Treatment of Radial Nonunion with Corticocancellous Bone Graft and Fascia of Anterolateral Thigh Free Flap: The Wrap Technique

Summary: The management of nonunion of the forearm bones is a challenging task. Multiple factors have been associated with the establishment of forearm nonunion, such as the fracture position and complexity, general condition of the patient, and the previously utilized surgical technique. The optimal surgical treatment of a bone gap remains a subject of discussion. Autogenous corticocancellous bone grafts and vascularized bone flaps have been used with differing results. The authors describe a technique for the treatment of posttraumatic nonunion of the radius with a 5-cm bone gap using the free anterolateral thigh fascial flap wrapped around a tricortical iliac bone graft. The fracture healed after 5 weeks. The use of a vascularized tissue wrapped around the bone graft resulted in a well-healed bone and no signs of resorption after 2 years of follow-up. A bone graft wrapped by a fascial flap could magnify the restorative effect on the bone defect because of its dual role of constructing vascularization and inducing tissue regeneration.

http://ift.tt/2jDQTG9

High-grade Angiosarcoma Associated with Ruptured Breast Implants

Summary: Since the serendipitous discovery that implanted polymers cause sarcomas in rats, much research has been conducted to prove or disprove a link between silicone breast implants and/or polymer-based materials and breast cancer. In light of an initial report that 35% of rats implanted with a variety of polymers developed fibrosarcomas, we report a case of primary angiosarcoma found in a patient presenting with bilateral rupture of gel-filled breast implants.

http://ift.tt/2jDQLGU

Parent-Child Adrenocortical Concordance in Early Childhood: The Moderating Role of Parental Depression and Child Temperament

Publication date: Available online 29 January 2017
Source:Biological Psychology
Author(s): Stephanie M. Merwin, Victoria C. Smith, Marissa Kushner, Edward P. Lemay, Lea R. Dougherty
This study examined biological concordance between parent and child morning cortisol and whether parent and child-level risk factors for depression moderated this association. Participants included 136 parents and their preschool-aged children. Parents and children obtained salivary cortisol samples at waking, and 30 and 45minutes post-waking across two days to assess the cortisol awakening response. Parental lifetime depression was assessed using a clinical interview and child temperamental negative emotionality (NE) and positive emotionality (PE) were assessed using an observational laboratory-based assessment. Results indicated significant parent-child concordance between both average cortisol levels and cortisol fluctuations across waking. Greater concordance was observed for dyads with parents with a lifetime history of depression and with children high in NE and PE. These parent- and child-level moderators were associated with different indices of concordance. Findings highlight the need to examine the role of parent and child risk factors for depression on parent-child adrenocortical concordanc



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Conflict and Performance Monitoring throughout the Lifespan: An Event-Related Potential (ERP) and Temporospatial Component Analysis

Publication date: Available online 28 January 2017
Source:Biological Psychology
Author(s): Ann Clawson, Peter E. Clayson, Cierra M. Keith, Christina Catron, Michael J. Larson
Cognitive control includes higher-level cognitive processes used to evaluate environmental conflict. Given the importance of cognitive control in regulating behavior, understanding the developmental course of these processes may contribute to a greater understanding of normal and abnormal development. We examined behavioral (response times [RTs], error rates) and event-related potential data (N2, error-related negativity [ERN], correct-response negativity [CRN], error positivity [Pe]) during a flanker task in cross-sectional groups of 45 youth (ages 8-18), 52 younger adults (ages 20-28), and 58 older adults (ages 56-91). Younger adults displayed the most efficient processing, including significantly reduced CRN and N2 amplitude, increased Pe amplitude, and significantly better task performance than youth or older adults (e.g., faster RTs, fewer errors). Youth displayed larger CRN and N2, attenuated Pe, and significantly worse task performance than younger adults. Older adults fell either between youth and younger adults (e.g., CRN amplitudes, N2 amplitudes) or displayed neural and behavioral performance that was similar to youth (e.g., Pe amplitudes, error rates). These findings point to underdeveloped neural and cognitive processes early in life and reduced efficiency in older adulthood, contributing to poor implementation and modulation of cognitive control in response to conflict. Thus, cognitive control processing appears to reach peak performance and efficiency in younger adulthood, marked by improved task performance with less neural activation.



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Variation of hardness, microstructure, and Laves phase distribution in direct laser deposited alloy 718 cuboids

Publication date: 5 April 2017
Source:Materials & Design, Volume 119
Author(s): Erica L. Stevens, Jakub Toman, Albert C. To, Markus Chmielus
Property anisotropy and its unpredictability in direct laser-deposited material is a drawback to this additive manufacturing method. In this study, direct laser deposition was used to build three-dimensional cuboids of Ni-based superalloy 718, which were examined with microscopy, and analyzed for hardness trends with contour mapping. Secondary electron and backscatter electron contrast imaging were used in conjunction with electron backscatter diffraction to understand microstructure. It is found that hardness decreased with increasing height and linear energy used during deposition. Also, the hardness of the inner hatching was higher than the outer contour, in both planar and cross-sectional surfaces. After an examination of grain structure and phase distribution, it is proposed that the hardness trends are caused by a combination of detrimental Laves phase and strengthening γ″ phase distribution.

Graphical abstract

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Effects of composition and growth rate on the microstructure transformation of β-rods/lamellae/α-rods in directionally solidified Mg-Li alloy

Publication date: 5 April 2017
Source:Materials & Design, Volume 119
Author(s): Dan Liu, Huawei Zhang, Yanxiang Li, Xiang Chen, Yuan Liu
Mg-Li alloy is a unique system with a narrow dual-phase region and superstructure transformation. These characteristics will have significant influence on the solidification behavior. Using Bridgman-type vacuum furnace with liquid metal cooling method, the directional solidification experiments were performed on alloys with different Li contents (6.3wt.%, 6.6wt.%, 6.9wt.%, 7.2wt.%, 7.5wt.%, 7.8wt.%) at varied growth rates (3μm/s, 5μm/s, 10μm/s, 15μm/s, maximum to 21μm/s). As the Li content increases, the microstructures transform from divorced eutectic structure to lamellar structure, then to lamellae/α-Mg rod mixed structure, and finally to α-Mg rod-like structure. Fully eutectic structure is produced at a wide range of off-eutectic compositions. The effect of growth rate on the α-Mg rod-like structure is mainly to diminish the inter-rod spacing as growth rate increases, while additionally to affect the morphology of lamellar structure. High growth rate is found to be beneficial for producing straight and uniform lamellar structure. The eutectic spacing of Mg-Li system is one or two orders of magnitude lager than most other alloy systems. Moreover, a controllable three-stage transformation of β-rods/lamellae/α-rods is achieved in one single alloy system. A structure selection map is also given to define the microstructure transformation of the Mg-Li alloys.

Graphical abstract

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Chloroethylating nitrosoureas in cancer therapy: DNA damage, repair and cell death signaling

Publication date: Available online 29 January 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Teodora Nikolova, Wynand P. Roos, Oliver H. Krämer, Herwig M. Strik, Bernd Kaina
Chloroethylating nitrosoureas (CNU), such as lomustine, nimustine, semustine, carmustine and fotemustine are used for the treatment of malignant gliomas, brain metastases of different origin, melanomas and Hodgkin disease. They alkylate the DNA bases and give rise to the formation of monoadducts and subsequently interstrand crosslinks (ICL). ICL are critical cytotoxic DNA lesions that link the DNA strands covalently and block DNA replication and transcription. As a result, S phase progression is inhibited and cells are triggered to undergo apoptosis and necrosis, which both contribute to the effectiveness of CNU-based cancer therapy. However, tumor cells resist chemotherapy through the repair of CNU-induced DNA damage. The suicide enzyme O⁶-methylguanine-DNA methyltransferase (MGMT) removes the precursor DNA lesion O⁶-chloroethylguanine prior to its conversion into ICL. In cells lacking MGMT, the formed ICL evoke complex enzymatic networks to accomplish their removal. Here we discuss the mechanism of ICL repair as a survival strategy of healthy and cancer cells and DNA damage signaling as a mechanism contributing to CNU-induced cell death. We also discuss therapeutic implications and strategies based on sequential and simultaneous treatment with CNU and the methylating drug temozolomide.



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Looking for phosphate-accumulating bacteria in activated sludge processes: a multidisciplinary approach

Abstract

Over the past decades, an increasing need in renewable resources has progressively appeared. This trend concerns not only fossil fuels but also mineral resources. Wastewater and sewage sludge contain significant concentrations in phosphate and can be considered as a fertilizer source of the utmost importance. In wastewater treatment plants, the biological uptake of phosphate is performed by a specific microbiota: the phosphate-accumulating organisms. These microorganisms are recovered in sewage sludge. Here, we aimed to investigate the occurrence of phosphate accumulators in four wastewater treatment plants. A 16S metagenetic analysis identified the main bacterial phyla extracted from the aerobic treatment: α-Proteobacteria, β-Proteobacteria, and Sphingobacteria. An enrichment stage was performed to stimulate the specific growth of phosphate-accumulating bacteria in an acetate medium. An analysis of metabolic activities of sulfur and phosphorus highlighted strong modifications related to phosphorus and much less distinguishable effects with sulfur. A solid acetate medium containing 5-Br-4-Cl-3-indolyl phosphate was used to select potential phosphate-accumulating bacteria from the enriched consortia. The positive strains have been found to belong in the genera Acinetobacter, Corynebacterium, and Pseudomonas. Finally, electron microscopy was applied to the strains and allowed to confirm the presence of polyphosphate granules. Some of these bacteria contained granules the size of which exceeded 100 nm.

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Infraspecific variability in baseline element composition of the epiphytic lichen Pseudevernia furfuracea in remote areas: implications for biomonitoring of air pollution

Abstract

The epiphytic lichen Pseudevernia furfuracea is widely used as biomonitor of airborne trace elements and other contaminants and consists of two taxonomic varieties (var. furfuracea and var. ceratea). Here, we assessed the occurrence of inter-varietal differences in the elemental composition of paired samples of var. furfuracea and var. ceratea collected in 20 remote sites of Italian mountains. The concentration of 40 elements was measured by inductively coupled plasma mass spectroscopy, after digestion with HNO₃ and aqua regia. The magnitude of inter-varietal differences compared to the effect of large-scale site-dependent environmental factors (i.e., lithological substrate, host tree species, and altitude) on overall element content was explored by multivariate analysis techniques and tested by generalized linear mixed modeling (GLMM). Further GLMMs were separately fitted for each element testing taxonomic-related variability against uncertainty associated to the analytical procedure. Inter-varietal differences were statistically significant only for Hg and P, with higher content in var. ceratea at most sites, and for Mg and Zn, showing the opposite pattern. Since the elemental composition of P. furfuracea in remote sites was mostly affected by local lithology and climatic conditions, our results confirm that lichen material for active biomonitoring should be collected in a single ecologically homogeneous remote area. We also indicate sites in the Eastern Alps where P. furfuracea showed the minimum content of most elements, which are suggested as locations to collect lichen material for transplants. Besides the context-dependency at large spatial scale, variations of elemental composition apparently related to taxonomy, could possibly be due to unequal incidence of morphological traits of the collected material. Further research is needed to clarify this issue, and how it affects bioaccumulation phenomena.

http://ift.tt/2jDkorV

A global prospective of income distribution and its effect on life cycle assessment of municipal solid waste management: a review

Abstract

This study reviewed the municipal solid waste (MSW) composition, the management practices, and the use of life cycle assessment (LCA) tool for MSW management (MSWM) options in the various income group countries. LCA studies require inventory data, which is difficult to procure for any country including higher income group countries, and this issue gets compounded in low-income and lower middle-income group countries, which limits the implementation of LCA. This paper compared the use of LCA for MSWM between high-income and low-income group countries and also highlights the gap in using LCA for MSWM. A very limited number of LCA studies on MSWM were found for low-income group countries in comparison to high-income group countries. The study also provided a critical discussion on the challenges in applications of LCA in MSWM for better solid waste management in low-income and lower middle-income group countries. The study will help in taking up LCA studies in low-income countries to improve the overall MSWM efficiency.

http://ift.tt/2kGeMLa

Biosynthesis of metal nanoparticles using three marine plant species: anti-algal efficiencies against “ Oscillatoria simplicissima ”

Abstract

This study aims at controlling of the cyanobacteria Oscillatoria simplicissima, those that produce neurotoxins and have negative impacts on the aquatic organisms, using biosynthesized metal nanoparticles (NPs). Silver-NPs (Ag-NPs) have been successfully biosynthesized using Nannochloropsis oculata and Tetraselmis tetrathele cultures. Also, Ag-NPs and iron oxide-NPs (Fe₃O₄-NPs) were synthesized by Halophila stipulacea aqueous extract. The structural composition of the different biosynthesized NPs was studied. The algae cultures and the extract were used as reductants of AgNO₃, and brown colors due to Ag-NP biosynthesis were observed. Silver signals were recorded in their corresponding EDX spectra. FTIR analyses showed that proteins in N. oculata and T. tetrathele cultures reduced AgNO₃, and aromatic compounds stabilized the biogenic Ag-NPs. H. stipulacea extract contains proteins and polyphenols that could be in charge for the reduction of silver and iron ions into nanoparticles and polysaccharides which stabilized the biosynthesized Ag-NPs and Fe₃O₄-NPs. The Ag-NPs biosynthesized by T. tetrathele cultures and H. stipulacea aqueous extract exerted outstanding negative impacts on O. simplicissima (optical density and total chlorophyll) and the Ag-NPs biosynthesized using N. oculata culture exerted the moderate performance. The study results suggest that the bioactive compounds present in the FTIR profiles of the Ag-NPs and or ionic silver may be the main contributors in their anti-algal effects. A trial to use the biosynthesized Fe₃O₄-NPs using H. stipulacea aqueous extract to separate Ag-NPs was successfully carried out. Since the synthesis and applications of nanomaterials is a hot subject of research, the study outcomes not only provide a green approach for the synthesis of metal-NPs but also open the way for more nanoparticle applications.

http://ift.tt/2jDrZqb

Presence and distribution of current-use pesticides in surface marine sediments from a Mediterranean coastal lagoon (SE Spain)

Abstract

The spatial and seasonal distributions of current-use pesticides (CUPs), including triazines, organophosphorus pesticides, and tributylphosphate, were characterized in surface sediments from the Mar Menor lagoon during 2009 and 2010. The impact of two flash flood events on the input of CUPs and their distribution in the lagoon were also assessed. The total (dissolved + sorbed phase) input of CUPs in the two flash floods through the El Albujón watercourse into the lagoon was estimated at 38.9 kg, of which 9.9 kg corresponded to organophosphorus pesticides and 5.5 kg to triazines. CUP distribution onto sediments was not homogeneous in the lagoon due to the different contaminant sources, sediment types, and the physicochemical and hydrodynamic conditions of the Mar Menor lagoon. Thirteen CUPs were detected in 2009 and 19 in 2010, including mainly herbicides, insecticides, and the additive tributylphosphate. Mean CUP concentrations in the lagoon were generally below 20 ng g⁻¹, except for chlorpyrifos and tributylphosphate in 2010. The highest concentrations were detected in depositional areas of the lagoon, in the area of influence of the El Albujón watercourse and other wadis with groundwater contributions such as El Mirador (north) and Los Alcázares (east) and that of marine water from El Estacio channel. In fact, the maximum concentration was detected close to El Albujón watercourse (chlorpyrifos, 102.8 ng g⁻¹ dry weight). Four herbicides, two insecticides, two fungicides, and tributylphosphate showed a risk quotient higher than 1, with that for chlorpyrifos ranging from 96 to 35,200 after flash flood events.

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Electrodes inspired by nature

Publication date: Available online 28 January 2017
Source:Materials Today
Author(s): Laurie Donaldson




http://ift.tt/2kGedVt

Graphene helps silicone rubber composites heal

Publication date: Available online 28 January 2017
Source:Materials Today
Author(s): Cordelia Sealy




http://ift.tt/2kGkCMH

Materials award for Editor-in-Chief of ‘Composites Science and Technology’

Publication date: Available online 28 January 2017
Source:Materials Today
Author(s): David Bradley




http://ift.tt/2kGg4tH

Sensor that measures glucose in tears

Publication date: Available online 28 January 2017
Source:Materials Today
Author(s): Laurie Donaldson




http://ift.tt/2kGnzfX

Rockcress against heavy metal

Publication date: Available online 28 January 2017
Source:Materials Today
Author(s): David Bradley




http://ift.tt/2kGg5hf

Velvety scaffold sticks to cells

Publication date: Available online 28 January 2017
Source:Materials Today
Author(s): Cordelia Sealy




http://ift.tt/2kGfBn4

Harvard enters superconducting spin cycle

Publication date: Available online 28 January 2017
Source:Materials Today
Author(s): David Bradley




http://ift.tt/2kGnGMT

Spiked carbon dioxide conversion

Publication date: Available online 28 January 2017
Source:Materials Today
Author(s): David Bradley




http://ift.tt/2kGnxER

TMOs reviewed to advantage

Publication date: Available online 28 January 2017
Source:Materials Today
Author(s): Laurie Donaldson




http://ift.tt/2kGmKbd

Perovskite films improve on solar cells

Publication date: Available online 28 January 2017
Source:Materials Today
Author(s): Laurie Donaldson




http://ift.tt/2kGln87

Immunotolerant indoleamine-2,3-dioxygenase increases in condyloma acuminata

Abstract

Background

The tryptophan-depleting enzyme indoleamine-2,3-dioxygenase (IDO) is critical for the regulation of immune tolerance and plays an important role in immune-associated skin diseases.

Objectives

To analyze the level of IDO in condyloma acuminata (CA) and its role in this condition.

Methods

IDO expression was assessed in the skin and peripheral blood of healthy subjects and patients with CA. To assess the role of skin IDO in immunity, the ability of isolated epidermal cells to metabolize tryptophan and the influence on polyclonal T cell mitogen (PHA)-stimulated T cell proliferation were explored.

Results

IDO median fluorescence intensities (MFIs) in peripheral blood mononuclear cells (PBMCs) from CA patients were similar to those from healthy controls. Immunohistochemistry showed that IDO(+) cells were rare in normal skin and the control skin of CA patients but were greatly accumulated in wart tissue. Most fluorescence signals of IDO(+) cells were not overlapping with those of CD1a(+) Langerhans cells (LCs). HPV DNA probe in situ hybridization showed a large number of IDO(+) cells in the HPV(-) site. Keratinocytes (KCs) in the skin of healthy subjects and the circumcised skin of CA patients could minimally transform tryptophan into kynurenine, but IDO-competent epidermal cells from warts could transform tryptophan. In addition, these IDO-competent epidermal cells could inhibit PHA-stimulated T cell proliferation. The addition of an IDO inhibitor 1-MT restored the inhibited T cell proliferation.

Conclusion

Abnormally localized high IDO expression might be involved in the formation of a local immune tolerant microenvironment.

This article is protected by copyright. All rights reserved.

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Organisation of the dermal matrix impacts the biomechanical properties of skin

Summary

Background

Human skin has the crucial roles of maintaining homeostasis and protecting against external environment. It offers protection against mechanical trauma due to the reversible deformation of its structure; these biomechanical properties are amenable to dynamic testing using non-invasive devices.

Objectives

To characterise the biomechanical properties of young, white Caucasian and black African/African-Caribbean skin from different anatomical sites; and to relate underlying skin architecture to biomechanical function.

Methods

Using cutometry and ballistometry, the biomechanical properties of buttock and dorsal forearm skin were determined in black African/African-Caribbean (n=18) and white Caucasian (n=20) individuals aged 18-30 years. Skin biopsies were obtained from a subset of the volunteers (black African/African-Caribbean: n=5; white Caucasian: n=6) and processed for histological and immunohistochemical detection of the major elastic fibre components and fibrillar collagens.

Results

We have determined that healthy skin from young African and Caucasian individuals has similar biomechanical properties (F3) in that skin is resilient (capable of returning to its original position following deformation; R1), exhibits minimal fatigue (R4) and is highly elastic (R2, R5 and R7). At the histological level, skin with these biomechanical properties is imbued with strong interdigitation of the rete ridges at the dermal-epidermal junction (DEJ) and candelabra-like arrays of elastic fibres throughout the papillary dermis. Dramatic disruption to this highly organised arrangement of elastic fibres, effacement of the rete ridges and alterations to the alignment of the fibrillar collagens is apparent in white Caucasian forearm and coincides with a marked decline in biomechanical function.

Conclusions

Maintenance of skin architecture – both epidermal morphology and elastic fibre arrangement – is essential for optimal skin biomechanical properties. Disruption to underlying skin architecture, as observed in young white Caucasian forearm, compromises biomechanical function.

http://ift.tt/2kAcvSy

A case report of disappearing pigmented skin lesions associated with pembrolizumab treatment for metastatic melanoma

Abstract

Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death (PD)-1 receptor. Common cutaneous adverse side effects of PD-1 inhibitors include maculopapular rash, pruritus, vitiligo, and lichenoid skin and mucosal reactions. Here, we describe a man in his sixties with metastatic melanoma treated with pembrolizumab who subsequently developed fading or disappearance of pigmented skin lesions, lightening of the skin, and poliosis of the eyebrows, eyelashes, and scalp and body hair. Compared to baseline high-resolution three-dimensional total body photography, we observed fading or disappearing of solar lentigines, seborrheic keratoses, and melanocytic naevi, suggesting that PD-1 inhibitors may affect the evolution of these benign skin lesions. With dermatoscopic follow-up, altered lesions showed either blue-grey peppering/granularity or fading in colour without other identifiable features. No halo lesions or lesions with surrounding inflammation were identified. One changed pigmented lesion that showed blue-grey peppering/granularity on dermoscopy was biopsied and interpreted as a macular seborrheic keratosis with melanophages. Further studies are required to elucidate the effects of PD-1 inhibition on benign skin lesions.

This article is protected by copyright. All rights reserved.

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Recommendations for treatment in Folliculotropic Mycosis Fungoides: Report of the Dutch Cutaneous Lymphoma Group

Summary

Background

Folliculotropic mycosis fungoides (FMF) is an aggressive variant of mycosis fungoides (MF) and generally less responsive to standard skin-directed therapies (SDTs). Recent studies distinguished an indolent (early-stage FMF) and a more aggressive (advanced-stage FMF) subgroup. The optimal treatment for both subgroups needs still to be defined.

Objectives

Evaluation of initial treatment results in patients with early- and advanced-stage FMF.

Methods

203 Patients (84 early-stage, 102 advanced-stage, 17 extracutaneous FMF), included in the Dutch Cutaneous Lymphoma Registry between 1985 and 2014 were studied. Type and results of initial treatment were retrieved from the Dutch Registry. Main outcomes were complete remission (CR), sustained complete remission (SCR), partial remission (>50% improvement; PR) and overall response (OR; CR+PR).

Results

Patients with early-stage FMF were treated with non-aggressive SDTs in 67 of 84 cases, resulting in CR and OR of 28% and 83% for monotherapy topical steroids, 0% and 83% for UVB and 30% and 88% for PUVA, respectively. In patients with advanced-stage FMF these SDTs were less effective (combined CR and OR: 10% and 52%, respectively). In patients with advanced-stage FMF local radiotherapy (CR 63%; OR: 100%), total skin electron beam irradiation (CR: 59%; OR: 100%) and PUVA combined with local radiotherapy (CR: 5%; OR: 75%) were most effective.

Conclusions

The results of the present study demonstrate that not all patients with FMF should be treated aggressively. Patients with early-stage FMF may benefit very well from standard SDTs also used in early-stage classic MF and have an excellent prognosis.

This article is protected by copyright. All rights reserved.

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Prostate-specific antigen density is predictive of outcome in suboptimal prostate seed brachytherapy

Publication date: Available online 28 January 2017
Source:Brachytherapy
Author(s): David Benzaquen, Guila Delouya, Cynthia Ménard, Maroie Barkati, Daniel Taussky
PurposeIn prostate seed brachytherapy, a D90 of <130 Gy is an accepted predictive factor for biochemical failure (BF). We studied whether there is a subpopulation that does not need additional treatment after a suboptimal permanent seed brachytherapy implantation.Methods and MaterialsA total of 486 patients who had either BF or a minimum followup of 48 months without BF were identified. BF was defined according to the Phoenix definition (nadir prostate-specific antigen + 2). Univariate and multivariate analyses were performed, adjusting for known prognostic factors such as D90 and prostate-specific antigen density (PSAD) of ≥0.15 ng/mL/cm³, to evaluate their ability to predict BF.ResultsMedian followup for patients without BF was 72 months (interquartile range 56–96). BF-free recurrence rate at 5 years was 95% and at 8 years 88%. In univariate analysis, PSAD and cancer of the prostate risk assessment score were predictive of BF. On multivariate analysis, none of the factors remained significant. The best prognosis had patients with a low PSAD (<0.15 ng/mL/cm³) and an optimal implant at 30 days after implantation (as defined by D90 ≥ 130 Gy) compared to patients with both factors unfavorable (p = 0.006). A favorable PSAD was associate with a good prognosis, independently of the D90 (<130 Gy vs. ≥130 Gy, p = 0.7).ConclusionsPatients with a PSAD of <0.15 ng/mL/cm³ have little risk of BF, even in the case of a suboptimal implant. These results need to be validated in other patients' cohorts.



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Influence of irradiation by a novel CO 2 9.3-μm short-pulsed laser on sealant bond strength

Abstract

The objective of this in vitro study was to evaluate whether irradiation of enamel with a novel CO₂ 9.3-μm short-pulsed laser using energies that enhance caries resistance influences the shear bond strength of composite resin sealants to the irradiated enamel. Seventy bovine and 240 human enamel samples were irradiated with a 9.3-μm carbon dioxide laser (Solea, Convergent Dental, Inc., Natick, MA) with four different laser energies known to enhance caries resistance or ablate enamel (pulse duration from 3 μs at 1.6 mJ/pulse to 43 μs at 14.9 mJ/pulse with fluences between 3.3 and 30.4 J/cm², pulse repetition rate between 4.1 and 41.3 Hz, beam diameter of 0.25 mm and 1-mm spiral pattern, and focus distance of 4–15 mm). Irradiation was performed "freehand" or using a computerized, motor-driven stage. Enamel etching was achieved with 37% phosphoric acid (Scotchbond Universal etchant, 3M ESPE, St. Paul, MN). As bonding agent, Adper Single Bond Plus was used followed by placing Z250 Filtek Supreme flowable composite resin (both 3M ESPE). After 24 h water storage, a single-plane shear bond test was performed (UltraTester, Ultradent Products, Inc., South Jordan, UT). All laser-irradiated samples showed equal or higher bond strength than non-laser-treated controls. The highest shear bond strength values were observed with the 3-μs pulse duration/0.25-mm laser pattern (mean ± SD = 31.90 ± 2.50 MPa), representing a significant 27.4% bond strength increase over the controls (25.04 ± 2.80 MPa, P ≤ 0.0001). Two other caries-preventive irradiation (3 μs/1 mm and 7 μs/0.25 mm) and one ablative pattern (23 μs/0.25 mm) achieved significantly increased bond strength compared to the controls. Bovine enamel also showed in all test groups increased shear bond strength over the controls. Computerized motor-driven stage irradiation did not show superior bond strength values over the clinically more relevant freehand irradiation. Enamel that is made caries-resistant with CO₂ 9.3-μm short-pulsed laser irradiation showed at least equal or significantly higher shear bond strength to pit and fissure sealants than non-laser-irradiated enamel. The risk of a sealant failure due to CO₂ 9.3-μm short-pulsed laser irradiation appears reduced. If additional laser ablation is required before placing a sealant, the CO₂ 9.3-μm enamel laser-cut showed equivalent or superior bond strength to a flowable sealant.

http://ift.tt/2ji3QHn

Relaxation behavior of polyurethane networks with different composition and crosslinking density

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Martin Zajac, Heike Kahl, Bernd Schade, Thomas Rödel, Madalena Dionisio, Mario Beiner
The relaxation behavior of a series of solvent free polyurethane model networks with variable cross-link density prepared based on different commercial diols and a diisocyanate containing component are studied by differential scanning calorimetry (DSC), dynamic-mechanical analysis (DMA) and dielectric relaxation spectroscopy (DRS). A systematic decrease of the calorimetric glass temperature Tg as well as of the softening temperatures Tα^DMA and Tα^DRS from relaxation methods is observed with increasing length of the diol sequences between neighbored diisocyanate units acting as cross-linker. This trend is explained based on an internal plasticization of the polymeric network by long, highly mobile diol units containing an increasing fraction of methylene sequences. Cold crystallization effects are only indicated for the longest diol sequence under investigation. This is understood as a consequence of a large fraction of methylene sequences in combination with weaker geometrical constraints. Two secondary relaxations, β and γ, are observed in the glassy state for all amorphous samples at low temperatures by dielectric spectroscopy indicating the existence of localized motions in the polyurethane networks. Below Tg these relaxation processes are practically unaffected by changes in the length of the diol units and the softening behavior of the polymeric model networks. Interrelations between secondary β relaxation and cooperative α dynamics are indicated. An onset of the dielectric α relaxation strength Δεα is observed for all amorphous polyurethane networks. A linear extrapolation of Δεα vs. 1/T gives onset temperatures Ton which are in good agreement with αβ crossover temperatures Tαβ being the temperature where the difference between α and β relaxation times τα−τβ approaches a minimum. This finding supports an onset of the cooperative α motions in the αβ crossover region as reported in the previous literature for many other glass forming materials.

Graphical abstract

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Superheat-resistant polymers with low coefficients of thermal expansion

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Masatoshi Hasegawa, Yuki Hoshino, Natsumi Katsura, Junichi Ishii
Here, we report superheat-resistant polymers, poly(benzoxazole imide)s (PBOI), with very low coefficients of thermal expansion (CTE) and sufficient ductility for applications as the plastic substrates of organic light-emitting diode (OLED) displays. Diamines incorporating benzoxazole (BO) units were synthesized for this purpose. A PBOI derived from a BO-containing diamine and 3,3′,4,4′-biphenyltetracarboxylic dianhydride (s-BPDA) has excellent properties that are superior to those of s-BPDA/p-phenylenediamine (p-PDA) polyimide such as an undetectable Tg, a very low CTE (9.6 ppm K⁻¹), a very high the 5% weight loss temperature (Td⁵ = 592 °C) in N2, and good ductility while remaining the highest level of non-flammability (UL-94, V-0). The use of another BO-incorporating diamine permitted further improvement in the target properties: an extremely high Td⁵ (609 °C) in N2 and a considerably low CTE (3.3 ppm K⁻¹) close to that of a silicon wafer. These results show that the PBOIs examined in this work are promising candidates for use as the plastic substrates in OLED displays.

Graphical abstract

http://ift.tt/2kG6OWh

White-light emissive materials based on dynamic polymerization in supramolecular chemistry

Publication date: Available online 28 January 2017
Source:Polymer
Author(s): Yuji Kubo, Ryuhei Nishiyabu
Polymer-based materials with white-light emission have attracted much attention because of their potential applications as organic light-emitting diodes (OLEDs) and bright sensor materials. Synthesizing one polymer to cover the entire region of visible light is not easy. In addition, facile mixing of multiple kinds of emissive polymers can cause unfavorable interactions between them, making it difficult for chemists to prepare materials with this type of emission. Recently, much effort has been devoted to proposing efficient strategies toward this end, which involve multilayer systems with blends of different color-emitting polymers, single-layer polymer blends, and polymer hosts doped with fluorescent or phosphorescent dyes. By fine tuning the primary colors, i.e., red, green, and blue, or two complementary colors, e.g., cyan and orange, supramolecular polymerization can create one-dimensional assemblies with dynamic and reversible non-covalent bonds, such as hydrogen bonds, metal coordination, electrostatic interactions, hydrophobic interactions, and π‒π stacking interactions. Such adaptive and alterable features could control the amount of color-emissive components in systems where the management of energy transfer is possible. Furthermore, orthogonal polymerization provides well-defined three-dimensional assemblies. In this context, dynamic covalent bond-based polymers are also suitable to create white-light emissive materials that are relevant to supramolecular polymers. This review describes the preparation of white-light emissive materials using a rational approach based on dynamic polymerization in supramolecular chemistry.

Graphical abstract

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Electrocatalytic water treatment using carbon nanotube filters modified with metal oxides

Abstract

This study examined the electrocatalytic activity of multi-walled carbon nanotube (CNT) filters for remediation of aqueous phenol in a sodium sulfate electrolyte. CNT filters were loaded with antimony-doped tin oxide (Sb-SnO₂; SS) and bismuth- and antimony-codoped tin oxide (Bi-Sb-SnO₂; BSS) via electrosorption at 2 V for 1 h and then assembled into a flow-through batch reactor as anode–cathode couples with perforated titanium foils. The as-synthesized pristine CNT filters were composed of 50–60-nm-thick tubular carbons with smooth surfaces, whereas the tubes composing the SS-CNT and BSS-CNT filters were slightly thicker and bumpy, because they were coated with SS and BSS particles ~50 nm in size. Electrochemical characterization of the samples indicated a positive shift in the onset potential and a decrease in the current magnitude in the modified CNT filters due to passivation and oxidation inhibition of the bare CNT filters. These filters exhibited a similar adsorption capacity for phenol (5–8%), whereas loadings of SS and BSS enhanced the degradation rate of phenol by ~1.5 and 2.1 times, respectively. In particular, the total organic carbon removal performance and mineralization efficiency of the BSS-CNT filters were approximately twice those of the bare CNT filters. The BSS-CNT filters also exhibited an enhanced oxidation of ferrocyanide [Fe^II(CN)₆⁴⁻], which was not adsorbed onto the CNT filters. The enhanced electrocatalytic performance of the modified CNT filters was attributed to an effective generation of OH radicals. The surfaces of the filters were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy.

http://ift.tt/2kf5jNX

Nonlinear Dynamical Analysis of Sleep Electroencephalography using Fractal and Entropy Approaches

The analysis of electroencephalography (EEG) recordings has attracted increasing interest in recent decades and provides the pivotal scientific tool for researchers to quantitatively study brain activity during sleep, and has extended our knowledge of the fundamental mechanisms of sleep physiology. Conventional EEG analyses are mostly based on Fourier transform technique which assumes linearity and stationarity of the signal being analyzed. However, due to the complex and dynamical characteristics of EEG, nonlinear approaches are more appropriate for assessing the intrinsic dynamics of EEG and exploring the physiological mechanisms of brain activity during sleep.

http://ift.tt/2k4CZLQ

Medication induced sleepwalking: A systematic review

Medications that trigger sleepwalking may inadvertently put the patient at risk of injury to themselves and/or others, and contribute to poor treatment adherence. The aim of this study was to systematically review the literature to identify drugs that may increase the risk of sleepwalking. A search of CINAHL, EMBASE, PsycINFO, PubMed, and ScienceDirect was conducted with the keywords 'sleepwalking' OR 'somnambulism'. Of the original 83 sourced papers, 62 met the inclusion criteria and were subsequently included for review.

http://ift.tt/2jCXNLR

Intracerebral injection of CpG oligonucleotide for patients with de novo glioblastoma—A phase II multicentric, randomised study

Publication date: March 2017
Source:European Journal of Cancer, Volume 73
Author(s): Renata Ursu, Alexandre Carpentier, Philippe Metellus, Vincent Lubrano, Florence Laigle-Donadey, Laurent Capelle, Jacques Guyotat, Olivier Langlois, Luc Bauchet, Kristell Desseaux, Annick Tibi, Olivier Chinot, Jérôme Lambert, Antoine F. Carpentier
BackgroundImmunostimulating oligodeoxynucleotides containing unmethylated cytosine-guanosine motifs (CpG-ODN) have shown a promising efficacy in several cancer models when injected locally. A previous phase II study of CpG-ODN in patients with recurrent glioblastoma (GBM) has suggested some activity and has shown a limited toxicity. This multicentre single-blinded randomised phase II trial was designed to study the efficacy of a local treatment by CpG-ODN in patients with de novo glioblastomas.Patients and methodsPatients with a newly diagnosed glioblastoma underwent large surgical resection and CpG-ODN was randomly administrated locally around the surgical cavity. The patients were then treated according to standard of care (SOC) with radiotherapy and temozolomide. The primary objective was 2-year survival. Secondary outcomes were progression free survival (PFS), and tolerance.ResultsEighty-one (81) patients were randomly assigned to receive CpG-ODN plus SOC (39 patients) or SOC (42 patients). The 2-year overall survival was 31% (19%; 49%) in the CpG-ODN arm and 26% (16%; 44%) in the SOC arm. The median PFS was 9 months in the CpG-ODN arm and 8.5 months in the SOC arm. The incidence of adverse events was similar in both arms; although fever and post-operative haematoma were more frequent in the CpG-ODN arm.ConclusionsLocal immunotherapy with CpG-ODN injected into the surgical cavity after tumour removal and followed by SOC, although well tolerated, does not improve survival of patients with newly diagnosed GBM.



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Anti-müllerian hormone levels and evolution in women of reproductive age with breast cancer treated with chemotherapy

Publication date: March 2017
Source:European Journal of Cancer, Volume 74
Author(s): T. Fréour, P. Barrière, D. Masson
BackgroundLong-term consequences of cancer treatments in young women, and especially fertility issues, are gaining attention as survival rates increase. Breast cancer is the most frequent malignancy in women of reproductive age.AimThe purpose of this review is to describe serum anti-müllerian hormone (AMH) level at diagnosis and its evolution during and after chemotherapy in women of reproductive age treated for breast cancer. Second, the impact of taxanes on AMH, the association between AMH and amenorrhea, and the comparison of AMH with other hormonal markers of ovarian reserve were studied.MethodsA systematic PubMed search was conducted on all articles, published up to April 2016 and related to AMH in women suffering from breast cancer using the following key words: AMH, müllerian-inhibiting substance, ovarian reserve, ovarian function, breast cancer, gonadotoxicity, ovarian toxicity, amenorrhea, chemotherapy, and menopause.ResultsAMH levels rapidly fall down to undetectable levels in most women during chemotherapy and generally persist at very low levels in most women after the treatment. Taxanes seem to impact negatively ovarian function, but data on ovarian reserve are scarce. AMH is a predictor of the occurrence of chemotherapy-related amenorrhea and is the most relevant hormonal marker of ovarian reserve.ConclusionSerum AMH is a relevant tool for ovarian reserve assessment and follow-up during treatment in premenopausal women with breast cancer. Further large prospective studies are necessary to determine its predictive interest for post-treatment residual fertility, and eventually use it in fertility preservation counseling before treatment initiation.



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Segmental Latissimus Dorsi Free Flap Attempting to Preserve Function at the Donor Site: Anatomical and Clinical Experiences

J reconstr Microsurg
DOI: 10.1055/s-0036-1597835

Background The purpose of the present study was to evaluate arm and shoulder function prospectively after transfer of the lateral segment of the latissimus dorsi (LD) muscle. Methods In this study, 20 specimens of LD muscles from 10 cadavers were dissected to determine the relationship between the artery and the nerve. Twenty patients were recruited and functional disability was determined by the Disabilities of Arm, Shoulder, and Hand (DASH), and muscle strength by needle electromyography (EMG) before surgery and at five different time points postoperatively. Results Two specimens (10%) had no medial branch arising from the thoracodorsal artery. The pedicle length of the lateral branch was longer than that of the medial branch (mean 10.41 vs. 9.27 cm, p = 0.03). All DASH scores and EMG amplitudes at half a month postoperative decreased compared with those preoperatively, with no significant difference at 3 months postoperative. Conclusion Lateral segmental LD muscle transfer, leaving the residual segment motor function intact, can be recommended as an alternative for moderate and small-size bone exposure wounds, especially in the lower extremities, that minimizes loss of donor-site function.
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Different mechanisms in learning different second languages: Evidence from English speakers learning Chinese and Spanish

Publication date: 1 March 2017
Source:NeuroImage, Volume 148
Author(s): Fan Cao, Bethany L. Sussman, Valeria Rios, Xin Yan, Zhao Wang, Gregory J. Spray, Ryan M. Mack
Word reading has been found to be associated with different neural networks in different languages, with greater involvement of the lexical pathway for opaque languages and greater invovlement of the sub-lexical pathway for transparent langauges. However, we do not know whether this language divergence can be demonstrated in second langauge learners, how learner's metalinguistic ability would modulate the langauge divergence, or whether learning method would interact with the language divergence. In this study, we attempted to answer these questions by comparing brain activations of Chinese and Spanish word reading in native English-speaking adults who learned Chinese and Spanish over a 2 week period under three learning conditions: phonological, handwriting, and passive viewing. We found that mapping orthography to phonology in Chinese had greater activation in the left inferior frontal gyrus (IFG) and left inferior temporal gyrus (ITG) than in Spanish, suggesting greater invovlement of the lexical pathway in opaque langauges. In contrast, Spanish words evoked greater activation in the left superior temporal gyrus (STG) than English, suggesting greater invovlement of the sublexical pathway for transparant languages. Furthermore, brain-behavior correlation analyses found that higher phonological awareness and rapid naming were associated with greater activation in the bilateral IFG for Chinese and in the bilateral STG for Spanish, suggesting greater language divergence in participants with higher meta-linguistic awareness. Finally, a significant interaction between the language and learning condition was found in the left STG and middle frontal gyrus (MFG), with greater activation in handwriting learning than viewing learning in the left STG only for Spanish, and greater activation in handwriting learning than phonological learning in the left MFG only for Chinese. These findings suggest that handwriting facilitates assembled phonology in Spanish and addressed phonology in Chinese. In summary, our study suggests different mechanisms in learning different L2s, providing important insights into neural plasticity and important implications in second language education.



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In Memoriam: Peter H. Berman, M.D. December 29, 1931 - September 1, 2016

Publication date: Available online 28 January 2017
Source:Pediatric Neurology
Author(s): Barry S. Russman, Gihan Tennekoon, Don Younkin




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In memoriam: Bruce O. Berg, M.D. January 2, 1931 - October 5, 2016

Publication date: Available online 28 January 2017
Source:Pediatric Neurology
Author(s): Kenneth F. Swaiman, Donna Ferriero




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ERCC1 polymorphisms and oxaliplatin. A review of the literature and a monocentric experience in the absence of a ‘sliding doors’ trial

Publication date: Available online 28 January 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): V. Formica, E. Doldo, F.R. Antonetti, A. Nardecchia, P. Ferroni, S. Riondino, C. Morelli, H.T. Arkenau, F. Guadagni, A. Orlandi, M. Roselli
Excision repair cross-complementation group 1 (ERCC1) is a key component in DNA repair mechanisms and may influence the tumor DNA-targeting effect of the chemotherapeutic agent oxaliplatin. Germline ERCC1 polymorphisms may alter the protein expression and published data on their predictive and prognostic value have so far been contradictory. In the present article we review available evidence on the clinical role and utility of ERCC1 polymorphisms and, in the absence of a 'perfect' trial, what we call the 'sliding doors' trial, we present the data of ERCC1 genotyping in our local patient population finding a useful predictive value for oxaliplatin-induced risk of anemia.



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Targeting HIF-2 α in clear cell renal cell carcinoma: A promising therapeutic strategy

Publication date: Available online 28 January 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Olga Martínez-Sáez, Pablo Gajate Borau, Teresa Alonso-Gordoa, Javier Molina-Cerrillo, Enrique Grande
The loss of the Von Hippel-Lindau tumor suppressor (VHL) is a key oncogenic event in the vast majority of patients with clear cell renal cell carcinoma (ccRCC). With the loss of the VHL protein (pVHL) function, the hypoxia inducible factor α (HIF-α) accumulates inside the tumor cell and dimerizes with HIF-β. The HIF-α/HIF-β complex transcriptionally activates hundreds of genes promoting the adaptation to hypoxia that is implicated in tumor development. There is growing evidence showing that HIF-2α subunit has a central role in ccRCC over HIF-1α. Thus, efforts have been made to specifically target this pathway. PT2385 and PT2399 are first-in-class, orally available, small molecule inhibitors of HIF-2 that selectively disrupt the heterodimerization of HIF-2α with HIF-1β. Preclinical and clinical data indicate that these new molecules are effective in blocking cancer cell growth, proliferation, and tumor angiogenesis characteristic in ccRCC.Treatment with HIF-2α specific antagonists, either alone or in combination with immunotherapy or other antiangiogenic agents have the potential to transform the therapeutic landscape in this tumor in the future. Herein, we summarize the molecular background behind the use of HIF-2α inhibitors in ccRCC and give an overview of the development of new agents in this setting.



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Early disturbances in multimodal evoked potentials as a prognostic factor for long-term disability in relapsing-remitting multiple sclerosis patients

Publication date: Available online 28 January 2017
Source:Clinical Neurophysiology
Author(s): Frédéric London, Souraya El Sankari, Vincent van Pesch
ObjectiveThe aim of this study was to investigate whether early alterations in evoked potentials (EP) have a prognostic value in relapsing-remitting multiple sclerosis (RRMS).MethodsWe retrospectively selected 108 early MS patients with a neurological follow-up ranging from 5 to 15 years, in whom multimodal EPs (visual, brainstem auditory, somatosensory and motor) were performed at diagnosis. A conventional ordinal score was used to quantify the observed abnormalities.ResultsThe extent of change in the composite EP score was well correlated to the Expanded Disability Status Scale (EDSS) at ten years (Y10) and up to 15 years (Y11-15) after disease onset. Analysis of the predictive value of the EP score showed an increased risk of disability progression at Y10 and Y11-15 of 60% (p < 0.0001) and 73% (p < 0.0001) respectively in patients with an EP score >4. Conversely, the risk of disability progression at Y10 and Y11-15 associated with a lower EP score (⩽ 4) was reduced to 16% and 20% respectively.ConclusionsOur data support the good predictive value for long-term disability progression of multimodal EPs performed early after disease onset in RRMS patients.SignificanceThis study, performed in a homogeneous RRMS cohort with long term follow-up, demonstrates the value of an early comprehensive neurophysiological assessment as a marker for future disability.



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When EEG is bad for you

Publication date: Available online 28 January 2017
Source:Clinical Neurophysiology
Author(s): Selim R. Benbadis, Pierre Thomas




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Subthalamic or Red Nucleus? A puzzling question arising during intraoperative recording for DBS

Publication date: Available online 28 January 2017
Source:Clinical Neurophysiology
Author(s): A. Merola, G. Mandybur, K. Biddell, T.K. Tareen, H. Wilson-Perez, A.J. Espay, A.P. Duker




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Targeting HIF-2 α in clear cell renal cell carcinoma: A promising therapeutic strategy

Publication date: Available online 28 January 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Olga Martínez-Sáez, Pablo Gajate Borau, Teresa Alonso-Gordoa, Javier Molina-Cerrillo, Enrique Grande
The loss of the Von Hippel-Lindau tumor suppressor (VHL) is a key oncogenic event in the vast majority of patients with clear cell renal cell carcinoma (ccRCC). With the loss of the VHL protein (pVHL) function, the hypoxia inducible factor α (HIF-α) accumulates inside the tumor cell and dimerizes with HIF-β. The HIF-α/HIF-β complex transcriptionally activates hundreds of genes promoting the adaptation to hypoxia that is implicated in tumor development. There is growing evidence showing that HIF-2α subunit has a central role in ccRCC over HIF-1α. Thus, efforts have been made to specifically target this pathway. PT2385 and PT2399 are first-in-class, orally available, small molecule inhibitors of HIF-2 that selectively disrupt the heterodimerization of HIF-2α with HIF-1β. Preclinical and clinical data indicate that these new molecules are effective in blocking cancer cell growth, proliferation, and tumor angiogenesis characteristic in ccRCC.Treatment with HIF-2α specific antagonists, either alone or in combination with immunotherapy or other antiangiogenic agents have the potential to transform the therapeutic landscape in this tumor in the future. Herein, we summarize the molecular background behind the use of HIF-2α inhibitors in ccRCC and give an overview of the development of new agents in this setting.



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Editorial Board Members

Publication date: 1 January 2017
Source:Advanced Drug Delivery Reviews, Volume 108





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Editorial: Editors’ Collection 2016

Publication date: 1 January 2017
Source:Advanced Drug Delivery Reviews, Volume 108
Author(s): Hamidreza Ghandehari




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Challenges and strategies in anti-cancer nanomedicine development: An industry perspective

Publication date: 1 January 2017
Source:Advanced Drug Delivery Reviews, Volume 108
Author(s): Jennifer I. Hare, Twan Lammers, Marianne B. Ashford, Sanyogitta Puri, Gert Storm, Simon T. Barry
Successfully translating anti-cancer nanomedicines from pre-clinical proof of concept to demonstration of therapeutic value in the clinic is challenging. Having made significant advances with drug delivery technologies, we must learn from other areas of oncology drug development, where patient stratification and target-driven design have improved patient outcomes. We should evolve our nanomedicine development strategies to build the patient and disease into the line of sight from the outset. The success of small molecule targeted therapies has been significantly improved by employing a specific decision-making framework, such as AstraZeneca's 5R principle: right target/efficacy, right tissue/exposure, right safety, right patient, and right commercial potential. With appropriate investment and collaboration to generate a platform of evidence supporting the end clinical application, a similar framework can be established for enhancing nanomedicine translation and performance. Building informative data packages to answer these questions requires the following: (I) an improved understanding of the heterogeneity of clinical cancers and of the biological factors influencing the behaviour of nanomedicines in patient tumours; (II) a transition from formulation-driven research to disease-driven development; (III) the implementation of more relevant animal models and testing protocols; and (IV) the pre-selection of the patients most likely to respond to nanomedicine therapies. These challenges must be overcome to improve (the cost-effectiveness of) nanomedicine development and translation, and they are key to establishing superior therapies for patients.

Graphical abstract

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Investigation of Asymmetric and Symmetric Dimethylarginine Levels after Iloprost Treatment in Patients with Buerger's Disease

Publication date: Available online 28 January 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): S. Senol, A. Senol
ObjectiveThe aim of this study was to compare the levels of acetyl-dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and the l-arginine/ADMA ratio before and after iloprost treatment in patients with Buerger's disease.MethodsBetween January 2011 and December 2015, data from 44 patients (36 males, 8 females, mean age 48.7 ± 18.1 years) with the diagnosis of Fontaine Stage III–IV Buerger's disease were included. Iloprost infusion was administered intravenously through the forearm veins for 7 days at a dose of 0.5–1.5 ng/kg/min over 16 h. Blood samples were collected before and after treatment for measurement of ADMA, SDMA, and l-arginine. ADMA, SDMA, l-arginine levels were measured using high performance liquid chromatography (HPLC).ResultsAfter iloprost treatment, ADMA and SDMA levels significantly decreased (p = .001). The increase in the l-arginine levels was not significant (p = .16). However, the l-arginine/ADMA ratio increased significantly (p = .001).ConclusionIloprost treatment decreases ADMA and SDMA, which are associated with endothelial dysfunctions in patients with Buerger's disease. Of note, the still higher than normal range of SDMA levels after iloprost treatment suggests that treatment should continue until SDMA levels are within the normal range in this patient population.



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Formulating a poorly water soluble drug into an oral solution suitable for paediatric patients; lorazepam as a model drug

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): A.C. van der Vossen, I. van der Velde, O.S.N.M. Smeets, D.J. Postma, M. Eckhardt, A. Vermes, B.C.P. Koch, A.G. Vulto, L.M. Hanff
IntroductionMany drugs are unavailable in suitable oral paediatric dosage forms, and pharmacists often have to compound drugs to provide paediatric patients with an acceptable formulation in the right dose. Liquid formulations offer the advantage of dosing flexibility and ease of administration to young patients, but drug substances often show poor aqueous solubility. The objective of this work was to study different solvents and matrices to design a liquid formulation for poorly water soluble drugs, using lorazepam as model drug.MethodsThree different formulation strategies were explored to improve the solubility. Firstly, water-soluble organic solvents were used to improve the aqueous solubility directly, secondly, ionic surfactants were used to solubilise the model drug, and thirdly, complexation of lorazepam with cyclodextrin was studied. Specific attention was paid to excipients, adequate taste correction and palatability. For the final formulation, physical and chemical stability and microbiological quality were assessed for 12months.ResultsAn organic solvent based formulation, containing a mixture of polyethylene glycol and glycerol 85%, with a minimum amount of propylene glycol, proved to be physically and chemically stable. Development of the non-ionic surfactants formulation was discontinued due to taste problems. The cyclodextrin formulations were physically stable, but lorazepam content declined to 90% within five months. The final formulation contained in volume concentration (%v/v) 87% glycerol, 10% polyethylene glycol 400 and 3% propylene glycol. Orange essence was the preferred taste corrector. The formulation remained stable for 12months at 4°C, with lorazepam content remaining >95%. Related substances increased during the study period but remained below 2%. In-use stability was proven up to 4weeks.ConclusionAn organic solvent based oral formulation was shown to be superior to a non-ionic surfactant based formulation or a cyclodextrin formulation. These results may help to formulate paediatric formulations of other poorly water soluble drugs, to aid pharmacy compounding.

Graphical abstract

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American Thyroid Association (ATA) is looking for patients with hypothyroidism taking hormone treatment to complete survey

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The post American Thyroid Association (ATA) is looking for patients with hypothyroidism taking hormone treatment to complete survey appeared first on American Thyroid Association.

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Epigallocatechin gallate induces a hepatospecific decrease in the CYP3A expression level by altering intestinal flora

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): Nobutomo Ikarashi, Sosuke Ogawa, Ryuta Hirobe, Risako Kon, Yoshiki Kusunoki, Marin Yamashita, Nanaho Mizukami, Miho Kaneko, Nobuyuki Wakui, Yoshiaki Machida, Kiyoshi Sugiyama
In previous studies, we showed that a high-dose intake of green tea polyphenol (GP) induced a hepatospecific decrease in the expression and activity of the drug-metabolizing enzyme cytochrome P450 3A (CYP3A). In this study, we examined whether this decrease in CYP3A expression is induced by epigallocatechin gallate (EGCG), which is the main component of GP. After a diet containing 1.5% EGCG was given to mice, the hepatic CYP3A expression was measured. The level of intestinal bacteria of Clostridium spp., the concentration of lithocholic acid (LCA) in the feces, and the level of the translocation of pregnane X receptor (PXR) to the nucleus in the liver were examined. A decrease in the CYP3A expression level was observed beginning on the second day of the treatment with EGCG. The level of translocation of PXR to the nucleus was significantly lower in the EGCG group. The fecal level of LCA was clearly decreased by the EGCG treatment. The level of intestinal bacteria of Clostridium spp. was also decreased by the EGCG treatment. It is clear that the hepatospecific decrease in the CYP3A expression level observed after a high-dose intake of GP was caused by EGCG. Because EGCG, which is not absorbed from the intestine, causes a decrease in the level of LCA-producing bacteria in the colon, the level of LCA in the liver decreases, resulting in a decrease in the nuclear translocation of PXR, which in turn leads to the observed decrease in the expression level of CYP3A.

Graphical abstract

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Endocrine Pathology Society Hubert Wolfe Award for 2016: Call for Nominations

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Targeting HIF-2 α in clear cell renal cell carcinoma: A promising therapeutic strategy

Publication date: Available online 28 January 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Olga Martínez-Sáez, Pablo Gajate Borau, Teresa Alonso-Gordoa, Javier Molina-Cerrillo, Enrique Grande
The loss of the Von Hippel-Lindau tumor suppressor (VHL) is a key oncogenic event in the vast majority of patients with clear cell renal cell carcinoma (ccRCC). With the loss of the VHL protein (pVHL) function, the hypoxia inducible factor α (HIF-α) accumulates inside the tumor cell and dimerizes with HIF-β. The HIF-α/HIF-β complex transcriptionally activates hundreds of genes promoting the adaptation to hypoxia that is implicated in tumor development. There is growing evidence showing that HIF-2α subunit has a central role in ccRCC over HIF-1α. Thus, efforts have been made to specifically target this pathway. PT2385 and PT2399 are first-in-class, orally available, small molecule inhibitors of HIF-2 that selectively disrupt the heterodimerization of HIF-2α with HIF-1β. Preclinical and clinical data indicate that these new molecules are effective in blocking cancer cell growth, proliferation, and tumor angiogenesis characteristic in ccRCC.Treatment with HIF-2α specific antagonists, either alone or in combination with immunotherapy or other antiangiogenic agents have the potential to transform the therapeutic landscape in this tumor in the future. Herein, we summarize the molecular background behind the use of HIF-2α inhibitors in ccRCC and give an overview of the development of new agents in this setting.



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Instructions to Authors

Publication date: February 2017
Source:The Kaohsiung Journal of Medical Sciences, Volume 33, Issue 2





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Source:The Kaohsiung Journal of Medical Sciences, Volume 33, Issue 2





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Source:The Kaohsiung Journal of Medical Sciences, Volume 33, Issue 2





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Publication date: February 2017
Source:The Kaohsiung Journal of Medical Sciences, Volume 33, Issue 2





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Publication date: February 2017
Source:The Kaohsiung Journal of Medical Sciences, Volume 33, Issue 2





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A Deep Learning Approach for the Analysis of Masses in Mammograms with Minimal User Intervention

Publication date: Available online 28 January 2017
Source:Medical Image Analysis
Author(s): Neeraj Dhungel, Gustavo Carneiro, Andrew P. Bradley
We present an integrated methodology for detecting, segmenting and classifying breast masses from mammograms with minimal user intervention. This is a long standing problem due to low signal-to-noise ratio in the visualisation of breast masses, combined with their large variability in terms of shape, size, appearance and location. We break the problem down into three stages: mass detection, mass segmentation, and mass classification. For the detection, we propose a cascade of deep learning methods to select hypotheses that are refined based on Bayesian optimisation. For the segmentation, we propose the use of deep structured output learning that is subsequently refined by a level set method. Finally, for the classification, we propose the use of a deep learning classifier, which is pre-trained with a regression to hand-crafted feature values and fine-tuned based on the annotations of the breast mass classification dataset. We test our proposed system on the publicly available INbreast dataset and compare the results with the current state-of-the-art methodologies. This evaluation shows that our system detects 90% of masses at 1 false positive per image, has a segmentation accuracy of around 0.85 (Dice index) on the correctly detected masses, and overall classifies masses as malignant or benign with sensitivity (Se) of 0.98 and specificity (Sp) of 0.7.

Graphical abstract

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Systemic sclerosis and exposure to heavy metals: A case control study of 100 patients and 300 controls

Publication date: Available online 27 January 2017
Source:Autoimmunity Reviews
Author(s): I. Marie, J-F. Gehanno, M. Bubenheim, A-B. Duval-Modeste, P. Joly, S. Dominique, P. Bravard, D. Noël, A-F. Cailleux, J. Weber, P. Lagoutte, J. Benichou, H. Levesque, J-P. Goullé
Objective.This case control study assessed: the relationship of systemic sclerosis (SSc) related to exposure to heavy metals, the risk of SSc related to occupational exposure in male and female patients.MethodsFrom 2005 to 2008, 100 patients with a definite diagnosis of SSc were included in the study; 3 age, gender, and smoking habits matched controls were selected for each patient. All SSc patients and controls underwent detection and quantification of heavy metal traces in hair samples, using multi-element inductively coupled plasma mass spectrometry (ICP-MS).ResultsSSc patients exhibited higher median levels of the following metals: antimony (p=0.001), cadmium (p=0.0003), lead (p=0.02), mercury (p=0.02), molybdenum (p=0.04), palladium (p<0.001) and zinc (p=0.0003). A marked association between SSc and occupational exposure was further found for: 1) antimony (p=0.008) and platinum (p=0.04) in male patients; and 2) antimony (p=0.02), cadmium (p=0.001), lead (p=0.03), mercury (p=0.03), palladium (p=0.0003) and zinc (p=0.0001) in female patientsConclusionThe results show the impact of occupational risk factors in the development of SSc for: antimony, cadmium, lead, mercury, molybdenum, palladium and zinc. Thus, occupational exposure should be systematically checked in all SSc patients at diagnosis. Finally, the association between SSc and occupational exposure may be variable according to patients" gender.



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Inflammatory eye disease: pre-treatment assessment of patients prior to commencing immunosuppressive and biologic therapy: Recommendations from an expert committee

Publication date: Available online 27 January 2017
Source:Autoimmunity Reviews
Author(s): Denis Wakefield, Peter McCluskey, Gerhild Wildner, Stephan Thurau, Gregory Carr, Soon-Phaik Chee, John Forrester, Andrew Dick, Bernard Hudson, Susan Lightman, Justine Smith, Ilknur Tugal-Tutkun
AimTo outline recommendations from an expert committee on the assessment and investigation of patients with severe inflammatory eye disease commencing immunosuppressive and/or biologic therapy.MethodThe approach to assessment is based on the clinical experience of an expert committee and a review of the literature with regard to corticosteroids, immunosuppressive drug and biologic therapy and other adjunct therapy in the management of patients with severe sight-threatening inflammatory eye disease.ConclusionWe recommend a careful assessment and consultative approach by ophthalmologists or physicians experienced in the use of immunosuppressive agents for all patients commencing immunosuppressive and/or biologic therapy for sight threatening inflammatory eye disease with the aim of preventing infection, cardiovascular, metabolic and bone disease and reducing iatrogenic side effects.



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Gender balance in patients with systemic lupus erythrematosus

Publication date: Available online 27 January 2017
Source:Autoimmunity Reviews
Author(s): Audrey A Margery-Muir, Christine Bundell, Delia Nelson, David M Groth, John D Wetherall
Factors are reviewed that contribute to the contemporary view of a disproportionate prevalence and incidence SLE in females. Recent studies on the epidemiology of SLE report that global Incidences and prevalences of SLE for Caucasian and Black populations are of the order of 5.5 and 13.1 per year and 81 and 212 per 100,000 persons respectively. Both parameters displayed age dependent variation over a 90-year lifespan. The female to male (F:M) incidence of SLE varied with age, being approximately 1 during the first decade of life, followed by a sharp increase to 9 during the 4th decade, thence declining in subsequent decades before an increase during the 7th or 8th decades. A cognate review of SLE diagnosis in neonates revealed a F:M ratio of ≈1.2, consistent with the epidemiology review and the sporadic nature of SLE. Notional estimates of disease duration showed a steady increase from a base level for both males and females. The linear trend line for males was always lower than the trend line for females, supporting clinical experience that SLE is a more severe disease in males. Over a 14-year interval ending in 2012, the notional duration of SLE increased from 10 to 15years to 20–25years, probably reflecting advances in diagnosis and clinical practice.A metastudy of SLE concordance in twins revealed a 75% discordance in monozygotic twins compared to a 95% discordance in dizygotic twins confirming the importance of environmental factors in susceptibility to SLE. The elevated discordance in dizygotic SLE twins (and between siblings) suggests a role for the intrinsic genomic sexual dimorphism due to divergence of Y chromosome regulatory loci from their X chromosome homologues due to lack of recombination of mammalian sex chromosomes over evolutionary time.Estimates were made of the incidences of SLE in males and females based on population data for nine autosomal deficiency loci of major effect, plus expected male prevalence associated with Kleinfelter's syndrome and female prevalence associated with Triple X syndrome. These genetic abnormalities accounted for ≈4% of female and ≈23% of male Caucasoid prevalence and for SLE resulting in a F:M ratio of ≈0.17. It may be deduced therefore that the impressive preponderance of SLE in females arises from a combination of environmental triggers and susceptibility loci of relatively small effect acting between the interval from the mini-puberty of childhood to the peak of reproductive adulthood. It is in this cohort of females, and especially in the black population, that combinations of loci of minor effect acting together with environmental factors initiate defective apoptosis resulting in consequential autoimmune disease especially SLE. We postulate that because apoptosis is itself a very complex process, and defective apoptosis is an important contributor to SLE, there will be many combinations of susceptibility loci and environmental stimuli that can result in SLE (and other autoimmune disease(s)), of varying severity.



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Characterization of isolated retinal vasculitis. Analysis of a cohort from a single center and literature review

Publication date: Available online 27 January 2017
Source:Autoimmunity Reviews
Author(s): Laura Pelegrín, José Hernández-Rodríguez, Gerard Espinosa, Víctor Llorenç, Maite Sainz-de-la-Maza, José R. Fontenla, José A. Martínez, Maria C. Cid, Alfredo Adán
IntroductionIsolated retinal vasculitis (IRV) is an inflammatory condition of unknown etiology confined to the retinal vessels. In contrast to secondary retinal vasculitis (RV), IRV has not been well characterized.ObjectiveTo describe and characterize isolated forms of RV.MethodsWe performed a retrospective review (2006–2016) of IRV patients from a multidisciplinary Uveitis Unit. RV diagnosis was based on funduscopic and fluorescein angiography findings. To distinguish between secondary RV and IRV, evaluations included clinical assessment, laboratory inflammatory, autoimmune and microbiological markers and chest radiography. Ophthalmological features at disease onset, therapeutic interventions, ocular relapses, visual outcomes and laboratory findings were recorded. Our cases were subsequently compared with those from a literature review.ResultsAmong 192 patients with RV, 11 (5.7%) were diagnosed with IRV. Seven patients with initially presumed IRV were reclassified as secondary after further evaluation. IRV generally affected adult women. Bilateral ocular involvement and retinal phlebitis were common findings. 72% of patients presented with visual loss, which was severe in 27%. Treatments used included systemic glucocorticoids (82%), additional immunosuppressive agents (27%), intravitreal therapy (37%), panretinal photocoagulation (37%) and pars plana vitrectomy (26%). The annual relapse rate was 0.46. Although final visual acuity was considered good in 86%, 45% experienced worsening and only 27% improved.ConclusionsIRV is a rare sight-threatening condition. Despite intensive local and systemic immunosuppressive treatment, visual improvement is observed in only 27% of cases. When IRV is suspected, a differential diagnosis excluding a systemic disease is always warranted. A multidisciplinary approach and a guided clinical, laboratory and imaging evaluation has proven to be useful to distinguish retinal single-organ vasculitis from secondary forms of RV.



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Can innate and autoimmune reactivity forecast early and advance stages of age-related macular degeneration?

Publication date: Available online 28 January 2017
Source:Autoimmunity Reviews
Author(s): Grazyna Adamus
Age-related macular degeneration (AMD) is a major cause of central vision loss in persons over 55years of age in developed countries. AMD is a complex disease in which genetic, environmental and inflammatory factors influence its onset and progression. Elevation in serum anti-retinal autoantibodies, plasma and local activation of complement proteins of the alternative pathway, and increase in secretion of proinflammatory cytokines have been seen over the course of disease. Genetic studies of AMD patients confirmed that genetic variants affecting the alternative complement pathway have a major influence on AMD risk. Because the heterogeneity of this disease there is no sufficient strategy to identify the disease onset and progression sole based eye examination, thus identification of reliable serological biomarkers for diagnosis, prognosis and response to treatment by sampling patient's blood. This review provides an outline of the current knowledge on possible serological (autoantibodies, complement factors, cytokines, chemokines) and related genetic biomarkers relevant to the pathology of AMD, and discusses their application for prediction of disease activity and prognosis in AMD.



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Microglia in CNS development: shaping the brain for the future

Publication date: Available online 28 January 2017
Source:Progress in Neurobiology
Author(s): Coralie-Anne Mosser, Sofia Baptista, Isabelle Arnoux, Etienne Audinat
Microglial cells are the resident macrophages of the central nervous system (CNS) and are mainly known for their roles in neuropathologies. However, major recent developments have revealed that these immune cells actively interact with neurons in physiological conditions and can modulate the fate and functions of synapses. Originating from myeloid precursors born in the yolk sac, microglial cells invade the CNS during early embryonic development. As a consequence they can potentially influence neuronal proliferation, migration and differentiation as well as the formation and maturation of neuronal networks, thereby contributing to the entire shaping of the CNS. We review here recent evidence indicating that microglial cells are indeed involved in crucial steps of the CNS development, including neuronal survival and apoptosis, axonal growth, migration of neurons, pruning of supernumerary synapses and functional maturation of developing synapses. We also discuss current hypotheses proposing that diverting microglial cells of their physiological functions, by promoting the expression of an immune phenotype during development, may be central to neurodevelopmental disorders such as autism, schizophrenia and epilepsy.



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Practice makes perfect: Performance optimisation in ‘arboreal’ parkour athletes illuminates the evolutionary ecology of great ape anatomy

Publication date: February 2017
Source:Journal of Human Evolution, Volume 103
Author(s): Lewis G. Halsey, Samuel R.L. Coward, Robin H. Crompton, Susannah K.S. Thorpe
An animal's size is central to its ecology, yet remarkably little is known about the selective pressures that drive this trait. A particularly compelling example is how ancestral apes evolved large body mass in such a physically and energetically challenging environment as the forest canopy, where weight-bearing branches and lianas are flexible, irregular and discontinuous, and the majority of preferred foods are situated on the most flexible branches at the periphery of tree crowns. To date the issue has been intractable due to a lack of relevant fossil material, the limited capacity of the fossil record to reconstruct an animal's behavioural ecology and the inability to measure energy consumption in freely moving apes. We studied the oxygen consumption of parkour athletes while they traversed an arboreal-like course as an elite model ape, to test the ecomorphological and behavioural mechanisms by which a large-bodied ape could optimize its energetic performance during tree-based locomotion. Our results show that familiarity with the arboreal-like course allowed the athletes to substantially reduce their energy expenditure. Furthermore, athletes with larger arm spans and shorter legs were particularly adept at finding energetic savings. Our results flesh out the scanty fossil record to offer evidence that long, strong arms, broad chests and a strong axial system, combined with the frequent use of uniform branch-to-branch arboreal pathways, were critical to off-setting the mechanical and energetic demands of large mass in ancestral apes.



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The Middle Stone Age human fossil record from Klasies River Main Site

Publication date: February 2017
Source:Journal of Human Evolution, Volume 103
Author(s): Frederick E. Grine, Sarah Wurz, Curtis W. Marean
The paleoanthropological significance of Klasies River Main Site derives from its abundant Middle Stone Age (MSA) archaeological debris and the hominin fossils that have featured in discussions about modern human emergence. Despite their significance, the human remains have yet to be contextualized within the spatial, stratigraphic and geochronological framework of the site. We provide an updated overview of the stratigraphy and geochronology of the site, and review the human fossil record in this context. We also provide the first anatomical interpretations of many of the cranial vault fragments. Five hominin specimens derive from the Upper Member and six from the lowermost LBS Member. The vast majority – nearly 40 cataloged specimens – come from the SAS Member; many of these are from a single stratigraphic horizon in a relatively small area in Cave 1. There is a strong cranial bias to the sample; just over 70% of skeletal remains are from the skull. The postcranial skeleton is poorly represented. Excluding the three metatarsals, there are only three long bones in the sample – a clavicle, a proximal radius, and a proximal ulna. Remarkably, humeral, femoral and tibial diaphyses, which are the most durable elements in terms of cortical bone thickness and density, are absent. However, the proportional representation of hominin remains is reminiscent of the "Klasies Pattern" shown by the MSA large bovid skeletal parts. To some degree, this may reflect the excavation and recovery methods that were employed. The vast bulk of the human fossils represent adults. Only three undoubted juvenile individuals are represented – each by a deciduous tooth. This contrasts with other MSA sites along the southern coast of South Africa, where human remains are predominantly juvenile, usually in the form of (possibly exfoliated) deciduous teeth. However, this apparent dissimilarity may also reflect different excavation techniques.



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Clinical Thyroidology High-Impact Articles

FREE ACCESS through February 10, 2017
Read Now:

Does Meta-Analysis Prove Which Factors Predict Relapse After Antithyroid Drugs Are Discontinued?
Stephen W. Spaulding

Thyroid Cancer Overdiagnosis Is a Result of Screening Programs in South Korea
Elizabeth N. Pearce

The Increased Incidence of Thyroid Cancer Is Worldwide
Jerome M. Hershman

Lymph Node Mapping with Ultrasound Is Highly Useful in the Preoperative Workup of Patients with Thyroid Cancer
Martin Biermann

 

The post Clinical Thyroidology High-Impact Articles appeared first on American Thyroid Association.

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Nanotechnology for delivery of gemcitabine to treat pancreatic cancer

Publication date: April 2017
Source:Biomedicine & Pharmacotherapy, Volume 88
Author(s): Gebremariam Birhanu, Hamid Akbari Javar, Ehsan Seyedjafari, Ali Zandi-Karimi
Pancreatic cancer (PC) is one of the most deadly and quickly fatal human cancers with a 5-year mortality rate close to 100%. Its prognosis is very poor, mainly because of its hostile biological behavior and late onset of symptoms for clinical diagnosis; these bring limitations on therapeutic interventions. Factors contributing for the difficulties in treating PC include: high rate of drug resistance, fast metastasis to different organs, poor prognosis and relapse of the tumor after therapy. After being approved by US FDA 1997, Gemcitabine (Gem) is the first line and the gold standard drug for all stages of advanced PC till now. However, its efficacy is unsatisfactory, mainly due to; its chemical instability and poor cellular uptake, resulting in an extremely short half-life and low bioavailability. To solve this drawbacks and increase the therapeutic outcome important progress has been achieved in the field of nanotechnology and offers a promising and effective alternative. This review mainly focus on the most commonly investigated nanoparticle (NP) delivery systems of Gem for PC treatment and the latest progresses achieved. Novel nanocarriers with better tumor targeting efficiencies and maximum treatment outcome to treat this deadly due are given much attention.



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Factors Associated with the Use of Hyaluronic Acid and Corticosteroid Injections among Patients with Radiographically Confirmed Knee Osteoarthritis: A Retrospective Data Analysis

Publication date: Available online 28 January 2017
Source:Clinical Therapeutics
Author(s): Kate L. Lapane, Shao-Hsien Liu, Catherine E. Dubé, Jeffrey B. Driban, Timothy E. McAlindon, Charles B. Eaton
PurposeDespite the rapid proliferation of hyaluronate (HA) and corticosteroid (CO) injections and clinical guidelines regarding their use in osteoarthritis (OA), information on the characteristics of people receiving these injections is scarce. We describe the use of injections among adults with radiographically confirmed knee OA and identify factors associated with injection use.MethodsWe used publicly available data from the Osteoarthritis Initiative (OAI), an international collaboration sponsored by the National Institutes of Health, and included participants with ≥1 radiographically confirmed knee OA (Kellgren-Lawrence grade ≥2 [definite osteophytes and possible joint space narrowing (JSN) on anteroposterior weight-bearing radiograph]) at baseline. We matched 415 participants who received at least 1 HA and/or CO injection during the 6-month interval before 1 of the first 7 annual follow-up assessments to 1841 injection nonusers by randomly selecting a study visit to match the distribution observed in the injection users. Multinomial logistic regression models were used for identifying factors associated with injection use, including sociodemographic and clinical/functional factors.FindingsEighteen percent of the 2256 patients identified as having knee OA had received at least 1 injection (years 1–7, 16.9%, 13.7%, 16.6%, 13.5%, 15.9%, 13.5%, and 9.9%, respectively), most commonly with CO (68.4%). HA and CO were more commonly injected in those with a higher annual household income (adjusted odds ratio [aOR] [95% CI] with HA, US ≥$50,000 vs <$25,000, 3.63; [1.20–10.99]) and less commonly in black patients (HA, 0.19 [0.06–0.55]). Greater Kellgren-Lawrence grade (grade 4 vs 2) was associated with an increased likelihood (aOR [95% CI]) of having received HA (4.79 [2.47–9.30]), CO (1.56 [1.04–2.34]), or both (4.94 [1.99–12.27]).ImplicationsThe receipt of HA or CO injection may be associated with higher socioeconomic positioning and indicators of greater disease severity in patients with knee OA.



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Phosphodiesterase Type 5 Inhibitors for the Treatment of Erectile Dysfunction: Pharmacology and Clinical Impact of the Sildenafil Citrate Orodispersible Tablet Formulation

Publication date: Available online 28 January 2017
Source:Clinical Therapeutics
Author(s): Francesco Scaglione, Shaantanu Donde, Tarek A. Hassan, Emmanuele A. Jannini
PurposeThe purpose of this review is to provide an overview of the pharmacology, tolerability, and efficacy of the different phosphodiesterase type 5 (PDE5) inhibitors available for the treatment of erectile dysfunction (ED), with a special focus on the sildenafil orodispersible tablet (ODT) formulation.MethodsA literature search was performed in PubMed, EMBASE, and Cochrane Reviews using the terms erectile dysfunction, patient preference, sildenafil, and PDE5 inhibitors to identify articles published in English between May 1, 2006, and November 18, 2016. A total of 29 studies were included in this review.FindingsThere are substantial data in the literature on the use of PDE5 inhibitors for the treatment of ED. Oral PDE5 inhibitors have been found to be efficacious in the treatment of ED based on results from standard tools used to assess treatment outcomes, such as the Global Assessment Questionnaire 1. In addition, PDE5 inhibitors are defined as well tolerated because of the low occurrence of serious adverse effects or discomfort. Mild adverse reactions, compared with a placebo, include headache, flushing, dyspepsia, abnormal vision, nasal congestion, back pain, myalgia, nausea, dizziness, and rash. Both the film-coated tablet and ODT formulations of sildenafil with or without water have equivalent systemic exposure. However, use of a sildenafil ODT formulation offers a convenient alternative method of administration that would be advantageous for patients with ED.ImplicationsAccording to the published literature, the PDE5 inhibitors are considered an effective and well-tolerated option for the treatment of ED as determined by data generated from standard instruments used in the assessment of treatment outcomes in ED and reported types and severity of adverse effects. The sildenafil ODT formulation, which disintegrates rapidly in the mouth, is an alternative to the solid film-coated tablet formulation that offers administration benefit with the potential to improve treatment adherence, thereby enhancing the sexual health and sense of psychological well-being of patients and their partners.



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Cost-effectiveness Analysis for Apixaban in the Acute Treatment and Prevention of Venous Thromboembolism in the Netherlands

Publication date: Available online 28 January 2017
Source:Clinical Therapeutics
Author(s): Lisa A. de Jong, Evgeni Dvortsin, Kristel J. Janssen, Maarten J. Postma
PurposeLow-molecular weight heparin (LMWH) followed by vitamin K antagonists (VKAs) are the current standard treatment of acute venous thromboembolism (VTE) and prevention of recurrent VTE. The direct oral anticoagulant apixaban was recently found noninferior in efficacy and superior in preventing major bleeding compared with LMWH/VKAs in the AMPLIFY (Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy) trial. The objective of this study was to calculate the cost-effectiveness of apixaban compared with LMWH/VKA in the treatment of acute VTE and prevention of recurrent VTE in the Netherlands.MethodsA Markov model was designed to simulate a cohort of 1,000 VTE patients receiving either apixaban or LMWH/VKA. Transition probabilities, costs, and utilities were obtained from the AMPLIFY trial and other literature. The incremental cost-effectiveness ratio (ICER) was calculated from the societal perspective; therefore, the model included both direct (inside and outside the health care sector) and indirect costs. In the univariate and probabilistic sensitivity analyses (PSAs) the robustness of the results was tested, and various additional scenario analyses were conducted.FindingsIn the base-case analysis, apixaban saved €236 and 0.044 quality-adjusted life years (QALYs) and 0.039 LYs were gained compared with LMWH/VKA. In the univariate sensitivity analysis the model appeared to be robust. The results of 2,000 iterations in the PSA found that the probability of apixaban being cost-effective at a willingness-to-pay threshold of €20,000/QALY was 100% and cost-saving was 94%. The scenario of 18-month treatment duration was the only scenario not indicating cost-savings with an ICER of €425/QALY.ImplicationsIn acute anticoagulation use apixaban was found to be cost-saving. A longer anticoagulation period (18 months) resulted in a higher difference in drug costs, indicating a higher ICER. The cost-effectiveness of long-term or life-long use should be examined in future research.



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Photoactive materials based on semiconducting nanocarbons-A challenge opening new possibilities for photocatalysis

Publication date: Available online 28 January 2017
Source:Journal of Energy Chemistry
Author(s): Siglinda Perathoner, Claudio Ampelli, Shiming Chen, Rosalba Passalacqua, Dangsheng Su, Gabriele Centi
This perspective paper introduces the concept that nanocarbons and related materials such as carbon dots are an interesting intrinsic photocatalytic semiconducting material, and not only a modifier of the existing (semiconducting) materials to prepare hybrid materials. The semiconducting properties of the nanocarbons, and the possibility to have the band gap within the visible-light region through defect band engineering, introduction of light heteroatoms and control/manipulation of the curvature or surface functionalization are discussed. These materials are conceptually different from the "classical" semiconducting photocatalysts, because semiconductor domains with tuneable characteristics are embedded in a conductive carbon matrix, with the presence of various functional groups (as C=O groups) enhancing charge separation by trapping electrons. These nanocarbons open a range of new possibilities for photocatalysis both for energetic and environmental applications. The use of nanocarbons as quantum dots and photoluminescent materials was also analysed.

Graphical abstract

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Dynamic versus Isometric Electromechanical Delay in Non-Fatigued and Fatigued Muscle: A Combined Electromyographic, Mechanomyographic, and Force Approach

Publication date: Available online 27 January 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Cory M. Smith, Terry J. Housh, Ethan C. Hill, Glen O. Johnson, Richard J. Schmidt
This study used a combined electromyographic, mechanomyographic, and force approach to identify electromechanical delay (EMD) from the onsets of the electromyographic to force signals (EMDE-F), onsets of the electromyographic to mechanomyogrpahic signals (EMDE-M), and onsets of mechanomyographic to force signals (EMDM-F). The purposes of the current study were to examine: 1) the differences in EMDE-F, EMDE-M, and EMDM-F from the vastus lateralis during maximal, voluntary dynamic (1 repetition maximum [1-RM]) and isometric (maximal voluntary isometric contraction [MVIC]) muscle actions; and 2) the effects of fatigue on EMDE-F, EMDM-F, and EMDE-M. Ten men performed pretest and posttest 1-RM and MVIC leg extension muscle actions. The fatiguing workbout consisted of 70% 1-RM dynamic constant external resistance leg extension muscle actions to failure. The results indicated that there were no significant differences between 1-RM and MVIC EMDE-F, EMDE-M, or EMDM-F. There were, however, significant fatigue-induced increases in EMDE-F (94% and 63%), EMDE-M (107%), and EMDM-F (63%) for both the 1-RM and MVIC measurements. Therefore, these findings demonstrated the effects of fatigue on EMD measures and supported comparisons among studies which examined dynamic or isometric EMD measures from the vastus lateralis using a combined electromyographic, mechanomyographic, and force approach.



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A comparison of gluteus medius, gluteus minimus and tensor facia latae muscle activation during gait in post-menopausal women with and without greater trochanteric pain syndrome

Publication date: Available online 27 January 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Charlotte Ganderton, Tania Pizzari, Tanya Harle, Jill Cook, Adam Semciw
The effect of greater trochanteric pain syndrome (GTPS) on gluteus medius (GMed) and minimus (GMin) activation in post-menopausal women is unknown. The aim of this study was to compare segmental muscle activation and variability of the GMed, GMin and tensor fascia latae (TFL) during gait in post-menopausal women with and without GTPS.Intramuscular electrodes were inserted into segments of GMin (x2) and GMed (x3) and a surface electrode placed on TFL. Ten control participants and 8 with GTPS completed six walking trials. Peak amplitude, average amplitude and time to peak from each phase of the gait cycle (0-30%, 30%- toe off (TO), total stance and swing) were compared between groups using independent t-tests and effect-size (ES) calculations. Variability of muscle activation was calculated using the mean coefficient of variation (CV). Reversal of anterior GMin electromyographic burst pattern and greater average muscle activity was found in the GTPS group compared to controls: 0-TO for anterior GMin (p<0.05), anterior and middle GMed (p<0.01); 0-30% for posterior GMin and GMed. No significant differences were identified in TFL. Overall, this study found increased segmental gluteal muscle activation, decreased hip abduction strength, and reduced variability in muscle activation in post-menopausal women with GTPS, compared with controls.



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