Mammary Stem Cells: Premise, Properties, and Perspectives

Publication date: Available online 6 May 2017
Source:Trends in Cell Biology
Author(s): Bethan Lloyd-Lewis, Olivia B. Harris, Christine J. Watson, Felicity M. Davis
Adult mammary stem cells (MaSCs) drive postnatal organogenesis and remodeling in the mammary gland, and their longevity and potential have important implications for breast cancer. However, despite intense investigation the identity, location, and differentiation potential of MaSCs remain subject to deliberation. The application of genetic lineage-tracing models, combined with quantitative 3D imaging and biophysical methods, has provided new insights into the mammary epithelial hierarchy that challenge classical definitions of MaSC potency and behaviors. We review here recent advances – discussing fundamental unresolved properties of MaSC potency, dynamics, and plasticity – and point to evolving technologies that promise to shed new light on this intractable debate. Elucidation of the physiological mammary differentiation hierarchy is paramount to understanding the complex heterogeneous breast cancer landscape.



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Mitochondria Bioenergetic and Cognitive Functions: The Cannabinoid Link

Publication date: Available online 6 May 2017
Source:Trends in Cell Biology
Author(s): Giacomo Mancini, Tamas L. Horvath
Despite the well-known role of chronic mitochondrial dysfunction in the pathophysiology of the brain, the impact of acute impairment of mitochondrial activity by cannabinoids on higher brain functions is unknown. In a recent paper in Nature, Hebert-Chatelain et al. elegantly uncovered the essential role that bioenergetic processes have in the regulation of higher brain functions, such as learning and memory.



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eIF4E phosphorylation by MST1 reduces translation of a subset of mRNAs, but increases lncRNA translation

Publication date: Available online 6 May 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Kyung-Won Min, Sylvia Davila, Richard W. Zealy, Lawson T. Lloyd, In Young Lee, Rumi Lee, Kyung Hye Roh, Ahjin Jung, Jacek Jemielity, Eui-Ju Choi, Jeong Ho Chang, Je-Hyun Yoon
Post-transcriptional gene regulation is an important step in eukaryotic gene expression. The last step to govern production of nascent peptides is during the process of mRNA translation. mRNA translation is controlled by many translation initiation factors that are susceptible to post-translational modifications. Here we report that one of the translation initiation factors, eIF4E, is phosphorylated by Mammalian Ste20-like kinase (MST1). Upon phosphorylation, eIF4E weakly interacts with the 5′ CAP to inhibit mRNA translation. Simultaneously, active polyribosome is more associated with long noncoding RNAs (lncRNAs). Moreover, linc00689-derived a micropeptide, STORM (Stress- and TNF-α-activated ORF Micropeptide), is induced by TNF-α-induced and MST1-mediated eIF4E phosphorylation exhibits molecular mimicry of SRP19 and, thus, competes for 7SL RNA. Our findings have uncovered a novel function of MST1 in mRNA and lncRNA translation by direct phosphorylation of eIF4E. This novel signaling pathway will provide new platforms for mRNA regulation of mRNA translation via post-translational protein modification.



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Intrinsically Disordered Proteins Adaptively Reorganize Cellular Matter During Stress

Publication date: Available online 6 May 2017
Source:Trends in Biochemical Sciences
Author(s): Sreenivas Chavali, Alexander Gunnarsson, M. Madan Babu
Intrinsically disordered proteins (IDPs) can protect cells from diverse stresses by forming higher order assemblies such as reversible aggregates or granules. Recently, Boothby et al. show that IDPs protect tardigrades against desiccation by forming a glass-like amorphous matrix, highlighting that material properties of disordered proteins can confer adaptation during stress.



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Carboxylated aurone derivatives as potent inhibitors of xanthine oxidase

Publication date: Available online 6 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Oxana V. Muzychka, Oleksandr L. Kobzar, Antonina V. Popova, Mykhaylo S. Frasinyuk, Andriy I. Vovk
Xanthine oxidase is a potential target for treatment of hyperuricemia and gout. In this study, a number of A- and B-ring carboxylated aurone derivatives were synthesized and evaluated for their ability to inhibit xanthine oxidase in vitro. According to the results obtained, two different ranges of inhibitory activity were observed. The aurones with carboxylic acid group at the 4'-position of B-ring were found to be potent inhibitors of the enzyme with IC50 values in the low micromolar range. The effects of these compounds were about 50 fold higher than of A-ring modified aurones with carboxymethoxy group at the 6-position. The binding modes of the carboxylated aurones in the active site of xanthine oxidase were explained using molecular docking calculations.

Graphical abstract

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Design and synthesis of novel photoinduced electron transfer-based hybridization probes

Publication date: Available online 6 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Chika Yokoyama, Kosuke Nakamoto, Yoshihito Ueno
Photoinduced electron transfer (PeT)-based hybridization probe is a linear and quencher-free oligonucleotide (ON) probe for DNA or RNA detection. In this report, we designed and synthesized novel adenosine analogues for PeT-based hybridization probe. In particular, the analogue containing a piperazinomethyl moiety showed effective quenching property under physiological conditions. When the probe containing the analogue was hybridized with a complementary DNA or RNA, the fluorescence increased 3- or 4-fold, respectively, compared to the single-stranded state.

Graphical abstract

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Discovery, synthesis, and structure-activity relations of 3,4-dihydro-1H-spiro(naphthalene-2,2'-piperidin)-1-ones as potassium-competitive acid blockers

Publication date: Available online 6 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Toshihiro Imaeda, Koji Ono, Kazuo Nakai, Yasunobu Hori, Jun Matsukawa, Terufumi Takagi, Yasushi Fujioka, Naoki Tarui, Mitsuyo Kondo, Akio Imanishi, Nobuhiro Inatomi, Masahiro Kajino, Fumio Itoh, Haruyuki Nishida
With the aim to discover a gastric antisecretory agent more potent than the existing proton pump inhibitors, novel 3,4-dihydro-1H-spiro(naphthalene-2,2′-piperidin)-1-one derivatives, which could occupy two important lipophilic pockets (described as LP-1 and LP-2) of H⁺,K⁺-ATPase and can strongly bind to the K⁺-binding site, were designed based on a docking model. Among the compounds synthesized, compound 4d showed a strong H⁺,K⁺-ATPase-inhibitory activity and a high stomach concentration in rats, resulting in potent inhibitory action on histamine-stimulated gastric acid secretion in rats. Furthermore, 4d exerted significant inhibitory action on histamine-stimulated gastric-acid secretion in rats with a rapid onset and moderate duration of action after the administration. These findings may lead to a new insight into the drug design of potassium-competitive acid blockers.

Graphical abstract

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Sulfonamide inhibition profiles of the β-carbonic anhydrase from the pathogenic bacterium Francisella tularensis responsible of the febrile illness tularemia

Publication date: Available online 6 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Sonia Del Prete, Daniela Vullo, Sameh M. Osman, Zeid AlOthman, Claudiu T. Supuran, Clemente Capasso
A new β-class carbonic anhydrase (CA, EC 4.2.1.1) has been cloned, purified and characterized in the genome of the pathogenic bacterium Francisella tularensis responsible of the febrile illness tularemia. This enzyme, FtuβCA, showed a kcat of 9.8 x 10⁵ s^-1 and a kcat/KM of 8.9 x 10⁷ M^-1 s^-1 for the CO2 hydration, physiological reaction, being one of the most effective β-CAs known to date, with a catalytic activity only 1.68-times lower than that of the human(h) isoform hCA II. A panel of 39 simple aromatic and heterocyclic sulfonamides, as well as clinically used drugs incorporating sulfonamide/sulfamate zinc-binding groups, was used to investigate the inhibition profile of FtuβCA with these classes of derivatives. The enzyme generally showed a weaker affinity for these inhibitors compared to other α- and β-CAs investigated earlier, with only acetazolamide and its deacetylated precursor having inhibition constant < 1 µM. Indeed, the two compounds acetazolamide AAZ and its deacetylated precursor 13 (KIs of 655-770 nM), as well as metanilamide and methazolamide (KIs of 2.53-2.92 µM) were the best FtuβCA inhibitors detected so far. As the physiological role of bacterial β-CAs is poorly understood for the virulence/life cycle of these pathogens, the present study may constitute a starting point for the design of effective pathogenic bacteria CA inhibitors with potential use as antiinfectives

Graphical abstract

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Potential anti-gout constituents as xanthine oxidase inhibitor from the fruits of Stauntonia brachyanthera

Publication date: Available online 6 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Dan Liu, Dandan Wang, Wei Yang, Dali Meng
With the aim of finding a better xanthine oxidase inhibitor with potential anti-gout properties, the studies on the fruit of Stauntonia brachyanthera were carried out, which led to the isolation of 12 glycosides, including 4 new nor-oleanane triterpenoids. Their structures were determined by comprehensive spectroscopic (NMR and HR MS) analysis. Two compounds (4 and 11) exhibited significant inhibitory activities on xanthine oxidase with IC50 values of 5.22 and 1.60 µM, respectively. Another five compounds (1, 2, 3, 8 and 10) showed qualified activities. The results suggested that the existences of nor-oleanane triterpenoids and flavonoids in the fruits were responsible for the inhibitory activity on xanthine oxidase that could cut off the production of uric acid. Nor-oleanane triterpenoids, a new leading XO inhibitor, is worthyoffurtherstudies on molecularbiology level for its mechanisms.

Graphical abstract

http://ift.tt/2pm74bW

Screening for bioactive natural products from a 67-compound library of Glycyrrhiza inflata

Publication date: Available online 6 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Yan Lin, Yi Kuang, Kai Li, Shuang Wang, Wei Song, Xue Qiao, Gulnar Sabir, Min Ye
Licorice shows a variety of pharmacological activities. This work aims to discover bioactive natural products from one botanical source of licorice, Glycyrrhiza inflata. A total of 67 free phenolics were isolated to form a compound library. Based on the bioactivities of licorice, these compounds were screened using cell- or enzyme-based bioassay methods. A total of 11 compounds exhibited potent cytotoxic activities against three human cancer cell lines (HepG2, SW480 and MCF7), while showed little toxicity on human normal cell lines LO2 and HEK293T. A number of chalcones showed remarkable anti-inflammatory activities. Among them, 2 (licochalcone B, IC50 8.78 μM), 10 (licoagrochalcone C, IC50 9.35 μM) and 13 (licochalcone E, IC50 9.09 μM) exhibited the most potent inhibitory activities on LPS-induced NO production, whereas 1, 8, 10, 12 and 13 (IC50 13.9, 7.27, 2.44, 6.67 and 3.83 μM) showed potent inhibitory activities on NF-κB transcription. Nine prenylated phenolics were found to be PTP1B inhibitors. Particularly, licoagrochalcone A (4), kanzonol C (7), 2′-hydroxyisolupalbigenin (35), gancaonin Q (45), glisoflavanone (50) and glabrol (53) showed IC50 values of 0.31-0.97 μM. Compounds 24 (semilicoisoflavone B, IC50 0.25 μM), 26 (allolicoisoflavone B, IC50 0.80 μM) and 64 (glabridin, IC50 0.10 μM) showed noticeable tyrosinase inhibitory activities. Most of the above bioactive compounds were reported for the first time.

Graphical abstract

http://ift.tt/2pmoV27

Upregulation of miR-195 accelerates oxidative stress-induced retinal endothelial cell injury by targeting mitofusin 2 in diabetic rats

Publication date: Available online 6 May 2017
Source:Molecular and Cellular Endocrinology
Author(s): Rui Zhang, Qian Garrett, Huimin Zhou, Xiaoxi Wu, Yueran Mao, Ximing Cui, Bing Xie, Zanchao Liu, Dongsheng Cui, Lei Jiang, Qingfu Zhang, Shunjiang Xu
This study was performed to investigate the oxidative stress-induced miRNA changes in relation to pathogenesis of diabetic retinopathy (DR) and to establish a functional link between miRNAs and oxidative stress-induced retinal endothelial cell injury. Our results demonstrated that oxidative stress could induce alterations of miRNA expression profile, including up-regulation of miR-195 in the diabetic retina or cultured HMRECs after exposed to H2O2 or HG (P < 0.05). Oxidative stress also resulted in a significant reduction of MFN2 expression in diabetic retina or HMRECs (P < 0.05). Overexpression of miR-195 reduced MFN2 protein levels, and induced tube formation and increased permeability of diabetic retinal vasculature. The luciferase reporter assay confirmed that miR-195 binds to the 3′ -untranslated region (3′-UTR) of MFN2 mRNA. This study suggested that miR-195 played a critical role in oxidative stress-induced retinal endothelial cell injury by targeting MFN2 in diabetic rats.



http://ift.tt/2qNKUjT

Histidine-functionalized graphene quantum dot-graphene micro-aerogel based voltammetric sensing of dopamine

Publication date: October 2017
Source:Sensors and Actuators B: Chemical, Volume 250
Author(s): Li Ruiyi, Qing Sili, Li Zhangyi, Liu Ling, Li Zaijun
Histidine-functionalized graphene quantum dots (His-GQDs) made via thermal pyrolysis of citric acid and histidine are combined with Zn²⁺ ions to form Zn-His-GQD complex. The complex was employed as the solid surfactant for stabilizing toluene-in-graphene oxide aqueous dispersion emulsion. The graphene oxide in the Pickering emulsion was slowly reduced by addition of hydrazine hydrate and leads to the formation of graphene micro-gel. The micro-gel was treated by freeze-drying, acid washing and thermal annealing to obtain His-GQD-graphene micro-aerogel (His-GQD-GMA). The as-prepared hybrid offers a three-dimensional architecture with well-defined porous structures, in which the His-GQDs were well dispersed and fixed on the graphene sheets. The all-carbon hybrid provides excellent electron/ion conductivity, electro-catalytic activity and structural stability. The sensor based on the His-GQD-GMA exhibits ultrasensitive electrochemical response to dopamine. Its differential pulse voltammetric signal linearly increases with the increase of dopamine concentration in the range from 1.0×10⁻⁹M to 8.0×10⁻⁵M with the detection limit of 2.9×10⁻¹⁰M (at a S/N ratio of 3). The sensitivity is much better than that of the reported graphene sensors for dopamine. The analytical method has been successfully applied in the detection of dopamine in rat brain. The study also opens a window on the electronic properties of graphene aerogel and graphene quantum dots as well their hybrids to meet needs of further applications in sensors, catalysis and energy storage and conversion devices.

Graphical abstract

http://ift.tt/2qcw9dq

Iron mineralogy as a fingerprint of former steelmaking activities in river sediments

Publication date: 1 December 2017
Source:Science of The Total Environment, Volumes 599–600
Author(s): Hussein Jaafar Kanbar, Emmanuelle Montargès-Pelletier, Benoit Losson, Isabelle Bihannic, Renaud Gley, Allan Bauer, Frederic Villieras, Luc Manceau, Antoine G. El Samrani, Veronique Kazpard, Laurence Mansuy-Huault
Submerged sediment cores were collected upstream of a dam in the Orne River, northeastern France. This dam was built in the context of steelmaking to constitute a water reservoir for blast furnace cooling and wet cleaning of furnace smokes. The dam also enhanced sediment deposition in the upstream zone. This study was performed to unravel the contamination status of sediments and to evidence possible contribution sources. The sediment layers were analyzed for water content, grain size, chemical composition, crystalline phases at a bulk scale and poorly crystalline and amorphous phases at a sub-micrometer scale. Visual aspect, texture, color, and chemical and mineralogical analyses showed that the settled sediments were mainly composed of fine black matter, certainly comprising steelmaking by-products. Those materials were highly enriched with Fe, Zn, Pb and other trace metals, except for a relatively thin layer of surficial sediments that had settled more recently. Bulk mineralogy revealed crystalline iron minerals, such as magnetite, goethite, wuestite and pyrite, in the deep layers of the sediment cores. Furthermore, microscopic investigations evidenced the presence of ferrospheres, goethite nanoparticles and newly formed Fe-aluminosilicates; all originating from the former steelmaking facilities. The variation of iron mineralogy, combined with specific chemical profiles and other sediment features, demonstrate the different contributions that constitute the sediment deposit. Furthermore, chemical and mineralogical features of goethite and Fe-aluminosilicates could be used as a fingerprint for such contaminated sediments.

Graphical abstract

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Essential and toxic element concentrations in monofloral honeys from southern Croatia

Publication date: 1 November 2017
Source:Food Chemistry, Volume 234
Author(s): Nina Bilandžić, Ivana Tlak Gajger, Marina Kosanović, Bruno Čalopek, Marija Sedak, Božica Solomun Kolanović, Ivana Varenina, Đurđica Božić Luburić, Ines Varga, Maja Đokić
The concentrations of 24 elements in seven honey types (multifloral, heather, common heather, bearberry, sage, mandarin orange-blossom and honeydew) collected in southern Mediterranean regions of Croatia were determined using ICP-MS. Significant differences were found in the concentrations of Ag, As, Ba, Cu, Co, Fe, K, Mg, Mn, Mo, Na, Ni, Se, Sb, U and Th (p<0.05, all) among honeys. The highest element concentrations were determined in honeydew honeys, with the exception of multifloral (Ca, Cr, Mo, Se), common heather (Mg, Na), bearberry (Ba, Fe, Pb) and sage (Ag) honeys. Among the floral honeys, the highest concentrations were found in multifloral honey (Al, As, Be, Ca, Cr, Mn, Mo, Ni, Se, Th and U), common heather (Co, K, Mg, Na, V), sage (Ag, Cd, Cu), and bearberry (Ba, Fe, Pb, Sb, Zn). The results contribute to the evidence supporting the role of botanical origin on the elemental composition of honey.



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Study of all-optical switching properties of zinc phthalocyanine thin film by pump-probe technique

Publication date: 1 October 2017
Source:Optics & Laser Technology, Volume 95
Author(s): Anil Kumar, Rajesh Punia, Arun K. Gupta, Devendra Mohan, Kirti Kapoor
The nonlinear optical absorption, refraction and switching behavior of Zinc phthalocyanine (Zn(II)Pc) thin films are reported. Z-scan technique is employed to study the nonlinear absorption and nonlinear refraction behavior of the thin films with nanosecond pulses of Nd:YAG laser at ∼532nm. Optical switching behavior of the dye is studied using pump-probe technique with ∼5ns pulses of Nd:YAG at ∼532nm as the pump beam and ∼632.8nm cw He-Ne laser as the probe beam. The switching behavior of the dye is attributed to excited state absorption (ESA) of the probe beam by the dye molecules. Probe beam modulation with increasing pump intensity is also investigated.



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Statin use after esophageal cancer diagnosis and survival: A population based cohort study

Publication date: June 2017
Source:Cancer Epidemiology, Volume 48
Author(s): Chris R. Cardwell, Andrew D. Spence, Carmel M. Hughes, Liam J. Murray
BackgroundA recent epidemiological study of esophageal cancer patients concluded statin use post-diagnosis was associated with large (38%) and significant reductions in cancer-specific mortality. We investigated statin use and cancer-specific mortality in a large population-based cohort of esophageal cancer patients.MethodsNewly diagnosed [2009–2012] esophageal cancer patients were identified from the Scottish Cancer Registry and linked with the Prescribing Information System and Scotland Death Records (to January 2015). Time-dependent Cox regression models were used to calculate hazard ratios (HR) for cancer-specific mortality and 95% confidence intervals (CIs) by post-diagnostic statin use (using a 6 month lag to reduce reverse causation) and to adjust these HRs for potential confounders.Results1921 esophageal cancer patients were included in the main analysis, of whom 651 (34%) used statins after diagnosis. There was little evidence of a reduction in esophageal cancer-specific mortality in statin users compared with non-users after diagnosis (adjusted HR=0.93, 95% CI, 0.81, 1.07) and no dose response associations were seen. However, statin users compared with non-users in the year before diagnosis had a weak reduction in esophageal cancer-specific mortality (adjusted HR=0.88, 95% CI, 0.79, 0.99).ConclusionsIn this large population-based esophageal cancer cohort, there was little evidence of a reduction in esophageal cancer-specific mortality with statin use after diagnosis.



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Evisceration With Injectable Hydrogel Implant in a Rabbit Model

Purpose: To determine the safety, durability, and biocompatibility of 2.5% polyacrylamide hydrogel (Aquamid, Specialty European Pharma, Ltd., London, UK) as an injectable viscoelastic implant following evisceration in a rabbit model. Methods: The protocol was reviewed and approved by the Wake Forest Institutional Animal Care and Use Committee. Adult New Zealand rabbits underwent cornea-sparing evisceration of the right eye with injection of 2.5% polyacrylamide hydrogel implant. The rabbits were sacrificed after 2 weeks (n = 1), 5 weeks (n = 2), 12 weeks (n = 3), 25 weeks (n = 3), and 1 year (n = 3) to evaluate the implant volume and host reaction to the implant. Both eyes were enucleated and their diameters were measured. The eviscerated eyes were fixed in formalin and processed using routine histopathologic methods to assess inflammatory reaction and vascularization. Results: The implant material was well tolerated with a moderate giant cell reaction seen at 6 weeks that improved over time. Extensive vascularization of the implant was noted starting at 6 weeks. There was excellent maintenance of globe volume that did not diminish over time. The relative diameters of the eviscerated eyes compared with control were 89 ± 6% (mean% ± SD) at 12 weeks (n = 3), 94 ± 2% at 25 weeks (n = 3), and 93 ± 4% at 1 year (n = 3). Conclusion: With further study, injectable 2.5% polyacrylamide hydrogel may provide an excellent alternative to solid orbital implants. The implant material was universally well tolerated and maintained appropriate volume in the orbit for the study period of 1 year. Extensive vascularization of the implant was noted indicating biointegration.

http://ift.tt/2qNR6bJ

Conjunctival Lymphoma in a Patient on Fingolimod for Relapsing-Remitting Multiple Sclerosis

The authors describe a 39-year-old woman treated with fingolimod for relapsing-remitting multiple sclerosis for 2 years who then developed a bilateral conjunctival mucosa-associated lymphoid tissue lymphoma. Fingolimod treatment for multiple sclerosis has been associated with lymphoma in 3 previously reported cases. This is the first case of ocular adnexal lymphoma presumed to be due to fingolimod. Given that ophthalmologists regularly monitor many patients on fingolimod for fingolimod-associated macular edema and ophthalmic manifestations of multiple sclerosis, the authors hope to alert physicians of the possibility of ocular adnexal lymphoma in these patients.

http://ift.tt/2qNDtsK

Transarterial Embolization of a Spontaneous Intraorbital Arteriovenous Fistula With n-BCA Glue

Arteriovenous fistulae of the orbit are exceedingly rare. They are high-flow vascular malformations involving a fistula from the ophthalmic artery to one of the draining ophthalmic veins. Presenting symptoms can mimic those of carotid cavernous fistulae or of ophthalmic venous varices, and include diplopia, proptosis, chemosis, decreased visual acuity, and retro-orbital pain. Very few case reports are published on the treatment of this aggressive vascular malformation, and they uniformly describe techniques involving a transvenous access for the embolization of the fistula.1–6 To the best of authors' knowledge, they report the first case of transarterial embolization of an intraorbital AVF.

http://ift.tt/2qNBxAy

Tissue Engineering in Ophthalmology: Implications for Eyelid Reconstruction

Purpose: Bioengineering aims to produce functional tissue replacements to repair defects and has been widely investigated over the past few decades. We aimed to review the available literature on the application of tissue engineering in ophthalmology, with a particular focus on ophthalmic plastic surgery and potential applications for eyelid reconstruction. Methods: A literature search was performed on the MEDLINE database using the keywords "bioengineering," "tissue engineering," and "ophthalmology." Articles written in English were included. Results: There is a substantial body of work on tissue engineering of the cornea. Other structures in ophthalmology investigated include the conjunctiva, lacrimal gland, and orbital bone. We also discuss the potential application of tissue engineering in eyelid reconstruction. Conclusion: Tissue engineering represents the future of regenerative and reconstructive medicine, with significant potential applications in ophthalmic plastic surgery.

http://ift.tt/2qNCBnW

Clinical Response to Tocilizumab in Severe Thyroid Eye Disease

Tocilizumab, in a preliminary study, was reported to be an effective therapy for moderate to severe thyroid eye disease. The authors describe the clinical response of 2 severe thyroid eye disease cases refractory to intravenous steroids and orbital decompression. Both patients demonstrated improved clinical activity scores with minimal side effects after tocilizumab therapy. In addition, post tocilizumab orbital fat biopsies demonstrated benign adipose tissue without evidence of inflammatory cells.

http://ift.tt/2qNR4R9

Correction of Lower Eyelid Retraction Using Acellular Human Dermis During Orbital Decompression

Purpose: To investigate the surgical outcome of grafting acellular human dermis compared with concurrent lower eyelid retractor recession during swinging eyelid orbital decompression for correction of lower eyelid retraction in patients with Graves' orbitopathy. Methods: Institutional Review Board-approved retrospective nonrandomized study of 54 Graves' orbitopathy patients (95 eyes) from 2008 to 2012. Patients who received decompression were divided into 3 groups: Group 1 with conjunctival lengthening using 0.3-mm thickness AlloDerm (36 eyes), Group 2 with inferior retractor recession (33 eyes), and Group 3 with decompression only (26 eyes). Outcome measures included lower eyelid height, inferior sclera show, cosmetic appearance, and complications. Results: Baseline clinical characteristics and the degree of improvement of exophthalmos were not different between groups. Preoperative MRD2 was higher in group 1 (8.0 mm) than in groups 2 (6.9 mm, p

http://ift.tt/2qNCCbu

Dacryoendoscopic Features in a Case of Canaliculitis With Concretions

No abstract available

http://ift.tt/2qNGkSt

Acute Orbital Syndrome in Herpes Zoster Ophthalmicus: Clinical Features of 7 Cases

Purpose: To report a series of patients with herpes zoster ophthalmicus and associated acute orbital syndrome with corresponding radiographic findings. Methods: Medical records of 7 patients with herpes zoster ophthalmicus with acute orbital findings were reviewed. Clinical presentation, radiography, and treatment outcomes were assessed. Results: One man and 6 women with a median age of 70 years (range 47–84) presented with herpes zoster ophthalmicus with acute clinical orbital signs. Two of the 7 patients had compromised immune systems, with 1 patient having chronic lymphocytic leukemia and another infected with human immunodeficiency virus. Clinical orbital findings included proptosis, blepharoptosis, ophthalmoplegia, diplopia, and visual loss. Orbital imaging detailed such findings as myositis in all 7 patients, dacryoadenitis in 2 patients, and optic nerve sheath enhancement in 1 patient. Treatment with intravenous acyclovir was universal in all 7 patients and in 2 cases systemic corticosteroids were also administered. Orbital signs improved in all patients over several months. Conclusions: Herpes zoster ophthalmicus can rarely cause an acute orbital syndrome and the authors present what may be the largest series of such patients to date. Herpes zoster ophthalmicus can affect various orbital structures including the lacrimal gland, extraocular muscles, cranial nerves and optic nerve sheath. A careful clinical examination and detailed orbital radiography are critical in proper diagnosis and treatment of such patients. Improvement of symptoms and signs with antiviral therapy can be expected; however, complete resolution does not always occur. The role of systemic steroids in treatment of orbital disease is yet to be determined.

http://ift.tt/2qNIgKH

The Bleph and the Brain: The Effect of Upper Eyelid Surgery on Chronic Headaches

Purpose: To determine effect of upper eyelid surgery on headache symptoms. Methods: Consecutive adults undergoing upper eyelid surgery for obscuration of superior visual field, who also reported headache symptoms for greater than 1 year completed a pre- and postoperative Headache Impact Test-6 quality of life questionnaire (study group). A cohort of patients undergoing other oculoplastic procedures with headaches also completed the questionnaire pre- and postoperatively (control group). The study was conducted over a 2-year period. Neither the patients nor the study investigators were masked. Results: Twenty-eight patients met criteria for the study group, and 19 patients in the control group. Mean age was 58.7 and 60.7 years, respectively. There was no statistically significant difference in preoperative location of headaches. There was no significant difference in mean Headache Impact Test-6 scores preoperatively, 57.7 study group, 58.1 control group, p = 0.86. Mean postoperative scores were lower (improved) in the study arm, 45.3, as compared with the control arm, 58.6, p

http://ift.tt/2qNDtce

Clinical Features and Treatment Outcomes of Orbital Inflammatory Disease in Singapore: A 10-Year Clinicopathologic Review

Purpose: 1) To assess the clinical profile and treatment outcomes of orbital inflammatory disease in the local population, and 2) classify patients using current histopathological criteria. Methods: Ten-year retrospective clinicopathologic review of patients diagnosed with orbital inflammatory disease who underwent tissue biopsy from January 2001 to December 2011 at a tertiary referral centre in Singapore. Data collection included patient demographics, clinical presentation, investigations, systemic disease, histopathology review, clinical classification, medical and surgical management, response to treatment and recurrence rates. Results: The study comprised 70 patients. Thirty-seven (52.9%) had nonspecific inflammation distributed as follows: lacrimal (n = 23), diffuse (n = 5), anterior (n = 5), myositic (n = 4). Thirty-three (47.1%) had specific inflammation of the following subtypes: idiopathic sclerosing inflammation (n = 9), granulomatous disorders (n = 8), transitional lesions (n = 5), vasculitis (n = 4), and others (n = 7). A total of 76.8% of patients received oral prednisolone, with a median duration of three months. Response to treatment was good in 71.9% of patients. Recurrence occurred in 22 (32.8%) patients at a mean interval of 20 months after completion of treatment, and was higher in myositic and vasculitic subtypes. There was no significant correlation between duration of treatment and recurrence. Conclusions: This study has re-emphasized the importance and utility of orbital biopsy and histopathologic typing for optimal management of orbital inflammatory disease. It has also improved the knowledge of the rate and response to treatment of its various subtypes.

http://ift.tt/2qNM5jf

Aesthetic Abstracts and Citations

No abstract available

http://ift.tt/2qciGlL

Thyroid-Related Orbital Decompression Surgery: A Multivariate Analysis of Risk Factors and Outcomes

Purpose: Despite the number of publications on orbital decompression surgery for thyroid eye disease, there are few comparative studies and most studies are underpowered. The goal of the study is to use multivariable analysis to identify independent patient and disease-related predictors of response to decompression surgery and of need for secondary decompressions. Methods: The authors retrospectively reviewed all patients who underwent transorbital thyroid-related orbital decompression surgery at the Kellogg Eye Center of the University of Michigan between 1999 and 2014. Demographic, medical, and surgical covariates were collected. Decompression techniques included medial, lateral, and balanced decompressions, with or without orbital fat removal. Main outcomes included proptosis reduction and secondary decompressions, both analyzed at the orbital level. Univariate and multivariable analyses (with adjustment for interorbit correlation) were conducted to determine predictors of the outcomes of interest. Results: Mean proptosis reduction was 3.8 ± 2.4 mm (mean ± standard deviation, N = 420 orbits). The secondary decompression rate was 13.8% (82/594). On multivariable mixed linear regression, larger preoperative proptosis (p

http://ift.tt/2qc9P3l

Ethmoid Silent Sinus Syndrome Following Orbital Trauma

A 55-year-old man presented with progressive "enophthalmos" of his ocular prosthesis, 12 years after secondary orbital implant placement following evisceration of a severe traumatic globe rupture. The medial orbital wall was found to be displaced inwards, associated with ethmoid sinus opacification, and consistent with post traumatic silent sinus syndrome affecting the ethmoid paranasal sinuses. The authors present the clinical and radiological findings, review the literature on silent sinus syndrome of nonmaxillary sinuses, and discuss the possible mechanisms for his presentation.

http://ift.tt/2qclU8X

Virtual Fitting, Selection, and Cutting of Preformed Anatomic Orbital Implants

Purpose: To evaluate the usage of preoperative digital anatomic implant evaluation in internal orbital fractures. Methods: An IRB-approved review of cases of orbital fracture repair was conducted and cases where digital implant modeling was performed were selected for comprehensive review. The surgical time of these cases was also compared with surgeon and implant matched controls. Results: A total of 25 patients and 26 orbits underwent preoperative virtual fitting and were reviewed. There were no complications or revision surgeries needed. Postoperative assessment demonstrated accuracy to the preoperative target with an average maximum deviation of 1.9 mm. Conclusions: Preoperative digital fracture assessment, implant manufacturer and size selection, and virtual cutting guide creation provides additional tools for orbital surgeons to achieve anatomic restoration without significant differences in operating time.

http://ift.tt/2qcq4NZ

Familial Incomplete Punctal Canalization: Clinical and Fourier Domain Optical Coherence Tomography Features

Incomplete punctal canalization is a form of punctal dysgenesis with membranous noncanalization and can be confused with punctal agenesis. The clinical and diagnostic features are known; however, familial incomplete punctal canalization has not been reported earlier. A family with 3 affected members is presented in this series with similar incomplete punctal canalization and nasolacrimal duct obstructions. After membranotomy and endoscopic dacryocystorhinostomy with bicanalicular intubation, all of them are free of epiphora at last visit.

http://ift.tt/2qckQBS

Periorbital Autologous Fat Grafting in Facial Nerve Palsy

Purpose: To report outcomes and complications of periorbital autologous fat grafting (AFG) in improving volume loss-related symmetry and function in facial nerve palsy patients and to assess patient satisfaction. Methods: A retrospective, noncomparative review of all facial nerve palsy patients who underwent periorbital AFG at single center over a 4-year period. Two independent graders objectively assessed standard photographs for any change in volume loss and symmetry: pre- and postoperative periods (early, 0–2 months; intermediate, 3–9 months; and late, >10 months). Any adverse outcomes were recorded. Patient satisfaction was assessed by questionnaire survey. Results: A total of 18 facial nerve palsy patients (13 females) underwent periorbital AFG between February 2011 and 2015. Mean age was 51.9 ± 15.3 years (range, 26–76). Mean follow up was 6.8 ± 4.6 (range, 0.5–15) months. Photographs of 14 patients were eligible for evaluation. Tear trough visibility (p

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A Conjunctival Melanoma Causing Bloody Tears

No abstract available

http://ift.tt/2qcqFPS

“Silent Sinus Syndrome” Following Orbital Trauma: A Case Series and Review of the Literature

Purpose: To describe the demographics, presentation, and treatment of "silent sinus syndrome" (SSS) diagnosed following orbital trauma and review the literature on this topic. Methods: A retrospective review of 6 consecutive cases of SSS following trauma seen by the authors from 2004 to 2015. Data collected included patient demographics, details of previous trauma, clinical presentation, imaging findings, surgery performed, outcome, and follow up. Results: Six patients were identified presenting with SSS following orbital floor fracture. All cases developed progressive enophthalmos due to maxillary sinus atelectasis on average 8 months after their initial trauma (range, 3–16 months). The appearance of the maxillary sinus on CT was indistinguishable from the changes seen in spontaneous SSS. All 6 patients had surgical repair, which included maxillary sinus reventilation and surgery to build up the orbital floor and correct the enophthalmos in 4 patients, maxillary sinus reventilation surgery only in 1 patient and surgery to build up the orbital floor only in 1 patient. There was a reduction of enophthalmos and globe dystopia in all cases with no significant complications. Conclusions: Changes in the maxillary sinus after orbital floor fracture may occur in the months following the initial trauma and the changes are indistinguishable from those seen in spontaneous SSS. The mechanism is presumed to be obstruction of the natural ostium of the maxillary sinus, accumulation of secretions and the development of negative pressure within the sinus leading to its collapse.

http://ift.tt/2qc9Owj

Re: “Secondary Orbital Reconstruction in Patients With Prior Orbital Fracture Repair”

No abstract available

http://ift.tt/2qNOUAJ

Orbitofacial Metastatic Basal Cell Carcinoma: Report of 10 Cases

Purpose: To explore the clinical features, management, and prognosis of metastatic basal cell carcinoma originating in the orbitofacial region. Methods: Ten cases of orbitofacial metastatic basal cell carcinoma were identified by searching databases at 2 institutions from 1995 to 2015. A retrospective chart review was performed. Main outcome measures included patient demographics, lesion size, location of metastases, histologic subtype, recurrence rate, time between primary tumor diagnosis and metastasis, perineural invasion, treatment modalities, and survival from time of metastasis. Results: The median tumor size at largest dimension was 3.3 cm (range, 1.9–11.5 cm), and 6 of 10 patients had at least 1 local recurrence before metastasis (range, 0–2 recurrences). The most common sites of metastasis included the ipsilateral parotid gland (n = 6) and cervical lymph nodes (n = 5). Histologic subtypes included infiltrative (n = 5), basosquamous (n = 2), nodular (n = 1), and mixed (n = 1). The median time from primary tumor diagnosis to metastasis was 7.5 years (range, 0–13). The median survival time from diagnosis of metastasis to last documented encounter or death was 5.3 years (range, 7 months–22.8 years). Treatment regimens included surgical excision, radiotherapy, and hedgehog inhibitors. Conclusions: Based on our findings, the following features may be markers of high risk orbitofacial basal cell carcinoma: 1) increasing tumor size, 2) local recurrence of the primary tumor, 3) aggressive histologic subtype, and 4) perineural invasion. Screening should include close observation of the primary site and tissues in the distribution of regional lymphatics, particularly the parotid gland and cervical lymph nodes.

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Intestinal absorption mechanisms of 2′-deoxy-2′-β-fluoro-4′-azidocytidine, a cytidine analog for AIDS treatment, and its interaction with P-glycoprotein, multidrug resistance-associated protein 2 and breast cancer resistance protein

Publication date: Available online 6 May 2017
Source:European Journal of Pharmaceutical Sciences
Author(s): Yixian Liu, Bingjie Liu, Yan Zhang, Youmei Peng, Chenzheng Huang, Ning Wang, Jinhua Jiang, Qingduan Wang, Junbiao Chang
2′-Deoxy-2′-β-fluoro-4′-azidocytidine (FNC), a cytidine analog, has attracted great interest because of its potent activity against wild-type and multidrug-resistant HIV. The purpose of current study was to investigate the absorption mechanisms of FNC in the small intestine, as well as the interactions between FNC and P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). The experiments were performed using Caco-2 cells and the rat small intestine. The uptake experiment indicated that FNC concentration, extracellular pH and the incubated temperature could influence the uptake of FNC in Caco-2 cells. NaN3, verapamil, probenecid, MK571 and GF120918 could significantly increase the FNC uptake in Caco-2 cells. The transport experiment showed that both the absorption and secretion of FNC were concentration dependent. The secretion of FNC was approximately 2-fold greater than the absorption. In the presence of verapamil, probenecid, MK571 or GF120918, the efflux ratio decreased by >50%. In everted rat intestine, the absorption of FNC also depended on its concentration and was not significantly different in the different segments of the small intestine. Real-time RT-PCR results indicated that the gene expressions of P-gp, MRP2 and BCRP were up-regulated after exposure to FNC. The reduction in accumulation of rhodamine 123 after treatment with FNC revealed its ability to up-regulate P-gp activity. In conclusion, FNC was completely absorbed by passive diffusion and active transport mechanisms. P-gp, MRP2 and BCRP could influence the absorption of FNC in the small intestine. FNC could modulate the gene expressions of P-gp, MRP2 and BCRP, and increase the activity of P-gp.

Graphical abstract

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Unmasking efavirenz neurotoxicity: Time matters to the underlying mechanisms

Publication date: Available online 6 May 2017
Source:European Journal of Pharmaceutical Sciences
Author(s): Nádia M. Grilo, M. João Correia, Joana P. Miranda, Madalena Cipriano, Jacinta Serpa, M. Matilde Marques, Emília C. Monteiro, Alexandra M.M. Antunes, Lucília N. Diogo, Sofia A. Pereira
Efavirenz is an anti-HIV drug that presents relevant short- and long-term central nervous system adverse reactions. Its main metabolite (8-hydroxy-efavirenz) was demonstrated to be a more potent neurotoxin than efavirenz itself. This work was aimed to understand how efavirenz biotransformation to 8-hydroxy-efavirenz is related to its short- and long-term neuro-adverse reactions. To access those mechanisms, the expression and activity of Cyp2b enzymes as well as the thiolomic signature (low molecular weight thiols plus S-thiolated proteins) were longitudinally evaluated in the hepatic and brain tissues of rats exposed to efavirenz during 10 and 36days. Efavirenz and 8-hydroxy-efavirenz plasma concentrations were monitored at the same time points. Cyp2b induction had a delayed onset in liver (p<0.001), translating into increases in Cyp2b activity in liver and 8-hydroxy-efavirenz plasma concentration (p<0.001). Moreover, an increase in S-cysteinyl-glycinylated proteins (p<0.001) and in free low molecular weight thiols was also observed in liver. A distinct scenario was observed in hippocampus, which showed an underexpression of Cyp2b as well as a decrease in S-cysteinylated and S-glutathionylated proteins. Additionally, the observed changes in tissues were associated with a marked increase of S-glutathionylation in plasma. Our data suggest that the time course of efavirenz biotransformation results from different mechanisms for its short- and long-term neurotoxicity. The difference in the redox profile between liver and hippocampus might explain why, despite being mostly metabolized by the liver, this drug is neurotoxic. If translated to clinical practice, this evidence will have important implications in efavirenz short- and long-term neurotoxicity prevention and management.

Graphical abstract

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A comparative study of chromatographic behavior and lipophilicity of selected natural styryl lactones, their derivatives and analogues

Publication date: Available online 6 May 2017
Source:European Journal of Pharmaceutical Sciences
Author(s): Milica Ž. Karadžić, Davor M. Lončar, Goran Benedeković, Ivana Kovačević, Velimir Popsavin, Strahinja Z. Kovačević, Lidija R. Jevrić, Sanja O. Podunavac-Kuzmanović
This study is based on the analyses of the retention behavior of selected natural styryl lactones and their synthetic analogues in reversed-phase high-performance liquid chromatography. Chromatographic separations were achieved applying ZORBAX SB-C18 column and two different mobile phases: methanol-water and acetonitrile-water. Chromatographic lipophilicity of the analyzed compounds was defined by logk0 constant and correlated with in silico molecular descriptors. According to the statistical validation parameters, obtained results indicate that the presented linear and multiple quantitative structure-retention relationship models can successfully predict the chromatographic lipophilicity of structurally similar compounds. Hierarchical cluster analyses (HCA) was applied in order to group similar compounds according to their chromatographic and in silico lipophilicity. It can be concluded that chromatographic systems with methanol-water were better for modelling of logk0. Modelling was performed in order to characterize compounds regarding their lipophilicity profiles as future drug candidates.

Graphical abstract

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Evaluation of a biphasic in vitro dissolution test for estimating the bioavailability of carbamazepine polymorphic forms

Publication date: Available online 6 May 2017
Source:European Journal of Pharmaceutical Sciences
Author(s): Jia Deng, Sven Staufenbiel, Roland Bodmeier
The purpose of this study was to discriminate three crystal forms of carbamazepine (a BCS II drug) by in vitro dissolution testing and to correlate in vitro data with published in vivo data. A biphasic dissolution system (phosphate buffer pH6.8 and octanol) was used to evaluate the dissolution of the three polymorphic forms and to compare it with conventional single phase dissolution tests performed under sink and non-sink conditions. Similar dissolution profiles of three polymorphic forms were observed in the conventional dissolution test under sink conditions. Although a difference in dissolution was seen in the single phase dissolution test under non-sink conditions as well as in the aqueous phase of the biphasic test, little relevance for in vivo data was observed. In contrast, the biphasic dissolution system could discriminate between the different polymorphic forms in the octanol phase with a ranking of form III>form I>dihydrate form. This was in agreement with the in vivo performance. The dissolved drug available for oral absorption, which was dominated by dissolution and solution-mediated phase transformation, could be reflected in the biphasic dissolution test. Moreover, a good correlation was established between in vitro dissolution in the octanol phase of the biphasic test and in vivo pharmacokinetic data (R²=0.99). The biphasic dissolution method is a valuable tool to discriminate between different crystal forms in the formulations of poorly soluble drugs.

Graphical abstract

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New drugs for the treatment of Mycobacterium tuberculosis infection

Publication date: July 2017
Source:Biomedicine & Pharmacotherapy, Volume 91
Author(s): Manaf AlMatar, Husam AlMandeal, Işıl Var, Begüm Kayar, Fatih Köksal
Tuberculosis presents a grave challenge to health, globally instigating 1.5 million mortalities each year. Following the breakthrough of first-line anti-TB medication, the number of mortalities reduced greatly; nonetheless, the swift appearance of tuberculosis which was drug-resistant, as well as the capability of the bacterium to survive and stay dormant are a considerable problem for public health. In order to address this issue, several novel possible candidates for tuberculosis therapy have been subjected to clinical trials of late. The novel antimycobacterial agents are acquired from different categories of medications, operate through a range of action systems, and are at various phases of advancement. We therefore talk about the present methods of treating tuberculosis and novel anti-TB agents with their action method, in order to advance awareness of these new compounds and medications.

Graphical abstract

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The genetic basis of deafness in populations of African descent

Publication date: Available online 6 May 2017
Source:Journal of Genetics and Genomics
Author(s): Jason R. Rudman, Rosemary I. Kabahuma, Sara E. Bressler, Yong Feng, Susan H. Blanton, Denise Yan, Xue-Zhong Liu
Hearing loss is the most common sensorineural disorder worldwide and is associated with more than 1000 mutations in more than 90 genes. While mutations in genes such as GJB2 (gap-junction protein β 2) and GJB6 (gap-junction protein β 6) are highly prevalent in Caucasian, Asian, and Middle Eastern populations, they are rare in both native African populations and those of African descent. The objective of this paper is to review the current knowledge regarding the epidemiology and genetics of hearing loss in African populations with a focus on native sub-Saharan African populations. Environmental etiologies related to poor access to healthcare and perinatal care account for the majority of cases. Syndromic etiologies including Waardenburg, Pendred, and Usher syndromes are uncommon causes of hearing loss in these populations. Of the non-syndromic causes, common mutations in GJB2 and GJB6 are rarely implicated in populations of African descent. Recent use of next-generation sequencing (NGS) has identified several candidate deafness genes in African populations from Nigeria and South Africa that are unique when compared to common causative mutations worldwide. Researchers also recently described a dominant mutation in MYO3a in an African American family with nonsyndromic hearing loss. The use of NGS and specialized panels will aid in identifying rare and novel mutations in a more cost and time effective manner. The identification of common hearing loss mutations in indigenous African populations will pave the way for translation into genetic deafness research in populations of African descent worldwide.



http://ift.tt/2qEirj8

Guiding Multimodal Registration with Learned Optimization Updates

Publication date: Available online 6 May 2017
Source:Medical Image Analysis
Author(s): Benjamin Gutierrez-Becker, Diana Mateus, Loic Peter, Nassir Navab
In this paper, we address the multimodal registration problem from a novel perspective, aiming to predict the transformation aligning images directly from their visual appearance. We formulate the prediction as a supervised regression task, with joint image descriptors as input and the output are the parameters of the transformation that guide the moving image towards alignment. We model the joint local appearance with context aware descriptors that capture both local and global cues simultaneously in the two modalities, while the regression function is based on the gradient boosted trees method capable of handling the very large contextual feature space. The good properties of our predictions allow us to couple them with a simple gradient-based optimization for the final registration. Our approach can be applied to any transformation parametrization as well as a broad range of modality pairs. Our method learns the relationship between the intensity distributions of a pair of modalities by using prior knowledge in the form of a small training set of aligned image pairs (in the order of 1 to 5 in our experiments). We demonstrate the flexibility and generality of our method by evaluating its performance on a variety of multimodal imaging pairs obtained from two publicly available datasets, RIRE (brain MR, CT and PET) and IXI (brain MR). We also show results for the very challenging deformable registration of Intravascular Ultrasound and Histology images. In these experiments, our approach has a larger capture range when compared to other state-of-the-art methods, while improving registration accuracy in complex cases.

Graphical abstract

http://ift.tt/2qbWbNM

A Machine-Learning Graph-Based Approach for 3D Segmentation of Bruch’s Membrane Opening from Glaucomatous SD-OCT Volumes

Publication date: Available online 6 May 2017
Source:Medical Image Analysis
Author(s): Mohammad Saleh Miri, Michael D. Abràmoff, Young H. Kwon, Milan Sonka, Mona K. Garvin
Bruch's membrane opening-minimum rim width (BMO-MRW) is a recently proposed structural parameter which estimates the remaining nerve fiber bundles in the retina and is superior to other conventional structural parameters for diagnosing glaucoma. Measuring this structural parameter requires identification of BMO locations within spectral domain-optical coherence tomography (SD-OCT) volumes. While most automated approaches for segmentation of the BMO either segment the 2D projection of BMO points or identify BMO points in individual B-scans, in this work, we propose a machine-learning graph-based approach for true 3D segmentation of BMO from glaucomatous SD-OCT volumes. The problem is formulated as an optimization problem for finding a 3D path within the SD-OCT volume. In particular, the SD-OCT volumes are transferred to the radial domain where the closed loop BMO points in the original volume form a path within the radial volume. The estimated location of BMO points in 3D are identified by finding the projected location of BMO points using a graph-theoretic approach and mapping the projected locations onto the Bruch's membrane (BM) surface. Dynamic programming is employed in order to find the 3D BMO locations as the minimum-cost path within the volume. In order to compute the cost function needed for finding the minimum-cost path, a random forest classifier is utilized to learn a BMO model, obtained by extracting intensity features from the volumes in the training set, and computing the required 3D cost function. The proposed method is tested on 44 glaucoma patients and evaluated using manual delineations. Results show that the proposed method successfully identifies the 3D BMO locations and has significantly smaller errors compared to the existing 3D BMO identification approaches.

Graphical abstract

http://ift.tt/2qbWJDd

The AGES-Reykjavik study atlases: Non-Linear multi-Spectral template and atlases for studies of the ageing brain

Publication date: Available online 6 May 2017
Source:Medical Image Analysis
Author(s): Lars Forsberg, Sigurdur Sigurdsson, Jesper Fredriksson, Asdis Egilsdottir, Bryndis Oskarsdottir, Olafur Kjartansson, Mark A. van Buchem, Lenore J. Launer, Vilmundur Gudnason, Alex Zijdenbos
Quantitative analyses of brain structures from Magnetic Resonance (MR) image data are often performed using automatic segmentation algorithms. Many of these algorithms rely on templates and atlases in a common coordinate space. Most freely available brain atlases are generated from relatively young individuals and not always derived from well-defined cohort studies. In this paper, we introduce a publicly available multi-spectral template with corresponding tissue probability atlases and regional atlases, optimised to use in studies of ageing cohorts (mean age 75± 5 years). Furthermore, we provide validation data from a regional segmentation pipeline to assure the integrity of the dataset.

Graphical abstract

http://ift.tt/2qbWgRA

An etiological model of disordered eating behaviors among Brazilian women

Publication date: 1 September 2017
Source:Appetite, Volume 116
Author(s): Pedro Henrique Berbert de Carvalho, Marle dos Santos Alvarenga, Maria Elisa Caputo Ferreira
The Tripartite Influence Model posits that parents, peers and media influences mediated by internalization and appearance social comparison are predictors of body dissatisfaction, a key risk factor for eating disorders. However, the Tripartite Influence Model has not been tested in Brazil where the people are known to have high levels of body image and appearance concerns. This study aimed to test an adapted Tripartite Influence Model of body dissatisfaction and disordered eating behaviors among Brazilian women. A sample of 741 undergraduate students (Mage = 23.55 years, SD = 4.09) completed measures of sociocultural influences, internalization of body ideal, social appearance comparison, body dissatisfaction, muscularity dissatisfaction, disordered eating and body change behaviors. Structural equation modeling analyses indicated that the proposed etiological model for Brazilian women has good fit indexes (χ²(2064) = 6793.232; p = 0.0001; χ²/gl = 3.29; CFI = 0.82; PCFI = 0.79; RMSEA = 0.056 [IC90% = 0.053–0.057]). Parent and media influences were related with both internalization and social comparison, while peer influence with social comparison. A full mediation model was found, with both internalization and social comparison contributing to body dissatisfaction. Finally, body dissatisfaction was associated with disordered eating behaviors. The findings inform the importance of considering cultural aspects that influence body image and eating behaviors, and highlight the validity of the proposed etiological model for Brazilian women, that can be used for research and clinical purposes.



http://ift.tt/2phKgJu

Back-of-pack information in substitutive food choices: A process-tracking study in participants intending to eat healthy

Publication date: 1 September 2017
Source:Appetite, Volume 116
Author(s): Vincent J. van Buul, Catherine A.W. Bolman, Fred J.P.H. Brouns, Lilian Lechner
People are increasingly aware of the positive effects of a healthy diet. Concurrently, daily food consumption decisions – choices about both the quality and quantity of food that is ingested – are steered more by what consumers consider healthy. Despite the increased aim to eat healthier, however, consumers often do not read or incorrectly interpret on-pack nutrition information, resulting in suboptimal food choices in terms of health. This study aims to unravel the determinants of such inadvertent food choices from these consumers. In an online process-tracking study, we measured the actual usage of available back-of-pack nutrition information during substitutive food choices made by 240 participants who had the intention to eat healthy. Using mouse-tracking software in a computerized task in which participants had to make dichotomous food choices (e.g., coconut oil or olive oil for baking), we measured the frequency and time of nutritional information considered. Combined with demographic and psychosocial data, including information on the level of intention, action planning, self-efficacy, and nutrition literacy, we were able to model the determinants of inadvertent unhealthy substitutive food choices in a sequential multiple regression (R² = 0.40). In these consumers who intended to eat healthy, the quantity of obtained nutrition information significantly contributed as an associative factor of the percentage of healthy food choices made. Moreover, the level of correct answers in a nutrition literacy test, as well as taste preferences, significantly predicted the percentage of healthier choices. We discuss that common psychosocial determinants of healthy behavior, such as intention, action planning, and self-efficacy, need to be augmented with a person's actual reading and understanding of nutrition information to better explain the variance in healthy food choice behavior.



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Editors / Publication Information

Publication date: 1 July 2017
Source:Appetite, Volume 114





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Comparison of pharyngocutaneous fistula closure with and without bacterial cellulose in a rat model

Publication date: Available online 6 May 2017
Source:Auris Nasus Larynx
Author(s): Berat Demir, Murat Sarı, Adem Binnetoglu, Ali Cemal Yumusakhuylu, Deniz Filinte, İshak Özel Tekin, Tekin Bağlam, Abdullah Çağlar Batman
ObjectiveThe present study aimed to compare the effects of bacterial cellulose used for closure of pharyngocutaneous fistulae, a complication of total laryngectomy, with those of primary sutures in a rat model.MethodsThirty female Sprague-Dawley underwent experimental pharyngoesophagotomy and were grouped depending on the material used for pharyngocutaneous fistula closure: group I, which received primary sutures alone, group II, which received bacterial cellulose alone; and group III, which received both. After 7 days, the rats were sacrificed. Pharyngocutaneous fistula development was assessed, the gross wound was inspected, and histological examination was conducted.ResultsPharyngocutaneous fistulae developed in 12 rats (41%) in all: 6 from group I (21%), 4 from group II (14%) and 2 from group III (7%).ConclusionFibroblast density and inflammatory cell infiltration were significantly greater in group III than group I. We concluded that bacterial cellulose may be useful for pharyngocutaneous fistula closure.



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Recurrent plexiform schwannoma involving the carotid canal

Publication date: Available online 6 May 2017
Source:Auris Nasus Larynx
Author(s): Kei Ijichi, Masahiro Muto, Ayako Masaki, Shingo Murakami
Plexiform schwannoma (PS) is a rare variety of benign nerve sheath tumor characterized by a multinodular plexiform growth pattern. PS is usually confined to the head and neck or skin. The pre-operative diagnosis of PS is difficult, and this has lead to a common misdiagnosis as a schwannoma. In addition, studies have indicated that an incomplete resection of PS often results in tumor recurrence. Here we describe a rare case of PS presented in the parapharyngeal space. Our case involved a 36-year-old man with swelling of the pharynx, who presented with a soft cervical mass. MRI revealed a multinodular mass in the left parapharyngeal space, and further pathological diagnosis by the referral hospital indicated schwannoma. A cervical approach was taken and the tumor was removed with preservation of the nerve sheath by intracapsular resection. The tumor recurred within one year after the first surgery in the same lesion of the left parapharyngeal space. The second surgical approach was a combination of a facial dismasking flap and trans-pterygopalatine fossa. The mass was resected completely, and the diagnosis of PS was confirmed by histopathology. While schwannoma commonly occurs in the head and neck, parapharyngeal space PS is rare, and pre-operative pathological diagnosis of PS is difficult. MRI studies of PS revealed distinctive features that we found useful in pre-operative diagnosis. Intracapsular resection of PS with nerve preservation has a very high recurrence rate of the tumor. Therefore, if MRI findings suggest PS we recommend removing the tumor completely without nerve preservation will offer the most curative outcome.



http://ift.tt/2pT6WBv

Inadequacy of current pediatric epinephrine autoinjector needle length for use in infants and toddlers

Epinephrine injection represents the standard of care for anaphylaxis treatment. It is most effective if delivered intramuscularly, whereas inadvertent intraosseous injection may be harmful. The needle length in current pediatric epinephrine autoinjectors (EAIs) is 12.7 mm; however, the ideal needle length for infants and toddlers weighing less than 15 kg is unknown.

http://ift.tt/2pT3mHN

Inadequacy of current pediatric epinephrine autoinjector needle length for use in infants and toddlers

Epinephrine injection represents the standard of care for anaphylaxis treatment. It is most effective if delivered intramuscularly, whereas inadvertent intraosseous injection may be harmful. The needle length in current pediatric epinephrine autoinjectors (EAIs) is 12.7 mm; however, the ideal needle length for infants and toddlers weighing less than 15 kg is unknown.

http://ift.tt/2pT3mHN

Three-dimensional morphometrics of thoracic vertebrae in Neandertals and the fossil evidence from El Sidrón (Asturias, Northern Spain)

Publication date: July 2017
Source:Journal of Human Evolution, Volume 108
Author(s): Markus Bastir, Daniel García Martínez, Luis Rios, Antonio Higuero, Alon Barash, Sandra Martelli, Antonio García Tabernero, Almudena Estalrrich, Rosa Huguet, Marco de la Rasilla, Antonio Rosas
Well preserved thoracic vertebrae of Neandertals are rare. However, such fossils are important as their three-dimensional (3D) spatial configuration can contribute to the understanding of the size and shape of the thoracic spine and the entire thorax. This is because the vertebral body and transverse processes provide the articulation and attachment sites for the ribs. Dorsal orientation of the transverse processes relative to the vertebral body also rotates the attached ribs in a way that could affect thorax width. Previous research indicates possible evidence for greater dorsal orientation of the transverse processes and small vertebral body heights in Neandertals, but their 3D vertebral structure has not yet been addressed. Here we present 15 new vertebral remains from the El Sidrón Neandertals (Asturias, Northern Spain) and used 3D geometric morphometrics to address the above issues by comparing two particularly well preserved El Sidrón remains (SD-1619, SD-1641) with thoracic vertebrae from other Neandertals and a sample of anatomically modern humans. Centroid sizes of El Sidrón vertebrae are within the human range. Neandertals have larger T1 and probably also T2. The El Sidrón vertebrae are similar in 3D shape to those of other Neandertals, which differ from Homo sapiens particularly in central-lower regions (T6–T10) of the thoracic spine. Differences include more dorsally and cranially oriented transverse processes, less caudally oriented spinous processes, and vertebral bodies that are anteroposteriorly and craniocaudally short. The results fit with current reconstructions of Neandertal thorax morphology.



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Have We Come as Far as We Had Hoped? Discrimination in the Residency Interview

Publication date: Available online 5 May 2017
Source:Journal of Surgical Education
Author(s): Kara Hessel, Peter DiPasco, Lyndsey Kilgore, Casey Shelley, Alvin Perry, Jamie Wagner
ObjectiveThe primary objective was to use a pilot survey of fourth-year medical students at our institution to determine if female residency applicants were asked potentially illegal questions regarding family status and childbearing more frequently than male applicants. Secondary objectives included comparing the use of potentially illegal questions in surgical versus nonsurgical specialties and between community and academic residency programs.DesignA 20-item questionnaire was distributed to all fourth-year medical students at the University of Kansas School of Medicine. Data were analyzed in SPSS using descriptive statistics, bivariate analysis, and multivariate analysis.SettingUniversity of Kansas Health System, Tertiary Care Center.ParticipantsFourth-year medical students from the University of Kansas School of Medicine.ResultsThere were 57 survey respondents (51% male and 49% female). Female applicants were more likely to report being asked about their desire to have a family than male applicants (32% vs. 3%, respectively, p = 0.041). However, male and female students were equally likely to report being asked specifically if they had or intended to have children (p = 0.194). No significant differences were found in potentially illegal question-asking between surgical and nonsurgical specialties or between community-based and academic programs.ConclusionsAlthough women now represent 47% of the applicant pool, gender discrimination in the residency interview has not been eradicated. Women are more likely to report potentially illegal questions regarding their desire to have a family on residency interviews than men. Community and academic programs appear to ask similar numbers and types of potentially illegal questions. Further study is warranted to determine if these findings apply to the entire applicant pool. Further education of interviewers is necessary regarding potentially illegal questions during the residency interview process.



http://ift.tt/2qE69Yf

Comparison of pharyngocutaneous fistula closure with and without bacterial cellulose in a rat model

The present study aimed to compare the effects of bacterial cellulose used for closure of pharyngocutaneous fistulae, a complication of total laryngectomy, with those of primary sutures in a rat model.

http://ift.tt/2pNRbNW

Recurrent plexiform schwannoma involving the carotid canal

Plexiform schwannoma (PS) is a rare variety of benign nerve sheath tumor characterized by a multinodular plexiform growth pattern. PS is usually confined to the head and neck or skin. The pre-operative diagnosis of PS is difficult, and this has lead to a common misdiagnosis as a schwannoma. In addition, studies have indicated that an incomplete resection of PS often results in tumor recurrence. Here we describe a rare case of PS presented in the parapharyngeal space. Our case involved a 36-year-old man with swelling of the pharynx, who presented with a soft cervical mass.

http://ift.tt/2qNEp0o

Comparison of pharyngocutaneous fistula closure with and without bacterial cellulose in a rat model

The present study aimed to compare the effects of bacterial cellulose used for closure of pharyngocutaneous fistulae, a complication of total laryngectomy, with those of primary sutures in a rat model.

http://ift.tt/2pNRbNW

Recurrent plexiform schwannoma involving the carotid canal

Plexiform schwannoma (PS) is a rare variety of benign nerve sheath tumor characterized by a multinodular plexiform growth pattern. PS is usually confined to the head and neck or skin. The pre-operative diagnosis of PS is difficult, and this has lead to a common misdiagnosis as a schwannoma. In addition, studies have indicated that an incomplete resection of PS often results in tumor recurrence. Here we describe a rare case of PS presented in the parapharyngeal space. Our case involved a 36-year-old man with swelling of the pharynx, who presented with a soft cervical mass.

http://ift.tt/2qNEp0o

Development of nanomaterials for bone-targeted drug delivery

Publication date: Available online 6 May 2017
Source:Drug Discovery Today
Author(s): Hao Cheng, Aditya Chawla, Yafeng Yang, Yuxiao Li, Jin Zhang, Hae Lin Jang, Ali Khademhosseini
Bone is one of the major organs of the human body; it supports and protects other organs, produces blood cells, stores minerals, and regulates hormones. Therefore, disorders in bone can cause serious morbidity, complications, or mortality of patients. However, despite the significant occurrence of bone diseases, such as osteoarthritis (OA), osteoporosis (OP), non-union bone defects, bone cancer, and myeloma-related bone disease, their effective treatments remain a challenge. In this review, we highlight recent progress in the development of nanotechnology-based drug delivery for bone treatment, based on its improved delivery efficiency and safety. We summarize the most commonly used nanomaterials for bone drug delivery. We then discuss the targeting strategies of these nanomaterials to the diseased sites of bone tissue. We also highlight nanotechnology-based drug delivery to bone cells and subcellular organelles. We envision that nanotechnology-based drug delivery will serve as a powerful tool for developing treatments for currently incurable bone diseases.



http://ift.tt/2p7YUYC

Reply to: Influence of possible predictor variables on the outcome of primary oral squamous cell carcinoma: a retrospective study of 392 consecutive cases at a single centre

We have read the Letter to the Editor and thank you for the opportunity to respond to the concerns regarding our methodology/statistical analyses1. We appreciate the work of these colleagues and would like to comment on these considerations.

http://ift.tt/2pm9IOw

Awareness and knowledge of obstructive sleep apnea among the general population

Obstructive sleep apnea (OSA) is an increasingly prevalent condition that remains largely undiagnosed. We aimed to assess the level of awareness and knowledge of OSA among the general population.

http://ift.tt/2qN6dSH

Safety and efficacy of long-term use of sodium oxybate for narcolepsy with cataplexy in routine clinical practice

Sodium oxybate is licensed in Europe for the treatment of narcolepsy with cataplexy in adults. The aim of this study was to assess the efficacy and safety of sodium oxybate in clinical practice in patients with narcolepsy and cataplexy refractory to other treatments.

http://ift.tt/2qbZSDj

Spontaneous CSF rhinorrhea from the trigeminal canal in an adolescent

We report a case of a seventeen-year old, healthy, non-obese young woman who presented with retro-orbital headaches and metallictasting, left-sided rhinorrhea. Computed tomography revealed a defect along the medial wall of the canal of V2 within a well-pneumatized lateral recess of the left sphenoid sinus. Prior imaging obtained 4 years earlier in the context of nasal trauma showed no such defect - thus lending support for the arachnoid granulation hypothesis of spontaneous CSF leaks from the sphenoid sinus.

http://ift.tt/2p86fY2

Non-invasive methods to maintain cervical spine position after pediatric tracheal resections

To present our experience with two methods of neck stabilization after pediatric tracheal resection with primary anastomosis as possible alternatives to the traditional chest-chin suture.

http://ift.tt/2plZrCd

Role of microscopic spread beyond gross disease as an adverse prognostic factor in oral squamous cell carcinoma

Publication date: Available online 6 May 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Aseem Mishra, Sourav Datta, Akshat Malik, Apurva Garg, Deepa Nair, Sudhir Nair, Manish Mair, Munita Bal, Jaiprakash Agarwal, Pankaj Chaturvedi
IntroductionDespite meticulous surgery and proper adjuvant treatment, outcome of oral squamous cell carcinoma remains unpredictable. This shows that there may be other factors which should be considered while prognosticating these patients. Many a times there is spread of disease beyond the gross margin which can alter the margin status. We hypothesized that microscopic spread beyond gross disease may portend a poor prognosis.MethodThis is a retrospective study of prospectively collected data of 1025 treatment naïve oral squamous cell carcinoma patients. All patients underwent surgery from January 2012 to October 2013, this was followed by appropriate adjuvant treatment. Demographic and histopathological details were noted from the electronic medical records.ResultsMicroscopic spread beyond gross disease (MSGD) is associated with higher incidence of nodal positivity (p<0.046), perineural invasion (p<0.001), thicker tumors (p<0.024) and poor differentiation (p<0.060). The overall survival in patients with MSGD was 32.45 months versus 37.5 months in patients without MSGD (p<0.002).ConclusionTumors with MSGD tend to have a higher incidence of nodal metastasis, PNI and thicker tumors. Presence of MSGD was associated with lower overall survival as compared to those without.



http://ift.tt/2pO3UA5

Long-term follow-up after near-infrared fluorescence-guided resection of colorectal liver metastases: a retrospective multicenter analysis

Publication date: Available online 6 May 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Henricus J.M. Handgraaf, Leonora S.F. Boogerd, Diederik J. Höppener, Andrea Peloso, Babs G. Sibinga Mulder, Charlotte E.S. Hoogstins, Henk H. Hartgrink, Cornelis J.H. van de Velde, J. Sven D. Mieog, Rutger-Jan Swijnenburg, Hein Putter, Marcello Maestri, Andries E. Braat, John V. Frangioni, Alexander L. Vahrmeijer
BackgroundSeveral studies demonstrated that intraoperative near-infrared fluorescence (NIRF) imaging using indocyanine green (ICG) identifies (sub)capsular colorectal liver metastases (CRLM) missed by other techniques. It is unclear if this results in any survival benefit. This study evaluates long-term follow-up after NIRF-guided resection of CRLM using ICG.MethodsFirst, patients undergoing resection of CRLM with or without NIRF imaging were analyzed retrospectively. Perioperative details, liver-specific recurrence-free interval and overall survival were compared. Second, the prognosis of patients in whom additional metastases were identified solely by NIRF was studied.ResultsEighty-six patients underwent resection with NIRF imaging and 87 without. In significantly more patients of the NIRF imaging cohort additional metastases were identified during surgery (25% vs. 13%, p=0.04). Tumors identified solely by NIRF imaging were significantly smaller compared to additional metastases identified also by inspection, palpation or intraoperative ultrasound (3.2 ± 1.8 mm vs. 7.4 ± 2.6 mm, p<0.001). Liver-specific recurrence-free survival at 4 years was 47% with NIRF imaging and 39% without (hazard ratio at multivariate analysis 0.73, 95%CI 0.42-1.28, p=0.28). Overall survival at 4 years was 62% and 59%, respectively (p=0.79). No liver recurrences occurred within 3 years follow-up in 52% of patients in whom additional metastases were resected based on only NIRF imaging.ConclusionsThis study suggests that NIRF imaging identifies significantly more and smaller tumors during resection of CRLM, preventing recurrences in a subset of patients. Given its safety profile and low expense, routine use can be considered until tumor targeting fluorescent tracers are clinically available.



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Prognostic implications of occult nodal tumour cells in stage I and II colon cancer

Publication date: Available online 5 May 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Didi.A.M. Sloothaak, Ragna. L.A. van der Linden, Cornelis J.H. van de Velde, Willem A. Bemelman, Daan.J. Lips, J.C. van der Linden, Heleen Doornewaard, Pieter.J. Tanis, Koop Bosscha, Edwin S. van der Zaag, Christianne J. Buskens
INTRODUCTIONOccult nodal tumour cells should be categorised as micrometastasis (MMs) and isolated tumour cells (ITCs). A recent meta-analysis demonstrated that MMs, but not ITCs, are prognostic for disease recurrence in patients with stage I/II colon cancer.AIMS & METHODS: The objective of this retrospective multicenter study was to correlate MMs and ITCs to characteristics of the primary tumour, and to determine their prognostic value in patients with stage I/II colon cancer.RESULTS192 patient were included in the study with a median follow up of 46 month (IQR 33-81 months). MMs were found in eight patients (4.2%), ITCs in 37 (19.3%) and occult tumour cells were absent in 147 patients (76.6%). Between these groups, tumour differentiation and venous or lymphatic invasion was equally distributed. Advanced stage (pT3/pT4) was found in 66.0% of patients without occult tumour cells (97/147), 72.9% of patients with ITCs (27/37), and 100% in patients with MMs (8/8), although this was a non-significant trend. Patients with MMs showed a significantly reduced 3 year-disease free survival compared to patients with ITCs or patients without occult tumour cells (75,0% versus 88,0% and 94,8%, respectively, p=0.005). When adjusted for T-stage, MMs independently predicted recurrence of cancer (OR 7.6 95%CI 1.5-37.4, p=0.012)CONCLUSIONIn this study, the incidence of MMs and ITCs in patients with stage I/II colon cancer was 4.2% and 19.3%, respectively. MMs were associated with an reduced 3 year disease free survival rate, but ITCs were not.

Teaser

This study analysed the occurrence of nodal micrometastasis (MMs) and isolated tumour cells (ITCs) in relation to characteristics of the primary tumour and oncological outcome in 192 patients with stage I/II colon cancer. Nodal micrometastasis were associated with pT-stage and disease recurrence, but ITCs were not.


http://ift.tt/2pNVOHJ

The management of soft tissue tumours of the abdominal wall

Publication date: Available online 6 May 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): H.G. Smith, D. Tzanis, C. Messiou, C. Benson, J.A. van der Hage, M. Fiore, S. Bonvalot, A.J. Hayes
Background: Soft tissue tumours of the abdominal wall account for approximately 10% of all soft tissue tumours. Tumours at this site comprise a heterogeneous group of pathologies with distinct clinical behaviours and responses to treatment. The management of these tumours has largely been extrapolated from studies of soft tissue tumours at other sites. This review aims to summarise the existing data relating to abdominal wall tumours and suggest principles for managing soft tissue tumours at this site.MethodsRelevant articles were retrieved from a comprehensive literature search using the PubMed database. Key words included abdominal wall, soft tissue tumours, surgery, radiotherapy and chemotherapy. No restrictions on publication date were used.ResultsThe most common pathologies presenting in the abdominal wall are desmoid tumours, soft-tissue sarcoma and dermatofibrosarcoma protuberans (DFSP). Desmoid tumours should be managed with an initial period of observation, with surgery reserved for progressive lesions. Surgery should be the primary treatment for soft-tissue sarcomas and DFSP, with radiotherapy reserved for large-high grade tumours and preferentially given pre-operatively.ConclusionsAbdominal wall tumours are rare and should be managed in centres with experience in the management of soft tissue tumours. Management should be tailored to the biological behaviour of specific pathologies.



http://ift.tt/2pNKETe

Occurrence of 25 pharmaceuticals in Taihu Lake and their removal from two urban drinking water treatment plants and a constructed wetland

Abstract

Pharmaceuticals in drinking water sources have raised significant concerns due to their persistent input and potential human health risks. The seasonal occurrence of 25 pharmaceuticals including 23 antibiotics, paracetamol (PAR), and carbamazepine (CMZ) in Taihu Lake was investigated; meanwhile, the distribution and removal of these pharmaceuticals in two drinking water treatment plants (DWTPs) and a constructed wetland were evaluated. A high detection frequency (>70%) in the Taihu Lake was observed for nearly all the 25 pharmaceutics. Chlortetracycline (234.7 ng L⁻¹), chloramphenicol (27.1 ng L⁻¹), erythromycin (72.6 ng L⁻¹), PAR (71.7 ng L⁻¹), and CMZP (23.6 ng L⁻¹) are compounds with both a high detection frequency (100%) and the highest concentrations, suggesting their wide use in the Taihu Basin. Higher concentrations of chloramphenicols, macrolides, PAR, and CMZP were observed in dry season than in wet season, probably due to the low flow conditions of the lake in winter and the properties of pharmaceuticals. The overall contamination levels of antibiotic pharmaceutics (0.2–74.9 ng L⁻¹) in the Taihu Lake were lower than or comparable to those reported worldwide. However, for nonantibiotic pharmaceutics, PAR (45.0 ng L⁻¹) and CMZP (14.5 ng L⁻¹), significantly higher concentrations were observed in the Taihu Lake than at a global scale. High detection frequencies of 25 pharmaceuticals were observed in both the two DWTPs (100%) and the wetland (>60%) except for florfenicol and sulfapyridine. The removal efficacies of the studied pharmaceuticals in DWTP B with advanced treatment processes including ozonation and granular activated carbon filtration (16.7–100%) were superior to DWTP A with conventional treatment processes (2.9–100%), except for sulfonamides. Wetland C with the constructed root channel technology was efficient (24.2–100%) for removing most pharmaceuticals. This work suggests that the application of cost-effective technologies such as constructed wetlands should be considered as an efficient alternative for removing pharmaceuticals from water supply sources.

http://ift.tt/2phyizn

Model study of combined electrical and near-infrared neural stimulation on the bullfrog sciatic nerve

Abstract

This paper implemented a model study of combined electrical and near-infrared (808 nm) neural stimulation (NINS) on the bullfrog sciatic nerve. The model includes a COMSOL model to calculate the electric-field distribution of the surrounding area of the nerve, a Monte Carlo model to simulate light transport and absorption in the bullfrog sciatic nerve during NINS, and a NEURON model to simulate the neural electrophysiology changes under electrical stimulus and laser irradiation. The optical thermal effect is considered the main mechanism during NINS. Therefore, thermal change during laser irradiation was calculated by the Monte Carlo method, and the temperature distribution was then transferred to the NEURON model to stimulate the sciatic nerve. The effects on thermal response by adjusting the laser spot size, energy of the beam, and the absorption coefficient of the nerve are analyzed. The effect of the ambient temperature on the electrical stimulation or laser stimulation and the interaction between laser irradiation and electrical stimulation are also studied. The results indicate that the needed stimulus threshold for neural activation or inhibition is reduced by laser irradiation. Additionally, the needed laser energy for blocking the action potential is reduced by electrical stimulus. Both electrical and laser stimulation are affected by the ambient temperature. These results provide references for subsequent animal experiments and could be of great help to future basic and applied studies of infrared neural stimulation (INS).

http://ift.tt/2phprxH

Thallium release from acid mine drainages: Speciation in river and tap water from Valdicastello mining district (northwest Tuscany)

Publication date: 15 August 2017
Source:Talanta, Volume 171
Author(s): Beatrice Campanella, Corinne Casiot, Massimo Onor, Martina Perotti, Riccardo Petrini, Emilia Bramanti
In this work we present an advantageous method for the simultaneous separation and detection of Tl(I) and Tl(III) species through ion chromatography coupled with on-line inductively coupled plasma – mass spectrometry. Chromatographic separation between Tl(III) and Tl(I) was achieved in less than two minutes. The method was validated by recovery experiments on real samples, and by comparing the sum of the concentrations of individual Tl species with total thallium values obtained from continuous flow ICP-MS. The experimental procedure offers an accurate, sensitive and interference-free method for Tl speciation at trace levels in environmental samples. This allowed us to investigate the Tl speciation in acid mine drainages (AMD), surface waters and springs in a mining catchment in Valdicastello Carducci (Tuscany, Italy), where severe Tl contamination ad been evidenced previously. This study shows for the first time that Tl(III), in addition to Tl(I), is present in considerable amounts in water samples affected by acid mining outflow, raising the question of the origin of this thermodynamically unstable species.

Graphical abstract

http://ift.tt/2qNb2LR

Apparent biochemical thyrotoxicosis due to assay interference by high-dose biotin given for multiple sclerosis

http://ift.tt/2qbvedg

Melanoma antigens and related immunological markers

Publication date: Available online 6 May 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Jacob Pitcovski, Ehud Shahar, Elina Aizenshtein, Raphael Gorodetsky
Melanoma is a highly lethal cancer deriving from transformed dermal melanocytes. Early diagnosed primary melanoma may be curable, but the cure-rate of more advanced stages is limited, with high mortality rate. With the progression of the tumor, the melanocytes overexpress intracellular or cell-surface molecules, including ectopic normal and tumor-specific proteins. Some of these induce a specific immune response by T and B lymphocytes. Antibodies raised against melanoma antigens were proposed for differential disease diagnosis, staging, prognosis and evaluation of treatment efficiency. Nevertheless, treatments based on stimulation of specific anti-melanoma immune responses have had only limited success. It seems that efficient immunotherapy should become more feasible pending on finding new adequate antigens to target. New insights into immune regulation of the tumor microenvironment and its progression may help the development of more successful treatments. We present here up-to-date information on known major melanoma-associated antigens, which could serve as tools for diagnosis as well as for clinical immunotherapy. This approach with promising results for treating some other selected malignancies is still experimental with a very limited success in melanoma. The development of new immune modulators of the tumor microenvironment and neo-antigens may be additional promising directions and may open new opportunities for the immunotherapy of melanoma.



http://ift.tt/2qDR9JX

The neural basis of deficient response inhibition in children with neurofibromatosis type 1: Evidence from a functional MRI study

Publication date: Available online 6 May 2017
Source:Cortex
Author(s): Natalie A. Pride, Mayuresh S. Korgaonkar, Kathryn N. North, Belinda Barton, Jonathan M. Payne
Impaired response inhibition is a predominant feature of several neuropsychiatric disorders; in general the underlying aetiology of these disorders and associated impairments is unknown. The common occurrence of impaired response inhibition in a single gene disorder such as neurofibromatosis type 1 (NF1), provides a valuable opportunity to explore its mechanistic basis through the study of gene-brain-behaviour interactions. We used functional brain imaging with a Go/No-Go task to examine the neural substrates of response inhibition in children with NF1 and age and gender matched typically developing subjects. Children with NF1 were found to have abnormal activation patterns in several cortical regions, with significantly reduced activation in the inferior occipital gyrus, the fusiform gyrus/posterior cerebellum, the pre-supplementary motor area and the inferior frontal gyrus. Importantly, activation in the right inferior frontal gyrus was associated with faster task reaction times and impairment in sustained attention in subjects with NF1. Our study supports the hypothesis that a network of regions typically associated with response inhibition is dysfunctional in children with NF1 and suggests this dysfunction is linked to cognitive impairment in this disorder.



http://ift.tt/2qbng3t

Sensorimotor Experience and Verb-Category Mapping in Human Sensory, Motor and Parietal Neurons

Publication date: Available online 6 May 2017
Source:Cortex
Author(s): Ying Yang, Michael Walsh Dickey, Julie Fiez, Brian Murphy, Tom Mitchell, Jennifer Collinger, Elizabeth Tyler-Kabara, Michael Boninger, Wei Wang
Semantic grounding is the process of relating meaning to symbols (e.g., words). It is the foundation for creating a representational symbolic system such as language. Semantic grounding for verb meaning is hypothesized to be achieved through two mechanisms: sensorimotor mapping, i.e., directly encoding the sensorimotor experiences the verb describes, and verb-category mapping, i.e., encoding the abstract category a verb belongs to. These two mechanisms were investigated by examining neuronal-level spike (i.e. neuronal action potential) activities from the motor, somatosensory and parietal areas in two human participants. Motor and a portion of somatosensory neurons were found to be involved in primarily sensorimotor mapping, while parietal and some somatosensory neurons were found to be involved in both sensorimotor and verb-category mapping. The time course of the spike activities and the selective tuning pattern of these neurons indicate that they belong to a large neural network used for semantic processing. This study is the first step towards understanding how words are processed by neurons.



http://ift.tt/2qbnyYl

Thalamic control of functional cortical connectivity

Publication date: June 2017
Source:Current Opinion in Neurobiology, Volume 44
Author(s): Miho Nakajima, Michael M Halassa
The thalamus is an evolutionarily conserved structure with extensive reciprocal connections to cortical regions. While its role in transmitting sensory signals is well-studied, its broader engagement in cognition is unclear. In this review, we discuss evidence that the thalamus regulates functional connectivity within and between cortical regions, determining how a cognitive process is implemented across distributed cortical microcircuits. Within this framework, thalamic circuits do not necessarily determine the categorical content of a cognitive process (e.g., sensory details in feature-based attention), but rather provide a route by which task-relevant cortical representations are sustained and coordinated. Additionally, thalamic control of cortical connectivity bridges general arousal to the specific processing of categorical content, providing an intermediate level of cognitive and circuit description that will facilitate mapping neural computations onto thought and behavior.



http://ift.tt/2pSkJs4

NMR-Based Pharmacometabonomics: A New Paradigm for Personalised or Precision Medicine

Publication date: Available online 6 May 2017
Source:Progress in Nuclear Magnetic Resonance Spectroscopy
Author(s): Jeremy R. Everett
Metabolic profiling by NMR spectroscopy or hyphenated mass spectrometry, known as metabonomics or metabolomics, is an important tool for systems-based approaches in biology and medicine. The experiments are typically done in a diagnostic fashion where changes in metabolite profiles are interpreted as a consequence of an intervention or event; be that a change in diet, the administration of a drug, physical exertion or the onset of a disease. By contrast, pharmacometabonomics takes a prognostic approach to metabolic profiling, in order to predict the effects of drug dosing before it occurs. Differences in pre-dose metabolite profiles between groups of subjects are used to predict post-dose differences in response to drug administration. Thus the paradigm is inverted and pharmacometabonomics is the metabolic equivalent of pharmacogenomics. Although the field is still in its infancy, it is expected that pharmacometabonomics, alongside pharmacogenomics, will assist with the delivery of personalised or precision medicine to patients, which is a critical goal of 21^st century healthcare.

Graphical abstract

http://ift.tt/2plbrnD

Validity of Robot-based Assessments of Upper Extremity Function

Publication date: Available online 5 May 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Alison McKenzie, Lucy Dodakian, Jill See, Vu Le, Erin Burke Quinlan, Claire Bridgford, Daniel Head, Vy L. Han, Steven C. Cramer
ObjectiveTo examine the validity of 5 robot-based assessments of arm motor function post-stroke.DesignCross sectional.SettingOutpatient clinical research center.ParticipantsVolunteer sample of 40 participants, age >18 years, 3-6 months post-stroke, with arm motor deficits that had plateaued.InterventionNone.Main Outcome MeasuresClinical standards included the Fugl-Meyer ArmMotor Scale (FMA), and 5 secondary motor outcomes: hand/wrist subsection of the FMA; Action Research Arm Test (ART); Box & Blocks test (B/B); hand subscale of Stroke Impact Scale-2 (SIS); and the Barthel Index (BI). Robot-based assessments included: wrist targeting; finger targeting; finger movement speed; reaction time; and a robotic version of the (B/B) test. Anatomical measures included percentage injury to the corticospinal tract (CST) and primary motor cortex (M1, hand region) obtained from MRI .ResultsSubjects had moderate-severe impairment (arm FMA scores = 35.6±14.4, range 13.5-60). Performance on the robot-based tests, including speed (r=0.82, p<0.0001), wrist targeting (r=0.72, p<0.0001), and finger targeting (r=0.67, p<0.0001) correlated significantly with the FMA scores. Wrist targeting (r=0.57 - 0.82) and finger targeting (r=0.49 - 0.68) correlated significantly with all 5 secondary motor outcomes and with percent CST injury. The robotic version of the B/B correlated significantly with the clinical B/B test but was less prone to floor effect. Robot-based assessments were comparable to FMA score in relation to percent CST injury and superior in relation to M1 hand injury.ConclusionsThe current findings support using a battery of robot-based methods for assessing the upper extremity motor function in subjects with chronic stroke.



http://ift.tt/2pNmSXM

Immediate effects of mirror therapy in patients with shoulder pain and decreased range of motion

Publication date: Available online 5 May 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Adriaan Louw, Emilio J. Puentedura, Dave Reese, Paula Parker, Terra Miller, Paul Mintken
ObjectiveTo determine the effects of a brief single component of the graded motor imagery (GMI) sequence (mirror therapy) on active range of motion (AROM), pain, fear-avoidance and pain catastrophization in patients with shoulder pain.DesignSingle-blind case seriesSettingThree outpatient physical therapy clinicsParticipantsPatients with shoulder pain and limited AROM.InterventionsPatients moved their unaffected shoulder through comfortable AROM in front of a mirror so that it appeared that they were moving their affected shoulder.Main Outcome Measure(s)We measured pain, pain catastrophization, fear-avoidance and AROM in 69 consecutive patients with shoulder pain and limited AROM before and immediately after mirror therapy.ResultsThere were significant differences in self-reported pain (p=.014), Pain Catastrophization (p<.001), and the Tampa Scale of Kinesiophobia (p=.012) immediately after mirror therapy, although the means did not meet or exceed the minimal detectable change (MDC) for each outcome measure. There was a significant increase (mean = 14.5°) in affected shoulder flexion AROM immediately post-mirror therapy (p<0.001), which exceeded the MDC of 8 degrees.ConclusionsA brief mirror therapy intervention can result in statistically significant improvements in pain, pain catastrophization, fear-avoidance and shoulder flexion AROM in patients presenting with shoulder pain with limited AROM. The immediate changes may allow a quicker transition to multimodal treatment, including manual therapy and exercise in these patients. Further studies, including randomized controlled trials, are needed to investigate these findings and determine longer term effects.



http://ift.tt/2pl517R