Anxiety Sensitivity and Sleep Disturbance: Investigating Associations among Patients with Co-occurring Anxiety and Substance Use Disorders

Publication date: Available online 7 November 2017
Source:Journal of Anxiety Disorders
Author(s): Laura J. Dixon, Aaron A. Lee, Kim L. Gratz, Matthew T. Tull
Sleep disturbance is a common problem among individuals with anxiety and substance use disorders (SUD). Anxiety sensitivity (AS) is elevated in patients with anxiety disorders and SUD and has been linked to sleep-related problems, including insomnia and somnolence (i.e., daytime sleepiness). We examined the unique roles of AS cognitive, physical, and social concerns in sleep disturbance among a sample of 99 residential SUD patients with anxiety disorders. Clinical levels of insomnia or somnolence were evidenced by 53.5% of the sample. Consistent with predictions, AS physical concerns was significantly associated with insomnia, and AS cognitive concerns was significantly related to insomnia and somnolence. Hierarchical linear regression models were conducted to test the association of AS cognitive and physical concerns with insomnia and somnolence symptoms while controlling for relevant factors. AS cognitive concerns accounted for unique variance, above and beyond withdrawal symptoms, anxiety, and depressive symptoms, in the model examining insomnia symptoms (B=0.30, SE=0.13, p=.023). Results suggest that AS cognitive concerns may represent an important transdiagnostic mechanism underlying sleep disturbance among individuals with dual diagnosis.



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Multifunctional pH sensitive 3D scaffolds for treatment and prevention of bone infection

Publication date: Available online 8 November 2017
Source:Acta Biomaterialia
Author(s): Mónica Cicuéndez, Juan C. Doadrio, Ana Hernández, M. Teresa Portolés, Isabel Izquierdo-Barba, María Vallet-Regí
Multifunctional-therapeutic three-dimensional (3D) scaffolds have been prepared. These biomaterials are able to destroy the S. aureus bacterial biofilm and to allow bone regeneration at the same time. The present study is focused on the design of pH sensitive 3D hierarchical meso-macroporous 3D scaffolds based on MGHA nanocomposite formed by a mesostructured glassy network with embedded hydroxyapatite nanoparticles, whose mesopores have been loaded with levofloxacin (Levo) as antibacterial agent. These 3D platforms exhibit controlled and pH-dependent Levo release, sustained over time at physiological pH (7.4) and notably increased at infection pH (6.7 and 5.5), which is due to the different interaction rate between diverse Levo species and the silica matrix. These 3D systems are able to inhibit the S. aureus growth and to destroy the bacterial biofilm without cytotoxic effects on human osteoblasts and allowing an adequate colonization and differentiation of preosteoblastic cells on their surface. These findings suggest promising applications of these hierarchical MGHA nanocomposite 3D scaffolds for the treatment and prevention of bone infection.Statement of significanceMultifunctional 3D nanocomposite scaffolds with the ability for loading and sustained delivery of an antimicrobial agent, to eliminate and prevent bone infection and at the same time to contribute to bone regeneration process without cytotoxic effects on the surrounding tissue has been proposed. These 3D scaffolds exhibit a sustained levofloxacin delivery at physiological pH (pH 7.4), which increasing notably when pH decreases to characteristic values of bone infection process (pH 6.7 and pH 5.5). In vitro competitive assays between preosteoblastic and bacteria onto the 3D scaffold surface demonstrated an adequate osteoblast colonization in entire scaffold surface together with the ability to eliminate bacteria contamination.

Graphical abstract

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Fatigue performance of additively manufactured meta-biomaterials: the effects of topology and material type

Publication date: Available online 8 November 2017
Source:Acta Biomaterialia
Author(s): S.M. Ahmadi, R. Hedayati, Y. Li, K. Lietaert, N. Tümer, A. Fatemi, C.D. Rans, B. Pouran, H. Weinans, A.A. Zadpoor
Additive manufacturing (AM) techniques enable fabrication of bone-mimicking meta-biomaterials with unprecedented combinations of topological, mechanical, and mass transport properties. The mechanical performance of AM meta-biomaterials is a direct function of their topological design. It is, however, not clear to what extent the material type is important in determining the fatigue behavior of such biomaterials. We therefore aimed to determine the isolated and modulated effects of topological design and material type on the fatigue response of metallic meta-biomaterials fabricated with selective laser melting. Towards that end, we designed and additively manufactured Co-Cr meta-biomaterials with three types of repeating unit cells and three to four porosities per type of repeating unit cell. The AM meta-biomaterials were then mechanically tested to obtain their normalized S-N curves. The obtained S-N curves of Co-Cr meta-biomaterials were compared to those of meta-biomaterials with same topological designs but made from other materials, i.e. Ti-6Al-4V, tantalum, and pure titanium, available from our previous studies. We found the material type to be far more important than the topological design in determining the normalized fatigue strength of our AM metallic meta-biomaterials. This is the opposite of what we have found for the quasi-static mechanical properties of the same meta-biomaterials. The effects of material type, manufacturing imperfections, and topological design were different in the high and low cycle fatigue regions. That is likely because the cyclic response of meta-biomaterials depends not only on the static and fatigue strengths of the bulk material but also on other factors that may include strut roughness, distribution of the micro-pores created inside the struts during the AM process, and plasticity.Statement of SignificanceMeta-biomaterials are a special class of metamaterials with unusual or unprecedented combinations of mechanical, physical (e.g. mass transport), and biological properties. Topologically complex and additively manufactured meta-biomaterials have been shown to improve bone regeneration and osseointegration. The mechanical properties of such biomaterials are directly related to their topological design and material type. However, previous studies of such biomaterials have largely neglected the effects of material type, instead focusing on topological design. We show here that neglecting the effects of material type is unjustified. We studied the isolated and combined effects of topological design and material type on the normalized S-N curves of metallic bone-mimicking biomaterials and found them to be more strongly dependent on the material type than topological design.

Graphical abstract

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Surface modifications and oxidative degradation in MPC-grafted highly cross-linked polyethylene liners retrieved from short-term total hip arthroplasty

Publication date: Available online 7 November 2017
Source:Acta Biomaterialia
Author(s): Shine Tone, Masahiro Hasegawa, Leonardo Puppulin, Giuseppe Pezzotti, Akihiro Sudo
Highly cross-linked polyethylene (HXLPE) hip liners grafted with 2-methacryloyloxyethyl phosphorylcholine (MPC) on their bearing surfaces have recently been commercialized as components of a new generation of artificial hip joints, while improvements in wear resistance and biocompatibility were reported based on in vitro studies. The present study aimed at evaluating the surface modification and oxidative degradation in short-term retrieved MPC-grafted liners by X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared spectroscopy (FT-IR) with attenuated total reflection (ATR) equipment and Raman spectroscopy. In none of 3 samples of retrieved MPC-grafted liners, detectable MPC graft remained on the bearing surfaces although 2 samples yet contained remains of MPC polymer in their rim zone. These results revealed that the MPC polymer might have quickly disappeared from the bearing surface under in vivo loading, which is more severe than the in vitro one. Furthermore, a detectable oxidation index (OI) value (>0.1) was not only observed in any zone of any sample investigated, but also in the rim zones of Samples 1 and 2, which surprisingly experienced the most remarkable increase in OI value detected in this study. We thus confirmed that: (i) annealing of HXLPE cannot completely remove free radicals; (ii) the MPC graft has no beneficial effect in protecting HXLPE against oxidation and wear; and, (iii) lipid absorption occurred even in the rim zone where the MPC layer remained. Based on these evidences we consider that the declaimed advanced MPC technology is not a suitable one to elongate the in vivo lifetime of hip joints.Statement of significanceSeveral studies reported that highly crosslinked polyethylene (HXLPE) have resulted in reduced wear in total hip arthroplasty. Beyond those studies, HXLPE hip liners grafted with 2-methacryloyloxyethyl phosphorylcholine (MPC) on their bearing surface were extensively studied in vitro and then commercialized as a new generation of artificial hip joints. The present study reports for the first time results about the evaluation of surface modification and oxidative degradation in retrieved the MPC grafted liners. The findings of this investigation clearly show that the MPC layer has been peeled off on the bearing surface of the liner main wear zone although the MPC layer remained on the surface of the rim zones. Furthermore, we assessed the microstructural modifications and the oxidation drifts that occurred in vivo in the hip joints despite the presence of the MPC layer.

Graphical abstract

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Lectin-Conjugated pH-Responsive Mesoporous Silica Nanoparticles for Targeted Bone Cancer Treatment

Publication date: Available online 7 November 2017
Source:Acta Biomaterialia
Author(s): Marina Martínez-Carmona, Daniel Lozano, Montserrat Colilla, María Vallet-Regí
A novel multifunctional nanodevice based in doxorubicin (DOX)-loaded mesoporous silica nanoparticles (MSNs) as nanoplatforms for the assembly of different building blocks has been developed for bone cancer treatment. These building blocks consists of: i) a polyacrylic acid (PAA) capping layer grafted to MSNs via an acid-cleavable acetal linker, to minimize premature cargo release and provide the nanosystem of pH-responsive drug delivery ability; and ii) a targeting ligand, the plant lectin concanavalin A (ConA), able to selectively recognize, bind and internalize owing to certain cell-surface glycans, such as sialic acids (SA), overexpressed in given tumor cells. This multifunctional nanosystem exhibits a noticeable higher internalization degree into human osteosarcoma cells (HOS), overexpressing SA, compared to healthy preosteoblast cells (MC3T3-E1). Moreover, the results indicate that small DOX loading (2.5 µg mL^-1) leads to almost 100% of osteosarcoma cell death in comparison with healthy bone cells, which significantly preserve their viability. Besides, this nanodevice has a cytotoxicity on tumor cells 8-fold higher than that caused by the free drug. These findings demonstrate that the synergistic combination of different building blocks into a unique nanoplatform increases antitumor effectiveness and decreases toxicity towards normal cells. This line of attack opens up new insights in targeted bone cancer therapy.Statement of SignificanceThe development of highly selective and efficient tumor-targeted smart drug delivery nanodevices remains a great challenge in nanomedicine. This work reports the design and optimization of a multifunctional nanosystem based on mesoporous silica nanoparticles (MSNs) featuring selectivity towards human osteosarcoma cells and pH-responsive antitumor drug delivery capability. The novelty and originality of this manuscript relies on proving that the synergistic assembly of different building blocks into a unique nanoplatform increases antitumor effectiveness and decreases toxicity towards healthy cells, which constitutes a new paradigm in targeted bone cancer therapy.

Graphical abstract

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Understanding the structural drivers governing glass – water interactions in borosilicate based model bioactive glasses

Publication date: Available online 7 November 2017
Source:Acta Biomaterialia
Author(s): Nicholas Stone-Weiss, Eric M. Pierce, Randall E. Youngman, Ozgur Gulbiten, Nicholas J. Smith, Jincheng Du, Ashutosh Goel
The past decade has witnessed a significant upsurge in the development of borate and borosilicate based resorbable bioactive glasses owing to their faster degradation rate in comparison to their silicate counterparts. However, due to our lack of understanding about the fundamental science governing the aqueous corrosion of these glasses, most of the borate/borosilicate based bioactive glasses reported in the literature have been designed by "trial–and–error" approach. With an ever-increasing demand for their application in treating a broad spectrum of non-skeletal health problems, it is becoming increasingly difficult to design advanced glass formulations using the same conventional approach. Therefore, a paradigm shift from the "trial–and–error" approach to "materials–by–design" approach is required to develop new-generations of bioactive glasses with controlled release of functional ions tailored for specific patients and disease states, whereby material functions and properties can be predicted from first principles. Realizing this goal, however, requires a thorough understanding of the complex sequence of reactions that control the dissolution kinetics of bioactive glasses and the structural drivers that govern them. While there is a considerable amount of literature published on chemical dissolution behavior and apatite-forming ability of potentially bioactive glasses, the majority of this literature has been produced on silicate glass chemistries using different experimental and measurement protocols. It follows that inter-comparison of different datasets reveals inconsistencies between experimental groups. There are also some major experimental challenges or choices that need to be carefully navigated to unearth the mechanisms governing the chemical degradation behavior and kinetics of boron-containing bioactive glasses, and to accurately determine the composition–structure–property relationships. In order to address these challenges, a simplified borosilicate based model melt-quenched bioactive glass system has been studied to depict the impact of thermal history on its molecular structure and dissolution behavior in water. It has been shown that the methodology of quenching of the glass melt impacts the dissolution rate of the studied glasses by 1.5× to 3× times depending on the changes induced in their molecular structure due to variation in thermal history. Further, a recommendation has been made to study dissolution behavior of bioactive glasses using surface area of the sample – to – volume of solution (SA/V) approach instead of the currently followed mass of sample – to – volume of solution approach. The structural and chemical dissolution data obtained from bioactive glasses following the approach presented in this paper can be used to develop the structural descriptors and potential energy functions over a broad range of bioactive glass compositions.Statement of SignificanceRealizing the goal of designing third generation bioactive glasses requires a thorough understanding of the complex sequence of reactions that control their rate of degradation (in physiological fluids) and the structural drivers that control them. In this article, we have highlighted some major experimental challenges and choices that need to be carefully navigated in order to unearth the mechanisms governing the chemical dissolution behavior of borosilicate based bioactive glasses. The proposed experimental approach allows us to gain a new level of conceptual understanding about the composition–structure–property relationships in these glass systems, and which can be applied to attain a significant leap in designing borosilicate based bioactive glasses with controlled dissolution rates tailored for specific patient and disease states.

Graphical abstract

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Mono vs multilayer Fibronectin coatings on polar/hydrophobic/ionic polyurethanes: Altering surface interactions with human monocytes

Publication date: Available online 8 November 2017
Source:Acta Biomaterialia
Author(s): Audrey Gossart, Kyle G. Battiston, Adeline Gand, Emmanuel Pauthe, J Paul Santerre
Monocyte interactions with materials that are biofunctionalized with fibronectin (Fn) are of interest because of the documented literature which associates this protein with white blood cell function at implant sites. A degradable-polar hydrophobic ionic polyurethane (D-PHI), has been reported to promote an anti-inflammatory response from human monocytes. The aim of the current work was to study the influence of intrinsic D-PHI material chemistry on Fn adsorption (mono and multi-layer structures), and to investigate the influence of such chemistry on the structural state of the Fn, as well as the latter's influence on the activity of human monocytes on the protein coated substrates. Significant differences in Fn adsorption, surface hydrophobicity and the availability of defined peptide sequences (N terminal, C terminal or Cell Binding Domain) for the Fn in mono vs multilayer structures were observed as a function of the changes in intrinsic material chemistry. A D-PHI-formulated polyurethane substrate with subtle changes in anionic and hydrophobic domain content relative to the polar non-ionic urethane/carbonate groups within the polymer matrix promoted the lowest activation of monocytes, in the presence of multi-layer Fn constructs. These results highlight the importance of chemical heterogeneity as a design parameter for biomaterial surfaces, and establishes a desired strategy for controlling human monocyte activity at the surface of devices, when these are coated with multi-layer Fn structures. The latter is an important step towards functionalizing the materials with multi-layer protein drug carriers as interventional therapeutic agents.Statement of SignificanceThe control of the behavior of monocytes, especially migration and activation, is of crucial interest to modulate the inflammatory response at the site of implanted biomaterial. Several studies report the influence of adsorbed serum proteins on the behavior of monocytes on biomaterials. However, few studies show the influence of surface chemical group distribution on the controlled adsorption and the subsequent induced conformation- of mono versus multi-layer assembled structures generated from specific proteins implicated in wound repair. The current research considered the role of Fn adsorption and conformation in thin films while interacting with the intrinsic chemistry of segmented block polyurethanes; and the influence of the former on modulation and activation of human monocytes.

Graphical abstract

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3-Dimensional inkjet printing of macro structures from silver nanoparticles

Publication date: 5 February 2018
Source:Materials & Design, Volume 139
Author(s): Jayasheelan Vaithilingam, Ehab Saleh, Lars Körner, Ricky D. Wildman, Richard J.M. Hague, Richard K. Leach, Christopher J. Tuck
The adoption of additive manufacturing technology is gaining interest for processing precious metals. In this study, the capability of inkjet printing was explored to fabricate macroscopic parts from commercial silver nanoparticle ink (AgNPs). A bespoke JETx® three dimensional (3D) inkjet printing machine was used to print and subsequently sinter up to 1000 layers of AgNPs using an infrared source. Examination of the sample using X-ray computed tomography and scanning electron microscopy revealed the existence of both micro- and nano-scale pores within the structure. Pinning effect, residual surface temperature, insufficient droplet overlap and surface defects were the key factors contributing to the voids. Elemental mapping confirmed the structure to be composed of 87% of silver along with carbon and oxygen. The 750dpi sample showed a 25% reduction in nanopores and 77% lower micro-pores compared to the 600dpi sample. In terms of hardness, the 750dpi sample was 29% harder than the 600dpi sample, showcasing samples with higher print resolution can contribute towards less voids and improved mechanical properties. Thus by demonstrating the possibility to fabricate dense parts from AgNPs using inkjet technology, this study opens a novel route for processing nano-scale particulates and precious metals in 3D.

Graphical abstract

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A highly-aligned lamellar structure of ice-templated LiFePO4 cathode for enhanced rate capability

Publication date: 5 February 2018
Source:Materials & Design, Volume 139
Author(s): Wook Ki Jung, Changyeon Baek, Joo-Hyung Kim, San Moon, Dong Seok Kim, Young Hwa Jung, Do Kyung Kim
Ice-templating has been widely investigated in various energy-related fields owing to the simple and inexpensive process of this method which results highly-ordered lamellar structures. Lamellar structures offer larger active areas for ionic conductivity and a short mean free path of electrons. Here, an ice-templated LiFePO4 cathode was introduced to achieve higher rate capability with a minimized carbon source. The fabricated highly-aligned porous structure demonstrates superior rate performance during the discharge process compared to electrodes which use conventional slurry casting. This enhanced performance is mainly attributed to the aligned porous structure, which facilitates the rapid transfer of electrons from the bulk to a current collector and also provides a good distribution of contact sites with Li ions in the electrolytes.

Graphical abstract

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The design of ultra-broadband selective near-perfect absorber based on photonic structures to achieve near-ideal daytime radiative cooling

Publication date: 5 February 2018
Source:Materials & Design, Volume 139
Author(s): Dong Wu, Chang Liu, Zenghui Xu, Yumin Liu, Zhongyuan Yu, Li Yu, Lei Chen, Ruifang Li, Rui Ma, Han Ye
Passive cooling, which cools without any electricity input, has had a great impact on global energy consumption. The recent progress on radiative cooling has many potential applications in efficient passive cooling. During the day, this strategy uses the maximized infrared emissivity via the atmospheric transparency windows for radiating heat and minimizing solar absorption. However, the realization of daytime radiative coolers with ideal selective mid-infrared emissivity is still a great challenge. Here, we firstly design and numerically demonstrate a near-ideal radiative cooler operating below the ambient temperature, achieving both broadband selective emissivity in the infrared atmospheric window and extremely low absorption in the entire solar spectrum, realizing a net cooling power exceeding 122W/m² at ambient temperature. The cooling effect can still persist under significant nonradiative heat exchange conditions. The design of multi-layer all-dielectric micropyramid structure in this work not only solves the shortcoming of poor mid-infrared selectivity in planar photonics device, but also overcomes the disadvantage of high solar absorption in metal/dielectric metamaterials. The comparisons of physics mechanism between this multi-layer all-dielectric structure and previously reported multi-layer metal/dielectric structure also are investigated clearly. Thus, this study can help pave the way for designing ideal daytime radiative coolers.

Graphical abstract

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Editorial Board

Publication date: 5 January 2018
Source:Materials & Design, Volume 137





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A Survey on Recent Medical School Graduate Comfort With the Level 1 Milestones

Publication date: Available online 7 November 2017
Source:Journal of Surgical Education
Author(s): Michael E. Petravick, J. Lawrence Marsh, Matthew D. Karam, Douglas R. Dirschl
ObjectiveThe Next Accreditation System implemented 5 levels of milestones for orthopedic surgery residents in 2013. The Level 1 milestones were noted as those "expected of an incoming resident." While the milestones were intended for assessing resident progression and readiness for independent practice, this designation can also be used to assess how well prepared graduating medical students are for beginning an orthopedic surgery residency. The primary objective of this paper is to measure recent medical school graduate comfort with the Level 1 milestones.Design, Setting, and ParticipantsIn June 2015, the program directors for the Midwest Orthopaedic Surgical Skills (MOSS) Consortium affiliated residency programs were sent an online survey for distribution to the recent medical school graduates who matched at their respective programs. The survey was about recent graduate comfort with the Level 1 milestone handles associated with 16 orthopedic milestones spanning multiple subspecialties. Responses were grouped based on comfort with individual milestone handles with orthopedic conditions (e.g., carpal tunnel) or with broader categories spanning orthopedic milestones (e.g., imaging).ResultsIn all, 66 of 112 graduates (58.9%) responded. Of 60 milestone handles surveyed, respondents were "Comfortable" with an average of 31.6 ± 14.2 handles with some conditions performing much better than others. The median "Comfortable" response rate was 31 handles. The 8 broader categories had "Comfortable" response rates between 35% and 70%. All 8 orthopedic conditions had significantly higher "Comfortable" response rates for "Evaluation & Knowledge" handles than for "Decision Making & Treatment" handles.ConclusionsMost recent medical student graduates who matched into an orthopedic surgery residencies are only comfortable with about half of the Level 1 milestone handles even though they are expected to meet the Level 1 milestones upon beginning residency. This finding suggests the development of an assessment based on the Level 1 milestones would be appropriate to better inform both graduate and undergraduate medical education in orthopedic surgery.



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Curriculum Using the In-Situ Operating Room Setting

Publication date: Available online 7 November 2017
Source:Journal of Surgical Education
Author(s): Raghavendra Rao, Robert C. Caskey, Lily Owei, Kathleen O'Connor, Elijah Riddle, Daniel T. Dempsey, Joshua Atkins, Dimitry Baranov, Gregory Motuk, Ari D. Brooks, Noel Williams, Jon Morris, Kristoffel Dumon
ObjectiveThe American College of Surgeons/Association of Program Directors in Surgery is a comprehensive, simulation-based curriculum for General Surgery residents which exists in 3 phases. While phases 1 and 2 deal with core skills and advanced procedures respectively, phase 3 targets team-based skills. To date, the 3rd phase of this curriculum has not seen wide scale implementation. This is a pilot study to verify the feasibility of implementing the phase 3 curriculum in the in-situ setting.DesignIn our initial attempt to implement Phase 3 at our institution, we chose to perform the training in an in-situ setting within an operating room (OR) at our main hospital, despite our having a separate simulation center. By choosing the in-situ OR environment for this training we were able to minimize concerns regarding resident and faculty availability and able to successfully complete 8 separate sessions during the academic year. During 7 sessions, 2 separate scenarios were performed while a single scenario was performed in 1 session. This single session was excluded from analysis, leaving a total of 14 scenarios to evaluate. The unique scenarios included laparoscopic crisis, postoperative myocardial infarction, anaphylaxis, and postoperative hypotension. All sessions were audiovisually recorded. In order to evaluate the effect of the training, the videos were viewed by 3 independent reviewers and all surgery, anesthesia and nursing participants were rated using the NOTECHs II scale. Degree of inter-rater agreement was established. The difference between the first and second simulations on the same day was then assessed. In addition, participant opinions of the simulations were assessed through electronic surveys following the training.SettingTertiary Care University Hospital.ParticipantsWe performed a total of 8 sessions, for a total of 15 scenarios. Eight surgery residents at the postgraduate year 1 (PGY1)-PGY3 level, 16 anesthesia residents at the PGY3-PGY4 level, 16 nurses and 13 ancillary staff participated.ResultsFrom the first to the second scenario, the total team NOTECHs II score increased from 69.4 ± 1.4 to 77.3 ± 0.5 (p = 0.007). The NOTECHs II scores for each subteam also improved, from 24.2 ± 0.6 to 26.4 ± 0.5 (p = 0.007) for surgery residents, 23.7 ± 0.9 to 26.7 ± 0.4 (p = 0.03) for anesthesia, and 21.6 ± 0.3 to 24.3 ± 0.5 (p = 0.01) for nursing. The inter-rater reliability as measured by Kendall's coefficient of concordance was modest for the whole team score. Most of the participant responses were either favorable or strongly favorable.ConclusionThe in-situ OR environment is both a unique and effective setting to perform team-based training. Furthermore, training in the in-situ setting minimizes or removes many of the logistic issues involved in designing and implementing team-based training curricula for general surgery residency programs. However, we found that administrative and departmental (surgery, anesthesia, and nursing) "buy in" as well as protected faculty time for education were all necessary for in-situ training to be successful. NOTECHs II is an established scale for the evaluation of teams in this simulation setting and appears to be a valid tool based on the results of this study. However, further assessment of inter-rater reliability as well as improved training of evaluators are necessary to determine if inter-rater reliability can improve.



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The Educational Opportunities Provided by a Pediatric Orthopedic Urgent Case Review Conference: Keep Score to Provide a Better Experience

Publication date: Available online 7 November 2017
Source:Journal of Surgical Education
Author(s): Eric D. Shirley, Radu Gheorghe, Kevin M. Neal, Gary Kiebzak, Steven L. Frick
ObjectiveTo evaluate the distribution of conditions presented at a case conference to assess resident educational exposure to acute pediatric orthopedic conditions.DesignRetrospective review of emergency department and inpatient consultations presented at a daily pediatric orthopedic case conference over a 3-year period. Consultations were divided into 3-month resident rotation blocks for analysis.SettingTertiary children's hospital in the southern United States which host residents from 2 orthopedic surgery residency programs.ParticipantsThe case conference is attended by pediatric orthopedic surgeons, 1 pediatric orthopedic fellow, and 4 PGY III/IV residents.ResultsA total of 1762 consultations were presented at the conference. The consultations were obtained for traumatic injuries, 86.5% (1524/1762); infections, 7.7% (136/1762); and congenital/other problems, 5.8% (102/1762). The 3 most common consultations per rotation were fractures: both-bone forearm (mean, 46.1; range: 24-64), supracondylar humerus (mean, 23.8; range: 17-31), and distal radius (mean, 13.8; range: 7-33). Less common consultations per rotation were septic arthritis (mean, 1.6; range: 0-5), child abuse (mean, 1.3; range: 0-5), Monteggia fracture (mean, 0.3; range: 0-1), compartment syndrome (mean, 0.2; range: 0-1) and patella sleeve fracture (mean, 0.1; range: 0-1).ConclusionsThere was a large disparity between conditions in the number of times presented and reviewed within a 3-month rotation at the daily case conference, with some important conditions not being discussed at all in each rotation. This finding documents a disadvantage of case conferences based on limiting discussion to current patients, and highlights an opportunity for educational improvement.



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Harnessing designed nanoparticles: Current strategies and future perspectives in cancer immunotherapy

Publication date: Available online 6 November 2017
Source:Nano Today
Author(s): Sung Duk Jo, Gi-Hoon Nam, Gijung Kwak, Yoosoo Yang, Ick Chan Kwon
Although cancer immunotherapy, represented by chimeric antigen receptor (CAR) T-cell therapy and immune checkpoint-blockade therapies, has shown durable outcomes, the percentage of patients that respond to these approaches remains modest to date. However, encouraging recent advances suggest that nanotechnology has the potential to enhance the efficacy of such immunotherapies by improving the delivery, biodistribution, and release-kinetics of immunostimulatory small molecules and biologics in targeted tissues. A variety of synthetic nanoparticles, including polymeric nanoparticles, liposomes and inorganic nanoparticles, can be engineered according to their intended uses in cancer immunotherapy. Notably, nature-derived nanoparticles have emerged as a new class of immunotherapeutics. In this review, we describe state-of-the-art strategies for cancer immunotherapy using designed nanoparticles. We also highlight key translational challenges and opportunities in this rapidly growing field.

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Graphene heterojunctions from the bottom up

Publication date: Available online 6 November 2017
Source:Nano Today





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Nano additive unlocks 3d printing of alloys

Publication date: Available online 7 November 2017
Source:Nano Today





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Recipe for a Successful Hybrid Academic-Community Radiology Practice

Publication date: Available online 7 November 2017
Source:Academic Radiology
Author(s): Kaela L. Gusenbauer, Michael N. Patlas, Ania Z. Kielar, Douglas S. Katz




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From bench to clinical trials the EORTC experience in biology-based clinical cancer research

Publication date: Available online 6 November 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Konstantinos Tryfonidis, Katherine Hartmann, Marie Morfouace, Denis Lacombe
For over 50years the European Organization for Research and Treatment of Cancer (EORTC) has delivered major advances in cancer clinical research and cancer therapeutics. The introduction of molecularly targeted agents has led to significant improvements in outcome for patients with specific tumor types; however conventional chemotherapy remains the mainstay of treatment for the majority of patients. Due to increasing knowledge about the diversity of molecular pathways driving malignant progression, strategies to integrate biology into clinical research and development are continuously evolving. The challenges and the experience of the EORTC regarding how translational research is to be an indispensable component of the clinical research environment, which aims to deliver more sophisticated treatment approaches will be discussed in this perspective article.



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Maspin expression and subcellular localization in invasive ductal carcinoma of the breast: Prognostic significance and relation to microvessel density

Publication date: Available online 7 November 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Duaa S. Helal, Dina M. El-Guindy
Maspin (Mammary serine protease inhibitor) is a tumor suppressor serine. Its clinical significance and role in breast carcinoma are contradictory and inconclusive. Researches demonstrated that the function of maspin differs according to its subcellular localization. This study was conducted to investigate the expression of maspin in invasive ductal carcinoma (IDC) of the breast with special emphasis on its subcellular localization and to evaluate its prognostic role in relation to clinicopathological parameters and microvessel density (MVD) of the tumor. The expression of maspin was evaluated immunohistochemically in 45 IDC cases. The positive rate of maspin expression was 73.3%. Maspin positivity was significantly related to higher tumor grade (p value = 0.041), nodal metastasis (p value = 0.044), perineural invasion (p value = 0.047), and high CD34+MVD (p value = 0.002). Nuclear maspin was detected in 36.6% whereas cytoplasmic maspin was detected in 63.4% of maspin positive cases. A significant inverse relationship was observed between nuclear maspin and high tumor grade (p value = 0.016), and nodal metastasis (p value = 0.047). These results suggest that maspin expression has a prognostic role in breast cancer. Maspin expression is related to increased angiogenesis. Subcellular localization of maspin can strongly affect cancer prognosis. Cytoplasmic maspin relates to poor prognostic parameters whereas nuclear maspin relates to good prognostic ones.



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Enhancement of CO2 reduction activity under visible light irradiation over Zn-based metal sulfides by combination with Ru-complex catalysts

Publication date: May 2018
Source:Applied Catalysis B: Environmental, Volume 224
Author(s): Tomiko M. Suzuki, Tomoaki Takayama, Shunsuke Sato, Akihide Iwase, Akihiko Kudo, Takeshi Morikawa
Hybrid photocatalysts composed of metal sulfide semiconductors combined with various Ru-complex catalysts were synthesized for use during visible light-driven CO2 reduction with powder suspension systems. A variety of Zn-based sulfides, including Ni-doped ZnS, (CuGa)0.8Zn0.4S2 and (AgIn)0.22Zn1.56S2, were adopted by conducting the CO2 reduction reaction in acetonitrile containing an electron donor. The photocatalytic activities were found to be largely dependent on the basic characteristics of the Ru-complex and the metal sulfide. The results demonstrate that several of these sulfide semiconductors improve the CO2 reduction selectivity when employed in the semiconductor/metal-complex system, and that (AgIn)0.22Zn1.56S2 or Ni (0.2mol%)-doped ZnS combined with a neutral Ru-complex incorporating a phosphonate ligand [Ru(4,4′-diphosphonate-2,2′-bipyridine)(CO)2Cl2] exhibit the highest CO2 photoconversion activity when synthesizing formic acid, with a turnover number above 100, which catalysts were stable for 16h irradiation. These results suggest that metal sulfides are potential candidates for use in powdered semiconductor/metal-complex systems for selective CO2 photoreduction.

Graphical abstract

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Photocatalytic CO2 conversion on highly ordered mesoporous materials: Comparisons of metal oxides and compound semiconductors

Publication date: May 2018
Source:Applied Catalysis B: Environmental, Volume 224
Author(s): Yoon Yun Lee, Han Sol Jung, Ji Man Kim, Yong Tae Kang
In this study, the ordered mesoporous metal oxides (TiO2 and SnO2) and compound semiconductors (ZnS, ZnSe, CdS, and CdSe) are manufactured and they exhibit several micrometers (μm) of particle size, and high surface area of about 100m²g⁻¹. Well-developed crystallinities are prepared via simple nano-replication method by using a 3-D bicontinuous cubic Ia3d meso-structured ordered mesoporous silica KIT-6 as a hard-template. The visible-light-driven photocatalytic CO2 conversion into CH4 is carried out in the presence of H2O over various mesoporous materials. Prepared mesoporous materials show different light absorption behaviors and photocatalytic activities for conversion of CO2. The mesoporous compound semiconductors show higher CO yield rates than the mesoporous metal oxides, while mesoporous metal oxides show higher CH4 yield rates than the mesoporous compound semiconductors. Compared to the commercial TiO2 material (P25, Degussa), the mesoporous metal oxides (TiO2, SnO2) show 9 to 10 times higher yields of CH4 and 2 to 3 times higher yields of CO owing to their high surface area. Especially, the mesoporous ZnS shows the highest CH4 yield rate (3.620μmolgcat⁻¹h⁻¹) and the mesoporous CdSe shows the highest CO yield rate (5.884μmolgcat⁻¹h⁻¹) out of all photocatalysts considered in the present study. Although mesoporous CdS and ZnSe have great visible light absorption properties, they show relatively low CH4 yield rates.

Graphical abstract

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Room temperature Zinc-metallation of cationic porphyrin at graphene surface and enhanced photoelectrocatalytic activity

Publication date: 15 March 2018
Source:Applied Surface Science, Volume 434
Author(s): Rongjin Zeng, Guoliang Chen, Chungang Xiong, Gengxian Li, Yinzhi Zheng, Jian Chen, Yunfei Long, Shu Chen
A stable zincporphyrin functionalized graphene nanocomposite was prepared by using positively charged cationic porphyrin (5,10,15,20-tetra(4-propyl pyridinio) porphyrin, TPPyP) and successive reduced graphene oxide (rGO) with tuned negative charge. The nanocomposite preparation was accompanied first by distinct electrostatic interactions and π-π stacking between TPPyP and rGO, and followed by fast Zinc-metallation at room temperature. In contrast to free TPPyP with Zn²⁺, the incorporation reaction is very slow at room temperature and heating or reflux conditions are required to increase the metallation rate. While at the surface of rGO nanosheet, the Zinc-metallation of TPPyP was greatly accelerated to 30min at 25°C in aqueous solution. The interaction process and composites formation were fully revealed by significant variations in UV–vis absorption spectra, X-ray photoelectron spectra (XPS) measurements, atomic force microscope (AFM) images, and fluorescence spectra. Furthermore, photoelectrochemical activity of resultant rGO/TPPyP-Zn nanocomposites was evaluated under visible-light irradiation, and enhancement of the photoelectrocatalytic reduction of CO2 was achieved.

Graphical abstract

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A comparative study on laser induced shock cleaning of radioactive contaminants in air and water

Publication date: 1 March 2018
Source:Optics & Laser Technology, Volume 100
Author(s): Aniruddha Kumar, Manisha Prasad, R.B. Bhatt, P.G. Behere, D.J. Biswas
Efficient removal of Uranium-di-oxide (UO2) particulates from stainless steel surface was effected by Nd-YAG laser induced plasma shock waves in air as well as in water environment. The propagation velocity of the generated shock wave was measured by employing the photo-acoustic probe deflection method. Monitoring of the alpha activity of the sample with a ZnS (Ag) scintillation detector before and after the laser exposure allowed the estimation of decontamination efficiency defined as the percentage removal of the initial activity. Experiments were carried out to study the effect of laser pulse energy, number of laser exposures, orientation of the sample, the separation between the substrate surface and the onset point of the shock wave on the de-contamination efficiency. The most optimised cleaning was found to occur when the laser beam impinged normally on the sample that was immersed in water and placed at a distance of ∼0.7 mm from the laser focal spot. Analysis of the cleaned surface by optical microscopes established that laser induced shock cleaning in no way altered the surface property. The shock force generated in both air and water has been estimated theoretically and has been found to exceed the Van der Waal's binding force for spherical contaminant particulate.



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Dependence of nonlinear optical properties of Ag2S@ZnS core-shells on Zinc precursor and capping agent

Publication date: 1 March 2018
Source:Optics & Laser Technology, Volume 100
Author(s): M. Dehghanipour, M. Khanzadeh, M. Karimipour, M. Molaei
In this research, four different types of Ag2S@ZnS core-shells were synthesized and their nonlinear optical (NLO) properties were investigated using a Z-scan technique by a 532 nm laser diode. Here, Ag2S and ZnS nanoparticles were also synthesized and their NLO properties were compared with Ag2S@ZnS core-shells. It was observed that the NLO properties of Ag2S@ZnS quantum dots significantly increased by increasing the values of Zn(NO3)2 and thioglycolic acid (TGA). It was also observed that the NLO properties of Ag2S@ZnS core-shells for 0.1 g of Zn(NO3)2 and 7000 μl TGA is higher than sole Ag2S and ZnS nanoparticles. In open aperture Z-scan curve of ZnS sample, a saturable absorption peak was observed and this peak was seen also in type of Ag2S@ZnS nanoparticles which the value of Zn(NO3)2 much more.



http://ift.tt/2jbo8D3

Visibility of mammographically occult breast cancer on diffusion-weighted MRI versus ultrasound

Publication date: May–June 2018
Source:Clinical Imaging, Volume 49
Author(s): Nita Amornsiripanitch, Habib Rahbar, Averi E. Kitsch, Diana L. Lam, Brett Weitzel, Savannah C. Partridge
PurposeTo investigate the visibility of mammographically occult breast cancers on diffusion-weighted MRI (DWI) versus ultrasound.Materials and methodsMammographically occult breast cancers (n=60) initially detected on contrast-enhanced MRI that underwent pre-biopsy targeted ultrasound were retrospectively evaluated for visibility on DWI and ultrasound.ResultsMore cancers were visible on DWI than ultrasound (78% vs. 63%; p=0.049), with 32 (53%) visible on both and 7 (12%) not visible on either. Visibility differences were more significant in larger lesions (92% vs. 68%, p=0.006).ConclusionDWI may detect more mammographically occult cancers than ultrasound, warranting further investigation as an alternative supplemental screening technique.



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3-O-Glyceryl-2-O-hexyl ascorbate suppresses melanogenesis by interfering with intracellular melanosome transport and suppressing tyrosinase protein synthesis

Summary

Background

Ascorbic acid (AsA) has multifunctional benefits on skin beauty, such as the reduction in oxidative stress and the induction of collagen production. Among them, the prevention and improvement of skin pigmentation by AsA is a most important benefit for people. However, it is well known that AsA not only is quite unstable in formulations but it also has a low capability of skin penetration due to its hydrophilic property. In addition, existing water-soluble AsA derivatives that were developed to improve its stability also have low skin penetration.

Aim

To investigate the potential of a newly synthesized amphiphilic derivative of AsA, 3-O-Glyceryl-2-O-hexyl ascorbate (VC-HG), which has an added glyceryl group and a hexyl group, on skin beauty focusing on its skin lightening/whitening effects.

Methods

DNA microarray analysis and real-time PCR were used to clarify the effects of VC-HG on melanogenesis using B16 mouse melanoma cells. The effects of VC-HG on melanin synthesis, tyrosinase protein levels, and the inhibition of tyrosinase activity were evaluated.

Results

DNA microarray analysis revealed that treatment with VC-HG downregulated the expression of genes encoding tyrosinase and MyosinVa. Further, real-time PCR analysis showed the downregulation of tyrosinase, MyosinVa, Rab27a, and Kinesin mRNAs following VC-HG treatment. In addition, VC-HG caused decreases in tyrosinase protein levels and melanin synthesis.

Conclusion

We conclude that VC-HG has an impact on skin lightening/whitening by inhibiting tyrosinase protein synthesis and interfering with intracellular melanosome transport.

http://ift.tt/2AqhQnc

A critical role for very long-chain fatty acid elongases in oleic acid-mediated Saccharomyces cerevisiae cytotoxicity

Publication date: Available online 6 November 2017
Source:Microbiological Research
Author(s): Qiao Wang, Xiuxiu Du, Ke Ma, Ping Shi, Wenbin Liu, Jing Sun, Min Peng, Zhiwei Huang
Elongases FEN1/ELO2 and SUR4/ELO3 are important enzymes involved in the elongation of long-chain fatty acids (LCFAs) to very long-chain fatty acids (VLCFAs) in Saccharomyces cerevisiae. The molecular mechanism of the involvement of these elongases in lipotoxicity is unclear. In the present study, we investigated the role of VLCFA elongases in oleic acid-mediated yeast cytotoxicity. The spot test showed that yeast strains with the deletion of ELO2 or ELO3 were strikingly sensitive to oleic acid, while there was no change on the growth of strain with deleted ELO1 which was involved in the elongation of C14 fatty acid (FA) to C16 FA. By using GC-MS, the unsaturation index was increased in elo2△ and elo3△ mutants after treatment with oleic acid (OLA). However, the proportion of VLCFAs was increased in response to OLA in the wild-type strain. The growth inhibition of elo2△ and elo3△ could be partially rescued by two commonly used antioxidant agents N-acetyl cysteine (NAC) and Ascorbic acid (VC). The further study showed that exposure to excess OLA led to an increase in the levels of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS), and a decline in the quantity of reduced glutathione (GSH) in both the wild type and mutant strains. However, the antioxidant enzyme activities of superoxide dismutase (SOD) and catalase (CAT) were increased in the wild type and elo1△ strains, while they were significantly decreased in the mutants of elo2△ and elo3△ after treated with excess OLA. Thus, oxidative damage mainly contributed to the cell death induced by OLA in ole2△ and ole3△. Taken together, although disruption of ELO2 or ELO3 did not affect the cellular lipid unsaturation, they altered the distribution and propotion of cellular VLCFAs, leading to the cell membrane impairment, which augmented the ability of OLA to permeabilize the plasma membrane. The data suggest that the very long-chain fatty acids elongases ELO2 and ELO3 play important roles in lipotoxic cell death induced by OLA through maintaining a balanced FA composition in plasma membrane.



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5-hydroxymethyl-2-furaldehyde from marine bacterium Bacillus subtilis inhibits biofilm and virulence of Candida albicans

Publication date: Available online 8 November 2017
Source:Microbiological Research
Author(s): Ganapathy Ashwinkumar Subramenium, Thirukannamangai Krishnan Swetha, Prasanth Mani Iyer, Krishnaswamy Balamurugan, Shunmugiah Karutha Pandian
Candida albicans is considered as the primary etiologic agent of candidiasis, a very common fungal infection in human. The yeast to hyphal transition and ability to form hypoxic biofilm on medical devices is well allied with virulence and antifungal resistance of C. albicans. Antagonistic agents that inhibit biofilm formation and alter susceptibility of C. albicans to conventional antifungals is of profound need. The present study explores the antibiofilm efficacy of Bacillus subtilis, a marine bacterial isolate from Palk Bay against C. albicans. Mass spectrometric analysis of ethyl acetate extract of B. subtilis unveiled 5-hydroxymethyl-2-furaldehyde (5HM2F) as one of its major components. 5HM2F demonstrated concentration dependent biofilm inhibition, which was also corroborated through microscopic analysis. Furthermore, 5HM2F was effective in inhibiting other virulence factors of C. albicans such as morphological transition and secreted hydrolases production. Fourier transform infrared spectroscopic analysis showed alteration in amide bond region. The reduction in ergosterol content and increased antifungal susceptibility was well allied with real time PCR result, which showed down regulation of genes involved in drug resistance mechanisms. In vivo study using Caenorhabditis elegans also substantiated the antivirulence efficacy of 5HM2F at in vivo condition. Thus, the present study reports the therapeutic potential of 5HM2F against C. albicans infections.

Graphical abstract

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Reactive oxygen species-independent apoptotic pathway by gold nanoparticles in Candida albicans

Publication date: Available online 6 November 2017
Source:Microbiological Research
Author(s): Minju Seong, Dong Gun Lee
Candida albicans is the most common pathogenic fungus in humans, causing cutaneous and life-threatening systemic infections. In this study, we confirmed using propidium iodide influx that gold nanoparticles (AuNPs), which are promising materials for use as antimicrobial agents, did not affect the membrane permeability of C. albicans. Thus, the fungal cell death mechanisms induced by AuNPs were assessed at intracellular levels including DNA damage, mitochondrial dysfunction, and reactive oxygen species (ROS) overproduction. AuNPs interacted with C. albicans DNA leading to increased nuclear condensation and DNA fragmentation. Changes in the mitochondria induced by AuNPs involving mass, Ca²⁺ concentrations, and membrane potential indicated dysfunction, though the level of intracellular and mitochondrial ROS were maintained. Although ROS signaling was not disrupted, DNA damage and mitochondrial dysfunction triggered the release of mitochondrial cytochrome c into the cytosol, metacaspase activation, and phosphatidylserine externalization. Additionally, the AuNPs-induced apoptotic pathway was not influenced by N-acetylcysteine, an ROS scavenger. This indicates that ROS signaling is not linked with the apoptosis. In conclusion, AuNPs induce ROS-independent apoptosis in C. albicans by causing DNA damage and mitochondria dysfunction.



http://ift.tt/2j9GHYa

Towards a defined ECM and small molecule based monolayer culture system for the expansion of mouse and human intestinal stem cells

Publication date: February 2018
Source:Biomaterials, Volume 154
Author(s): Zhixiang Tong, Keir Martyn, Andy Yang, Xiaolei Yin, Benjamin E. Mead, Nitin Joshi, Nicholas E. Sherman, Robert S. Langer, Jeffrey M. Karp
Current ISC culture systems face significant challenges such as animal-derived or undefined matrix compositions, batch-to-batch variability (e.g. Matrigel-based organoid culture), and complexity of assaying cell aggregates such as organoids which renders the research and clinical translation of ISCs challenging. Here, through screening for suitable ECM components, we report a defined, collagen based monolayer culture system that supports the growth of mouse and human intestinal epithelial cells (IECs) enriched for an Lgr5⁺ population comparable or higher to the levels found in a standard Matrigel-based organoid culture. The system, referred to as the Bolstering Lgr5 Transformational (BLT) Sandwich culture, comprises a collagen IV-coated porous substrate and a collagen I gel overlay which sandwich an IEC monolayer in between. The distinct collagen cues synergistically regulate IEC attachment, proliferation, and Lgr5 expression through maximizing the engagement of distinct cell surface adhesion receptors (i.e. integrin α2β1, integrin β4) and cell polarity. Further, we apply our BLT Sandwich system to identify that the addition of a bone morphogenetic protein (BMP) receptor inhibitor (LDN-193189) improves the expansion of Lgr5-GFP⁺ cells from mouse small intestinal crypts by nearly 2.5-fold. Notably, the BLT Sandwich culture is capable of expanding human-derived IECs with higher LGR5 mRNA levels than conventional Matrigel culture, providing superior expansion of human LGR5⁺ ISCs. Considering the key roles Lgr5⁺ ISCs play in intestinal epithelial homeostasis and regeneration, we envision that our BLT Sandwich culture system holds great potential for understanding and manipulating ISC biology in vitro (e.g. for modeling ISC-mediated gut diseases) or for expanding a large number of ISCs for clinical utility (e.g. for stem cell therapy).



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Guiding morphogenesis in cell-instructive microgels for therapeutic angiogenesis

Publication date: February 2018
Source:Biomaterials, Volume 154
Author(s): A.L. Torres, S.J. Bidarra, M.T. Pinto, P.C. Aguiar, E.A. Silva, C.C. Barrias
Efficient cell delivery strategies are urgently needed to improve the outcome of cell-based pro-angiogenic therapies. This study describes the design of an injectable cell delivery platform, based on biomaterial-guided morphogenesis principles. Soft high-mannuronic acid alginate microgels, oxidized and functionalized with integrin-binding peptides, provided adequate biochemical/biomechanical cues for the co-assembly of mesenchymal stem cells and outgrowth endothelial cells (OEC) into pre-vascularized microtissues. In vitro priming conditions regulated OEC tubulogenesis, which only occurred under normoxia (+O2) in the presence of angiogenic factors (+GF) and, importantly, did not revert in an ischemic-like environment. Primed (+O2+GF) microgel-entrapped cells secreted a large variety of angiogenesis-related proteins and produced endogenous extracellular-matrix, rich in fibronectin and collagen type I, fostering cell-cell/cell-matrix interactions and establishing a stable angiogenic niche. Extending the pre-culture time resulted in higher cell outward migration and in vivo angiogenic potential. Microgels partially disintegrated upon implantation in chick embryos, promoting interaction between pre-vascularized microtissues and the host. Preserved human vascular structures were still detected in vivo, and human cells showed the ability to migrate and integrate with the chick vasculature. Our results suggest that an integrated approach combining pro-angiogenic cells, cell-instructive microgels and adequate in vitro priming may provide the basis for successful therapeutic angiogenesis.

Graphical abstract

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Tumor targeted, stealthy and degradable bismuth nanoparticles for enhanced X-ray radiation therapy of breast cancer

Publication date: February 2018
Source:Biomaterials, Volume 154
Author(s): Junjie Deng, Shandong Xu, Weike Hu, Xiaojie Xun, Liyuan Zheng, Ming Su
Nanoparticles of heavy elements can be used as radiosensitizers to enhance X-ray radiation therapy, but a major roadblock in translating nanoparticle radiosensitizers into clinical practice of cancer treatment is related to the non-degradable nature of the nanoparticles, which can cause accumulation inside body and long-term toxicity. This paper reports the use of a folate-inserted, red blood cell membrane-modified bismuth (i.e., F-RBC bismuth) nanoparticles in X-ray radiation therapy for breast cancer, where cell membrane coating provides long blood circulation time, folate acts as tumor targeting agent, X-ray and bismuth nanoparticles interaction generates more free radicals for cancer cells damage, and physiological condition helps dissolve bismuth nanoparticles after treatment. Significant tumor inhibition and improved survival ratio in mice was confirmed when F-RBC bismuth nanoparticles were used to sensitize X-ray radiation. In vivo bio-distribution and histological analysis indicated F-RBC bismuth nanoparticles were excreted from animal body after 15 days and no evident damage or inflammatory was observed in major organs. Cell membrane modification and dissolution of bismuth nanoparticles in body allow the fine tune of the circulation, radiation enhancement and body clearance in such a way that treatment effect can be maximized and long term toxicity can be minimized.

Graphical abstract

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Development of PEGylated aspartic acid-modified liposome as a bone-targeting carrier for the delivery of paclitaxel and treatment of bone metastasis

Publication date: February 2018
Source:Biomaterials, Volume 154
Author(s): Shugo Yamashita, Hidemasa Katsumi, Nozomi Hibino, Yugo Isobe, Yumiko Yagi, Yuka Tanaka, Saki Yamada, Chihiro Naito, Akira Yamamoto
To prevent bone metastasis, we developed polyethylene glycol (PEG)-conjugated aspartic acid (Asp)-modified liposomes (PEG-Asp-Lipo) as a bone-targeting carrier of paclitaxel (PTX) by using Asp-modified 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE-Asp). The affinity of Asp-modified liposomes to hydroxyapatite increased as the concentration of DPPE-Asp increased. The bone accumulation of [³H]-labeled PEG(2)-Asp(33)-Lipo was approximately 24.6% 360 min after intravenous injection in mice, in contrast to 5.4% and 6.7% of [³H]-labeled normal Lipo and PEG(2)-Lipo, respectively. Similarly, [¹⁴C]-labeled PTX encapsulated into PEG(2)-Asp(33)-Lipo predominantly accumulated in the bone. Furthermore, using an in situ imaging experiment, we observed that near-infrared fluorescence-labeled PEG(2)-Asp(33)-Lipo selectively accumulated in the bone near the joint after intravenous injection in mice. We also found that FITC-labeled PEG(2)-Asp(33)-Lipo predominantly accumulated on eroded and quiescent bone surfaces. In a bone metastatic tumor mouse model, in which B16-BL6/Luc cells were injected into the left ventricle of female C57BL/6 mice, metastatic bone tumor growth was significantly inhibited by an intravenous injection of PEG(2)-Asp(33)-liposomal PTX. In contrast, PEGylated liposomal PTX hardly affected the growth of metastatic bone tumors. These findings indicate that PEG(2)-Asp(33)-Lipo is a promising bone-targeting carrier for the delivery of PTX and treatment of bone metastasis.

Graphical abstract

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An injectable, electrostatically interacting drug depot for the treatment of rheumatoid arthritis

Publication date: February 2018
Source:Biomaterials, Volume 154
Author(s): Ji Hoon Park, Seung Hun Park, Hye Yun Lee, Jin Woo Lee, Bo Keun Lee, Bun Yeoul Lee, Jae Ho Kim, Moon Suk Kim
To the best of our knowledge, no studies have yet examined the electrostatic interaction of polyelectrolytes with electrolyte drugs for the treatment of rheumatoid arthritis (RA). Here, an injectable, electrostatically interacting drug depot is described. We prepared methoxy polyethylene glycol-b-poly(ε-caprolactone)-ran-poly(l-lactic acid) (MC) diblock copolymers with a carboxylic acid group (MC-C) at the pendant position. MC-C was polyelectrolytes that exhibited negative zeta potentials. Sulfasalazine [Sul(−)] and minocycline [Min(+)], electrolyte RA drugs, exhibited negative and positive zeta potentials, respectively. The electrolyte RA drugs were loaded into the polyelectrolyte MC-C solution to prepare injectable, electrostatically interacting depot formulations. The formulation with an attractive electrostatic interaction [Min(+)-MC-C] exhibited gradual release of Min(+) from the MC-C depot over an extended period and suppressed the growth of inflammatory RAW 264.7 cells without affecting synovial cells. Mature chondrocytes were observed after H&E and safranin O staining of the cartilage of Min(+)-MC-C intra-articularly injected RA-induced rats. In comparison with other formulations, Min(+)-MC-C induced the suppression of the expression of pro-inflammatory proteins TNF-α and IL-1β in the articular knee joint, which resulted in the amelioration of RA. In conclusion, an injectable, electrostatically interacting depot formulation administered through intra-articular injection successfully provided almost complete amelioration of RA.



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Functional differences between healthy and diabetic endothelial cells on topographical cues

Publication date: January 2018
Source:Biomaterials, Volume 153
Author(s): Marie F.A. Cutiongco, Bryan M.X. Chua, Dawn J.H. Neo, Muhammad Rizwan, Evelyn K.F. Yim
The endothelial lining of blood vessels is severely affected in type II diabetes. Yet, there is still a paucity on the use of diabetic endothelial cells for study and assessment of implantable devices targeting vascular disease. This critically impairs our ability to determine appropriate topographical cues to be included in implantable devices that can be used to maintain or improve endothelial cell function in vivo. Here, the functional responses of healthy and diabetic human coronary arterial endothelial cells were studied and observed to differ depending on topography. Gratings (2 μm) maintained normal endothelial functions such as adhesiveness, angiogenic capacity and cell-cell junction formation, and reduced immunogenicity of healthy cells. However, a significant and consistent effect was not observed in diabetic cells. Instead, diabetic endothelial cells cultured on the perpendicularly aligned multi-scale hierarchical gratings (250 nm gratings on 2 μm gratings) drastically reduced the uptake of oxidized low-density lipoprotein, decreased immune activation, and accelerated cell migration. Concave microlens (1.8 μm diameter) topography was additionally observed to overwhelmingly deteriorate diabetic endothelial cell function. The results of this study support a new paradigm and approach in the design and testing of implantable devices and biomedical interventions for diabetic patients.

Graphical abstract

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Estimation of physiological sources of nonlinearity in blood oxygenation level-dependent contrast signals

Publication date: Available online 7 November 2017
Source:Magnetic Resonance Imaging
Author(s): Daehun Kang, Yul-Wan Sung, Satoshi Shioiri
Blood oxygenation level-dependent (BOLD) contrast appears through a variation in the transverse relaxation rate of magnetic resonance signals induced by neurovascular coupling and is known to have nonlinear characteristics along echo time (TE) due to the intra-vasculature. However, the physiological causes of this nonlinearity are unclear. We attempted to estimate the physiological information related to the nonlinearity of BOLD signals by using a two-compartment model. For this purpose, we used a multi-echo gradient-echo echo-planar imaging sequence and developed a computational method to estimate the physiological information from the TE-dependent BOLD signals. The results showed that the average chemical exchange time in the intra-vasculature varied during stimulation, which might be the essential source of the nonlinearity.



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A Novel Window Technique Using CO2 Laser, and a Review of Methods for Nail Matrix Biopsy of Longitudinal Melanonychia.

BACKGROUND: Nail matrix histopathological examination is essential to diagnose longitudinal melanonychia (LM). Several methods for nail matrix biopsy have been introduced but are often difficult to perform because of their invasiveness and technical difficulty. Therefore, a less invasive and novel biopsy technique is needed. OBJECTIVE: To introduce a window technique for nail matrix biopsy. MATERIALS AND METHODS: We retrospectively reviewed the medical records and histopathological specimens of patients with LM who underwent the window technique for nail matrix biopsy at our institution between September 2015 and December 2016. RESULTS: Eleven cases from 10 patients with LM were subjected to our tailored window technique assisted by carbon dioxide (CO2) laser and dermoscopy. We performed nail plate dermoscopy to select the biopsy site and used CO2 laser to create the window in the proximal nail plate. Nail matrix pigmentation was carefully investigated using intraoperative dermoscopy. The technique established appropriate diagnosis in 11 LM cases, without significant complications, as follows: melanoma in situ (4 cases) and nail matrix activation (7 cases). CONCLUSION: The window technique assisted by CO2 laser and dermoscopy can be a minimally invasive and effective method for nail matrix LM biopsy under local anesthesia. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2zpz1oL

Staffing Metrics in Mohs Surgery.

No abstract available

http://ift.tt/2ydOXZT

Syringocystadenoma Papilliferum in Coexistence With Verrucous Carcinoma on the Face.

No abstract available

http://ift.tt/2zrcU1r

Commentary on Polyalkylimide.

No abstract available

http://ift.tt/2yeURKg

Factors Influencing Squamous Cell Carcinoma In Situ Recurrence and Implications for Treatment Choice.

BACKGROUND: Numerous treatment modalities have been reported for squamous cell carcinoma in situ (SCCIS). Risk factors for recurrence have not been systematically reviewed. OBJECTIVE: To systematically review and summarize the data on risk factors that contribute to recurrence of SCCIS. MATERIALS AND METHODS: A PubMed search was completed using the terms "SCCIS," "Bowen's disease," "Bowen's disease and recurrence," and "Bowen's disease and Mohs." These sources were cross-referenced for the terms "treatment," "management," "therapy," "recurrence," and "margins." Studies were selected on the basis of relevance and applicable treatments. RESULTS: Immunosuppression was the only variable with a statistically signficant association with progression or recurrence of SCCIS. Although there were no data directly correlating subclinical lateral extension or invasive squamous cell carcinoma within SCCIS with recurrence, evidence supports both of these as common features of SCCIS. Other potential recurrence risk factors for which there are limited supporting data included tumor size, depth of follicular extension, and location. CONCLUSION: Immunosuppression was the only risk factor associated with increased risk of tumor recurrence. Subclinical tumor extension and occult invasive squamous cell carcinoma are relatively common features that theoretically could increase recurrence risk. These factors should be considered when deciding upon treatment for SCCIS. Further study is required to quantify variables that influence recurrence and to identify optimal treatment options. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2zoICfz

Dermoscopic Guidance of Talimogene Laherparepvec Injection for Metastatic Melanoma.

No abstract available

http://ift.tt/2zpyG5t

Estrogen receptor beta maintains expression of KLF15 to prevent cardiac myocyte hypertrophy in female rodents

Publication date: Available online 7 November 2017
Source:Molecular and Cellular Endocrinology
Author(s): Neil Hoa, Lisheng Ge, Kenneth S. Korach, Ellis R. Levin
Maintaining a healthy, anti-hypertrophic state in the heart prevents progression to cardiac failure. In humans, angiotensin II (AngII) indirectly and directly stimulates hypertrophy and progression, while estrogens acting through estrogen receptor beta (ERβ) inhibit these AngII actions. The KLF15 transcription factor has been purported to provide anti-hypertrophic action. In cultured neonatal rat cardiomyocytes, we found AngII inhibited KLF1 expression and nuclear localization, substantially prevented by estradiol (E2) or β-LGND2 (β-LGND2), an ERβ agonist. AngII stimulation of transforming growth factor beta expression in the myocytes activated p38α kinase via TAK1 kinase, inhibiting KLF15 expression. All was comparably reduced by E2 or β-LGND2. Knockdown of KLF15 in the myocytes induced myocyte hypertrophy and limited the anti-hypertrophic actions of E2 and β-LGND2. Key aspects were confirmed in an in-vivo model of cardiac hypertrophy. Our findings define additional anti-hypertrophic effects of ERβ supporting testing specific receptor agonists in humans to prevent progression of cardiac disease.



http://ift.tt/2ye2ukn

Data-Driven Methods to Diversify Knowledge of Human Psychology

Publication date: Available online 7 November 2017
Source:Trends in Cognitive Sciences
Author(s): Rachael E. Jack, Carlos Crivelli, Thalia Wheatley
Psychology aims to understand real human behavior. However, cultural biases in the scientific process can constrain knowledge. We describe here how data-driven methods can relax these constraints to reveal new insights that theories can overlook. To advance knowledge we advocate a symbiotic approach that better combines data-driven methods with theory.



http://ift.tt/2j7Ma1R

Full title with Editorial board members

Publication date: 15 February 2018
Source:Behavioural Brain Research, Volume 338





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Effects of pharmacological manipulation of the kappa opioid receptors on the aversive effects of nicotine

Publication date: 15 February 2018
Source:Behavioural Brain Research, Volume 338
Author(s): Melissa Ward, Haval Norman, Manoranjan S D'Souza
Nicotine, an addictive component of tobacco smoke, produces both rewarding and aversive effects. Increasing the aversive effects of nicotine may help in promoting smoking cessation. However, neural targets mediating the aversive effects of nicotine have not been fully identified. In this study, we evaluated the role of kappa opioid receptors (KORs) in the aversive effects of nicotine (0.4 mg/kg, base; s.c.) using the nicotine-induced conditioned taste aversion (CTA) model in Wistar rats. The KORs were activated using the selective KOR agonist (±)U-50,488H (0, 0.03, 0.15 & 0.3mg/kg; s.c.) and inhibited using the KOR antagonist nor-binaltorphimine (nor-BNI; 0, 15 & 30mg/kg; s.c.) in separate groups of rats using a between-subjects design. Pretreatment with the KOR agonist (±)U-50,488H (0.3mg/kg) significantly increased aversion for the nicotine-associated solution. Additionally, (±)U-50,488H (0.3mg/kg) on its own induced aversion to the flavored solution associated with it even in the absence of nicotine, suggesting that the KOR agonist induced increase in nicotine-induced aversion was an additive effect. Interestingly, administration of the KOR antagonist nor-BNI (30mg/kg) prior to conditioning with nicotine/saline, but not after conditioning with nicotine/saline, attenuated nicotine-induced aversive effects compared to saline controls. Taken together, these data suggest a role for KORs in the aversive effects of nicotine.



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Corrigendum to “TRPV1 modulates morphine-induced conditioned place preference via p38 MAPK in the nucleus accumbens” [Behav. Brain Res. 334 (2017) 26–33]

Publication date: 15 February 2018
Source:Behavioural Brain Research, Volume 338
Author(s): Sa-Ik Hong, Thi-Lien Nguyen, Shi-Xun Ma, Hyoung-Chun Kim, Seok-Yong Lee, Choon-Gon Jang




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Corrigendum to “Prodepressant- and anxiogenic-like effects of serotonin-selective, but not noradrenaline-selective, antidepressant agents in mice lacking α2-containing GABAA receptors” [Behav. Brain Res. 332 (2017) 172–179]

Publication date: 15 February 2018
Source:Behavioural Brain Research, Volume 338
Author(s): Rebecca S. Benham, Nishani B. Hewage, Raymond F. Suckow, Elif Engin, Uwe Rudolph




http://ift.tt/2m300Dx

A review on the chemotherapeutic potential of fisetin: In vitro evidences

Publication date: January 2018
Source:Biomedicine & Pharmacotherapy, Volume 97
Author(s): Kiruthika Sundarraj, Azhwar Raghunath, Ekambaram Perumal
During the past five decades, cancer cell lines are being successfully used as an in vitro model to discover the anti-cancer potential of plant secondary metabolites. Fisetin – the most popular polyphenol from fruits and vegetables, exhibits a repertoire of promising pharmacological features. Such versatile properties make fisetin an excellent anticancer agent and its efficacy as a chemotherapeutic agent against tumor heterogeneity from in vitro studies are encouraging. Fisetin is like a Pandora's box, as more research studies are being carried out, it reveals its new molecules within the cancer cells as therapeutic targets. These molecular targets orchestrate processes such as apoptosis, autophagic cell death, cell cycle, invasion, metastasis and angiogenesis in cancer cells. Besides apoptotic elicitation, fisetin's ability to induce autophagic cell death in cancer cells has been reported. This review examines the various molecular mechanisms of action elicited by fisetin leading to apoptosis and autophagic cell death as evidenced from cancer cell lines. In addition, the increased bioavailability and sustained release of fisetin improved through conjugation and enhanced effect of fisetin through synergism on various cancers are also highlighted.



http://ift.tt/2ArLGb2

Ovipositor morphology correlates with life history evolution in agaonid fig wasps

Publication date: Available online 7 November 2017
Source:Acta Oecologica
Author(s): Larissa Galante Elias, Finn Kjellberg, Fernando Henrique Antoniolli Farache, Eduardo A.B. Almeida, Jean-Yves Rasplus, Astrid Cruaud, Yan-Qiong Peng, Da-Rong Yang, Rodrigo Augusto Santinelo Pereira
The high adaptive success of parasitic Hymenoptera might be related to the use of different oviposition sites, allowing niche partitioning among co-occurring species resulting in life history specialization and diversification. In this scenario, evolutionary changes in life history and resources for oviposition can be associated with changes in ovipositor structure, allowing exploitation of different substrates for oviposition. We used a formal phylogenetic framework to investigate the evolution of ovipositor morphology and life history in agaonid wasps. We sampled 24 species with different life histories belonging to all main clades of Agaonidae including representatives of all described genera of non-pollinating fig wasps (NPFW). Our results show an overall correlation between ovipositor morphology and life history in agaonid fig wasps. Ovipositor morphologies seem to be related to constraints imposed by features of the oviposition sites since ovipositor morphology has experienced convergent evolution at least four times in Sycophaginae (Agaonidae) according to the resource used. Non-galling species have more distantly spaced teeth with uneven spacing, as opposed to the observed morphology of galling species. Our results suggest that the ancestral condition for ovipositor morphology was most likely the presence of one or two apical teeth. Regarding life history, ovary galling species that oviposit in receptive figs possibly represent the ancestral condition. Different ovipositor characteristics allow exploitation of new niches and may be related to resource partitioning and species co-existence in the fig-fig wasp system.



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Comparison of the antennal sensilla of females of four fig-wasps associated with Ficus auriculata

Publication date: Available online 7 November 2017
Source:Acta Oecologica
Author(s): Pei Yang, Zong-bo Li, Da-rong Yang, Yan-qiong Peng, Finn Kjellberg
A comparison was performed of the antennal sensilla of females of four chalcid wasp species Ceratosolen emarginatus Mayr, 1906, Sycophaga sp., Philotrypesis longicaudata Mayr, 1906, and Sycoscapter roxburghi Joseph, 1957, which are specific and obligatory associated with Ficus auriculata (Lour, 1790). The four species exhibit different oviposition strategies in the fig ovules where their offspring hatch and develop. Antennal sensilla morphology was evaluated using scanning electron microscopy. Females of the four species present 11 morphologically similar types of sensilla: trichoid sensilla, sensilla obscura, chaetica sensilla 1 and 2, which all have mechanosensory functions; uniporous basiconic sensilla, which are presumably contact chemosensilla; basiconic capitate peg sensilla, coeloconic sensilla 1, multiporous basiconic and placoid sensilla, which may be regarded as olfactory sensilla, and coeloconic sensilla 2 and 3, which are presumed to be proprioreceptors or pressure receptors. The four species have significant differences in the abundance and arrangement of trichoid sensilla and chaetica sensilla 1 on the flagellum. The coeloconic sensilla and sensilla obscura only occur on the antennae of C. emarginatus that enter figs. The chemosensilla which are presumably involved in host discrimination, i.e., basiconic sensilla, multiporous placoid sensilla and basiconic capitate peg sensilla, are similar in shape and configuration, although they present some differences in abundance. These findings provide practical information on the adaptations of fig wasps and the relationship between multisensory antennae and functions in fig wasp behaviour.



http://ift.tt/2AqngP8

Unique arginine array improves cytosolic localization of hydrocarbon-stapled peptides

Publication date: Available online 7 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Kim Quach, Jonathan LaRochelle, Xiao-Han Li, Elizabeth Rhoades, Alanna Schepartz
We have previously reported that miniature proteins containing a distinct array of 5 arginine residues on a folded α-helix–a penta-arg motif–traffic with high efficiency from endosomes into the cytosol and nucleus of mammalian cells. Here we evaluate whether a penta-arg motif can improve the intracellular trafficking of an otherwise impermeant hydrocarbon-stapled peptide, SAH-p53-4^Rho. We prepared a panel of SAH-p53-4^Rho variants containing penta-arg sequences with different spacings and axial arrangement and evaluated their overall uptake (as judged by flow cytometry) and their intracellular access (as determined by fluorescence correlation spectroscopy, FCS). One member of this panel reached the cytosol extremely well, matching the level achieved by SAH-p53-8^Rho, a previously reported and highly permeant hydrocarbon-stapled peptide. Notably, we found no relationship between cellular uptake as judged by flow cytometry and cytosolic access as determined by FCS. This result emphasizes the importance of accessing intracellular access directly via FCS or an analogous method and reiterates that overall uptake and endosomal release represent fundamentally different biological processes. To determine cytosolic and/or nuclear access, one must measure concentration directly using a quantitative tool such as FCS. Our results also suggest that optimal penetration of hydrocarbon-stapled peptides into the cell cytosol results when the penta-arg motif is located within more (as opposed to less) structured regions.

Graphical abstract

http://ift.tt/2yFfl3n

Thyroid High-Impact Articles

FREE ACCESS through November 21, 2017.
Read now:

Latest Impact Factor: 5.515
The Official Journal of: American Thyroid Association

The 2017 Bethesda System for Reporting Thyroid Cytopathology
Edmund S. Cibas, Syed Z. Ali 

The Role of Chemokines in Thyroid Carcinoma
Sharinie Yapa, Omar Mulla, Victoria Green, James England, John Greenman 

Childhood Thyroid Function Reference Ranges and Determinants: A Literature Overview and a Prospective Cohort Study
Ibrahim Önsesveren, Mirjana Barjaktarovic, Layal Chaker, Yolanda B. de Rijke, Vincent W.V. Jaddoe, Hanneke M. van Santen, Theo J. Visser, Robin P. Peeters, Tim I.M. Korevaar 

Temporal Changes in Thyroid Nodule Volume: Lack of Effect on Paranodular Thyroid Tissue Volume
Giorgio Grani, Rocco Bruno, Giuseppe Lucisano, Giuseppe Costante, Domenico Meringolo, Efisio Puxeddu, Massimo Torlontano, Salvatore Tumino, Marco Attard, Livia Lamartina, Antonio Nicolucci, David S. Cooper, Sebastiano Filetti, Cosimo Durante 

Projecting Survival in Papillary Thyroid Cancer: A Comparison of the Seventh and Eighth Editions of the American Joint Commission on Cancer/Union for International Cancer Control Staging Systems in Two Contemporary National Patient Cohorts
Lauren N. Pontius, Taofik O. Oyekunle, Samantha M. Thomas, Michael T. Stang, Randall P. Scheri, Sanziana A. Roman, Julie A. Sosa 

Automated MicroSPECT/MicroCT Image Analysis of the Mouse Thyroid Gland
Peng Cheng, Brynn Hollingsworth, Daniel Scarberry, Daniel H. Shen, Kimerly Powell, Sean C. Smart, John Beech, Xiaochao Sheng, Lawrence S. Kirschner, Chia-Hsiang Menq, Sissy M. Jhiang 

The post <i>Thyroid</i> High-Impact Articles appeared first on American Thyroid Association.

http://ift.tt/2AjaDV5

The anterolateral thigh flap with kiss technique for microsurgical reconstruction of oncological scalp defects

Defects after radical resection of scalp tumor feature extensive size, complexity of composite defect and poor elasticity of surrounding original tissue1. The anterolateral thigh (ALT) flap is one of the most frequently used workhorses for scalp reconstruction. However, most scalp defects are rounded instead of oval shaped and prone to be significantly wider than the maximal transverse diameter of classical ALT flap when direct closure of donor site is scheduled. Recently, Zhang et al.2 developed the concept of "economy in autologous flap transfer" and reported on the kiss technique in order to both reduce donor site morbidity and enable optimal soft tissue coverage.

http://ift.tt/2zprLvc

Sexually Diergic Hypothalamic-Pituitary-Adrenal Axis Responses to Selective and Non-Selective Muscarinic Antagonists Prior to Cholinergic Stimulation by Physostigmine in Rats

Publication date: Available online 7 November 2017
Source:Brain Research Bulletin
Author(s): Marissa A. Smail, Jessica L. Soles, Tracy E. Karwoski, Robert T. Rubin, Michael E. Rhodes
Central cholinergic systems regulate the hypothalamic-pituitary-adrenal (HPA) axis differentially in males and females (sexual diergism). We previously investigated the role of muscarinic receptors in this regulation by administering physostigmine (PHYSO), an acetylcholinesterase inhibitor, to male and female rats pretreated with scopolamine (SCOP), a nonselective muscarinic antagonist. SCOP pretreatment enhanced adrenocorticotropic hormone (ACTH) and corticosterone (CORT) responses in both sexes; males had greater ACTH responses while females had greater CORT responses. In the present study, we further explored the role of muscarinic receptor subtypes in HPA axis regulation by administering PHYSO to male and female rats following SCOP or various doses of either the M1 or the M2 selective muscarinic receptor antagonists, pirenzepine (PIREN) or methoctramine (METHO), respectively. Blood sampling occurred before and at multiple times after PHYSO. ACTH and CORT were determined by highly specific immunoassays. PIREN+PHYSO resulted in sustained, dose-dependent increases in ACTH and CORT: ACTH responses were similar in both sexes, CORT responses were greater in females, and percent changes from baseline for both hormones were greater in males. METHO+PHYSO resulted in overall decreases in ACTH and CORT: ACTH and CORT responses were higher in females but lower than those caused by PIREN or SCOP in both sexes, and percent changes from baseline were lower in males. Area under the curve analyses further supported these sexually diergic effects. These results suggest that specific muscarinic receptor subtypes differentially influence the HPA axis in a sexually diergic manner.



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Blockade of platelet-activating factor receptor attenuates abnormal behaviors induced by phencyclidine in mice through down-regulation of NF-κB

Publication date: Available online 7 November 2017
Source:Brain Research Bulletin
Author(s): The-Vinh Tran, Se Jin Park, Eun-Joo Shin, Hai-Quyen Tran, Ji Hoon Jeong, Choon-Gon Jang, Yu Jeung Lee, Seung-Yeol Nah, Toshitaka Nabeshima, Hyoung-Chun Kim
Accumulating evidence suggests that neuroinflammation is one of the important etiologic factors of abusive and neuropsychiatric disorders. Platelet-activating factor (PAF) is potent proinflammatory lipid mediat1or and plays a pivotal role in neuroinflammatory disorders through the specific PAF receptor (PAF-R). Phencyclidine (PCP) induces a psychotomimetic state that closely resembles schizophrenia. Here, we investigated the role of PAF-R in the abnormal behaviors induced by PCP in mice. Repeated treatment with PCP resulted in a significant increase in PAF-R gene expression in the prefrontal cortex (PFC) and in the hippocampus. This increase was more pronounced in the PFC than hippocampus. Treatment with PCP resulted in a significant increase in nuclear translocation of the nuclear factor kappa beta (NF-κB) p65 and DNA binding activity, indicating that the proinflammatory molecule NF-κB was increased through up-regulation of PAF-R. Consistently, NF-κB activation was significantly protected by the PAF-R antagonist, ginkgolide B (Gink B), in PAF-R knockout mice and by the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC). In addition, PCP-induced abnormal behaviors (i.e., reduced sociability, depression, cognitive impairment, and behavioral sensitization) were significantly attenuated by Gink B, in PAF-R knockout mice, and by PDTC. Importantly, PDTC did not significantly alter the attenuations observed in Gink B-treated mice or PAF-R knockout mice, indicating that NF-κB is a critical target for neuropsychotoxic modulation of PAF-R. Therefore, the results suggest that PAF-R mediates PCP-induced neuropsychotoxicity via a NF-κB-dependent mechanism, and that up-regulation of PAF-R may be associated with schizophrenia-like behavior in animal models.

Graphical abstract

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The efficacy of adrenocorticotropic hormone in a girl with anti-N-methyl-D-aspartate receptor encephalitis

Publication date: Available online 6 November 2017
Source:Brain and Development
Author(s): Mari Hatanaka, Shuichi Shimakawa, Akihisa Okumura, Jun Natsume, Miho Fukui, Shohei Nomura, Mitsuru Kashiwagi, Hiroshi Tamai
BackgroundImmunomodulatory therapy has shown some therapeutic benefits in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. In this report, we describe the use of adrenocorticotropic hormone (ACTH) immunotherapy with good outcome in a patient with anti-NMDAR encephalitis.Subject and MethodsA 4-year-old girl developed convulsions in her right arm and leg without impaired consciousness. These convulsions occurred frequently in clusters of 10–20 events of 10–20 s duration. She was admitted to our hospital on the 6th day following her initial series of convulsions. Flaccid paralysis of the right hand and leg was also found. Interictal electroencephalography showed high-amplitude slow waves. No abnormal findings were shown on MRI. ^99mTc-ECD brain SPECT on the 14th day showed hyperperfusion in the left hemisphere, including the left basal ganglia. The convulsions ceased following the oral administration of valproic acid on the 10th day; however, paralysis associated with choreic dyskinesia of the right arm and leg remained. ACTH immunotherapy was then performed on the 15th day. We identified the presence of N-methyl-D-aspartate receptor antibody in CSF samples taken on the 6th day. After ACTH therapy, the patient fully recovered from the paralysis associated with choreic dyskinesia of the right arm and leg. She has not had a relapse and has not required medication for over a year.ConclusionACTH immunotherapy may be a useful treatment option for patients with anti-NMDAR encephalitis, although further evaluation is required.



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Histone Marks in the ‘Driver’s Seat’: Functional Roles in Steering the Transcription Cycle

Publication date: Available online 6 November 2017
Source:Trends in Biochemical Sciences
Author(s): Leah A. Gates, Charles E. Foulds, Bert W. O'Malley
Particular chromatin modifications are associated with different states of gene transcription, yet our understanding of which modifications are causal 'drivers' in promoting transcription is incomplete. Here, we discuss new developments describing the ordered, mechanistic role of select histone marks occurring during distinct steps in the RNA polymerase II (Pol II) transcription cycle. In particular, we highlight the interplay between histone marks in specifying the 'next step' of transcription. While many studies have described correlative relationships between histone marks and their occupancy at distinct gene regions, we focus on studies that elucidate clear functional consequences of specific histone marks during different stages of transcription. These recent discoveries have refined our current mechanistic understanding of how histone marks promote Pol II transcriptional progression.



http://ift.tt/2AjUKOa

Hidden Secrets of Sigma54 Promoters Revealed

Publication date: Available online 7 November 2017
Source:Trends in Biochemical Sciences
Author(s): Nan Hao, Keith E. Shearwin
Bacterial sigma54 (σ⁵⁴) promoters are the DNA-binding motif for σ⁵⁴-containing RNA polymerase (RNAP) holoenzymes. A recent study using a combination of synthetic oligonucleotide library screening, biochemical characterization, and bioinformatics has uncovered a new and unexpected role for σ⁵⁴ promoters, encoding a form of bacterial 'insulator sequence' to dampen unwanted translation.



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Shift to community-onset Clostridium difficile infection in the national Veterans Health Administration, 2003-2014

Publication date: Available online 7 November 2017
Source:American Journal of Infection Control
Author(s): Kelly R. Reveles, Mary Jo V. Pugh, Kenneth A. Lawson, Eric M. Mortensen, Jim M. Koeller, Jacqueline R. Argamany, Christopher R. Frei
BackgroundClostridium difficile infection (CDI) occurs frequently in inpatient settings; however, community-onset cases have been reported more frequently in recent years. This study evaluated hospital-onset and community-onset CDI in the national Veterans Health Administration (VHA) population over a 12-year period.MethodsThis was a retrospective cohort study of all adult VHA beneficiaries with CDI between October 1, 2002, and September 30, 2014. Data were obtained from the Veterans Affairs Informatics and Computing Infrastructure. CDI was categorized into community-associated CDI (CA-CDI); community-onset, health care facility-associated CDI; and health care facility-onset CDI (HCFO-CDI). Each type was described longitudinally and was assessed as an independent risk factor for health outcomes using multivariable logistic regression.ResultsOverall, 30,326 patients with a first CDI episode were included. HCFO-CDI was the predominant type (60.2%), followed by CO-HCFA-CDI (20.6%) and CA-CDI (19.2%). The proportion of patients with HCFO-CDI decreased from 73.5% during fiscal year 2003 to 53.2% during fiscal year 2014, whereas CA-CDI increased from 8.3% to 26.7%. HCFO-CDI was a positive predictor of severe CDI (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.59-1.84) and 30-day mortality (OR, 1.46; 95% CI, 1.32-1.61), but a negative predictor of 60-day recurrence (OR, 0.41; 95% CI, 0.37-0.46).ConclusionsHCFO-CDI was the predominant CDI type. The proportion of patients with CA-CDI increased and HCFO-CDI decreased in recent years. Patients with HCFO-CDI experienced higher rates of severe CDI and mortality.



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How do professional relationships influence surgical antibiotic prophylaxis decision making? A qualitative study

Publication date: Available online 7 November 2017
Source:American Journal of Infection Control
Author(s): Jennifer K. Broom, Alex F. Broom, Emma R. Kirby, Jeffrey J. Post
BackgroundSurgical antibiotic prophylaxis (SAP) is a critical area to optimize to reduce the escalation of antimicrobial resistance. This article explores the ways by which interpersonal relationships influence SAP decision making.MethodsTwenty surgeons and anesthetists participated in in-depth semistructured interviews on SAP prescribing. Results were analyzed using the framework approach.ResultsAnalysis revealed 3 ways by which interpersonal relationships influence SAP: relationship dynamics between the surgeon and the anesthetist determine appropriateness of SAP, particularly operative risk ownership; perceived hierarchies within, and between, surgical and anesthetist specialties influence antibiotic prescribing decisions; and surgical distance from the antimicrobial stewardship team, which influences use of antimicrobial stewardship principles.ConclusionsInterventions to optimize SAP are more likely to be effective in enacting sustained change if they consider the interpersonal and social contexts, including issues of familiarity and cohesiveness, hierarchical patterns, and sense of place within a team. Significant relational dynamics in SAP decision making are centered around risk; that is, personal/reputational risk to different professional groups and ownership of risk for individual patient outcomes. Risk must therefore be considered for sustainable SAP optimization interventions.



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Scholar : These new articles for International Journal of Rail Transportation are available online

The online platform for Taylor & Francis Online content New for International Journal of Rail Transportation and online now on Taylor & Francis Online: Original Articles Assessment of railway ground vibration in urban area using in-situ transfer mobilities and simulated vehicle-track interaction Georges Kouroussis , Konstantinos E. Vogiatzis & David P. Connolly Pages: 1-18 | DOI: 10.1080/23248378.2017.1399093 Browse articles in this special issue on: 'Advancements in Civil and Structural Engineering' To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.