is needed to prevent children from being enrolled in unnecessary, unfeasible, or scientifically invalid trials.



http://ift.tt/2kRUoHH

A Review of the Theoretical and Biological Understanding of the Nocebo and Placebo Phenomena

Publication date: Available online 1 February 2017
Source:Clinical Therapeutics
Author(s): Seetal Dodd, Olivia M. Dean, João Vian, Michael Berk
PurposePlacebos are commonly used in experimental and patient populations and are known to influence treatment outcomes. The mechanism of action of placebos has been investigated by several researchers. This review investigates the current knowledge regarding the theoretical and biological underpinning of the nocebo and placebo phenomena.MethodLiterature was searched using PubMed using the following keywords: nocebo, placebo, μ-opioid, dopamine, conditioning, and expectancy. Relevant papers were selected for review by the authors.FindingsThe roles of conditioning and expectancy, and characteristics associated with nocebo and placebo responses, are discussed. These factors affect nocebo and placebo responses, although their effect sizes vary greatly, depending on inter-individual differences and different experimental paradigms. The neurobiology of the nocebo and placebo phenomena is also reviewed, emphasizing the involvement of reward pathways, such as the μ-opioid and dopamine pathways. Neurobiological pathways have been investigated in a limited range of experimental paradigms, with the greatest efforts on experimental models of placebo analgesia. The interconnectedness of psychological and physiological drivers of nocebo and placebo responses is a core feature of these phenomena.ImplicationsFurther research is needed to fully understand the underpinnings of the nocebo and placebo phenomena. Neurobiology pathways need to be investigated in experimental paradigms that model the placebo response to a broader range of pathologies. Similarly, although many psychological factors and inter-individual characteristics have been identified as significant mediators and moderators of nocebo and placebo responses, the factors identified to date are unlikely to be exhaustive.



http://ift.tt/2kS0esH