A peel-off facial mask comprising myoinositol and trehalose-loaded liposomes improves adult female acne by reducing local hyperandrogenism and activating autophagy

Summary

Background

Hyperandrogenism and reduced skin autophagy have been implicated in the pathogenesis of adult female acne (AFA). Here, we tested whether a ready-to-use peel-off facial mask containing myoinositol (an androgen inhibitor) and trehalose-loaded liposomes (as activators of cutaneous autophagy) applied overnight every other day for 60 days can improve AFA. We also sought to investigate the molecular mechanisms underlying the clinical effects.

Objectives

We conducted an uncontrolled, open-label clinical study in 40 cases of AFA to investigate the effect of the facial mask on lesion count, sebum production (measured with the Sebutape® technique), and Global Acne Grading System (GAGS) scale. We also investigated the changes from baseline to the end of treatment in androgen and beclin-1 levels (as a marker of authophagy) in skin biopsy supernatants.

Methods

Forty Caucasian patients with AFA were enrolled. Changes in clinical and molecular endpoints before and after treatment were investigated.

Results

The mean counts of comedones, papules, pustules, and nodular lesions decreased significantly (all P<.001). The mean Sebutape® score was reduced from 3.4±0.6 to 1.8±0.2 (P<.001), whereas the mean GAGS scale score decreased from 16.8±5.3 at baseline to 9.8±4.6 after treatment (P<.001). A significant decrease in testosterone and dehydroepiandrosterone sulfate in skin biopsy supernatants was observed, whereas beclin-1 levels increased significantly (P<.001).

Conclusion

A ready-to-use peel-off facial mask containing myoinositol and trehalose-loaded liposomes improved the cosmetic appearance of AFA by reducing cutaneous androgen content and promoting skin autophagy.

http://ift.tt/2nSd0Mq

Overexpression of Drosha, DiGeorge syndrome critical region gene 8 (DGCR8), and Dicer mRNAs in the pathogenesis of psoriasis

Summary

Introduction

Psoriasis is a complex autoimmune inflammatory disease that occurs in genetically susceptible individuals and presents with the development of inflammatory plaques on the skin. Recent studies have indicated that microRNAs (miRNAs) play important roles in psoriasis.

Objective

To investigate whether expression of Drosha, DGCR8, and Dicer mRNAs is involved in the pathogenesis of psoriasis.

Methods

Biopsies were obtained from involved psoriatic skin (PP), noninvolved psoriatic skin (PN), and healthy skin (NN). Expression of Drosha, Dicer, and DGCR8 was assessed with real-time quantitative real-time PCR in 25 patients with psoriasis and 25 healthy volunteers.

Results

We observed that expression levels of Drosha, Dicer, and DGCR8 were upregulated in patients with psoriasis compared to the control group. However, the Drosha and Dicer expression levels were higher in PP tissues and PN tissues compared to NN tissues, but they were more upregulated in PP tissues compared to PN tissues (P<.001). Although the DGCR8 expression was higher in PP tissues and PN tissues compared to NN tissues, it was more upregulated in PN tissues compared to PP tissues (P<.001).

Conclusion

Our data demonstrate that upregulated expression of Drosha, DGCR8, and Dicer mRNAs may be involved in the pathogenesis of psoriasis.

http://ift.tt/2o1IOvm

PVDF-ionic liquid modified clay nanocomposites: Phase changes and shish-kebab structure

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): Eapen Thomas, C. Parvathy, Nisha Balachandran, S. Bhuvaneswari, K.P. Vijayalakshmi, Benny K. George
Crystalline behaviour of PVDF nanocomposite with 1-alkyl-3-methylimidazolium modified montmorillonite clay was analyzed. The phase change from α to β increased with alkyl chain length of the organic modifier in the filler; 1-alkyl-3-methylimidazolium clay and maximum conversion (99%) was observed for PVDF-1-hexadecyl-3-methylimidazolium modified clay composite with 2% loading. The phase conversion was evident from X-ray diffraction, DSC analysis and improved electrical properties. AFM analysis of PVDF-1-butyl-3-methylimidazolium montmorillonite clay composite (PVDF-C4) showed a shish-kebab structure while pristine PVDF and all other composites showed spherulite structures. Computational studies revealed that the extended chain α-phase forms the 'shish', the back bone and folded chain β-phase forms the 'kebab'. This was further supported by the superior mechanical properties for PVDF-C4 composite. Present work shows that introducing ionic liquid modified MMT-clay within the PVDF matrix enables nucleation of electroactive β phase and the presence of equal content of α and β phases can lead to the formation of self reinforced shish-kebab structures in PVDF.

Graphical abstract

http://ift.tt/2ngDWm3

Chemistry, polymer dynamics and mechanical properties of a two-part polyurethane elastomer during and after crosslinking. Part I: dry conditions

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): Bettina Zimmer, Christophe Nies, Christian Schmitt, Wulff Possart
Due to their chemical and morphological versatility, polyurethanes may be susceptible to fabrication conditions (curing procedure, moisture). Industry reports 'maturation' phenomena, i.e. unstable mechanical properties of PU elastomers and PU based adhesive joints right after fabrication. This paper elucidates the impact of fabrication conditions and possible causes of maturation. Chemical and physical bulk properties of a crosslinking two-part PU are monitored during and after cure in dry atmosphere (at room temperature followed by a post-cure). The influence of curing procedure is revealed by processes characteristic of the post-cure, i.e. chemical side reactions (allophanate, carbodiimide) and a new dielectric relaxation. Tensile tests demonstrate the practical relevance of the findings (mechanical modulus). Properties of the fully crosslinked, dryly stored PU are stable during a three-week observation, indicating that maturation is preventable by complete cure and dry conditions. In contrast, chemical crosslinking after an insufficient cure likely causes maturation phenomena.

Graphical abstract

http://ift.tt/2ngGnF3

Oxidatively stable thermosets derived from thermal copolymerization of acetylene-terminated imide monomer with an acetylenic monomer containing carborane

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): Shengli Cheng, Jianhua Han, Xin Wang, Kuanyu Yuan, Xigao Jian, Jinyan Wang
One acetylenic monomer (APCB) containing carborane with extremely thermal and thermo-oxidative stability was synthesized and used as the thermal copolymerization component with acetylene-terminated imide monomer (m-EFDA) to improve the thermal and thermo-oxidative stability of the polyimide materials. The curing behavior of the blends of imide monomer and APCB was investigated by FT-IR and DSC. Rheometer study showed that the addition of APCB into m-EFDA reduced the minimum complex viscosity of m-EFDA and lowered the temperature of the minimum viscosity. The thermal and thermo-oxidative stability of the thermoset derived from m-EFDA was greatly improved by the addition of APCB based on thermogravimetric analysis. m-EFDA with an addition of APCB at a loading level of 50 wt% exhibited a high char yield of 91.5% at 1000 °C in air and a weight retention of 95.6% was obtained after aging in air at 400 and 500 °C for 5 h, respectively.

Graphical abstract

http://ift.tt/2ngH69x

Topology driven structural transition of dendrimers with a dimensional cross-over

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): Gobind Ji Rai, Parbati Biswas
This contribution proposes the present day picture of dendrimers as a transition from a non-compact sphere to a dense space filling hyperbolic topology, which contradicts the existing perception of a dendrimer with a dense core and open periphery. The unusual maximum in the generation dependent intrinsic viscosity is analyzed within the framework of the optimized Rouse-Zimm theory with excluded volume interactions between the nearest non-bonded monomers. The position of this maximum represents the onset of this structural transition, which is accompanied by a change in the overall shape, characterized by a cross-over from the Euclidean to non-Euclidean dimensions. This structural transition is a characteristic feature of the topology of dendrimers. The actual available volume is a discontinuous function of generation, rather than a continuous cubic power-law in three dimensions. This implies that the core of dendrimers are dense, while the terminal groups are distributed throughout the core and periphery. Hence, large dendrimers, which are extremely dense objects with highly crowded peripheries exhibit fractal nature with a fractal dimension greater than 3.

Graphical abstract

http://ift.tt/2ngZYVS

Structural engineering of poly-(methacrylate) bearing push-pull type pendants oxindole-phenothiazine with tetrazole anchoring acceptor for efficient organic photovoltaic cells

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): Selvam Ramasamy, Mani Boopathy, Samuel Johnsanthoshkumar, Kathavarayan Subramanian
In this study, we report three new metal-free molecularly engineered pendant chromophore bearing polymers, coded POTZP1, POTZP2 and POTZP3. Push-pull methacrylate polymer-sensitizers consisting of phenothiazine as donor and oxindole as π-conjugating linker and tetrazole as anchoring/acceptor, were designed and synthesized for dye-sensitized solar cells (DSSCs). Optical, electrochemical and photovoltaic properties of the three polymers were systematically investigated. POTZP3-polymer incorporated di-anchoring tetrazole unit exhibited more effective inhibition of charge recombination and greater conducive to electron injection into TiO2 conduction band than the reference polymer (POTZP1) with only single anchor. Under AM 1.5 solar radiation (100 mW cm^─2), the POTZP3-based DSSC device exhibited an attractive power conversion efficiency (PCE, η) up to 5.91%, compared to 3.97% for the POTZP1-based device. The results indicate that the solar cell (TiO2/polymer) performance can be finely modulated through structural engineering of the polymer side-chain.

Graphical abstract

http://ift.tt/2ngAyHL

Swelling-diffusion-interfacial polymerized core-shell typed polystyrene/poly(3, 4-ethylenedioxythiophene) microspheres and their electro-responsive characteristics

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): Ji Su An, Il Jae Moon, Seung Hyuk Kwon, Hyoung Jin Choi
We synthesized core-shell structured conducting polystyrene/poly(3,4-ethylenedioxythiophene) (PS/PEDOT) microspheres and examined their electro-responsive electrorheological (ER) properties under an applied electric field when dispersed in a silicone oil. Monodisperse PS particles 1.05 μm in diameter were initially fabricated via dispersion polymerization, and PS/PEDOT microspheres with average diameters of approximately 1.07 μm were prepared by a swelling-diffusion-interfacial polymerization process. The morphology of the PS/PEDOT microspheres was confirmed by both field emission scanning electron microscopy and transmission electron microscopy, while their chemical structure was characterized by Fourier transform infrared spectroscopy. Formation of particle chains in the ER fluid was directly observed by optical microscopy under an applied electric field. The rheological behavior of the PS/PEDOT particle-based ER fluid was examined using a rotational rheometer on particles dispersed in silicone oil at a volume fraction of 10%. As the electric field was strengthened, the performance of the ER fluid was also enhanced. The dielectric spectra were also well correlated to their ER effects using an LCR meter.

Graphical abstract

http://ift.tt/2ngS7HL

Hypercrosslinked polyHIPEs as precursors to designable, hierarchically porous carbon foams

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): Robert T. Woodward, Arthur Jobbe-Duval, Sofia Marchesini, David B. Anthony, Camille Petit, Alexander Bismarck
Hierarchically porous carbon foams were produced by carbonization of hypercrosslinked polymerized high internal phase water-in-styrene/divinylbenzene emulsions (HIPEs). The hypercrosslinking of these poly(ST-co-DVB)HIPEs was achieved using a dimethoxymethane external crosslinker to 'knit' together aromatic groups within the polymers using Friedel-Crafts alkylation. By varying the amount of divinylbenzene (DVB) in the HIPE templates and subsequent polymers, the BET surface area and micropore volume of the hypercrosslinked analogues can be varied systematically, allowing for the production of carbon foams, or 'carboHIPEs', with varied surface areas, micropore volumes and pore-size distributions. The carboHIPEs retain the emulsion-templated macropores of the original polyHIPE, display excellent electrical conductivities and have surface areas of up to 417 m²/g, all the while eliminating the need for inorganic templates. The use of emulsion templates allows for pourable, mouldable precursors to designable carbonaceous materials.

Graphical abstract

http://ift.tt/2ngU9rw

Heterogeneity in polymer networks formed by a single copolymerization reaction: I. Gelation and pre-gel structure

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): D.M. Kroll, S.G. Croll
Coarse-grained molecular dynamics simulations of the formation of 3- and 6-functional polymer networks explicitly shows gelation via large dendritic clusters. The heterogeneous network structures are studied in detail; clusters have pendant structures and occupy significant volume fraction. Cluster fractal dimension and the Fisher exponent for cluster size are consistent with percolation theory and kinetic gelation models. Several criteria for determining gelation yield consistent results somewhat higher than the estimate for ideal networks on regular lattices. Almost all crosslink loop formation occurs after gelation just as traditional statistical theories assume. The presence and size of these clusters provide a natural explanation for density variations seen in microscopy studies of crosslinked polymers. The second paper in this series describes how the network structure develops after gelation. Large pendant structures, and more localized defects, persist and comprise a substantial fraction of material that is not contributing to network strength.

Graphical abstract

http://ift.tt/2ngAAzn

Effect of solvent on the dipole rotation of poly(vinylidene fluoride) during porous membrane formation by precipitation in alcohol baths

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): Hsu-Hsien Chang, Liang-Kuei Chang, Cheng-Dau Yang, Dar-Jong Lin, Liao-Ping Cheng
Microporous PVDF membranes were prepared by isothermal immersion precipitation of PVDF/DMSO and PVDF/TEP casting dopes in different alcohol baths. The formed membranes exhibited the so-called particulate morphology, being packed by interconnected crystalline particles of a similar size. For the alcohol/TEP/PVDF system, the particles appeared as sheaf-like spherulites consisting of curled lamellae with thickness of ∼15 nm. In contrast, for the alcohol/DMSO/PVDF system, the formed membranes comprise relatively compact globules whose surface was covered with granular objects of ca. 30 nm dia. Wide angle X-ray diffraction patterns of the membranes indicate that the sheaf-like crystals were of the α-type structure, while the compact globules the γ-type structure, as were confirmed by FTIR-ATR analyses. ¹⁹F NMR spectroscopy indicated that PVDF chains exhibited TG⁺TG⁻ conformation in TEP and T3G⁺T3G⁻ conformation in DMSO. These conformations remained unchanged during immersion-precipitation to yield the α- and γ-type crystal structures. The crystallinity of the membranes, as determined by X-ray diffraction and differential scanning calorimetry, was found to be ∼68%. Furthermore, desalination by membrane-distillation of 3.5% NaCl(aq) feed at 50 °C were carried to see the desalination capability of the membranes. High fluxes (10–13 LMH) and rejections (∼99.8%) were obtained for both types of membranes.

Graphical abstract

http://ift.tt/2ngFY5A

From a flexible hyperbranched polyimide to a microporous polyimide network: Microporous architecture and carbon dioxide adsorption

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): Hongyan Yao, Na Zhang, Kunzhi Shen, Ningning Song, Kaixiang Shi, Shiyang Zhu, Yunhe Zhang, Shaowei Guan
A dianhydride monomer 2, 5-bis(3, 4-dicarboxyphenoxy)-4′-phenylethynyl biphenyl (PEPHQDA) containing a chain extendable phenylethynyl pendant group has been successfully synthesized via successive nucleophilic substitution, Sonogashira cross-coupling, hydrolysis and dehydration reactions. A flexible microporous polyimide network has been prepared based on the use of triamine (TAPOB), affording hyperbranched polyimide, followed by the curing of phenylethynyl groups to give network structure. Specifically microporous features such as a well-defined surface morphology, microporous structure and nanometer-sized pore channels have been introduced to the flexible polyimide networks through this two-step pathway. This network exhibit a BET surface area (322 m² g⁻¹) as well as a comparable CO2 uptake (1.25 mmol g⁻¹ at 273 K and 1 bar) and enthalpy of adsorption (30.3 kJ mol⁻¹) to that of other microporous polyimides derived from rigid tridimensional monomers.

Graphical abstract

http://ift.tt/2ngRIVA

Modeling of gas solubility and permeability in glassy and rubbery membranes using lattice fluid theory

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): Sina Nabati Shoghl, Ahmadreza Raisi, Abdolreza Aroujalian
In this study, the lattice fluid (LF) and non-equilibrium lattice fluid (NELF) theories combined with the modified Fick's law and free volume theory were employed to develop mass transfer models for the prediction of gas sorption and permeation in glassy and rubbery membranes in a wide range of temperature and pressure. The finite element method using COMSOL multi-physics software was used to solve the governing transport equations. The gas sorption into the glassy membranes shows a non-equilibrium behavior in spite of the rubbery membranes in which the gas sorption is in the equilibrium state. The results indicated that the membranes with higher fractional free volume show higher solubility and diffusion coefficients. The proposed model can predict satisfactory the gas solubility and permeability in the glassy and rubbery membranes and determine the influence of operating pressure and temperature on the transport properties of the membranes without need of any adjustable parameters.

Graphical abstract

http://ift.tt/2ngZYFm

Bulk physical aging behavior of cross-linked polystyrene compared to its linear precursor: Effects of cross-linking and aging temperature

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): Kailong Jin, Lingqiao Li, John M. Torkelson
The bulk physical aging behavior of cross-linked polystyrene (PS) is directly compared to that of its linear precursor polystyrene-co-vinylbenzocyclobutene (PS-VBCB) with 8.5 or 12.5 mol% VBCB content. The VBCB units incorporated into a linear PS precursor cross-link with one another upon annealing at 250 °C. Physical aging rates of bulk PS-VBCB films before and after cross-linking are characterized using ellipsometry by monitoring the decrease in thickness during isothermal annealing at a specific aging temperature (Ta) below the glass transition temperature (Tg). Physical aging rates show strong dependences on Ta values, with neat PS, linear PS-VBCB precursors with 8.5 or 12.5 mol% VBCB, and cross-linked PS with 8.5 mol% VBCB exhibiting maxima at Ta - Tg = −40 to −30 °C. In contrast, cross-linked PS with 12.5 mol% VBCB exhibits a maximum aging rate at Ta - Tg = −65 to −45 °C. The distribution of Ta-dependent aging rates broadens in cross-linked PS samples compared to linear precursors, which is correlated with increased Tg breadth or heterogeneity after cross-linking. Comparisons of aging rates of cross-linked PS with linear precursors demonstrate that cross-linking can lead to an increased, decreased, or unchanged aging rate depending on the values of Ta and Ta - Tg: e.g., when Ta - Tg > −60 °C, both cross-linked PS samples have a lower aging rate compared to their linear precursors at the same Ta - Tg whereas the cross-linked PS exhibits a similar or even greater aging rate compared to the linear precursor when Ta - Tg < −60 °C. These results help to reconcile previous seemingly contradictory observations regarding effects of cross-linking on physical aging rates. To the best of our knowledge, cross-linking induced enhancement of physical aging rates of cross-linked polymers relative to their linear precursors at the same Ta - Tg value is being reported for the first time here.

Graphical abstract

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Crystal polymorphism of polylactides and poly(Pro-alt-CO): The metastable beta and gamma phases. Formation of homochiral PLLA phases in the PLLA/PDLA blends

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): Bernard Lotz, Gao Li, Xuesi Chen, Jordi Puiggali
Among the various crystalline phases of polylactides, an elusive orthorhombic gamma phase (γPLLA) had been obtained so far only by epitaxial crystallization on hexamethylbenzene. A recent work by J. Shao et al. (Macromolecules, 2013, 46, 6933) reports on two "novel modified crystallites" of PLLA obtained "under the confinement of stereocomplex PLLA/PDLA crystallites" produced on cooling blends of PLLA and PDLA from the melt at specific rates. These novel modified crystallites are metastable and transform to the stable αPLLA on heating. Reinterpretation of Shao et al.'s DSC and X-ray data suggests that one novel modified crystallite is the elusive γPLLA. The second form could be a disordered hexagonal phase that blends PDLA and PLLA three-fold helices, although the structural evidence is less compelling. In a parallel line of analysis, a crystal modification of the related alternating copolymer of propene and carbon monoxide (poly(Pro-alt-CO)) described as an orthorhombic structure very similar to γPLLA by Anokhin et al. (Polymer Science, Ser. A, Vol. 46, No. 1, 2004, pp. 52–60) must be reinterpreted as a trigonal frustrated phase, a phase that has already been observed in single crystals of this polymer.

Graphical abstract

http://ift.tt/2ngQHwT

Technetium-99m radiolabeled paclitaxel as an imaging probe for breast cancer in vivo

Publication date: May 2017
Source:Biomedicine & Pharmacotherapy, Volume 89
Author(s): Liziane O.F. Monteiro, Renata S. Fernandes, Luciano C. Castro, Valbert N. Cardoso, Mônica C. Oliveira, Danyelle M. Townsend, Alice Ferretti, Domenico Rubello, Elaine A. Leite, André L.B. de Barros
The high incidence and mortality of breast cancer supports efforts to develop innovative imaging probes to effectively diagnose, evaluate the extent of the tumor, and predict the efficacy of tumor treatments while concurrently and selectively delivering anticancer agents to the cancer tissue. In the present study we described the preparation of technetium–99m (^99mTc)-labeled paclitaxel (PTX) and evaluated its feasibility as a radiotracer for breast tumors (4T1) in BALB/c mice. Thin Layer Chromatography (TLC) was used to determine the radiochemical purity and in vitro stability of ^99mTc-PTX. PTX micelles showed a unimodal distribution with mean diameter of 13.46±0.06nm. High radiochemical purity (95.8±0.3%) and in vitro stability (over than 95%), up to 24h, were observed. Blood circulation time of ^99mTc-PTX was determined in healthy BALB/c mice. ^99mTc-PTX decays in a one-phase manner with a half-life of 464.3 minutes. Scintigraphic images and biodistribution were evaluated at 4, 8 and 24h after administration of ^99mTc-PTX in 4T1 tumor-bearing mice. The data showed a significant uptake in the liver, spleen and kidneys, due to the importance of these routes for excretion. Moreover, high tumor uptake was achieved, indicated by high tumor-to-muscle ratios. These findings indicate the usefulness of ^99mTc-PTX as a radiotracer to identify 4T1 tumor in animal models. In addition, ^99mTc-PTX might be used to follow-up treatment protocols in research, being able to provide information about tumor progression after therapy.



http://ift.tt/2ngWO4t

Angiomodulators in cancer therapy: New perspectives

Publication date: May 2017
Source:Biomedicine & Pharmacotherapy, Volume 89
Author(s): Lenka Varinska, Peter Kubatka, Jan Mojzis, Anthony Zulli, Katarina Gazdikova, Pavol Zubor, Dietrich Büsselberg, Martin Caprnda, Radka Opatrilova, Iveta Gasparova, Martin Klabusay, Martin Pec, Eitan Fibach, Mariusz Adamek, Peter Kruzliak
The formation of new blood vessels plays a crucial for the development and progression of pathophysiological changes associated with a variety of disorders, including carcinogenesis. Angiogenesis inhibitors (anti-angiogenics) are an important part of treatment for some types of cancer. Some natural products isolated from marine invertebrates have revealed antiangiogenic activities, which are diverse in structure and mechanisms of action. Many preclinical studies have generated new models for further modification and optimization of anti-angiogenic substances, and new information for mechanistic studies and new anti-cancer drug candidates for clinical practice. Moreover, in the last decade it has become apparent that galectins are important regulators of tumor angiogenesis, as well as microRNA. MicroRNAs have been validated to modulate endothelial cell migration or endothelial tube organization.In the present review we summarize the current knowledge regarding the role of marine-derived natural products, galectins and microRNAs in tumor angiogenesis.



http://ift.tt/2nmn0w1

Improved yeast delivery of fluconazole with a nanostructured lipid carrier system

Publication date: May 2017
Source:Biomedicine & Pharmacotherapy, Volume 89
Author(s): Hamid Reza Kelidari, Maryam Moazeni, Roghayeh Babaei, Majid Saeedi, Jafar Akbari, Parisa Islami Parkoohi, Mojtaba Nabili, Atefeh Abdollahi Gohar, Katayoun Morteza-Semnani, Ali Nokhodchi
Despite the growing trends in the number of patients at risk for invasive fungal infections, management with current antifungal agents results in complications due to changes in the epidemiology and drug susceptibility of invasive fungal infections. In the present research fluconazole-loaded nanostructured lipid carriers were prepared using probe ultrasonication techniques and investigated the efficacy of the optimal formulation on a large number of Candida species. The morphology of the obtained nanostructured lipid carriers was characterized by transmission-electron microscopy. The minimum inhibitory concentrations (MIC) for the new formulations against strains of Candida were investigated using the Clinical and Laboratory Standards Institute document M27-A3 and M27-S4 as a guideline. The fluconazole-loaded nanostructured lipid carriers presented a spherical shape with a mean diameter, zeta potential and entrapment efficiency of 126.4±15.2nm, −35.1±3.0mV, and 93.6±3.5%, respectively. The drug release from fluconazole-loaded nanostructured lipid carriers exhibited burst-release behavior at the initial stage followed by sustained release over 24h. Using a new formulation of fluconazole led to a significant decrease in MICs for all Candida groups (P<0.05). Furthermore, C. albicans isolates showed more susceptibility to fluconazole-loaded nanostructured lipid carriers than C. glabrata and C. parapsilosis (P<0.05). The MIC50 drug concentration was obtained as 0.0625, 0.031 and 0.25μg/ml for fluconazole-resistant strains of C. albicans, C. glabrata, and C. parapsilosis, respectively. In conclusion, a novel delivery system which can be used as part of a strategy to improve the antifungal activity of fluconazole against various Candida strains with different susceptibilities to conventional formulations of fluconazole was evaluated.



http://ift.tt/2ngPhT6

Caffeine prevents changes in muscle caused by high-intensity interval training

Publication date: May 2017
Source:Biomedicine & Pharmacotherapy, Volume 89
Author(s): Juliano M. Vieira, Jessié M. Gutierres, Fabiano B. Carvalho, Luciane B. Pereira, Liziele S. Oliveira, Vera Maria Morsch, Maria Rosa C. Schetinger, Marília V. Rodrigues, Jossiele Leitemperger, Vânia Loro, Cristina C. Krewer, Marina S. Vencato, Roselia M. Spanevello
The use of ergogenic substances such as caffeine has become a strategy to enhance sports performance. In the present study we evaluated the effects of high-intensity interval training (HIIT) associated with caffeine intake on acetylcholinesterase (AChE) and Ca²⁺ATPase activity and glycogen levels in the muscles of rats were evaluated. The animals were divided in groups: control, caffeine 4 or 8mg/kg, HIIT, HIIT plus caffeine 4 or caffeine 8mg/kg. Our results showed a decrease in glycogen levels in muscle in all trained groups after acute session exercise, while that an increase in glycogen levels was observed in all groups in relation to control in chronic exercise protocol. HIIT increases the thickness of the left ventricle and the Ca²⁺-ATPase activity and decrease the AChE activity in gastrocnemius muscle. Caffeine treatment prevents changes in enzymes activities as well as left ventricular hypertrophy adaptation induced by HIIT. Our findings suggest that caffeine modulates crucial pathways for muscle contraction in HIIT.



http://ift.tt/2nmmSwL

Pancreatoprotective effects of Geniotrigona thoracica stingless bee honey in streptozotocin-nicotinamide-induced male diabetic rats

Publication date: May 2017
Source:Biomedicine & Pharmacotherapy, Volume 89
Author(s): Muhammad Shakir Abdul Aziz, Nelli Giribabu, Pasupuleti Visweswara Rao, Naguib Salleh
Stingless bee honey (SLBH) has been claimed to possess multiple health benefits. Its anti-diabetic properties are however unknown. In this study, ability of SLBH from Geniotrigona thoracica stingless bee species in ameliorating pancreatic damage and in maintaining metabolic profiles were investigated in diabetic condition.MethodsSLBH at 1 and 2g/kg/b.w. was given orally to streptozotocin (STZ)-nicotinamide-induced male diabetic rats for 28days. Metabolic parameters (fasting blood glucose-FBG and lipid profiles-LP and serum insulin) were measured by biochemical assays. Distribution and expression level of insulin, oxidative stress marker i.e. catalase, inflammatory markers i.e. IKK-β, TNF-α, IL-1β and apoptosis marker i.e. caspase-9 in the pancreatic islets were identified and quantified respectively by immunohistochemistry. Levels of NF-κβ in pancreas were determined by enzyme-linked immunoassay (ELISA).ResultsSLBH administration to diabetic male rats prevented increase in FBG, total cholesterols (TC), triglyceride (TG) and low density lipoprotein (LDL) levels. However, high density lipoprotein (HDL) and serum insulin levels in diabetic rats receiving SLBH increased. Additionally, histopathological changes and expression level of oxidative stress, inflammation and apoptosis markers in pancreatic islets of diabetic rats decreased with increased expression level of insulin in the islets. LC–MS analysis revealed the presence of several compounds in SLBH that might be responsible for these effects.ConclusionsSLBH has great potential to be used as agent to protect the pancreas against damage and dysfunction where these could account for its anti-diabetic properties.



http://ift.tt/2ngAtUt

A peel-off facial mask comprising myoinositol and trehalose-loaded liposomes improves adult female acne by reducing local hyperandrogenism and activating autophagy

Summary

Background

Hyperandrogenism and reduced skin autophagy have been implicated in the pathogenesis of adult female acne (AFA). Here, we tested whether a ready-to-use peel-off facial mask containing myoinositol (an androgen inhibitor) and trehalose-loaded liposomes (as activators of cutaneous autophagy) applied overnight every other day for 60 days can improve AFA. We also sought to investigate the molecular mechanisms underlying the clinical effects.

Objectives

We conducted an uncontrolled, open-label clinical study in 40 cases of AFA to investigate the effect of the facial mask on lesion count, sebum production (measured with the Sebutape® technique), and Global Acne Grading System (GAGS) scale. We also investigated the changes from baseline to the end of treatment in androgen and beclin-1 levels (as a marker of authophagy) in skin biopsy supernatants.

Methods

Forty Caucasian patients with AFA were enrolled. Changes in clinical and molecular endpoints before and after treatment were investigated.

Results

The mean counts of comedones, papules, pustules, and nodular lesions decreased significantly (all P<.001). The mean Sebutape® score was reduced from 3.4±0.6 to 1.8±0.2 (P<.001), whereas the mean GAGS scale score decreased from 16.8±5.3 at baseline to 9.8±4.6 after treatment (P<.001). A significant decrease in testosterone and dehydroepiandrosterone sulfate in skin biopsy supernatants was observed, whereas beclin-1 levels increased significantly (P<.001).

Conclusion

A ready-to-use peel-off facial mask containing myoinositol and trehalose-loaded liposomes improved the cosmetic appearance of AFA by reducing cutaneous androgen content and promoting skin autophagy.

http://ift.tt/2nSd0Mq

Overexpression of Drosha, DiGeorge syndrome critical region gene 8 (DGCR8), and Dicer mRNAs in the pathogenesis of psoriasis

Summary

Introduction

Psoriasis is a complex autoimmune inflammatory disease that occurs in genetically susceptible individuals and presents with the development of inflammatory plaques on the skin. Recent studies have indicated that microRNAs (miRNAs) play important roles in psoriasis.

Objective

To investigate whether expression of Drosha, DGCR8, and Dicer mRNAs is involved in the pathogenesis of psoriasis.

Methods

Biopsies were obtained from involved psoriatic skin (PP), noninvolved psoriatic skin (PN), and healthy skin (NN). Expression of Drosha, Dicer, and DGCR8 was assessed with real-time quantitative real-time PCR in 25 patients with psoriasis and 25 healthy volunteers.

Results

We observed that expression levels of Drosha, Dicer, and DGCR8 were upregulated in patients with psoriasis compared to the control group. However, the Drosha and Dicer expression levels were higher in PP tissues and PN tissues compared to NN tissues, but they were more upregulated in PP tissues compared to PN tissues (P<.001). Although the DGCR8 expression was higher in PP tissues and PN tissues compared to NN tissues, it was more upregulated in PN tissues compared to PP tissues (P<.001).

Conclusion

Our data demonstrate that upregulated expression of Drosha, DGCR8, and Dicer mRNAs may be involved in the pathogenesis of psoriasis.

http://ift.tt/2o1IOvm

Case of lupus miliaris disseminatus faciei associated with marked formation of cysts, successfully treated with intralesional injections of triamcinolone acetonide

http://ift.tt/2mB5hCi

Acral lentiginous melanoma versus other melanoma: A single-center analysis in Japan

Abstract

We summarize herein our 14-year experience of conventional treatment outcomes before the era of molecular-targeted therapy and immunotherapy. Specifically, we conducted a retrospective review of our 252 patients with primary cutaneous melanoma (acral lentiginous melanoma [ALM], n = 121; non-acral lentiginous melanoma [non-ALM], n = 131), and compared the prognostic factors between ALM and non-ALM. Melanoma-specific survival and disease-free survival were estimated using the Kaplan–Meier method. Regarding the results, all patients were Japanese (106 male and 146 female), with a mean age of 60.1 years. Among ALM patients, age was elder and primary tumor size was larger than non-ALM. As for tumor thickness, in situ lesions were more frequently observed in ALM. There was no significant difference in the distribution of tumor thickness between the two groups when excluding the in situ lesions. For treatment of the primary melanoma, 248 patients (98.4%) had undergone curative surgical excision and 120 patients with more than 1 mm or ulcerated melanoma had undergone sentinel lymph node biopsy. Patients with systemic metastasis primarily underwent dacarbazine-based chemotherapy. The Kaplan–Meier survival curves revealed no significant difference in melanoma-specific survival and disease-free survival between those with ALM and non-ALM. The results also showed that both ALM and non-ALM, when they initially metastasize, first affect the regional lymph nodes. Incisional biopsy was not an adverse prognostic factor. These results suggest that ALM does not differ in its biological behavior from non-ALM, so we can consider ALM as being equivalent to non-ALM. The initial treatment for ALM and non-ALM can involve the same strategy.

http://ift.tt/2n3wpGe

Cutaneous spindle cell adenolipoma on the nose: A rare variant of lipoma

http://ift.tt/2mB38Xm

Infants' and Adults' Use of Temporal Cues in Consonant Discrimination.

Objectives: Adults can use slow temporal envelope cues, or amplitude modulation (AM), to identify speech sounds in quiet. Faster AM cues and the temporal fine structure, or frequency modulation (FM), play a more important role in noise. This study assessed whether fast and slow temporal modulation cues play a similar role in infants' speech perception by comparing the ability of normal-hearing 3-month-olds and adults to use slow temporal envelope cues in discriminating consonants contrasts. Design: English consonant-vowel syllables differing in voicing or place of articulation were processed by 2 tone-excited vocoders to replace the original FM cues with pure tones in 32 frequency bands. AM cues were extracted in each frequency band with 2 different cutoff frequencies, 256 or 8 Hz. Discrimination was assessed for infants and adults using an observer-based testing method, in quiet or in a speech-shaped noise. Results: For infants, the effect of eliminating fast AM cues was the same in quiet and in noise: a high proportion of infants discriminated when both fast and slow AM cues were available, but less than half of the infants also discriminated when only slow AM cues were preserved. For adults, the effect of eliminating fast AM cues was greater in noise than in quiet: All adults discriminated in quiet whether or not fast AM cues were available, but in noise eliminating fast AM cues reduced the percentage of adults reaching criterion from 71 to 21%. Conclusions: In quiet, infants seem to depend on fast AM cues more than adults do. In noise, adults seem to depend on FM cues to a greater extent than infants do. However, infants and adults are similarly affected by a loss of fast AM cues in noise. Experience with the native language seems to change the relative importance of different acoustic cues for speech perception. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Burden of Hearing Loss on Communication Partners and Its Influence on Pursuit of Hearing Evaluation.

Objective: Describe how the burden on the communication partner (CP) from the patient's hearing loss, as perceived by both the patient and their CP, influences a patient's pursuit of hearing evaluation. Design: Cross-sectional design. Demographics, perception of patient's hearing loss, and associated burden on the CP were collected from both patient and CP via online questionnaires. Patients and their CPs from Duke University Medical Center Otolaryngology Clinic, 55 to 75 years of age, being seen for any reason, who indicated a CP has expressed concern about their hearing. Final sample was 245 matched pairs. Results: Based on completed questionnaires, on average, patients perceived their own hearing loss as more burdensome to the CP than the CP did. However, CPs of patients who believed themselves to have no hearing handicap scored the patient's hearing loss 54.3% higher than the patient. The patient's perspective about the amount of burden their hearing loss placed on the CP predicted patients seeking a hearing evaluation. Conclusions: Recognition of early stage hearing loss and associated burden on CPs may be delayed in patients; CPs may help elucidate unrecognized concerns. Educational approaches that raise awareness of burden of hearing loss on CPs along with hearing loss indications could be a feasible, multidimensional strategy to promote help seeking behaviors. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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AMIStem Primary Hip System Prospective Post-marketing Multi-centre Surveillance Study

Conditions:   Osteoarthritis;   Arthritis;   Avascular Necrosis;   Fracture of the Femoral Neck or Head;   Congenital Hip Dysplasia
Intervention:   Device: AMIStem Hip System
Sponsor:   Medacta International SA
Recruiting - verified April 2016

http://ift.tt/2nP0soV

Endothelial Progenitor Cells in Cervical Cancer Patients Receiving Chemoradiation

Condition:   Cervical Cancer
Intervention:  
Sponsors:   Mackay Memorial Hospital;   National Science Council, Taiwan
Recruiting - verified March 2017

http://ift.tt/2n15hXO

AMIStem Primary Hip System Prospective Post-marketing Multi-centre Surveillance Study

Conditions:   Osteoarthritis;   Arthritis;   Avascular Necrosis;   Fracture of the Femoral Neck or Head;   Congenital Hip Dysplasia
Intervention:   Device: AMIStem Hip System
Sponsor:   Medacta International SA
Recruiting - verified April 2016

http://ift.tt/2nP0soV

Endothelial Progenitor Cells in Cervical Cancer Patients Receiving Chemoradiation

Condition:   Cervical Cancer
Intervention:  
Sponsors:   Mackay Memorial Hospital;   National Science Council, Taiwan
Recruiting - verified March 2017

http://ift.tt/2n15hXO

Counseling Will Be the Focus of CSD Teaching Conference at the University of Pittsburgh This Year

​The seventh biennial Communication Science and Disorders Teaching Conference at the University of Pittsburgh, which takes place June 15-17, 2017, will address the art and science of teaching counseling in the classroom and clinic. The three-day conference will give audiology faculty and clinical instructors the opportunity to discuss best practice in teaching counseling and benefit from resources shared by the conference faculty, which includes sample course or clinical handouts, practicum strategies, reference lists, take-home assignments, lab exercises, and practical exams. The program also includes breakout and poster sessions.

The conference will feature two prominent scholars in the field of audiology. Robert Sweetow, PhD, clinical professor in the department of otolaryngology – head and neck surgery at the University of California, San Francisco, will be the keynote speaker at the conference. Dr. Sweetow has served on the board of directors at the American Academy of Audiology, and is a prolific scholar who has written 25 textbook chapters and over 120 articles. Lisa Scott, PhD, CCC-SLP, director of clinical education and research associate in the School of Communication Science and Disorders at Florida State University, will serve as the moderator of the program. ​

Registration for the conference has not yet opened.  To be added to the registration mailing list, please email Lori Zitelli, AuD at zitellild@upmc.edu. 

Tags: conference, University of Pittsburgh, Communication Science and Disorders Teaching Conference, counseling, audiology, teaching

Published: 3/24/2017 3:01:00 PM

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Hypohidrosis and metal allergy: Trigger factors for unilateral lichen planus

Abstract

Unilateral lichen planus (LP) is a rare clinical variant of LP. The etiology of unilateral LP has not been clarified, although various causes have been reported because of the characteristic distribution. We focused on the contribution of metal allergy and sweating in the development of unilateral LP in this case. To confirm the presence of metal allergy, patch tests with metal allergens were performed. To investigate the cause of the unilateral distribution in unilateral LP, the function of sweating and sweat leaking in the dermis was assessed by a thermoregulatory sweat test and immunohistochemical staining of dermcidin. The patch tests with SnCl₂, H₂PtCl₆, ZnCl₂ and MnCl₂ were positive. The thermoregulatory sweat test using the starch–iodine method (Minor test) with sweating provoked by heat stimulation revealed hypohidrosis of the affected area, whereas no skin lesions were observed on the dorsal hand and wrist where sweating was normal. Histopathological examination showed keratin plugging of the acrosyringium and lymphocytic infiltrations in the papillary and subpapillary dermis around the intraepidermal and intradermal eccrine duct in the affected area. The immunohistochemical staining of dermcidin confirmed sweat leakage in the subpapillary dermis in the affected area. The symptoms refractory to the topical steroids were markedly improved after removal of the dental metals. The coexistence of metal allergy and sweat leakage in the hypohidrotic area may be involved in the development of unilateral LP.

http://ift.tt/2nxUTuz

Rheumatoid neutrophilic dermatitis in a patient taking tocilizumab for treatment of rheumatoid arthritis

http://ift.tt/2ofH40J

Japanese version of the Family Dermatology Life Quality Index: Translation and validation

Abstract

Skin conditions affect the quality of life (QoL) of patients and their family. To assess family members' QoL, a questionnaire uniquely designed for family members is necessary. We translated the Family Dermatology Life Quality Index (FDLQI), originally created and validated by Basra et al., into Japanese, and evaluated its reliability and validity. For psychometric evaluations, 150 dermatology patients and their family members were included. The Japanese version of the FDLQI showed high test–retest reliability (intraclass correlation coefficient = 0.95) and internal consistency reliability (Cronbach's alpha = 0.86). FDLQI scores significantly correlated with DLQI scores (r = 0.58, P < 0.01, Spearman's rho) and global question (GQ) which measured the patient's skin condition on a visual analog scale (r = 0.36, P < 0.01). Family members of patients with inflammatory skin diseases showed higher FDLQI scores than those with isolated lesions, but the difference was not statistically significant (P = 0.062, Mann–Whitney U-test). Responsiveness to change was demonstrated in a group in which the patient's skin condition was assessed as improved (n = 37, r = 0.46, P < 0.01) but not in that in which it became worse. The difference of the change between the two groups was statistically significant (P < 0.01). Additionally, the change in FDLQI scores and GQ were significantly correlated (r = 0.40, P < 0.01). Exploratory factor analysis suggested essential unidimensionality of the instrument. We showed acceptable validity and responsiveness of this Japanese version of FDLQI. Further clinical epidemiological studies are required to confirm this.

http://ift.tt/2nxYfxA

Increased number of mast cells in the dermis in actinic keratosis lesions effectively treated with imiquimod

Abstract

Actinic keratosis (AK) is a cutaneous cancer in situ which develops as a result of excessive exposure to ultraviolet (UV). Toll-like receptor (TLR)7 agonist imiquimod is a topical immune response modifier and is effective for the treatment of non-melanoma skin cancers. Recently, the diagnostic role of the dermatoscope has been reported in the course of treatment of AK. In addition, mast cells are now considered to contribute to both the innate and adaptive immune systems in topical imiquimod therapy. We assessed the effect of imiquimod treatment by dermatoscopic and immunohistochemical findings in 14 patients with a total of 21 AK lesions. With the dermatoscope, though the mean erythema score was not significantly different between the cured lesions and the unresponsive lesions, the erythema/red pseudo-network ("strawberry") pattern was decreased significantly in the cured lesions. By immunohistochemistry, the number of Ki-67-positive proliferative cells in the epidermis was decreased and that of CD117-positive mast cells in the dermis was increased in the responding lesions. To the best of our knowledge, this is the first study demonstrating that the number of mast cells in the dermis was increased in AK lesions effectively treated with imiquimod. Our present result suggests that mast cells may contribute an antitumor effect in human skin treated with topical imiquimod.

http://ift.tt/2ofzwLB

Case of bullous pemphigoid coexisting with anti-desmoglein autoantibodies

Abstract

A 79-year-old Japanese woman had clinical and histopathological features of bullous pemphigoid, while direct immunofluorescence test revealed C3 and immunoglobulin G depositions in the lower cell surfaces of the epidermis in addition to those in the dermoepidermal junction. Chemiluminescent enzyme immunoassays were positive for desmoglein-1 and -3 antibodies in addition to anti-BP180 antibodies. In an immunoblotting study, antibodies against both 180-kDa bullous pemphigoid antigen and 130-kDa pemphigus vulgaris antigen were detected. Based on these results, bullous pemphigoid coexisting with anti-desmoglein autoantibodies was diagnosed in this case.

http://ift.tt/2ny4pxv

Critical contribution of the interleukin-6/signal transducer and activator of transcription 3 axis to vasculopathy associated with systemic sclerosis

Abstract

Reflecting the critical role of interleukin (IL)-6 in systemic sclerosis (SSc), tocilizumab, an anti-IL-6 receptor antibody, is currently under a global phase III trial against skin sclerosis of this disease. We here demonstrate that the IL-6/signal transducer and activator of transcription 3 axis is broadly activated in various cell types in the lesional skin of SSc patients irrespective of disease subtypes, especially in endothelial cells. Importantly, 12 monthly infusions of tocilizumab improved nailfold capillary changes as well as skin sclerosis in a patient with diffuse cutaneous SSc. The present findings suggest a potential disease-modifying effect of tocilizumab on SSc vasculopathy.

http://ift.tt/2ofI1Gw

Surface ligands engineering of semiconductor quantum dots for chemosensory and biological applications

Publication date: Available online 24 March 2017
Source:Materials Today
Author(s): Jie Zhou, Yun Liu, Jian Tang, Weihua Tang
Featuring size-tunable electrical and optical properties, semiconductor quantum dots (QDs) are appealing intensive interests in developing ingenious luminescent materials for chemosensory and biological applications. The surface modification of QDs with functional ligands not only fine-tunes the physiochemical properties and fluorescence emission behaviors, but also induces the designated interplay between analytes and probes for special determination. In this review, the fundamental principles guiding the rational design of high-efficiency luminescent sensors with surface engineering are overviewed. The state-of-the-art applications of QDs-based probes are highlighted for the sensing of molecular substrates and ionic species as well as various biological applications, with the inherent recognition mechanisms elaborated for representative cases. The challenge and future research direction in this emerging and promising research field are also discussed.



http://ift.tt/2n1dj2P

Noncoronary Vascular Calcification, Bone Mineral Density, and Muscle Mass in Institutionalized Frail Nonagenarians

Rejuvenation Research , Vol. 0, No. 0.


http://ift.tt/2n1c8QR

Blunt cardiac injury due to trauma associated with snowboarding: a case report

Cardiac trauma is associated with a much higher mortality rate than injuries to other organ systems, even though cardiac trauma is identified in less than 10% of all trauma admissions. Here we report blunt tra...

http://ift.tt/2nxQurd

Did King Philip II of Ancient Macedonia Suffer a Zygomatico-Orbital Fracture? A Maxillofacial Surgeon's Approach

Cranial Maxillofac Trauma Reconstruction
DOI: 10.1055/s-0037-1601431

Philip II, father of Alexander the Great, succeeded his brother, Perdiccas III, to the throne of Macedonia in 360 BC. He has been described by historians as a generous king and military genius who managed to achieve his ambitious plans by expanding the Macedonian city-state over the whole Greek territory and the greater part of the Balkan Peninsula. The aim of our study was to present the evidence with regard to the facial injury of King Philip II of Macedonia and discuss the treatment of the wound by his famous physician, Critobulos. We reviewed the literature for historical, archaeological, and paleopathological evidence of King Philip's facial injury. We include a modern reconstruction of Philip's face based on the evidence of his injury by a team of anatomists and archaeologists from the Universities of Bristol and Manchester. In the light of the archaeological findings by Professor Andronikos and the paleopathological evidence by Musgrave, it can be claimed with confidence that King Philip II suffered a significant injury of his zygomaticomaxillary complex and supraorbital rim caused by an arrow as can be confirmed in many historical sources. To the best of our knowledge, this is the first attempt to present the trauma of King Philip II from a maxillofacial surgeon's point of view.
[...]

Thieme Medical Publishers, Inc. 333 Seventh Avenue, New York, NY 10001, USA

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2ofiIEs

Mineralocorticoid receptor and NaCl transport mechanisms in the renal distal nephron

A key role of aldosterone and mineralocorticoid receptor is to regulate fluid volume and K+ homeostasis in the body by acting on the renal distal nephron. Global responses of the kidney to elevated aldosterone levels are determined by the coordinate action of different constituent tubule cells, including principal cells, intercalated cells, and distal convoluted tubule cells. Recent studies on genetic mutations causing aldosterone overproduction have identified molecules involved in aldosterone biosynthesis in the adrenal gland, and there is also increasing evidence for mechanisms and signaling pathways regulating the balance between renal NaCl reabsorption and K+ secretion, the two major effects of aldosterone. In particular, recent studies have demonstrated that mineralocorticoid receptor in intercalated cells are selectively regulated by phosphorylation, which prevents ligand binding and activation. Moreover, the ubiquitin ligase complex composed of Kelch-like 3 and Cullin 3 acts downstream of angiotensin II and plasma K+ alterations, regulating Na-Cl cotransporter independently of aldosterone in distal convoluted tubule cells. These and other effects are integrated to produce appropriate kidney responses in a high-aldosterone state, and are implicated in fluid and electrolyte disorders in humans. This review summarizes the current knowledge on mechanisms modulating mineralocorticoid receptor and its downstream effectors in the distal nephron.

http://ift.tt/2o1o9Yo

Inflammatory Bowel Disease: Joint Management in Gastroenterology and Dermatology [Free article]

M.A. Sánchez-Martínez, E. Garcia-Planella, A. Laiz, L. Puig
Actas Dermosifiliogr.2017;108:184-91

Abstract - Full text - PDF

http://ift.tt/2nmb1P6

Clinicopathologic Variants of Mycosis Fungoides [Free article]

H. Muñoz-González, A.M. Molina-Ruiz, L. Requena
Actas Dermosifiliogr.2017;108:192-208

Abstract - Full text - PDF

http://ift.tt/2ngzmUS

Inflammatory Skin Conditions Associated With Radiotherapy [Free article]

I. Hernández Aragüés, A. Pulido Pérez, R. Suárez Fernández
Actas Dermosifiliogr.2017;108:209-20

Abstract - Full text - PDF

http://ift.tt/2nmeDAI

New Treatments for Hair Loss [Free article]

S. Vañó-Galván, F. Camacho
Actas Dermosifiliogr.2017;108:221-8

Abstract - Full text - PDF

http://ift.tt/2ngylw0

Cost of Cutaneous Melanoma by Tumor Stage: A descriptive analysis [Free article]

P. Serra-Arbeloa, Á.O. Rabines-Juárez, M.S. Álvarez-Ruiz, F. Guillén-Grima
Actas Dermosifiliogr.2017;108:229-36

Abstract - Full text - PDF

http://ift.tt/2nmeDkc

Objective Structured Clinical Examination as an Assessment Tool for Clinical Skills in Dermatology [Free article]

D. Saceda-Corralo, P. Fonda-Pascual, â.M. Moreno-Arrones, A. Alegre-Sánchez, Á. Hermosa-Gelbard, N. Jimèc)nez-Gómez, S. Vañó-Galván, P. Jaèc)n-Olasolo
Actas Dermosifiliogr.2017;108:237-43

Abstract - Full text - PDF

http://ift.tt/2ngxmfe

The impact of skin diseases on quality of life: A multicenter study [Free article]

G. Sanclemente, C. Burgos, J. Nova, F. Hernández, C. González, M.I. Reyes, N. Córdoba, Á. Arèc)valo, E. Melèc)ndez, J. Colmenares, S. Ariza, G. Hernández
Actas Dermosifiliogr.2017;108:244-52

Abstract - Full text - PDF

http://ift.tt/2nmcKnn

Extensive Acquired Telangiectasias: Comparison of Generalized Essential Telangiectasia and Cutaneous Collagenous Vasculopathy [Free article]

N. Knöpfel, A. Martín-Santiago, C. Saus, M.M. Escudero-Góngora, L.J. del Pozo, C. Gómez
Actas Dermosifiliogr.2017;108:e21-6

Abstract - Full text - PDF

http://ift.tt/2ngjAcx

Subcutaneous Tumor Deep to the Lateral Right Eyebrow [Free article]

P.P. García-Montero, A. Hernández-Nuñez, J.C. Tardío
Actas Dermosifiliogr.2017;108:253-4

Abstract - Full text - PDF

http://ift.tt/2nmfBNh

Rapidly Progressive Infiltrated Plaques in a Transplant Recipient [Free article]

I. Salgüero Fernández, F. Alfageme Roldán, D. Suarez Massa, G. Roustan Gullón
Actas Dermosifiliogr.2017;108:255-6

Abstract - Full text - PDF

http://ift.tt/2ngsd6P

RF- Insufficient Exposure to Sunlight and Global Mortality: Should We Advise Against or Recommend Sun Exposure? [Free article]

M.T. Monserrat-García, A. Ortíz-Prieto, P. Martín-Carrasco, J. Conejo-Mir-Sánchez
Actas Dermosifiliogr.2017;108:257-8

Abstract - Full text - PDF

http://ift.tt/2nm5bgB

Ulcerated Indurated Necrotic Plaque on the Chest Wall [Free article]

M.A. Flores-Terry, G. Romero-Aguilera, M. García-Arpa
Actas Dermosifiliogr.2017;108:259

Abstract - Full text - PDF

http://ift.tt/2nm3IHg

Bullous Pemphigoid on the Areola of Breast [Free article]

P. López Jiménez, Á. Vargas Nevado, E. Herrera Ceballos
Actas Dermosifiliogr.2017;108:260

Abstract - Full text - PDF

http://ift.tt/2ngws2t

Paraffin Wax Baths for the Treatment of Chronic Hand Eczema [Free article]

J.F. Mir-Bonafé, E. Serra-Baldrich, E. Rozas-Muñoz, L. Puig
Actas Dermosifiliogr.2017;108:261-4

Abstract - Full text - PDF

http://ift.tt/2nmefSD

Trichomycosis Axillaris: Clinical, Wood Lamp, and Dermoscopic Diagnostic Images [Free article]

E. Rojas Mora, A. Freites Martínez, A. Hernández-Núñez, J. Borbujo Martínez
Actas Dermosifiliogr.2017;108:264-5

Abstract - Full text - PDF

http://ift.tt/2ngp1Iu

Idiopathic Facial Aseptic Granuloma: Usefulness of Cutaneous Ultrasound [Free article]

I. Vázquez-Osorio, C.C. Álvarez-Cuesta, L. Rodríguez-González, E. Rodríguez-Díaz
Actas Dermosifiliogr.2017;108:266-8

Abstract - Full text - PDF

http://ift.tt/2nmeehx

Lymphangioma-like Kaposi sarcoma [Free article]

F. Martínez-Ortiz, M.P. Gómez Avivar
Actas Dermosifiliogr.2017;108:268-71

Abstract - Full text - PDF

http://ift.tt/2ngzjIG

Nodular Mucinosis Associated With Light-Chain Monoclonal Gammopathy of Uncertain Significance [Free article]

P. Rodríguez-Jiménez, P. Chicharro, A. Ascensión, D. de Argila, E. Daudén
Actas Dermosifiliogr.2017;108:272-3

Abstract - Full text - PDF

http://ift.tt/2nm7gZS

Initial Evaluation of the Adult Patient with Condylomata Acuminata [Free article]

A. Imbernón-Moya, J. Ballesteros
Actas Dermosifiliogr.2017;108:273-5

Abstract - Full text - PDF

http://ift.tt/2ngp0Eq

Herpetiforme Pemphigus: Report of a Pediatric Case [Free article]

V.L. Taliercio, B. Ferrari, M.E. Abad, M. Larralde
Actas Dermosifiliogr.2017;108:276-7

Abstract - Full text - PDF

http://ift.tt/2nmjbH7

Impact of School Peanut-Free Policies on Epinephrine Administration

In this retrospective study of epinephrine administration in Massachusetts public schools, schools with peanut-free tables, compared to without, had lower epinephrine administration rates. Other peanut restrictive policies did not affect epinephrine administration rates.

http://ift.tt/2n3AKJJ

Rhinovirus-induced first wheezing episode predicts atopic but not non-atopic asthma at school-age

The data suggest that sensitization, eczema and the rhinovirus etiology and atopic characteristics already at the first severe wheezing episode predict atopic but not non-atopic asthma at age 8 years, and therefore are worth assessing early.

http://ift.tt/2mB2Q2w

Novel Sensitization Trajectories in Childhood revealed by a Cluster Analysis

Sensitization in young children is a make-up of seven distinct patterns defined by the allergens and temporal profile and with different association to allergic disease.

http://ift.tt/2mBaBpd

Neonatal BCG-vaccination has no effect on recurrent wheeze in the first year of life. A randomized clinical trial

Neonatal BCG vaccination cannot be used prophylactically against recurrent wheeze in Denmark, but if a BCG vaccination is necessary for other reasons, the infant can be BCG vaccinated without concerns of recurrent wheeze.

http://ift.tt/2n3xTQR

Correlation between single photon emission computed tomography and histopathologic findings in condylar hyperplasia of the temporomandibular joint

To analyse the correlation between the level of activity measured in the single photon emission computed tomography (SPECT) and the pathological findings in patients with condylar hyperplasia (CH).

http://ift.tt/2o1eiBA

Morphological Variability in Second Language Learners: An Examination of Electrophysiological and Production Data.

Author: Aleman Banon, Jose; Miller, David; Rothman, Jason

DOI: 10.1037/xlm0000394

Publication Date: POST AUTHOR CORRECTIONS, 23 March 2017

http://ift.tt/2mB4OzY

Language Switching Across Modalities: Evidence From Bimodal Bilinguals.

Author: Dias, Patricia; Villameriel, Saul; Giezen, Marcel R.; Costello, Brendan; Carreiras, Manuel

DOI: 10.1037/xlm0000402

Publication Date: POST AUTHOR CORRECTIONS, 23 March 2017

http://ift.tt/2o1q3rY

How Perception Guides Action: Figure-Ground Segmentation Modulates Integration of Context Features into S-R Episodes.

Author: Frings, Christian; Rothermund, Klaus

DOI: 10.1037/xlm0000403

Publication Date: POST AUTHOR CORRECTIONS, 23 March 2017

http://ift.tt/2mARSKJ

The Sequence of Study Changes What Information Is Attended to, Encoded, and Remembered During Category Learning.

Author: Carvalho, Paulo F.; Goldstone, Robert L.

DOI: 10.1037/xlm0000406

Publication Date: POST AUTHOR CORRECTIONS, 23 March 2017

http://ift.tt/2o1n4jb

Blunt cardiac injury due to trauma associated with snowboarding: a case report

Cardiac trauma is associated with a much higher mortality rate than injuries to other organ systems, even though cardiac trauma is identified in less than 10% of all trauma admissions. Here we report blunt tra...

http://ift.tt/2nxQurd

Sensorimotor Mismapping in Poor-pitch Singing

This study proposes that there are two types of sensorimotor mismapping in poor-pitch singing: erroneous mapping and no mapping. We created operational definitions for the two types of mismapping based on the precision of pitch-matching and predicted that in the two types of mismapping, phonation differs in terms of accuracy and the dependence on the articulation consistency between the target and the intended vocal action. The study aimed to test this hypothesis by examining the reliability and criterion-related validity of the operational definitions.

http://ift.tt/2nxtpoC

The “Overdrive” Mode in the “Complete Vocal Technique”: A Preliminary Study

"Complete Vocal Technique," or CVT, is an internationally widespread method for teaching voice. It classifies voicing into four types, referred to as "vocal modes," one of which is called "Overdrive." The physiological correlates of these types are unclear. This study presents an attempt to analyze its voice source and formant frequency characteristics. A male and a female expert of CVT sang a set of "Overdrive" and falsetto tones on the syllable /pᴂ/. The voice source could be analyzed by inverse filtering in the case of the male subject.

http://ift.tt/2ofoi9D

Leg Movements during Sleep and Respiratory Events are not Causally Linked

I thank Dr. Walters for his thoughtful Letter to the Editor [1] which allows me to discuss additional aspects of the much-debated link between respiratory events and leg movements during sleep. Dr. Walters argues that the new World Association of Sleep Medicine (WASM) rules [2] for respiratory-related leg movements (in particular, the option to count movements that start up to 10.25 seconds after a sleep disordered breathing event), present at least two problems (see reference 1).

http://ift.tt/2nxwKE6

Frequency of snoring, rather than apnea-hypopnea index, predicts both cognitive and behavioral problems in young children

Primary snoring (PS) and obstructive sleep apnea (OSA) not only affect the quality of sleep in a large number of young children, but have also been repeatedly associated with a variety of behavioral and cognitive problems. However, little is known about the potentially differing relationships of behavioral and cognitive pathology within the sleep disordered breathing (SDB) spectrum.

http://ift.tt/2ofnIZv

Pulse wave amplitude reduction as a surrogate for cortical arousal during sleep hypopnea in children

The accuracy of respiratory polygraphy (RP) is limited because of the absence of electroencephalography (EEG). Pulse wave amplitude (PWA) reduction has been shown to be a marker of autonomic activation during arousal, and may represent a substitute for obstructive respiratory-related cortical arousal (RRCA). This study tested the hypothesis that PWA could be a surrogate for RRCA in detecting obstructive hypopnea (OH) in a pediatric population.

http://ift.tt/2nxB4n1

Prognostic significance of extracapsular spread of lymph node metastasis from oral squamous cell carcinoma in the clinically negative neck

The presence of extracapsular spread (ECS) in patients with oral squamous cell carcinoma (OSCC) indicates a poor prognosis and is associated with a higher risk of regional recurrence and distant metastasis. The aim of this study was to analyse this important feature of cervical lymph nodes in the clinically node-negative setting. The study included 61 patients with clinically T1–T3N0 OSCC who underwent primary surgical treatment; 52 were male and nine were female, and their median age was 57 years.

http://ift.tt/2n3i6BF

Long-term response in patient with recurrent oropharyngeal carcinoma treated with cetuximab, docetaxel and cisplatin (TPEx) as first-line treatment followed by cetuximab maintenance

Cetuximab, an anti-EGFR monoclonal antibody in combination with platinum and 5FU is the standard of care in first-line treatment of patients with recurrent head and neck squamous cell carcinoma (HNSCC), with an expected median outcome of 10months. For this population, development of efficacious and safer therapies is still needed.

http://ift.tt/2nRAwcB

Intratumoral Heterogeneity in Breast Cancer: A Comparison of Primary and Metastatic Breast Cancers

Intratumoral heterogeneity presents challenges in the management of cancer. To gain deeper insight in intratumoral heterogeneity at different levels and tumor sites for common biomarkers in breast cancers, this report examines seven cases of invasive breast cancer with multiple axillary nodal metastases and/or recurrences for immunohistochemical expression of estrogen receptors, progesterone receptors, human epidermal growth receptor 2, and Ki67 on all tissue blocks in both primary and metastatic tumors. The Oncologist 2017;22:1–4

http://ift.tt/2nREsd9

A Prospective Observational Study on Effect of Short-Term Periodic Steroid Premedication on Bone Metabolism in Gastrointestinal Cancer (ESPRESSO-01)

Background.

A multicenter prospective observational study evaluated the effect of gastrointestinal cancer chemotherapy with short-term periodic steroid premedication on bone metabolism.

Patients and Methods.

Seventy-four patients undergoing chemotherapy for gastrointestinal cancer were studied. The primary endpoints were changes in bone mineral densities (BMDs) and metabolic bone turnover 16 weeks after initiation of chemotherapy. BMDs, measured by dual-energy x-ray absorptiometry, and serum cross-linked N-telopeptides of type I collagen (sNTX), and bone alkaline phosphatase (sBAP) were assessed for evaluation of bone resorption and formation, respectively.

Results.

In 74.3% (55/74) of the patients, BMDs were significantly reduced at 16 weeks relative to baseline. The percent changes of BMD were –1.89% (95% confidence interval [CI], –2.67% to –1.11%: p < .0001) in the lumbar spine, –2.24% (95% CI, –3.59% to –0.89%: p = .002) in the total hip, and –2.05% (95% CI, –3.11% to –0.99%: p < .0001) in the femoral neck. Although there was no significant difference in sNTX levels during 16 weeks (p = .136), there was a significant increase in sBAP levels (p = .010). Decreased BMD was significantly linked to number of chemotherapy cycles (p = .02). There were no significant correlations between changes in BMDs and the primary site of malignancy, chemotherapy regimens, total cumulative steroid dose, steroid dose intensity, and additive steroid usage.

Conclusion.

Gastrointestinal cancer chemotherapy with periodic glucocorticoid premedication was associated with reduced BMD and increased sBAP levels, which were linked to number of chemotherapy cycles but independent of primary site, chemotherapy regimen, duration, and additive steroid usage. The Oncologist 2017;22:1–9

Implications for Practice.

Bone health and the management of treatment-related bone loss are important for cancer care. The present study showed that a significant decrease in bone mineral density (BMD) and an increase in serum bone alkaline phosphatase levels occurred in gastrointestinal cancer patients receiving chemotherapy, which were linked to number of chemotherapy cycles but were independent of primary site, chemotherapy regimen, total steroid dose, and steroid dose intensity. Surprisingly, it seems that the decreasing BMD levels after only 16 weeks of chemotherapy for gastrointestinal cancer were comparable to that of 12-month adjuvant aromatase inhibitor therapy for early-stage breast cancer patients.

http://ift.tt/2o1cfxu

Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer

Background.

Trastuzumab and pertuzumab are approved for the neoadjuvant treatment of human epidermal growth receptor 2 (HER2)-positive breast cancer, but cardiac safety data is limited. We report the cardiac safety of dose-dense doxorubicin and cyclophosphamide (AC) followed by paclitaxel, trastuzumab, and pertuzumab (THP) in the neoadjuvant setting followed by adjuvant trastuzumab-based therapy.

Methods.

Fifty-seven patients treated with neoadjuvant dose-dense AC-THP followed by adjuvant trastuzumab-based therapy between September 1, 2013, and March 1, 2015, were identified. The primary outcome was cardiac event rate, defined by heart failure (New York Heart Association [NYHA] class III/IV) or cardiac death. Patients underwent left ventricular ejection fraction (LVEF) monitoring at baseline, after AC, and serially during 1 year of anti-HER2 therapy.

Results.

The median age was 46 years (range 26–68). Two (3.5%) patients developed NYHA class III/IV heart failure 5 and 9 months after initiation of trastuzumab-based therapy, leading to permanent discontinuation of anti-HER2 treatment. Seven (12.3%) patients developed a significant LVEF decline (without NYHA class III/IV symptoms). The median LVEF was 65% (range 55%–75%) at baseline and 64% (range 53%–72%) after AC, and decreased to 60% (range 35%–70%), 60% (range 23%–73%), 61% (range 25%–73%), and 58% (range 28%–66%) after 3, 6, 9, and 12 months (± 6 weeks) of trastuzumab-based therapy.

Conclusion.

The incidence of NYHA class III/IV heart failure after neoadjuvant AC-THP (followed by adjuvant trastuzumab-based therapy) is comparable to rates reported in trials of sequential doxorubicin and trastuzumab. Our findings do not suggest an increased risk of cardiotoxicity from trastuzumab plus pertuzumab following a doxorubicin-based regimen. The Oncologist 2017;22:1–6

Implications for Practice: Dual anti-human epidermal growth receptor 2 (HER2) therapy with trastuzumab and pertuzumab combined with standard chemotherapy has received accelerated approval for the neoadjuvant treatment of stage II–III HER2-positive breast cancer. Cardiac safety data for trastuzumab and pertuzumab in this setting are limited to clinical trials that utilized epirubicin-based chemotherapy. Formalized investigations into the cardiac safety of trastuzumab and pertuzumab with doxorubicin- (rather than epirubicin) based regimens are important because these regimens are widely used for the adjuvant and neoadjuvant treatment of breast cancer. The known role of HER2 signaling in the physiological adaptive responses of the heart provides further rationale for study on the potential cardiotoxicity of dual anti-HER2 blockade. Findings from this retrospective study provide favorable preliminary data on the cardiac safety of trastuzumab and pertuzumab in combination with a regimen of neoadjuvant doxorubicin and cyclophosphamide followed by paclitaxel, one of the preferred breast cancer treatment regimens, according to the National Comprehensive Cancer Network.

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A Phase Ib Study of Sorafenib (BAY 43-9006) in Patients with Kaposi Sarcoma

Lessons Learned.

Oral targeted agents are desirable for treatment of Kaposi sarcoma (KS); however, in patients with HIV, drug–drug interactions must be considered. In this study to treat KS, sorafenib was poorly tolerated at doses less than those approved by the U.S. Food and Drug Administration for hepatocellular carcinoma and other cancers, and showed only modest activity.

Sorafenib's metabolism occurs via the CYP3A4 pathway, which is inhibited by ritonavir, a commonly used antiretroviral agent used by most patients in this study. Strong CYP3A4 inhibition by ritonavir may contribute to the observed sorafenib toxicity.

Alternate antiretroviral agents without predicted interactions are preferred for co-administration in patients with HIV and cancers for which sorafenib is indicated.

Background.

We conducted a phase Ib study of sorafenib, a vascular epithelial growth factor receptor (VEGFR), c-kit, and platelet derived growth factor receptor (PDGFR)-targeted treatment in Kaposi sarcoma (KS). We evaluated drug–drug interactions between sorafenib and ritonavir, an HIV medication with strong CYP3A4 inhibitory activity.

Methods.

Two cohorts were enrolled: HIV-related KS on ritonavir (Cohort R) and HIV-related or classical KS not receiving ritonavir (Cohort NR). Sorafenib dose level 1 in cohort R (R1) was 200 mg daily and 200 mg every 12 hours in cohort NR (NR1). Steady-state pharmacokinetics were evaluated at cycle 1, day 8. KS responses and correlative factors were assessed.

Results.

Ten patients (nine HIV⁺) were enrolled: R1 (eight), NR1 (two). Median CD4⁺ count (HIV⁺) was 500 cells/µL. Dose-limiting toxicities (DLTs) were grade 3 elevated lipase (R1), grade 4 thrombocytopenia (R1), and grade 3 hand-foot syndrome (NR1). Two of seven evaluable patients had a partial response (PR; 29%; 95% CI 4%–71%). Steady-state area under the curve of the dosing interval (AUC_TAU) of sorafenib was not significantly affected by ritonavir; however, a trend for decreased AUC_TAU of the CYP3A4 metabolite sorafenib-N-oxide (3.8-fold decrease; p = .08) suggests other metabolites may be increased.

Conclusion.

Sorafenib was poorly tolerated, and anti-KS activity was modest. Strong CYP3A4 inhibitors may contribute to sorafenib toxicity, and ritonavir has previously been shown to be a CYP3A4 inhibitor. Alternate antiretroviral agents without predicted interactions should be used when possible for concurrent administration with sorafenib. The Oncologist 2017;22:1–8

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In Memoriam: Umberto Veronesi (1925-2016)

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Robotics in Sinus and Skull Base Surgery

Transoral robotic surgery (TORS) has been proven to be safe and to yield acceptable oncological and functional outcomes for surgery of the oropharynx, hypopharynx, supraglottis, and glottis. TORS has been successful at reducing morbidity, improving quality of life, and providing access to areas that previously required mandibulotomy or other more radical approaches in the past. This has changed the paradigm of management of tumors in these anatomic locations. In this article, the authors review the recent literature discussing the role of robotic surgery in managing sinonasal and skull base pathology and discuss its current advantages and limitations.

http://ift.tt/2nOm5FG

Robotics in Sinus and Skull Base Surgery

Transoral robotic surgery (TORS) has been proven to be safe and to yield acceptable oncological and functional outcomes for surgery of the oropharynx, hypopharynx, supraglottis, and glottis. TORS has been successful at reducing morbidity, improving quality of life, and providing access to areas that previously required mandibulotomy or other more radical approaches in the past. This has changed the paradigm of management of tumors in these anatomic locations. In this article, the authors review the recent literature discussing the role of robotic surgery in managing sinonasal and skull base pathology and discuss its current advantages and limitations.

http://ift.tt/2nOm5FG

Asthma prevalence and severity in low-resource communities.

Purpose of review: The prevalence of asthma was thought to be low in most low-income countries, but several reports have indicated this is not always true. This is a narrative review of recent publications on the burden of asthma in low and middle-income countries (LMIC) and underprivileged communities from developed countries. Recent findings: Several studies have reported a low prevalence of asthma is LMIC, but indicate it is increasing. In the last few years, however, many surveys demonstrated this may not always be true. An analysis of the International Study for Asthma and Allergy in Childhood phase III database indicated although the prevalence of asthma among children and adolescents is higher in the developed countries, symptoms of asthma are often more severe in less affluent nations. The rate of uncontrolled asthma is also higher among underprivileged communities of developed countries. Secondary analysis of data generated by the WHO's world health survey performed among adults of 70 countries indicate symptoms of asthma are less frequent in middle-income countries and more frequent in the extremes, low income and high income. This sort of U shaped distribution suggests the disease (or syndrome) comprise more than one major phenotype related to diverse underlying mechanisms. In fact, recent reports show symptoms of asthma among the poor are associated with unhygienic living conditions, which may reduce the risk of atopy but increase the risk of nonatopic wheezing. Urbanization and exposure to air pollution also seem to contribute to an increasing prevalence severity of asthma in LMIC. Access to proper diagnosis and treatment with controller medications for asthma, specially with inhaled corticosteroids is feasible and cost-effective, reduce symptoms, health resource utilization, improves quality of life, and reduce mortality in low-resource settings. Summary: Prevalence of asthma was thought to be low in low-income countries, but several reports have indicated this is not always true. Under diagnosis, under treatment, exposure to air pollution, and unhygienic living conditions may contribute to a higher frequency and severity of symptoms of asthma among the poor. Proper diagnosis and treatment with controller medications for asthma is feasible and cost-effective in low-resource settings. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2nRnLPm

Asthma prevalence and severity in low-resource communities.

Purpose of review: The prevalence of asthma was thought to be low in most low-income countries, but several reports have indicated this is not always true. This is a narrative review of recent publications on the burden of asthma in low and middle-income countries (LMIC) and underprivileged communities from developed countries. Recent findings: Several studies have reported a low prevalence of asthma is LMIC, but indicate it is increasing. In the last few years, however, many surveys demonstrated this may not always be true. An analysis of the International Study for Asthma and Allergy in Childhood phase III database indicated although the prevalence of asthma among children and adolescents is higher in the developed countries, symptoms of asthma are often more severe in less affluent nations. The rate of uncontrolled asthma is also higher among underprivileged communities of developed countries. Secondary analysis of data generated by the WHO's world health survey performed among adults of 70 countries indicate symptoms of asthma are less frequent in middle-income countries and more frequent in the extremes, low income and high income. This sort of U shaped distribution suggests the disease (or syndrome) comprise more than one major phenotype related to diverse underlying mechanisms. In fact, recent reports show symptoms of asthma among the poor are associated with unhygienic living conditions, which may reduce the risk of atopy but increase the risk of nonatopic wheezing. Urbanization and exposure to air pollution also seem to contribute to an increasing prevalence severity of asthma in LMIC. Access to proper diagnosis and treatment with controller medications for asthma, specially with inhaled corticosteroids is feasible and cost-effective, reduce symptoms, health resource utilization, improves quality of life, and reduce mortality in low-resource settings. Summary: Prevalence of asthma was thought to be low in low-income countries, but several reports have indicated this is not always true. Under diagnosis, under treatment, exposure to air pollution, and unhygienic living conditions may contribute to a higher frequency and severity of symptoms of asthma among the poor. Proper diagnosis and treatment with controller medications for asthma is feasible and cost-effective in low-resource settings. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2nRnLPm

Semi-Local Tractography Strategies Using Neighborhood Information

Publication date: Available online 24 March 2017
Source:Medical Image Analysis
Author(s): Helen Schomburg, Thorsten Hohage
Fiber tractography based on Diffusion MRI measurements is a valuable tool for the detection and visual representation of neural pathways in vivo. We present a novel fiber orientation distribution function (ODF) based streamline tractography approach which incorporates information of neighboring regions derived from a Bayesian model. In each iteration step, the proposed algorithm defines a set of candidate fiber fragments continuing the already tracked path and assigns an a-posteriori probability. We compute the posterior as the normalized product of a likelihood function based on the given ODF-field and a prior distribution representing anatomical plausibility of a candidate fiber fragment with respect to tract curvature derived from the previously tracked fiber path by an extrapolation strategy. We derive both a deterministic tractography algorithm obtaining in each iteration a tracking direction by maximum a-posteriori estimation, as well as a probabilistic version drawing a direction from the marginalized posterior distribution. Compared to fiber tracking methods that rely only on the local ODF, the proposed algorithm proves more robust in the presence of noise and partial volume effects. We demonstrate the effectiveness of both our deterministic and probabilistic method on simulated, phantom, and in vivo data.

Graphical abstract

http://ift.tt/2n0S7tI

A Novel Method of Neo-osseous Flap Prefabrication: Induction of Free Calvarial Periosteum with Bioactive Glass

J reconstr Microsurg
DOI: 10.1055/s-0037-1598254

Background Reconstruction of craniofacial bone defects is a primary focus of craniofacial surgery. Although autogenous bone grafts remain as the gold standard, alloplastic materials have also gained widespread popularity due to their off-the-shelf availability, ease of use, and durability. In addition to replacing the missing bone, some of these alloplastic materials have also been found to induce new bone formation. Objectives In this study, the phenomenon of neo-osseous induction with bioactive glass was investigated for different implant-soft tissue configurations. Materials and Methods Thirty-two male, Wistar albino rats were divided into four equally numbered study groups. In group 1 (FP), adipofascial groin flaps were prefabricated with free periosteal grafts. In group 2 (FPB), adipofascial groin flaps were prefabricated with free periosteal grafts and bioactive glass. In group 3 (FB), adipofascial groin flaps were prefabricated with bioactive glass. In group 4 (control), adipofascial groin flaps were not prefabricated. Morphometric analyses of the prefabricated structures were performed using micro-CT. The histologic properties of the ectopic ossification were assessed by using a modified scoring system. Results Group 1 (FP) showed the greatest rate of mature lamellar bone formation. Group 2 (FBP) showed the greatest amount of bone density and volume. However, the addition of bioactive glass in group 2 (FBP) decreased the rate of mature lamellar bone formation when compared with group 1 (FP). Ectopic ossification was not observed in the control group. Conclusion Bioactive glass can be successfully used in the prefabrication of vascularized compound structures for the reconstruction of complex bone defects. However, interference with the periosteal induction of mature lamellar bone formation should be taken into consideration, especially in pediatric bone defects, which primarily rely on spontaneous osteogenesis through periosteal induction.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Asthma prevalence and severity in low-resource communities.

Purpose of review: The prevalence of asthma was thought to be low in most low-income countries, but several reports have indicated this is not always true. This is a narrative review of recent publications on the burden of asthma in low and middle-income countries (LMIC) and underprivileged communities from developed countries. Recent findings: Several studies have reported a low prevalence of asthma is LMIC, but indicate it is increasing. In the last few years, however, many surveys demonstrated this may not always be true. An analysis of the International Study for Asthma and Allergy in Childhood phase III database indicated although the prevalence of asthma among children and adolescents is higher in the developed countries, symptoms of asthma are often more severe in less affluent nations. The rate of uncontrolled asthma is also higher among underprivileged communities of developed countries. Secondary analysis of data generated by the WHO's world health survey performed among adults of 70 countries indicate symptoms of asthma are less frequent in middle-income countries and more frequent in the extremes, low income and high income. This sort of U shaped distribution suggests the disease (or syndrome) comprise more than one major phenotype related to diverse underlying mechanisms. In fact, recent reports show symptoms of asthma among the poor are associated with unhygienic living conditions, which may reduce the risk of atopy but increase the risk of nonatopic wheezing. Urbanization and exposure to air pollution also seem to contribute to an increasing prevalence severity of asthma in LMIC. Access to proper diagnosis and treatment with controller medications for asthma, specially with inhaled corticosteroids is feasible and cost-effective, reduce symptoms, health resource utilization, improves quality of life, and reduce mortality in low-resource settings. Summary: Prevalence of asthma was thought to be low in low-income countries, but several reports have indicated this is not always true. Under diagnosis, under treatment, exposure to air pollution, and unhygienic living conditions may contribute to a higher frequency and severity of symptoms of asthma among the poor. Proper diagnosis and treatment with controller medications for asthma is feasible and cost-effective in low-resource settings. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2nRnLPm

Cell Sheet Engineering Using the Stromal Vascular Fraction of Adipose Tissue as a Vascularization Strategy

Publication date: Available online 24 March 2017
Source:Acta Biomaterialia
Author(s): Marina Costa, Mariana T. Cerqueira, Tírcia C. Santos, Belém Sampaio-Marques, Paula Ludovico, Alexandra P. Marques, Rogério P. Pirraco, Rui L. Reis
Current vascularization strategies for Tissue Engineering constructs, in particular cell sheet-based, are limited by time-consuming and expensive endothelial cell isolation and/or by the complexity of using extrinsic growth factors. Herein, we propose an alternative strategy using angiogenic cell sheets (CS) obtained from the stromal vascular fraction (SVF) of adipose tissue that can be incorporated into more complex constructs. Cells from the SVF were cultured in normoxic and hypoxic conditions for up to 8 days in the absence of extrinsic growth factors. Immunocytochemistry against CD31 and CD146 revealed spontaneous organization in capillary-like structures, more complex after hypoxic conditioning. Inhibition of HIF-1α pathway hindered capillary-like structure formation in SVF cells cultured in hypoxia, suggesting a role of HIF-1α. Moreover, hypoxic SVF cells showed a trend for increased secretion of angiogenic factors, which was reflected in increased network formation by endothelial cells cultured on matrigel using that conditioned medium. In vivo implantation of SVF CS in a mouse hind limb ischemia model revealed that hypoxia-conditioned CS led to improved restoration of blood flow. Both in vitro and in vivo data suggest that SVF CS can be used as simple and cost-efficient tools to promote functional vascularization of TE constructs.Statement of SignificanceNeovascularization after implantation is a major obstacle for producing clinically viable Cell Sheet-based tissue engineered constructs. Strategies using endothelial cells and extrinsic angiogenic growth factors are expensive and time consuming and may raise concerns of tumorigenicity. In this manuscript, we describe a simplified approach using angiogenic Cell Sheets fabricated from the stromal vascular fraction of adipose tissue. The strong angiogenic behavior of these Cell Sheets, achieved without the use of external growth factors, was further stimulated by low oxygen culture. When implanted in an in vivo model of hind limb ischemia, the angiogenic Cell Sheets contributed to blood flux recovery. These Cell Sheets can therefore be used as a straightforward tool to increase the neovascularization of Cell Sheet-based thick constructs.

Graphical abstract

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Activatable bispecific liposomes bearing fibroblast activation protein directed single chain fragment / Trastuzumab deliver encapsulated cargo into the nuclei of tumor cells and the tumor microenvironment simultaneously

Publication date: Available online 24 March 2017
Source:Acta Biomaterialia
Author(s): Felista L. Tansi, Ronny Rüger, Claudia Böhm, Frank Steiniger, Roland E. Kontermann, Ulf K. Teichgraeber, Alfred Fahr, Ingrid Hilger
Molecular targeting plays a significant role in cancer diagnosis and therapy. However, the heterogeneity of tumors is a limiting obstacle for molecular targeting. Consequently, clinically approved drug delivery systems such as liposomes still rely on passive targeting to tumors, which does not address tumor heterogeneity. In this work, we therefore designed and elucidated the potentials of activatable bispecific targeted liposomes for simultaneous detection of fibroblast activation protein (FAP) and the human epidermal growth factor receptor 2 (HER2). The bispecific liposomes were encapsulated with fluorescence-quenched concentrations of the near-infrared fluorescent dye, DY-676-COOH, making them detectable solely post processing within target cells. The liposomes were endowed with a combination of single chain antibody fragments specific for FAP and HER2 respectively, or with the FAP single chain antibody fragment in combination with Trastuzumab, which is specific for HER2. The Trastuzumab based bispecific formulation, termed Bi-FAP/Tras-IL revealed delivery of the encapsulated dye into the nuclei of HER2 expressing cancer cells and caused cell death at significantly higher rates than the free Trastuzumab. Furthermore, fluorescence imaging and live microscopy of tumor models in mice substantiated the delivery of the encapsulated cargo into the nuclei of target tumor cells and tumor stromal fibroblasts. Hence, they convey potentials to address tumor plasticity, to improve targeted cancer therapy and reduce Trastuzumab resistance in the future.Statement of SignificanceThis work demonstrates the design of activatable bispecific liposomes aimed to target HER2, a poor prognosis tumor marker in many tumor types, and fibroblast activation protein (FAP), a universal tumor marker overexpressed on tumor fibroblasts and pericytes of almost all solid tumors. Encapsulating liposomes with a quenched concentration of a NIRF dye which only fluoresced after cellular degradation and activation enabled reliable visualization of the destination of the cargo in cells and animal studies. Conjugating single chain antibody fragments directed to FAP, together with Trastuzumab, a humanized monoclonal antibody for HER2 resulted in the activatable bispecific liposomes. In animal models of xenografted human breast tumors, the remarkable ability of the bispecific probes to simultaneously deliver the encapsulated dye into the nuclei of target tumor cells and tumor fibroblasts could be demonstrated. Hence, the bispecific probes represent model tools with high significance to address tumor heterogeneity and manage Trastuzumab resistance in the future.

Graphical abstract

http://ift.tt/2nRmS99

Newly developed method for mouse olfactory behavior tests using an automatic video tracking system

Publication date: Available online 24 March 2017
Source:Auris Nasus Larynx
Author(s): Hyung-Ju Cho, Yong Hyuk Lee, Bo Ra Kim, Hong-Kyung Kim, Hyo Jin Chung, Sang Chul Park, Je Kyung Seong, Joo-Heon Yoon, Chang-Hoon Kim
ObjectiveThe mouse is the most popular animal model in olfactory research. Behavior tests with odorants are essential for determining olfactory phenotype. To the best of our knowledge, the mouse olfactory behavior test has not been standardized, making the results vulnerable to inter-observer variation. We sought to develop a new mouse olfactory behavior test assessed by an automatic video tracking system with minimal inter-observer variation.MethodsA video-tracking system was used to automatically track mouse behavior in standard breeding cages with C57BL/6N mice. We tested two odorants (peanut butter for the preference test, 2MB acid for the avoidance test) and distilled water (for a control). Mouse behavior was recorded for 3min and analyzed. For the preference test, investigation time was measured. For the avoidance test, time spent in sectors away from the odorant zone was measured. To confirm our experimental settings, we also evaluated an anosmia mouse model prepared with intranasal administration of ZnSO4.ResultsAll strains of mice showed reproducible behavior patterns of preference or avoidance for the odorants. The anosmia mouse model, as expected, failed to show an olfactory ability for preference or avoidance, and this was well-matched by histologic changes caused by the ZnSO4 treatment. The automatic video tracking system successfully tracked and automatically calculated mouse behavior with good reproducibility.ConclusionOur olfactory behavior test offers a simple and accurate method to evaluate olfactory function in mice. This test can be utilized as a possible standard method to search for features of olfactory phenotypes in mice.



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Herbal remedies for urinary stones used in India and China: A review

Publication date: 5 May 2017
Source:Journal of Ethnopharmacology, Volume 203
Author(s): Deepak M. Kasote, Suresh D. Jagtap, Dinesh Thapa, Mahendra S. Khyade, Wendy R. Russell
Ethanopharmacological relevanceThe process of formation or appearance of a urinary stone anywhere in the renal tract is known as urolithiasis. It is a longstanding health problem, known to exist since early age of civilization. Records about symptoms, signs and treatment strategies of urinary stones diseases are found in the several ancient texts of traditional medicines such as Ayurveda, Traditional Chinese Medicine (TCM), Siddha and Unani. In Ayurveda, urolithiasis has been considered as one of the eight most troublesome diseases. Ayurvedic management and cure of urinary stone involves herbal formulas, alkaline liquids and surgical procedures. Whereas, TCM recommends polyherbal drugs, acupuncture and mexibustion for treatment of the urinary stones. Among these therapies, herbal remedies are in practice till today for the treatment and cure urinary stone diseases.Materials and methodsA comprehensive review of the scientific literature about pathophysiology of urinary stones and antiurolithiatic plants was undertaken using the following bibliographic databases: MEDLINE/PubMed, Scopus, Web of Knowledge and Google Scholar. The search was conducted from publications from all years until Dec., 2015 by combination of the search terms and Boolean operators; 'urinary stone' OR 'kidney stone' AND 'plant' OR 'medicine' OR 'antiurolithiatic plants'. Outputs were restricted to those completed studies only published in English. In this review, literatures about plants which are used as diuretic and/or in treatment urinary tract infections have not also been considered. The Plant List and Royal Botanical Garden, Kew databases were used to authenticate botanical names of plants. Books and monographs published in English were used to collect information about historical records of antiurolithiatic plants.ResultsRecent pharmacological interventions accredited ancient antiurolithiatic claims to several plants and their formulations. The majority of antiurolithiatic plants were found to either dissolve the stones or inhibit the process of urinary stone formation. Plants such as Phyllanthus niruri L. and Elymus repens (L.) Gould, as well as herbal products including 'Wu-Ling-San' formula, 'Cystone' and 'Herbmed' have been proved their utility as promising antiurolithiatic medicines in the different phases of clinical trials. In addition, some of the isolated phytochemicals such as berberine, lupeol, khelin, visnagin, 7-hydroxy-2′,4′,5′-trimethoxyisoflavone and 7-hydroxy-4′-methoxyisoflavone were reported to have potent antiurolithiatic activity.ConclusionIn ancient medicinal texts, antiurolithiatic potential has been ascribed to several plants and their formulations. Present scientific studies provide scientific evidences for few of these claims however, they are insufficient to establish many of these plants and herbal formulations as therapeutic remedies for the treatment and management of urinary stones. Conversely, findings of pre-clinical and clinical studies about some plants and herbal formulations are promising, which underlines the utility of herbal remedies as alternative medicines for the treatment and management of urinary stones in the future.

Graphical abstract

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