Vagus nerve stimulation improves locomotion and neuronal populations in a model of Parkinson's disease

Publication date: Available online 24 August 2017
Source:Brain Stimulation
Author(s): Ariana Q. Farrand, Kristi L. Helke, Rebecca A. Gregory, Monika Gooz, Vanessa K. Hinson, Heather A. Boger
BackgroundParkinson's disease (PD) is a progressive, neurodegenerative disorder with no disease-modifying therapies, and symptomatic treatments are often limited by debilitating side effects. In PD, locus coeruleus (LC) noradrenergic neurons degenerate prior to substantia nigra (SN) dopaminergic neurons. Vagus nerve stimulation (VNS) beneficially alters LC neurons, and decreases pro-inflammatory markers, allowing functional improvement of LC and its targets, making it a potential PD therapeutic.ObjectiveTo assess therapeutic potential of VNS in a PD model.MethodsTo mimic the progression of degeneration associated with PD, rats received a systemic injection of the noradrenergic neurotoxin DSP-4, followed one week later by bilateral intrastriatal injection of the dopaminergic neurotoxin 6-hydroxydopamine. At this time, a subset of rats also had vagus cuffs implanted. After eleven days, rats received a precise VNS regimen twice a day for ten days, and locomotion was measured during the afternoon session daily. Immediately following final stimulation, rats were euthanized, and left dorsal striatum, bilateral SN and LC were sectioned for immunohistochemical detection of monoaminergic neurons (tyrosine hydroxylase, TH), α-synuclein, astrocytes (GFAP) and microglia (Iba-1).ResultsVNS significantly increased locomotion of lesioned rats. It also resulted in increased expression of TH in striatum, SN, and LC; decreased expression of α-synuclein in SN; and decreased expression of glial markers in the SN and LC of lesioned rats. Additionally, after VNS, TH was higher in the LC and Iba-1 lower in the SN of saline-treated rats.ConclusionsThese data suggest that VNS has potential as a novel PD therapeutic.



http://ift.tt/2vjLKGK

Adjuvant Chemotherapy vs Observation for Patients With Adverse Features

This cohort study assesses the comparative effectiveness of adjuvant chemotherapy vs observation for patients with pT3/T4 and/or pN⁺ urothelial carcinoma of the bladder pretreated with neoadjuvant chemotherapy and radial cystectomy.

http://ift.tt/2w1tapH

Errors in Tables

In the Review titled "Biosimilars in Oncology in the United States: A Review," published online July 20, 2017, there were errors in Table 2 and Table 3. In Table 2, footnote "c" should have read "FDA-approved biosimilars; none are interchangeable; tbo-filgrastim was not approved under 351(k) Biosimilar Pathway." Footnote "d" should have broken at the colon, and the remaining statement should have been a new footnote "e." In addition, citation to footnote "d" was removed after "FDA approved" in column 1 and a new citation to footnote "e" was added to row 7 of column 2 after "ABP 215 (Amgen)." Finally, in Table 3, the "yes" designation in column 4, row 6 should have been "no." This article was corrected online.

http://ift.tt/2xfINbz

The Rest of Them

The small animals are onlymade of salt crystals rolledinto spheres, imperfect,blowing from right to left,

http://ift.tt/2w1zdL6

The Hereditary Paraganglioma-Pheochromocytoma Syndrome

To the Editor We read with interest the recent JAMA Oncology Clinical Challenge by Santamaria-Barria et al, which reviews the diagnosis, molecular biology, and treatment of metastatic gastrointestinal stromal tumor (GIST) in a 20-year-old woman who was 16 weeks pregnant. Educating readers about these rare and challenging cases is valuable, and we thank the authors and editorial board for their case selection. However, we believe that important hereditary risks relevant to this case should also be highlighted because diagnostic delays could have catastrophic implications.

http://ift.tt/2xfLIkB

Change in Pattern of Secondary Cancers After Kaposi Sarcoma

This longitudinal study tests the hypothesis that the secondary cancers developing in patients with Kaposi sarcoma have changed in recent years and assesses the risk of secondary cancers after Kaposi sarcoma in different periods using the Surveillance, Epidemiology, and End Results (SEER) program data.

http://ift.tt/2w1DBd4

The Hereditary Paraganglioma-Pheochromocytoma Syndrome—Reply

In Reply We thank Dr Hall and his colleagues for their thoughtful comments about our case report of a gastrointestinal stromal tumor (GIST) in a pregnant young woman. They highlighted the high incidence of succinate dehydrogenase (SDH) deficiency among patients with wild-type (WT) GISTs and the importance of performing germline testing of SDH genes in such patients to diagnose hereditary paraganglioma/pheochromocytoma syndrome (HPPS). The diagnostic criteria and clinical manifestations of HPPS have been detailed thoroughly in their letter. Therefore, we will take this opportunity to highlight some of the key features in the diagnosis and management of WT and SDH-deficient GIST.

http://ift.tt/2xfLE4l

Silencing of FUS in the common marmoset (Callithrix jacchus) brain via stereotaxic injection of an adeno-associated virus encoding shRNA

Publication date: Available online 24 August 2017
Source:Neuroscience Research
Author(s): Kuniyuki Endo, Shinsuke Ishigaki, Yoshito Masamizu, Yusuke Fujioka, Akiya Watakabe, Tetsuo Yamamori, Nobuhiko Hatanaka, Atsushi Nambu, Haruo Okado, Masahisa Katsuno, Hirohisa Watanabe, Masanori Matsuzaki, Gen Sobue
Fused in sarcoma (FUS) is an RNA binding protein that is involved in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). To establish the common marmoset (Callithrix jacchus) as a model for FTLD, we generated a stereotaxic injection-based marmoset model of FUS-silencing. We designed shRNAs against the marmoset FUS gene and generated an AAV9 virus encoding the most effective shRNA against FUS (shFUS). The AAV encoding shFUS (AAV-shFUS) was introduced into the frontal cortex of young adult marmosets, whereas AAV encoding a control shRNA was injected into the contralateral side. We obtained approximately 70–80% silencing of FUS following AAV-shFUS injection. Interestingly, FUS-silencing provoked a proliferation of astrocytes and microglias. Since FTLD is characterized by various emotional deficits, it would be helpful to establish a marmoset model of FUS-silencing in various brain tissues for investigating the pathomechanism of higher cognitive and behavioral dysfunction.



http://ift.tt/2wBr2qd

Berberine attenuates depressive-like behaviors by suppressing neuro-inflammation in stressed mice

Publication date: Available online 24 August 2017
Source:Brain Research Bulletin
Author(s): Ya-Min Liu, Le Niu, Lin-Lin Wang, Li Bai, Xiao-Yan Fang, Yu-Cheng Li, Li-Tao Yi
Berberine, the major constituent alkaloid originally from the famous Chinese herb Huanglian (Coptis chinensis), has been shown to exert antidepressant-like effects in rodents. However, it is still not clear the involvement of neuro-inflammation suppression in the effects of berberine. The purpose of this study was to determine whether berberine affects the neuro-inflammation system in mice induced by chronic unpredictable mild stress (CUMS). Berberine was orally administrated in normal or CUMS mice for successive four weeks. Behavioral evaluation showed that berberine prevented the depressive deficits both in sucrose preference test and novelty-suppressed feeding test. The elevation of hippocampal pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), as well as the activation of microglia were decreased by berberine. In addition, chronic berberine treatment inhibited nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway as the phosphorylated proteins of NF-κB, IκB kinase (IKK)α and IKKβ in the hippocampus were suppressed after berberine administration. Furthermore, inducible nitric oxide synthase (iNOS), one downstream target of NF-κB signaling pathway was also inhibited by berberine. In conclusion, these findings suggest that administration of berberine could prevent depressive-like behaviors in CUMS mice by suppressing neuro-inflammation in the hippocampus.



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Antidepressant-like effects of ginsenoside Rg2 in a chronic mild stress model of depression

Publication date: Available online 24 August 2017
Source:Brain Research Bulletin
Author(s): Ying Ren, Jin-Liang Wang, Xiang Zhang, Hao Wang, Ying Ye, Lu Song, Ying-Jie Wang, Meng-Jue Tu, Wei-Wei Wang, Lan Yang, Bo Jiang
Major depression is a common neuropsychiatric disease with high lifetime prevalence and high incidence of suicide. This study aimed to evaluate the antidepressant effects of ginsenoside Rg2 in mice, and the possible mechanism was also determined. A single injection of both Rg2 (10 and 20mg/kg) and fluoxetine (positive control, 20mg/kg) induced notable antidepressant-like effects in the forced swim test and tail suspension test without affecting the locomotor activity of mice, and the tests were done 30min after the injection. Also, repeated daily treatment of Rg2 and fluoxetine for the last 2 weeks fully reversed the chronic mild stress (6 weeks)-induced depressive-like symptoms in mice. Moreover, western blot analysis showed that Rg2 administration significantly increased the BDNF signaling pathway in hippocampus. Importantly, the usage of TrkB shRNA fully blocked the antidepressant effects of Rg2 in mice. Collectively, these results suggest that Rg2 produces an antidepressant-like effect in mice which is mediated, at least in part, through promoting the hippocampal BDNF signaling pathway.



http://ift.tt/2v9G1aF

Effects of rehabilitation training on apoptosis of nerve cells and the recovery of neural and motor functions in rats with ischemic stroke through the PI3K/Akt and Nrf2/ARE signaling pathways

Publication date: Available online 24 August 2017
Source:Brain Research Bulletin
Author(s): Xiao-Fei Jin, Shan Wang, Min Shen, Xin Wen, Xin-Rui Han, Jun-Chang Wu, Gao-Zhuo Tang, Dong-Mei Wu, Jun Lu, Yuan-Lin Zheng
This study was designed in order to investigate the effects between rehabilitation training on the apoptosis of nerve cells and the recovery of neural and motor functions of rats with ischemic stroke by way of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and nuclear factor E2-related factor 2/antioxidant responsive element (Nrf2/ARE) signaling pathways. In total, 110 healthy adult male Sprague-Dawley (SD) rats were selected in order to take part in this study. Ninety SD rats were used in order to establish the middle cerebral artery occlusion (MCAO), among which 80 rats were randomly assigned as part of the natural recovery, natural recovery+Rp-PI3K (the rats injected with PI3K/Akt inhibitor LY294002), rehabilitation training, and rehabilitation training+Rp-PI3K groups. Meanwhile, 20 rats were selected as part of the sham operation group. The neural and motor functions of these rats were evaluated using a balance beam test and the Bederson score. The mRNA expressions of PI3K, Akt, Nrf2 and HO-1 were measured using an RT-qPCR. The protein expressions of PI3K, p-PI3K, Akt, p-Akt, Nrf2 and HO-1 were also detected by using western blotting and the immunohistochemistry process. The cell cycle and cell apoptosis were detected by using a flow cytometry and TUNEL assay. The sham operation group exhibited lower neural and motor function scores than other groups. At the 7, 14, and 21 d marks of this study, the neural and motor function scores were increased in the natural recovery, natural recovery+Rp-PI3K, and rehabilitation training+Rp-PI3K groups in comparison with the rehabilitation training group but found to be decreased in the natural recovery group in comparison with the natural recovery+Rp-PI3K group. In comparison with the sham operation group, expressions of PI3K, Nrf2 and HO-1, and proportions of p-PI3K/PI3K and p-Akt/Akt were all higher in the natural recovery, rehabilitation training, and rehabilitation training+Rp-PI3K groups. Same trends were found in the rehabilitation training group in comparison with the natural recovery and rehabilitation training+Rp-PI3K groups, as well as in the natural recovery group in comparison with the natural recovery+Rp-PI3K group. In comparison with the sham operation and rehabilitation training groups, hippocampal nerve cells at G1 phase and the cells apoptosis were both elevated in the other three groups which were found to be decreased in the natural recovery group in comparison with the natural recovery+Rp-PI3K group. Our results indicated that the rehabilitation training can inhibit the apoptosis of nerve cells as well as promote the recovery of both neural and motor functions in rats with ischemic stroke by activation of the PI3K/Akt and Nrf2/ARE signaling pathways.



http://ift.tt/2vsTSE1

Aspirin resistance are associated with long-term recurrent stroke events after ischaemic stroke

Publication date: Available online 24 August 2017
Source:Brain Research Bulletin
Author(s): Ning Zhang, Zhenhua Wang, Lihong Zhou
ObjectiveTo investigate the prevalent of aspirin resistance (AR) in stroke and its association with recurrent stroke in 214 patients with ischemic stroke who were receiving aspirin before the stroke onset.MethodsTwo hundreds and fourteen acute stroke patients who previously received aspirin therapy (100mg/day for ≥7 days) were enrolled. Whole blood samples were collected for platelet aggregation testing. The result is expressed in aspirin reaction units (ARU). A cutoff of 550 ARU was used to determine the presence of AR. A follow-up period of 1year was performed to record stroke recurrence events.ResultsIn this study, the median age was 68 years (IQR, 60-77 years), and 118 (55.1%) were men. A total of 43 of 214 enrolled patients (20.1%) were AR. ARU levels were significantly higher in patients with recurrence than those without (514[IQR: 466–592] vs. 454[IQR: 411–499]; P <0.001). The stroke recurrence distribution across the ARU quartiles ranged between 7.41% (first quartile) to 40.74% (fourth quartile). In multivariate analyses, the 3th and 4th quartile of ARU was significantly associated with stroke recurrence during the observation period compared to the 1st quartile group, and the adjusted risk increased by 215% (OR=3.15 [95% CI 1.96–4.33], P=0.007) and 322% (4.22[2.56–7.16], P<0.001). In multivariate logistic regression analysis, AR was associated with a higher risk of stroke recurrence, and the adjusted risk increased by 365% (OR=4.65; 95% CI=2.99–8.16; P<0.001).ConclusionIn conclusion, AR is not uncommon in Chinese stroke patients who receive anti-platelet medications. Patients with AR may have a greater risk of suffering stroke recurrence events.



http://ift.tt/2vsWVfx

Tumor acidity-activatable Manganese Phosphate Nanoplatform for Amplification of Photodynamic Cancer Therapy and Magnetic Resonance Imaging

Publication date: Available online 24 August 2017
Source:Acta Biomaterialia
Author(s): Yongwei Hao, Cuixia Zheng, Lei Wang, Jinjie Zhang, Xiuxiu Niu, Qingling Song, Qianhua Feng, Hongjuan Zhao, Li Li, Hongling Zhang, Zhenzhong Zhang, Yun Zhang
Amorphous biodegradable metal phosphate nanomaterials are considered to possess great potential in cancer theranostic application due to their promise in providing ultra-sensitive pH-responsive therapeutic benefits and diagnostic functions simultaneously. Here we report the synthesis of photosensitising and acriflavine-carrying amorphous porous manganese phosphate (PMP) nanoparticles with ultra-sensitive pH-responsive degradability and their applications for a photoactivable synergistic nanosystem that imparts reactive oxygen species (ROS) induced cytotoxicity in synchrony with hypoxia-inducible factor 1α/vascular endothelial growth factor (HIF1α/VEGF) inhibitor that suppresses tumor growth and treatment escape signalling pathway. Carboxymethyl dextran (CMD) is chemically anchored on the surface of porous manganese phosphate theranostic system through the pH-responsive boronate esters. Upon the stimulus of the tumor acid microenvironment, manganese phosphate disintegrates and releases Mn²⁺ ions rapidly, which are responsible for the magnetic resonance imaging (MRI) effect. Meanwhile, the released photosensitizer chlorin e6 (Ce6) produces ROS under irradiation while acriflavine (ACF) inhibits the HIF-1α/VEGF pathway during the burst release of VEGF in tumour induced by photodynamic therapy (PDT), resulting in increased therapeutic efficacy. Considering the strong pH responsivity, MRI signal amplification and drug release profile, the PMP nanoparticles offer new prospects for tumor acidity-activatable theranostic application by amplifying the PDT through inhibiting the HIF-1α /VEGF pathway timely while enhancing the MRI effect.Statement of SignificanceIn this study, we report the synthesis of the tumor acidity-activatable amorphous porous manganese phosphate nanoparticles and their application for a photoactivable synergistic nanosystem that imparts reactive oxygen species (ROS) induced cytotoxicity in synchrony with hypoxia-inducible factor 1α/vascular endothelial growth factor (HIF-1α/VEGF) inhibitor that suppresses tumor growth and treatment escape signalling pathway. Besides, upon the stimulus of the tumor acid microenvironment, the manganese phosphate nanoparticles finally disintegrate and release Mn²⁺ ions rapidly, which are responsible for the magnetic resonance imaging (MRI) effect. This nanoplatform is featured with distinctive advantages such as ultra pH-responsive drug release, MRI function and rational drug combination exploiting the blockage of the treatment escape signalling pathway.

Graphical abstract

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A theranostic dental pulp capping agent with improved MRI and CT contrast and biological properties

Publication date: Available online 24 August 2017
Source:Acta Biomaterialia
Author(s): S. Mastrogiacomo, N. Güvener, W. Dou, H.S. Alghamdi, W.A. Camargo, J.G.O. Cremers, P.J.A. Borm, A. Heerschap, E. Oosterwijk, J.A. Jansen, X.F. Walboomers
Different materials have been used for vital dental pulp treatment. Preferably a pulp capping agent should show appropriate biological performance, excellent handling properties, and a good imaging contrast. These features can be delivered into a single material through the combination of therapeutic and diagnostic agents (i.e. theranostic). Calcium phosphate based composites (CPCs) are potentially ideal candidate for pulp treatment, although poor imaging contrast and poor dentino-inductive properties are limiting their clinical use. In this study, a theranostic dental pulp capping agent was developed. First, imaging properties of the CPC were improved by using a core-shell structured dual contrast agent (csDCA) consisting of superparamagnetic iron oxide (SPIO) and colloidal gold, as MRI and CT contrast agent respectively. Second, biological properties were implemented by using a dentinogenic factor (i.e. bone morphogenetic protein 2, BMP-2). The obtained CPC/csDCA/BMP-2 composite was tested in vivo, as direct pulp capping agent, in a male Habsi goat incisor model. Our outcomes showed no relevant alteration of the handling and mechanical properties (e.g. setting time, injectability, and compressive strength) by the incorporation of csDCA particles. In vivo results proved MRI contrast enhancement up to 7 weeks. Incisors treated with BMP-2 showed improved tertiary dentin deposition as well as faster cement degradation as measured by µCT assessment. In conclusion, the presented theranostic agent matches the imaging and regenerative requirements for pulp capping applications.Statement of SignificanceIn this study, we combined diagnostic and therapeutic agents in order to developed a theranostic pulp capping agent with enhanced MRI and CT contrast and improved dentin regeneration ability. In our study we cover all the steps from material preparation, mechanical and in vitro characterization, to in vivo study in a goat dental model. To the best of our knowledge, this is the first time that a theranostic pulp capping material have been developed and tested in an in vivo animal model. Our promising results in term of imaging contrast enhancement and of induction of new dentin formation, open a new scenario in the development of innovative dental materials.

Graphical abstract

http://ift.tt/2vjkfgr

The Effects Of Surface Processing On In-Vivo Corrosion Of Nitinol Stents In A Porcine Model

Publication date: Available online 24 August 2017
Source:Acta Biomaterialia
Author(s): Stacey J.L. Sullivan, Daniel Madamba, Shiril Sivan, Katie Miyashiro, Maureen L. Dreher, Christine Trépanier, Srinidhi Nagaraja
A major limitation with current assessments of corrosion in metallic medical devices is the lack of correlation between in-vitro and in vivo corrosion performance. Therefore, the objective of this study was to elucidate the relationship between pitting corrosion measured by breakdown potentials (Eb) in ASTM F2129 testing and corrosion resistance in vivo. Four groups of Nitinol stents were manufactured using different processing methods to create unique surface properties. The stents were implanted into iliac arteries of minipigs for six months and explanted for corrosion analysis. Scanning electron microscopy and energy dispersive x-ray spectrometry analyses indicated that stents with a thick complex thermal oxide (420 nm) and high corrosion resistance in-vitro (Eb = 975 ± 94 mV) were free from detectable corrosion in vivo and exhibited no changes in Ni/Ti ratio when compared to non-implanted controls. This result was also found in mechanically polished stents with a thin native oxide (4 nm; Eb = 767 ± 226 mV). In contrast, stents with a moderately thick thermal oxide (130 nm) and low corrosion resistance in-vitro (Eb = 111 ± 63 mV) posssessed corrosion with associated surface microcracks in vivo. In addition, Ni/Ti ratios in corroded regions were significantly lower compared to non-corroded adjacent areas on explanted stents. When stents were minimally processed (i.e. retained native tube oxide from drawing process), a thick thermal oxide was present (399 nm) with low in-vitro corrosion resistance (Eb = 68 ± 29 mV) resulting in extensive in-vivo pitting. These findings demonstrate that functional corrosion testing combined with a detailed understanding of the surface characteristics of a Nitinol medical device can provide insight into in-vivo corrosion resistance.Statement of SignificanceNitinol is a commonly used material in the medical device industry. However, correlations between surface processing of nitinol and in-vivo corrosion has yet to be established. Elucidating the link between in-vivo corrosion and pre-clinical characterization can aid in improved prediction of clinical safety and performance of nitinol devices. We addressed this knowledge gap by fabricating nitinol stents to possess distinct surface properties and evaluating their corrosion susceptibility both in-vitro and after six months of in-vivo exposure. Relationships between stent processing, surface characterization, corrosion bench testing, and outcomes from explanted devices are discussed. These findings highlight the importance of surface characterization in nitinol devices and provide in-vitro pitting corrosion levels that can induce in-vivo corrosion in nitinol stents.

Graphical abstract

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Nasal methicillin-resistant Staphylococcus aureus screening in patients with pneumonia: A powerful antimicrobial stewardship tool

Publication date: Available online 24 August 2017
Source:American Journal of Infection Control
Author(s): Ethan A. Smith, Howard S. Gold, Monica V. Mahoney, Elizabeth B. Hirsch, Stephanie E. Giancola, Graham M. Snyder, Gregory Marks, Hai Tran, Angela Hirai-Yang, Christopher McCoy




http://ift.tt/2v9zLQ8

Prognostic factors of health care–associated bloodstream infection in adult patients ≥40 years of age

Publication date: Available online 24 August 2017
Source:American Journal of Infection Control
Author(s): Hsuan-Yin Ma, I.-Chen Hung, Ya-Huei Huang, Ying-Ying Chang, Wang-Huei Sheng, Jann-Tay Wang, Wei-Chu Chie, Jen-pei Liu, Yee-Chun Chen
We investigated 401 geriatric patients and 453 middle-aged patients with health care–associated bloodstream infection (HABSI) at a medical center during January-December 2014. Compared with middle-aged patients, the geriatric group had higher 30-day mortality (31.2% vs 23.4%, P = .01). Body mass index, serum albumin concentration, Charlson comorbidity index score, vancomycin-resistant Enterococcus bacteremia, and high C-reactive protein levels predict poor outcomes for HABSI among adult patients.



http://ift.tt/2vsmHkd

Antibacterial effect and proposed mechanism of action of a topical surgical adhesive

Publication date: Available online 24 August 2017
Source:American Journal of Infection Control
Author(s): Daniel Prince, Zankhna Solanki, Remy Varughese, Jozef Mastej, Derek Prince
BackgroundMedical adhesives effectively hold closed approximated skin edges of wounds from surgical incisions, including punctures from minimally invasive surgery. In addition, they have been reported to be antibacterial against gram-positive bacteria.MethodsUsing membrane filtration to capture all organisms after contact with 2-octyl cyanoacrylate product for 3 minutes, we quantified the number of survivors. Controls were performed to rule out that the noted level of kill was caused by carryover product in the test system.ResultsWe found that the product kills >7 logs of gram-positive and gram-negative bacteria. The mechanism of action for the antibacterial effect is described as a function of very low water content.ConclusionsAs an antibacterial agent, the risk of nosocomial infection is greatly diminished, and an uneventful clinical result is facilitated. Bacterial growth cannot occur in the formulation and on contact death rapidly ensues as cellular water diffuses from the cell into the product.



http://ift.tt/2v9nj31

The virus defeating Madam Mim

Publication date: Available online 24 August 2017
Source:American Journal of Infection Control
Author(s): Antonio Perciaccante, Alessia Coralli




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Evaluation of contact precautions for methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus

Publication date: Available online 24 August 2017
Source:American Journal of Infection Control
Author(s): Ana Cecilia Bardossy, Muhammad Yasser Alsafadi, Patricia Starr, Eman Chami, Jennifer Pietsch, Daniela Moreno, Laura Johnson, George Alangaden, Marcus Zervos, Katherine Reyes
BackgroundThere are limited controlled data demonstrating contact precautions (CPs) prevent methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) infections in endemic settings. We evaluated changes in hospital-acquired MRSA and VRE infections after discontinuing CPs for these organisms.MethodsThis is a retrospective study done at an 800-bed teaching hospital in urban Detroit. CPs for MRSA and VRE were discontinued hospital-wide in 2013. Data on MRSA and VRE catheter-associated urinary tract infections (CAUTIs), ventilator-associated pneumonia (VAP), central line–associated bloodstream infections (CLABSIs), surgical site infections (SSIs), and hospital-acquired MRSA bacteremia (HA-MRSAB) rates were compared before and after CPs discontinuation.ResultsThere were 36,907 and 40,439 patients hospitalized during the two 12-month periods: CPs and no CPs. Infection rates in the CPs and no-CPs periods were as follows: (1) MRSA infections: VAP, 0.13 versus 0.11 (P = .84); CLABSI, 0.11 versus 0.19 (P = .45); SSI, 0 versus 0.14 (P = .50); and CAUTI, 0.025 versus 0.033 (P = .84); (2) VRE infections: CAUTI, 0.27 versus 0.13 (P = .19) and CLABSI, 0.29 versus 0.3 (P = .94); and (3) HA-MRSAB rates: 0.14 versus 0.11 (P = .55), respectively.ConclusionsDiscontinuation of CPs did not adversely impact endemic MRSA and VRE infection rates.



http://ift.tt/2v9Erpd

High mortality rate associated with KPC-producing Enterobacter cloacae in a Brazilian hospital

Publication date: Available online 23 August 2017
Source:American Journal of Infection Control
Author(s): Kesia Esther da Silva, Tháigor Rezek Varella, Graciela Mendonça dos Santos Bet, Cecília Godoy Carvalhaes, Maisa Estopa Correa, Nathalie Gaebler Vasconcelos, Julio Croda, Ana Cristina Gales, Simone Simionatto
We describe a clonal dissemination of KPC-producing Enterobacter cloacae in a Brazilian hospital. Patients diagnosed with theses isolates showed high mortality rate (41.8%) and were associated with previous use of antibiotics and urinary catheterization. Therefore, infection control measures and use of stricter antibiotic policies are required to control the spread of these organisms.



http://ift.tt/2vsjEZr

Successful strategy to decrease indwelling catheter utilization rates in an academic medical intensive care unit

Publication date: Available online 23 August 2017
Source:American Journal of Infection Control
Author(s): Sushilkumar Satish Gupta, Pavan Kumar Irukulla, Mangalore Amith Shenoy, Vimbai Nyemba, Diana Yacoub, Yizhak Kupfer
BackgroundDuration of indwelling urinary catheterization is an important risk factor for urinary tract infections. We devised a strategy to decrease the utilization of indwelling urinary catheters (IUCs). We also highlight the challenges of managing critically ill patients without IUCs and demonstrate some of the initiatives that we undertook to overcome these challenges.MethodsA retrospective observational outcomes review was performed in an adult medical intensive care unit (ICU) between January 2012 and December 2016. This period included a baseline and series of intervals, whereby different aspects of the strategies were implemented. IUC utilization ratio and catheter-associated urinary tract infection (CAUTI) rates were calculated.ResultsOur IUC utilization ratio had a statistically significant decrease from 0.92 (baseline) to 0.28 (after 3 interventions) (P < .0001). Similarly, CAUTI rates had a statistically significant decrease from 5.47 (baseline) to 1.08 (after 3 intervention) (P = .0134). These rates sustained a statistically significant difference over the 2-year follow-up period from the last intervention. Incontinence-associated dermatitis (IAD) was identified as a potential complication of not using an IUC. There was no statistically significant change in the IAD rates during 2013-2016.ConclusionsOur interventions demonstrated that aggressive and comprehensive IUC restriction protocol and provider training can lead to a successful decrease in IUC use, leading to a lower IUC utilization ratio and CAUTI rate in a large complex academic ICU setting.



http://ift.tt/2vrQoC0

Aripiprazole Prolonged Release Suspension for Injection (Abilify Maintena) (300 mg and 400 mg Vial) [Internet].

Schizophrenia is a chronic mental illness that requires lifelong treatment., Patients with schizophrenia are at an increased risk for numerous other medical illnesses, including suicide. In Canada, the disease affects about 1% of the population, or about 234,000 people (2004 data). Antipsychotic medications form the cornerstone of treatment for schizophrenia., Existing antipsychotic therapies fall into one of two classes: typical antipsychotics (TAP) and atypical antipsychotics (AAP). Both classes are considered equally effective in the treatment of positive symptoms. AAPs appear to be more effective in the treatment of negative symptoms. TAPs are associated with an increased incidence of adverse events (AEs) known as extrapyramidal symptoms (EPS); however, AAPs are associated with an increased risk of weight gain and metabolic AEs.

http://ift.tt/2v9zP2l

Developmental Follow-up of Children and Young People Born Preterm.

This guideline focuses on the specialist developmental support and surveillance needed for the early identification of developmental problems and disorders in children born preterm.

http://ift.tt/2vsCeAh

Assessment Tools for Palliative Care [Internet].

To (1) provide an overview of palliative care assessment tools designed to be completed by or with patients or caregivers, including which tools have been applied to clinical care, as quality indicators, or in evaluations of interventions, and (2) identify needs for future palliative care assessment tool development and evaluation.

http://ift.tt/2v9yYPm

Completion dissection or observation for sentinel-node metastasis in melanoma

http://ift.tt/2vsjSzH

Primary Epithelioid Angiosarcoma of Lung: Radiologic and Clinicopathologic Correlation

Fung Him Ng, San Ming Yu, Ophelia Ka Heng Wai, James Chi Sang Chan

Journal of Clinical Imaging Science 2017 7(1):33-33

Primary pulmonary angiosarcoma is extremely rare. It is often characterized by a clinically indolent course and delayed diagnosis. To date, there have been <20 cases reported. By far, little article correlates the clinical presentation, the imaging findings with the pathology. The authors present a case of middle-aged gentleman with primary pulmonary epithelioid angiosacroma which we initially thought as tuberculosis (TB) infection. A 60-year-old gentleman, with a history of 6 months on and off blood stained sputum, was admitted for an episode of massive hemoptysis. Urgent computed tomography (CT) bronchial arteriogram excluded any dilated bronchial artery. Patchy consolidation with multiple small centrilobular ground-glass nodules was noted at left upper lobe. The bronchoscopy was negative for malignancy and infection. Autoimmune workup was negative. Despite negative bronchoscopy, fungal, acid-fast bacilli culture and cytology, and anti-TB treatment were empirically given. However, his hemoptysis was unresolved. He was followed up with high-resolution CT after a month showed an enlarging left upper lobe mass surrounding by a ground glass halo. Left thoracotomy and left upper lobe lobectomy were performed. Epithelioid angiosacroma was found in histology. Radiologic and clinical-pathological findings were correlated in this paper.

http://ift.tt/2g8JdMY

The Utility of Dual Energy Computed Tomography in Musculoskeletal Imaging

Sachin Khanduri, Aakshit Goyal, Bhumika Singh, Mriganki Chaudhary, Tushar Sabharwal, Shreshtha Jain, Hritik Sharma

Journal of Clinical Imaging Science 2017 7(1):34-34

The objective of this article is to review the mechanisms, advantages and disadvantages of dual energy computed tomography (DECT) over conventional tomography (CT) in musculoskeletal imaging as DECT provides additional information about tissue composition and artifact reduction. This provides clinical utility in detection of urate crystals, bone marrow edema, reduction of beam hardening metallic artifact, and ligament and tendon analysis.

http://ift.tt/2it1DbU

Hypofractionated radiation therapy for basal and squamous cell skin cancer: A meta-analysis

Publication date: Available online 23 August 2017
Source:Radiotherapy and Oncology
Author(s): Nicholas G. Zaorsky, Charles T. Lee, Eddie Zhang, Scott W. Keith, Thomas J. Galloway
PurposeTo characterize the cosmetic outcomes and local recurrence (LR) rates of various hypofractionated radiation therapy (RT) regimens for skin basal and squamous cell cancers (BCCs/SCCs).MethodsA PICOS/PRISMA/MOOSE selection protocol was performed to identify 344 articles published between 1985–2016 evaluating patients with T1–2 N0 SCCs/BCCs treated with definitive RT. Biologically equivalent doses with α/β=3 (BED3s) were calculated. The primary endpoint was post-treatment cosmesis. Mixed effects regression models were used to estimate weighted linear relationships between BED3 and cosmetic outcomes.ResultsA total of 21 studies were identified detailing the treatment of 9729 skin BCC/SCC patients, across seven countries, with external beam RT (n=9255) or brachytherapy (n=474). Median follow-up was 36months (range: 12–77). Median dose was 45Gy/11 fractions (interquartile range: 37.5Gy/6–55Gy/18) at 4Gy/fraction (interquartile range: 2.5–6Gy); most hypofractionated 18.75Gy/1. There was a trend to decreased "good" cosmesis with higher total dose: −3.4% "good" cosmesis/10Gy BED3, p=0.01. Similarly, there was a trend to increased "fair" cosmesis with higher dose: +3.8% "fair" cosmesis/10Gy BED3,p=0.006. At a BED3 of 100Gy, the expected rate of "good" cosmesis is 79% (95% confidence interval: 70%, 88%). Hypofractionated schedules produced similar cosmesis to conventionally fractionated schedules, at the same BED3. Fewer than 8% of patients experienced "poor" cosmesis, independent of dose or fractionation regimen.ConclusionHypofractionated RT has favorable cosmesis for patients with skin BCCs/SCCs. We recommend clinicians consider these commonly-used regimens, which all have BED3 of ∼100Gy: 50Gy/15 fractions, 36.75Gy/7 fractions, or 35Gy/5 fractions, as they result in "good" cosmesis in 80% of patients.



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Caution is required in the implementation of 90-day mortality indicators for radiotherapy in a curative setting: A retrospective population-based analysis of over 16,000 episodes

Publication date: Available online 23 August 2017
Source:Radiotherapy and Oncology
Author(s): K. Spencer, R. Ellis, R. Birch, E. Dugdale, R. Turner, D. Sebag-Montefiore, G. Hall, A. Crellin, E. Morris
Background90-day mortality (90DM) has been proposed as a clinical indicator in radiotherapy delivered in a curative setting. No large scale assessment has been made. Its value in allowing robust comparisons between centres and facilitating service improvement is unknown.MethodsAll radiotherapy treatments delivered in a curative setting over seven years were extracted from the local electronic health record and linked to cancer registry data. 90DM rates were assessed and factors associated with this outcome were investigated using logistic regression. Cause of death was identified retrospectively further characterising the cause of 90DM.ResultsOverall 90DM was 1.25%. Levels varied widely with diagnosis (0.20–5.45%). Age (OR 1.066, 1.043–1.073), year of treatment (OR 0.900, 0.841–0.969) and diagnosis were significantly associated with 90DM on multi-variable logistic regression. Cause of death varied with diagnosis; 50.0% post-operative in rectal cancer, 40.4% treatment-related in head and neck cancer, 59.4% disease progression in lung cancer.ConclusionDespite the drive to report centre level comparative outcomes, this study demonstrates that 90DM cannot be adopted routinely asa clinical indicator due to significant population heterogeneity and low event rates. Further national investigation is needed to develop a meaningful robust indicator to deliver appropriate comparisons and drive improvements in care.



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A randomised controlled trial evaluating the utility of a patient Decision Aid to improve clinical trial (RAVES 08.03) related decision-making

Publication date: Available online 23 August 2017
Source:Radiotherapy and Oncology
Author(s): Puma Sundaresan, Brittany Ager, Sandra Turner, Dan Costa, Andrew Kneebone, Maria Pearse, Henry Woo, Stephanie Tesson, Ilona Juraskova, Phyllis Butow
Background and purposeRandomised controlled trials (RCTs) are considered the 'gold-standard' for evaluating medical treatments. However, patients and clinicians report difficulties with informed consent and recruitment. We evaluated the utility of a Decision Aid (DA) in reducing RCT-related decisional conflict, and improving RCT knowledge and recruitment.Materials and methodsPotential participants for a radiotherapy RCT were invited to participate in the current study. Participants were randomised to receive the RCT's participant information sheet with or without a DA. Questionnaires were administered at baseline, one and six months. The primary outcome measure was decisional conflict. Secondary outcome measures included knowledge regarding and recruitment to the RCT.Results129 men were randomised to the DA (63) and control (66) arms. Decisional conflict was significantly lower over 6-months (p=0.048) in the DA arm. Knowledge regarding the RCT was significantly higher at 6months (p=0.033) in the DA arm. 20.6% of the DA arm (13 of 63) and 9% of the control arm (6 of 66) entered the RCT.ConclusionsThis study demonstrates the utility of a DA in reducing decisional conflict and improving trial knowledge in men with cancer who are making decisions regarding RCT participation.



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Deep Brain Stimulation for the Treatment of Dejerine-Roussy Syndrome

Background/Aims: Patients who suffer from Dejerine-Roussy syndrome commonly experience severe poststroke hemibody pain which has historically been attributed to thalamic lesions. Despite pharmacological treatment, a significant proportion of the population is resistant to traditional therapy. Deep brain stimulation is often appropriate for the treatment of resistant populations. In this review we aim to summarize the targets that are used to treat Dejerine-Roussy syndrome and provide insight into their clinical efficacy. Methods: In reviewing the literature, we defined stimulation success as achievement of a minimum of 50% pain relief. Results: Contemporary targets for deep brain stimulation are the ventral posterior medial/ventral posterior lateral thalamic nuclei, periaqueductal/periventricular gray matter, the ventral striatum/anterior limb of the internal capsule, left centromedian thalamic nuclei, the nucleus ventrocaudalis parvocellularis internis, and the posterior limb of the internal capsule. Conclusions: Due to technological advancements in deep brain stimulation, its therapeutic effects must be reevaluated. Despite a lack of controlled evidence, deep brain stimulation has been effectively used as a therapeutic in clinical pain management. Further clinical investigation is needed to definitively evaluate the therapeutic efficacy of deep brain stimulation in treating the drug-resistant patient population.
Stereotact Funct Neurosurg 2017;95:298-306

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Nestle Impact Advanced Recovery in Improving Surgery Recovery in Patients With Head and Neck Cancer

Condition:   Head and Neck Carcinoma
Interventions:   Other: Best Practice;   Other: Laboratory Biomarker Analysis;   Dietary Supplement: Nutritional Intervention
Sponsors:   OHSU Knight Cancer Institute;   National Cancer Institute (NCI)
Not yet recruiting - verified August 2017

http://ift.tt/2wARD6O

Phase Ib/II of TG4001 and Avelumab in HPV16 Positive R/M Cancers and Expansion Cohort to Oropharyngeal SCCHN

Conditions:   Head and Neck Squamous Cell Carcinoma;   HPV Positive Oropharyngeal Squamous Cell Carcinoma;   HPV-Related Carcinoma
Interventions:   Biological: TG4001;   Drug: Avelumab
Sponsors:   Transgene;   Merck KGaA;   EMD Serono Research & Development Institute, Inc.;   Pfizer
Not yet recruiting - verified August 2017

http://ift.tt/2xvMfyp

Concrete and cement composites used for radioactive waste deposition

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Jaroslava Koťátková, Jan Zatloukal, Pavel Reiterman, Karel Kolář
This review article presents the current state-of-knowledge of the use of cementitious materials for radioactive waste disposal. An overview of radwaste management processes with respect to the classification of the waste type is given. The application of cementitious materials for waste disposal is divided into two main lines: i) as a matrix for direct immobilization of treated waste form; and ii) as an engineered barrier of secondary protection in the form of concrete or grout. In the first part the immobilization mechanisms of the waste by cement hydration products is briefly described and an up-to date knowledge about the performance of different cementitious materials is given, including both traditional cements and alternative binder systems. The advantages, disadvantages as well as gaps in the base of information in relation to individual materials are stated. The following part of the article is aimed at description of multi-barrier systems for intermediate level waste repositories. It provides examples of proposed concepts by countries with advanced waste management programmes. In the paper summary, the good knowledge of the material durability due to its vast experience from civil engineering is highlighted however with the urge for specific approach during design and construction of a repository in terms of stringent safety requirements.



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Calculations of individual doses for Techa River Cohort members exposed to atmospheric radioiodine from Mayak releases

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Bruce A. Napier, Paul W. Eslinger, Evgenia I. Tolstykh, Marina I. Vorobiova, Elena E. Tokareva, Boris N. Akhramenko, Victor A. Krivoschapov, Marina O. Degteva
Time-dependent thyroid doses were reconstructed for over 29,000 Techa River Cohort members living near the Mayak production facilities from ¹³¹I released to the atmosphere for all relevant exposure pathways. The calculational approach uses four general steps: 1) construct estimates of releases of ¹³¹I to the air from production facilities; 2) model the transport of ¹³¹I in the air and subsequent deposition on the ground and vegetation; 3) model the accumulation of ¹³¹I in environmental media; and 4) calculate individualized doses. The dose calculations are implemented in a Monte Carlo framework that produces best estimates and confidence intervals of dose time-histories. Other radionuclide contributors to thyroid dose were evaluated. The ¹³¹I contribution was 75–99% of the thyroid dose. The mean total thyroid dose for cohort members was 193 mGy and the median was 53 mGy. Thyroid doses for about 3% of cohort members were larger than 1 Gy. About 7% of children born in 1940–1950 had doses larger than 1 Gy. The uncertainty in the ¹³¹I dose estimates is low enough for this approach to be used in regional epidemiological studies.



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Survival of patients with advanced metastatic melanoma: the impact of novel therapies–update 2017

Publication date: September 2017
Source:European Journal of Cancer, Volume 83
Author(s): Selma Ugurel, Joachim Röhmel, Paolo A. Ascierto, Keith T. Flaherty, Jean Jacques Grob, Axel Hauschild, James Larkin, Georgina V. Long, Paul Lorigan, Grant A. McArthur, Antoni Ribas, Caroline Robert, Dirk Schadendorf, Claus Garbe
The treatment of metastatic melanoma is still undergoing a process of major change. The two most important novel therapeutic strategies, selective kinase inhibitors and immune checkpoint blockers, both significantly prolong survival times of patients with advanced metastatic disease. Different agents, dose regimens and combinations have been tested against each other vigorously within these two groups. However, results from prospective head-to-head comparative studies of both strategies are still lacking. We performed an exploratory analysis of survival data from selected clinical trials representative for the new treatment strategies in advanced metastatic melanoma. Eighty-three Kaplan–Meier survival curves from 25 trials were digitised and grouped by therapeutic strategy and treatment line. For each of these groups, mean survival curves were generated for progression-free (PFS) and overall survival (OS) by weighted averaging. Survival curves grouped together by therapeutic strategy revealed a high concordance, particularly in the first-line setting. For kinase inhibitors, the most favourable PFS and OS in all therapy lines were observed for combined BRAF plus MEK inhibition. For immune checkpoint inhibitors, combined PD-1 plus CTLA-4 inhibition demonstrated the best survival outcome in all categories except for OS in first-line therapy. For the latter, combined PD-1 plus CTLA-4 inhibition showed similar outcomes as single-agent PD-1 inhibition. Comparison of kinase inhibitors and checkpoint blockers revealed a superiority of combined BRAF plus MEK inhibition within the first 6 months, later changing to a superiority of PD-1 blockers alone or in combination with CTLA-4 blockers. These results need confirmation by prospective clinical trials.



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High-depth sequencing of paired primary and metastatic tumours: Implications for personalised medicine

Publication date: October 2017
Source:European Journal of Cancer, Volume 84
Author(s): T. Grellety, C. Lucchesi, I. Hostein, C. Auzanneau, E. Khalifa, I. Soubeyran, A. Italiano
BackgroundNext-generation sequencing of large panel of genes had been associated with clinical benefit in a significant proportion of patients with advanced cancer. However, the molecular profile of the primary tumour from the initial surgical specimen might significantly differ from the molecular profile in a tumour sample obtained from a biopsy of a metastatic site.Patients and methodsWe compare the genetic profile of primary tumours and paired metastases by using a large panel of cancer genes. Training and validation set including a total of 152 primary and metastatic tumour pairs were sequenced (up to 429 genes) focussing on variants described in the Catalogue of Somatic Mutations in Cancer (COSMIC).ResultsTraining and validation set including a total of 152 primary and metastatic tumour pairs were sequenced focussing on variants described in COSMIC. Agreement rate between the couples of primary and metastasis on COSMIC variants was 65% (24/37) and 43% (49/115) in the training and validation cohort, respectively. That rose to 74% (20/27) and 58% (42/73) when focussing on targetable mutations. In five cases, the discordance was related to appearance of secondary resistance mutation, giving a targetable refined agreement rate of 67% (67/100).ConclusionUp to 40% of paired primary tumour/metastases have discordant molecular profile. Liquid biopsies may overcome, in the near future, the limits of tumour tissue genotyping.



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Open-label, multicentre, randomised, phase II study of the EpSSG and the ITCC evaluating the addition of bevacizumab to chemotherapy in childhood and adolescent patients with metastatic soft tissue sarcoma (the BERNIE study)

Publication date: September 2017
Source:European Journal of Cancer, Volume 83
Author(s): Julia C. Chisholm, Johannes H.M. Merks, Michela Casanova, Gianni Bisogno, Daniel Orbach, Jean-Claude Gentet, Anne-Sophie Thomassin-Defachelles, Pascal Chastagner, Stephen Lowis, Milind Ronghe, Kieran McHugh, Rick R. van Rijn, Magalie Hilton, Jeanette Bachir, Sabine Fürst-Recktenwald, Birgit Geoerger, Odile Oberlin
PurposeWe evaluated the role of bevacizumab as part of the multi-modality treatment of children and adolescents with metastatic rhabdomyosarcoma (RMS) or non-rhabdomyosarcoma soft tissue sarcoma (NRSTS).Patients and methodsEligible patients aged ≥6 months to <18 years were randomised to receive induction chemotherapy (four cycles of IVADo + five cycles of IVA, ±bevacizumab), surgery and/or radiotherapy, followed by maintenance chemotherapy (12 cycles of low-dose cyclophosphamide + vinorelbine, ±bevacizumab). The primary objective was event-free survival (EFS) evaluated by an independent radiological review committee.ResultsOne hundred and fifty-four patients were randomised to receive chemotherapy alone (n = 80) or with bevacizumab (n = 74). At the data cut-off for the primary efficacy analysis, median EFS was 14.9 months (95% confidence interval [CI]: 10.8–35.9) with chemotherapy and 20.6 months (95% CI: 15.2–24.9) with bevacizumab plus chemotherapy (stratified hazard ratio [HR] = 0.93; 95% CI: 0.61–1.41; P = 0.72). The HR for EFS in patients with RMS (n = 103) was 1.24 (95% CI: 0.73–2.09) versus 0.64 (95% CI: 0.32–1.26) for those with NRSTS (n = 49). Objective response rate was 36.0% (95% CI: 25.2–47.9) with chemotherapy and 54.0% (95% CI: 40.9–66.6) with bevacizumab plus chemotherapy (difference of 18.0%; 95% CI: 0.6–35.3). There were no treatment-related deaths and no increased incidence of grade 3/4 toxicities with bevacizumab.ConclusionThe addition of bevacizumab to chemotherapy appeared tolerable in children and adolescents with metastatic RMS/NRSTS, but the primary end-point of EFS did not show statistically significant improvement.Trial registration: ClinicalTrials.gov, NCT00643565.



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Impact of gene-expression profiling in patients with early breast cancer when applied outside the guideline directed indication area

Publication date: October 2017
Source:European Journal of Cancer, Volume 84
Author(s): K. Schreuder, A. Kuijer, E.J. Th. Rutgers, C.H. Smorenburg, Th. van Dalen, S. Siesling
PurposeIn Dutch guidelines, gene expression profiles (GEP) are indicated in estrogen receptor positive early breast cancer patients in whom benefit of chemotherapy (CT) is uncertain based on traditional prognostic factors alone. Aim of the present study is to assess the use and impact of GEP on administration of adjuvant CT in breast cancer patients who have according to national guidelines a clear indication to either use or withhold adjuvant chemotherapy (clinical high or low risk).MethodsClinical low- and high-risk patients, according to Dutch breast cancer guidelines, diagnosed between 2011 and 2014 were selected from the Netherlands Cancer Registry. Influence of GEP use and GEP test result on CT administration was assessed with logistic regression.ResultsOverall, 26,425 patients were identified; 4.8% of patients with clinical low risk (444/9354), 7.5% of the patients with a clinical high risk (1281/17,071) received a GEP. GEP use was associated with significantly increased odds of CT administration in clinical low-risk patients (OR = 2.12 95% CI: 1.44–3.11). In clinical high-risk patients, GEP use was associated with a decreased frequency of CT administration (OR = 0.55, 95% CI: 0.48–0.63). Adherence to the GEP result was higher in clinical high-risk patients with a discordant GEP result as compared to clinical low-risk patients with a discordant GEP result: 71.7% vs. 52.2%, respectively.ConclusionGEP is frequently used outside the indicated area and significantly influenced the administration of adjuvant CT, although adherence to the test result was limited.



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Evaluation of survival across several treatment lines in metastatic colorectal cancer: Analysis of the FIRE-3 trial (AIO KRK0306)

Publication date: October 2017
Source:European Journal of Cancer, Volume 84
Author(s): D.P. Modest, I. Ricard, S. Stintzing, L. Fischer von Weikersthal, T. Decker, A. Kiani, U. Vehling-Kaiser, S.-E. Al-Batran, T. Heintges, C. Kahl, G. Seipelt, F. Kullmann, W. Scheithauer, M. Moehler, C.B. Westphalen, J.W. Holch, J.C. von Einem, S. Held, V. Heinemann
BackgroundWe explored the impacts of sequential application of various treatment lines on survival kinetics. Therefore, differences in overall survival (OS) observed in FIRE-3 were investigated in the context of time and exposure to applied treatment.Patients and methodsOS analyses (stratified by treatment with FOLFIRI plus either cetuximab or bevacizumab) were performed according to time intervals as well as using a Cox model to define changes of hazard ratio (HR) over time.ResultsThe fraction of patients with systemic treatment and time on treatment markedly decreases over treatment lines and time. OS evaluation by a Cox model indicated a trend towards a non-proportional hazard between treatment arms (P = 0.12/P = 0.09 for KRAS–intention-to-treat (ITT)/all-RAS wild-type populations, respectively). To improve the fit of the model, a change-point (point of curve separation) was estimated at 22.6 months (day 687) after randomisation. The HR between the two arms before 22.6 months was not significantly different from one. However, markedly different survival kinetics in favour of the cetuximab arm were apparent after the change-point (KRAS-ITT: P = 0.0018; HR, 0.60 [95% confidence interval [CI], 0.44–0.83] and RAS: P = 0.0006; HR, 0.51 [95% CI, 0.35–0.75]).ConclusionThe differences in OS favouring the cetuximab arm become apparent about 22.6 months after randomisation, indicating that only those patients who survive 22.6 months after randomisation benefit from the superiority of the cetuximab arm. When OS curves separate, only few patients receive active systemic treatment in short courses, suggesting that earlier treatment effects are responsible for later kinetics of survival curves.



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The fate of new fosfamides in phase III studies in advanced soft tissue sarcoma

Publication date: October 2017
Source:European Journal of Cancer, Volume 84
Author(s): Anastasia Constantinidou, Winette T.A. van der Graaf
For decades, doxorubicin alone or in combination with ifosfamide has been used in advanced soft tissue sarcoma (STS). In 2014, a comparison of doxorubicin alone versus the combination with ifosfamide (in the randomised phase III EORTC 62012) showed no difference in overall survival (OS), but a difference in response and progression-free survival (PFS) were observed in favour of the combination but at the expense of increased toxicity. Newer fosfamides, with slightly different modes of action, and potentially less toxicity, namely evofosfamide and palifosfamide have recently been tested in randomised phase III clinical trials in STS. The TH CR-406/SARC021 (June 2017) and the PICASSO III (September 2016) studies compared doxorubicin, as the standard arm, to doxorubicin in combination with evofosfamide and palifosfamide, respectively. In both studies, the combination arm produced increased response rates but at the expense of higher toxicity. However, there was no difference in OS or PFS in favour of the combination. Importantly, the median OS of patients receiving standard of care, doxorubicin, in both studies appeared improved from 12.8 months (95.5% CI 10.5–14·III) in the EORTC 62012 to 16.9 months (95% CI 14.8 to 22.9) in PICASSO III and 19.0 months (95% CI 16.2–22.4) in TH CR-406/SARC021. The results of these three randomised phase III studies highlight several critical issues related to the design and conduct of such trials in STS. We discuss these issues aiming to contribute to the ongoing debate about the optimal approach to perform clinical research in STS.



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A docking model of dapsone bound to HLA-B*13:01 explains the risk of dapsone hypersensitivity syndrome

Publication date: Available online 24 August 2017
Source:Journal of Dermatological Science
Author(s): Hideaki Watanabe, Yurie Watanabe, Yasuya Tashiro, Taisei Mushiroda, Takeshi Ozeki, Hideo Hashizume, Hirohiko Sueki, Toshinori Yamamoto, Naoko Utsunomiya-Tate, Hiroaki Gouda, Yoshio Kusakabe
BackgroundDapsone (4,4′-diaminodiphenylsulfone) has been widely used for the treatment of infections such as leprosy. Dapsone hypersensitivity syndrome (DHS) is a major side effect, developing in 0.5–3.6% of patients treated with dapsone, and its mortality rate is ∼10%. Recently, human leukocyte antigen (HLA)-B*13:01 was identified as a marker of susceptibility to DHS.ObjectivesTo investigate why HLA-B*13:01 is responsible for DHS from a structural point of view.MethodsFirst, we used homology modeling to derive the three-dimensional structures of HLA-B*13:01 (associated with DHS) and HLA-B*13:02 (not so associated despite strong sequence identity [99%] with HLA-B*13:01). Next, we used molecular docking, molecular dynamic simulations, and the molecular mechanics Poisson-Boltzman surface area method, to investigate the interactions of dapsone with HLA-B*13:01 and 13:02.ResultsWe found a crucial structural difference between HLA-B*13:01 and 13:02 in the F-pocket of the antigen-binding site. As Trp95 in the α-domain of HLA-B*13:02 is replaced with the less bulky Ile95 in HLA-B*13:01, we found an additional well-defined sub-pocket within the antigen-binding site of HLA-B*13:01. All three representative docking poses of dapsone against the antigen-binding site of HLA-B*13:01 used this unique sub-pocket, indicating its suitability for binding dapsone. However, HLA-B*13:02 does not seem to possess a binding pocket suitable for binding dapsone. Finally, a binding free energy calculation combined with a molecular dynamics simulation and the molecular mechanics Poisson-Boltzman surface area method indicated that the binding affinity of dapsone for HLA-B*13:01 would be much greater than that for HLA-B*13:02.ConclusionsOur computational results suggest that dapsone would fit within the structure of the antigen-recognition site of HLA-B*13:01. This may change the self-peptides that bind to HLA-B*13:01, explaining why HLA-B*13:01 is a marker of DHS susceptibility.



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Key signaling pathways in thyroid cancer

Whole genome sequencing approaches have provided unprecedented insights into the genetic lesions responsible for the onset, progression and dedifferentiation of various types of thyroid carcinomas. Through these efforts, the MAPK and PI3K signaling cascades have emerged as the main activation pathways implicated in thyroid tumorigenesis. The nature of these essential pathways is highly complex, with hundreds of components, multiple points of crosstalk, different subcellular localizations and with the ability to potentially regulate many cellular processes. Small-molecule inhibitors targeting key kinases of these pathways hold great promise as novel therapeutics and several have reached clinical trials. However, while some remarkable responses have been reported, the development of resistance remains a matter of concern and limits the benefit for patients. In this review, we discuss the latest findings on the major components of the MAPK and PI3K pathways, including their mechanisms of activation in physiological and pathological contexts, their genetic alterations with respect to the different types of thyroid carcinomas and the more relevant drugs designed to block their activity.

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Lack of NOD2 attenuates ovariectomy-induced bone loss via inhibition of osteoclasts

Nucleotide-binding oligomerization domain-2 (NOD2) is a pattern recognition receptor of the innate immune system. It interacts with serine–threonine kinases to induce activation of nuclear factor B (NF-B), which is important for receptor activator of nuclear factor kappa-B ligand (RANKL) signaling. We tested the idea that NOD2 modulates bone metabolism via an action on osteoclasts (OCs). The absence of NOD2 reduced ovariectomy-induced bone loss in mice, and lowered the area and the activity of OCs, by impairing RANKL signaling. It also reduced the level of reactive oxygen species (ROS), as well as of NF-B-DNA binding upon RANKL exposure. NOD2 was found to physically interact with nicotinamide adenine dinucleotide phosphate oxidase 1, and this led to increased production of ROS in OCs. Our data suggest that NOD2 contributes to bone loss in estrogen deficiency by elevating ROS levels in OCs.

http://ift.tt/2xvCMHk

Excretory/secretory proteases and mechanical movement of Anisakis pegreffii infective larvae in the penetration of BALB/c mice gastrointestine

Publication date: Available online 23 August 2017
Source:The Kaohsiung Journal of Medical Sciences
Author(s): June-Der Lee, Li-Yu Chung, Rong-Jyh Lin, Jiun-Jye Wang, Hong-Pin Tu, Chuan-Min Yen
Anisakiasis is a human parasitic disease caused by infection with the infective larvae of Anisakis. Accidental infection in humans causes the gastrointestinal pathophysiological effects of mechanical tissue damage by migrating larvae. The mechanism of the infective larval invasion and migration is suspected to involve larval excretory/secretory proteases and motility. This study demonstrates the penetration rate of the infective larvae of Anisakispegreffii in mouse gastrointestine depends on the time after infection, and that only 15% of larvae remain in the gastrointestinal tract 3 h after infection. Strong activities of matrix metalloproteinases (MMPs) and serine proteases, especially plasmin, were found in the excretory/secretory products of A. pegreffii; these can be inhibited by ONO-4817 and phenylmethylsulfonyl fluoride, respectively. The protease activity was also significantly decreased in another 1 h of cultivation of larvae in fresh 0.9% normal saline (NS) after previous cultivation for 48 h in NS. The motility scores of larvae were significantly lower after 48 h of cultivation in NS. The penetration rate of A. pegreffii larvae in the gastrointestine of infected mice sequentially were 90% in the freshly prepared, 68% in serine protease inhibited, 55% in MMPs inhibited larvae, and 16% in larvae cultivated in NS for 48 h. Therefore, this study demonstrates that MMPs and serine proteases excreted and secreted by A. pegreffii and the mechanical movement of infective larvae participate in the penetration of the gastrointestine of mice after infection.



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The F0F1 ATP synthase regulates human neutrophil migration through cytoplasmic proton extrusion coupled with ATP generation

Publication date: October 2017
Source:Molecular Immunology, Volume 90
Author(s): Jun Gao, Tian Zhang, Zhanfang Kang, Weijen Ting, Lingqing Xu, Dazhong Yin
Cytoplasmic alkalinization and extracellular adenosine triphosphate (ATP) signals are required for migration of chemokineactivated neutrophils, but the precise functions remain unclear. In this work, the effect of the plasma membrane-expressed F0F1-ATP synthase (FATPase) on human neutrophils was examined. We found F-ATPase to be involved in cytoplasm proton extrusion and extracellular ATP generation. Oligomycin A, an F-ATPase inhibitor that blocks proton transfer, inhibited cytoplasmic alkalinization, extracellular ATP generation, adhesion and chemotaxis in N-formyl-Met-Leu-Phe (fMLP)-stimulated neutrophils; however, adenosine diphosphate (ADP), a substrate and activator of F-ATPase, had the opposite effect. Further analysis revealed that cell surface F-ATPase can translocate to the leading edge of directional fMLP-stimulated neutrophils toward ADP hydrolyzed from pannexin 1 channel-released ATP, followed by F-ATPase-catalyzed ATP regeneration using ADP and protons transferred from the cytoplasm. Therefore, the membrane-expressed F-ATPase regulates human neutrophil migration via cytoplasm proton extrusion and extracellular ATP generation.



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Inside front cover

Publication date: 1 December 2017
Source:Talanta, Volume 175





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Editorial Board

Publication date: 1 December 2017
Source:Talanta, Volume 175





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Effect of HPV E6/E7 siRNA with Chemotherapeutic Agents on the Regulation of TP53/E2F Dynamic Behavior for Cell Fate Decisions

Publication date: October 2017
Source:Neoplasia, Volume 19, Issue 10
Author(s): Nirmal Rajasekaran, Hun Soon Jung, Soo Hyeon Bae, Chaithanya Chelakkot, Sungyoul Hong, Jong-Sun Choi, Dong-Seok Yim, Yu-Kyoung Oh, Yoon-La Choi, Young Kee Shin
Toxicity and resistance remain major challenges for advanced or recurrent cervical cancer therapies, as treatment requires high doses of chemotherapeutic agents. Restoration of TP53 and hypophosphorylated-retinoblastoma (pRB) proteins by human papillomavirus (HPV) E6/E7 siRNA sensitizes HPV-positive cervical cancer cells toward chemotherapeutic agents. Here, we investigated the therapeutic effects of E6/E7 siRNA on the dynamic behavior of TP53 and RB/E2F signaling networks in deciding the cell fate. The synergistic effect of HPV E6/E7 siRNA pool (SP) with chemotherapeutic agents on TP53 and RB/E2F signaling, proliferation, and apoptosis was analyzed in vitro and in vivo. Compared to the E6/E7 SP alone, E6/E7 SP with cisplatin treatment effectively restored TP53 and RB/E2F signaling and contributes to differences in cell fate, such as apoptosis or cell cycle arrest. We also developed a cellular dynamics model that includes TP53-RB/E2F dynamics and cell proliferation profiles, and confirmed its utility for investigating E6/E7 siRNA-based combination regimens. Using a dual reporter system, we further confirmed the cross talk between TP53 and RB/E2F signaling mechanisms. Treatment of E6/E7 SP cationic liposome (i.v.) with cisplatin and paclitaxel (i.p.) potentially inhibited tumor growth in BALB/c-nude mice. Altogether, our findings suggest that stabilization of TP53 and the RB/E2F repressor complex by E6/E7 SP combined with low-dose chemotherapy can effectively suppress tumor growth.



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Is there a socioeconomic variation in survival from renal tumours in children and young people resident in northern England (1968–2012)?

Publication date: October 2017
Source:Cancer Epidemiology, Volume 50, Part A
Author(s): Ugonna T. Offor, Nermine O. Basta, Peter W. James, Richard J.Q. McNally
BackgroundDespite strong evidence of a social gradient in cancer survival among UK adults, studies in children and young people remain inconclusive and have not included renal tumours. This study investigated the relationship between socioeconomic status and survival from renal tumours among children and young people.ProcedureKaplan-Meier estimation and Cox regression were used to analyse survival for all 209 renal tumours in children and young people (0–24 years) diagnosed 1968–2012 and registered by a specialist population-based registry. Sociodemographic and clinicopathologic variables, including paternal occupation at birth, were also analysed.ResultsNo significant disparity in overall renal tumour and Wilms tumour (WT) survival was observed according to paternal social class [p=0.988 and 0.808, respectively]. The strongest predictor of survival was stage, with late stage (III–IV) disease having a 4-fold higher risk of death compared to early stage (I–II) disease [p<0.001]. Similarly, high mortality-risk was seen for late stage WT in children aged 0–14 years (Hazard Ratio=6.37; 95% CI=2.60–15.59).ConclusionsThis study did not detect a significant social gradient in renal tumour survival. The identification of tumour stage as a strong predictor of survival irrespective of age, necessitates the development of appropriate public health interventions that target early diagnosis and treatment.



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Model based population PK-PD analysis of furosemide for BP lowering effect: A comparative study in primary and secondary hypertension

Publication date: 15 November 2017
Source:European Journal of Pharmaceutical Sciences, Volume 109
Author(s): Mahendra Shukla, Moustafa M.A. Ibrahim, Moon Jain, Swati Jaiswal, Abhisheak Sharma, Kashif Hanif, Jawahar Lal
Though numerous reports have demonstrated multiple mechanisms by which furosemide can exert its anti-hypertensive response. However, lack of studies describing PK-PD relationship for furosemide featuring its anti-hypertensive property has limited its usage as a blood pressure (BP) lowering agent. Serum concentrations and mean arterial BP were monitored following 40 and 80mgkg⁻¹ multiple oral dose of furosemide in spontaneously hypertensive rats (SHR) and DOCA-salt induced hypertensive (DOCA-salt) rats. A simultaneous population PK-PD relationship using Emax model with effect compartment was developed to compare the anti-hypertensive efficacy of furosemide in these rat models. A two-compartment PK model with Weibull-type absorption and first-order elimination best described the serum concentration-time profile of furosemide. In the present study, post dose serum concentrations of furosemide were found to be lower than the EC50. The EC50 predicted in DOCA-salt rats was found to be lower (4.5-fold), whereas the tolerance development was higher than that in SHR model. The PK-PD parameter estimates, particularly lower values of EC50, Ke and Q in DOCA-salt rats as compared to SHR, pinpointed the higher BP lowering efficacy of furosemide in volume overload induced hypertensive conditions. Insignificantly altered serum creatinine and electrolyte levels indicated a favorable side effect profile of furosemide. In conclusion, the final PK-PD model described the data well and provides detailed insights into the use of furosemide as an anti-hypertensive agent.

Graphical abstract

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Development and in vivo evaluation of chitosan beads for the colonic delivery of azathioprine for treatment of inflammatory bowel disease

Publication date: 15 November 2017
Source:European Journal of Pharmaceutical Sciences, Volume 109
Author(s): Abdelrahman M. Helmy, Mahmoud Elsabahy, Ghareb M. Soliman, Mahmoud A. Mahmoud, Elsayed A. Ibrahim
Azathioprine is a highly efficient immunosuppressant drug used for treatment of inflammatory bowel disease (IBD). Systemic administration of azathioprine results in delayed therapeutic effect and serious adverse reactions. In the current study, we have developed, for the first time, colon-targeted chitosan beads for delivery of azathioprine in colitis rabbit model. Several characterizations were performed for the azathioprine-loaded beads (e.g. drug encapsulation efficiency, drug loading capacity, yield, size, shape and compatibility with other ingredients). The in vitro release profiles of acid-resistant capsules filled with azathioprine-loaded beads showed that most of azathioprine was released in IBD colon simulating medium. The therapeutic effects of azathioprine-loaded beads and azathioprine crude drug were examined on acetic acid-induced colitis rabbit model. Improved therapeutic outcomes were observed in the animals treated with the azathioprine-loaded beads, as compared to the untreated animal controls and the animals treated with the azathioprine free drug, based on the clinical activity score, index of tissue edema, mortality rate, colon macroscopic score and colon histopathological features. In the animals treated with the azathioprine-loaded beads, the levels of the inflammatory mediators, myeloperoxidase enzyme and tumor necrosis factor-α, were significantly reduced to levels similar to those observed in the normal rabbits. Furthermore, the activities of the antioxidant enzymes, superoxide dismutase and catalase, were restored considerably in the animals treated with the drug-loaded beads. The azathioprine-loaded beads developed in the current study might have great potential in the management of IBD.

Graphical abstract

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Phospholipid based self-nanoemulsifying self-nanosuspension (p-SNESNS) as a dual solubilization approach for development of formulation with diminished food effect: Fast/fed in vivo pharmacokinetics study in human

Publication date: 15 November 2017
Source:European Journal of Pharmaceutical Sciences, Volume 109
Author(s): Emad B. Basalious, M. Abdallah Ahmed
The novel self- nanoemulsifying self-nanosuspension (SNESNS) combines the advantages of two efficient solubilization technologies; the nanoemulsion and the nanosuspension. The aim of this study is to test the efficiency of phospholipid based self-nanoemulsifying self-nanosuspension (p-SNESNS) formulation as a powerful tool to diminish the food effect on bioavailability of lurasidone hydrochloride as BCS Class II model drug. Phospholipid was incorporated into SNESNS to increase the solubilization power of the in-situ formed nanoemulsion and facilitate the dispersion of the in-situ formed nanosized drug particles. P-SNESNS was evaluated for particle size, Polydispersity index, in vitro dissolution and transmission electron microscopy (TEM). The drug amount dissolved after water dilution of LSD p-SNESNS was ~2 folds that dissolved after dilution of non-phospholipid SNESNS. The self-nanosuspension obtained by aqueous dilution of p-SNESNS kept the cubic morphology of LSD macroparticles. The high in vitro dissolution of LSD in the non-sink dissolution media (water and Phosphate buffer pH6.8) indicated that the p-SNESNS formulation had successfully increased the drug solubility irrespective of pH of the medium. The pharmacokinetics parameters of LSD p-SNESNS in humans were the same in both the fasted and fed states and were similar to those of LSD capsules in the fed state. Our results propose that p-SNESNS could be promising to increase patient compliance and drug efficiency of BCS class II antipsychotics by diminishing the food effect on their oral absorption and preventing the necessity to administer them with food.

Graphical abstract

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Development of a phosphorylated Momordica charantia protein system for inhibiting susceptible dose-dependent C. albicans to available antimycotics: An allosteric regulation of protein

Publication date: 15 November 2017
Source:European Journal of Pharmaceutical Sciences, Volume 109
Author(s): Yuanbiao Qiao, Li Song, Chenchen Zhu, Qian Wang, Tianyan Guo, Yanhua Yan, Qingshan Li
A regulatory Momordica charantia protein system was constructed allosterically by in vitro protein phosphorylation, in an attempt to evaluate antimycological pluripotency against dose-dependent susceptibilities in C. albicans. Fungal strain lineages susceptible to ketoconazole, econazole, miconazole, 5-flucytosine, nystatin and amphotericin B were prepared in laboratory, followed by identification via antifungal susceptibility testing. Protein phosphorylation was carried out in reactions with 5′-adenylic, guanidylic, cytidylic and uridylic acids and cyclic adenosine triphosphate, through catalysis of cyclin-dependent kinase 1, protein kinase A and protein kinase C respectively. Biochemical analysis of enzymatic reactions indicated the apparent Michaelis-Menten constants and maximal velocity values of 16.57–91.97mM and 55.56–208.33μM·min⁻¹, together with an approximate 1:1 reactant stoichiometric ratio. Three major protein phosphorylation sites were theoretically predicted at Thr255, Thr102 and Thr24 by a KinasePhos tool. Additionally, circular dichroism spectroscopy demonstrated that upon phosphorylation, protein folding structures were decreased in random coil, β6-sheet and α1-helix partial regions. McFarland equivalence standard testing yielded the concentration-dependent inhibition patterns, while fungus was grown in Sabouraud's dextrose agar. The minimal inhibitory concentrations of 0.16–0.51μM (at 50% response) were obtained for free protein and phosphorylated counterparts. With respect to the 3-cycling susceptibility testing regimen, individuals of total protein forms were administrated in-turn at 0.14μM/cycle. Relative inhibition ratios were retained to 66.13–81.04% of initial ones regarding the ketoconazole-susceptible C. albicans growth. An inhibitory protein system, with an advantage of decreasing antifungal susceptibilities to diverse antimycotics, was proposed because of regulatory pluripotency whereas little contribution to susceptibility in itself.

Graphical abstract

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Distribution of fluorescein sodium and triamcinolone acetonide in the simulated liquefied and vitrectomized Vitreous Model with simulated eye movements

Publication date: 15 November 2017
Source:European Journal of Pharmaceutical Sciences, Volume 109
Author(s): Sandra Stein, Malte Bogdahn, Christoph Rosenbaum, Werner Weitschies, Anne Seidlitz
Intravitreal administration is the method of choice for drug delivery to the posterior segment of the eye with special emphasis on the vitreous body and its surrounding retinal vasculature. In order to gain a better understanding of the underlying distribution processes, an in vitro model simulating the vitreous body (Vitreous Model, VM) and a system simulating the impact of movement on the VM (Eye Movement System, EyeMoS) was previously developed. In the study reported here, these systems were modified in regard to a standardized injection procedure, the diversity of simulated eye movements, extended periods of investigation, the opportunity to simulate the state after vitrectomy and in considering the physiological temperature. Fluorescein sodium (FS) and triamcinolone acetonide (TA) were used as (model) drugs to examine the drug distribution within the VM. Vitrectomy was simulated by replacing half the volume of the polyacrylamide gel that was used as vitreous substitute with the clinically used Siluron® 5000 whereas for a simulated liquefaction half the volume of the gel was replaced by buffer. A simulated liquefaction caused a 12-fold faster distribution of FS compared to the simulated juvenile VM, which was most likely caused by convective forces and mass transfer. Also, the injection technique (injection into the gel or into the buffer compartment) influenced the resulting distribution pattern. Without any liquefaction, the previously described initial injection channel occurred with both (model) drugs and, in the case of TA, remained almost unchanged during the investigation period of 72h. Simulating vitrectomized eyes, TA did not spread uniformly, but either remained in the depot or strongly sedimented within the VM suggesting that a homogenous distribution of a TA suspension is highly unlikely in vitrectomized eyes. High variabilities were observed with ex vivo animal eyes, demonstrating the limited benefit of explanted tissues for such distribution studies. The combination of the modified VM and EyeMoS seems a valuable tool for characterizing intravitreal dosage forms in a reproducible simulation of diversified eye movements and a partially liquefied or vitrectomized vitreous body.

Graphical abstract

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Pediatric Gastrointestinal Basidiobolomycosis mimicking Malignancy

Publication date: Available online 24 August 2017
Source:Medical Mycology Case Reports
Author(s): Zainab Almoosa, Mohammed Alsuhaibani, Sadeq AlDandan, Dayel Alshahrani
Basidiobolomycosis is a rare fungal infection with high prevalence in southwestern province of Saudi Arabia (Tohama region); it mainly causes subcutaneous infections and rarely gastrointestinal disease. Because of its indolent presentation, it is often misdiagnosed as IBD, tuberculosis or Malignancy.We are reporting a 7 year old Saudi girl with abdominal mass, fever and eosinophilia resembling malignancy on radiological and pathological picture fully recovered with only medical therapy in the form of oral Voriconazole 2012 Elsevier Ltd. All rights reserved.



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New fossils of Australopithecus anamensis from Kanapoi, West Turkana, Kenya (2012–2015)

Publication date: Available online 23 August 2017
Source:Journal of Human Evolution
Author(s): C.V. Ward, J.M. Plavcan, F.K. Manthi
Kanapoi, Kenya, has yielded the earliest evidence of the genus Australopithecus, Australopithecus anamensis. Renewed fieldwork from 2012 through 2015 yielded 18 new fossils attributable to this species. The new specimens include the second maxillary fragment known from a Kanapoi hominin and the first from a relatively young adult. The new maxilla has the distinctive rounded nasal aperture margin characteristic of A. anamensis. A second partial proximal tibia from the site is the first postcranial element from a small A. anamensis individual. A new partial mandible and complete mandibular dentition display distinctive Kanapoi hominin morphology, but the mandible displays a larger trigonid on its fourth premolar than any known so far. Two new complete sets of mandibular incisors are also notably large, especially the lateral ones, a distinctive feature of A. anamensis compared with Australopithecus afarensis. The new fossils also highlight the distinctive morphology of Kanapoi A. anamensis compared to later hominins.



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Scholar : These new articles for Addiction Research & Theory are available online

The online platform for Taylor & Francis Online content New for Addiction Research & Theory and online now on Taylor & Francis Online: Original Article The legalization of dangerous consumption: a comparison of cannabis and gambling policies in the three US states Janne Nikkinen Pages: 1-9 | DOI: 10.1080/16066359.2017.1366455 FREE ACCESS: Health Care for Women International: Research on Women's Health in Africa: Issues, Challenges & Opportunities To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Graphene sieve ions out water filtration

Publication date: Available online 24 August 2017
Source:Materials Today
Author(s): Cordelia Sealy




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Copper-containing nanoparticles boost bone repair

Publication date: Available online 24 August 2017
Source:Materials Today
Author(s): Cordelia Sealy




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Modern miracle materials

Publication date: Available online 24 August 2017
Source:Materials Today
Author(s): David Bradley




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Martian bricklayers

Publication date: Available online 24 August 2017
Source:Materials Today
Author(s): David Bradley




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Highly efficient infrared detector from metamaterials

Publication date: Available online 24 August 2017
Source:Materials Today
Author(s): Laurie Donaldson




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Improving batteries by mimicking nature

Publication date: Available online 24 August 2017
Source:Materials Today
Author(s): Laurie Donaldson




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Events Diary

Publication date: Available online 24 August 2017
Source:Materials Today





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Graphene oxide makes rubber stronger

Publication date: Available online 24 August 2017
Source:Materials Today
Author(s): Cordelia Sealy




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Solar-powered windows

Publication date: Available online 24 August 2017
Source:Materials Today
Author(s): David Bradley




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X-ray imaging of microchips fills the gap

Publication date: Available online 23 August 2017
Source:Materials Today
Author(s): Cordelia Sealy




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Shedding light on a soft synthetic retina

Publication date: Available online 23 August 2017
Source:Materials Today
Author(s): David Bradley




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Modeling solves ultrahard material problem

Publication date: Available online 23 August 2017
Source:Materials Today
Author(s): Cordelia Sealy




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Strength boost for naturally inspired nanocomposites

Publication date: Available online 23 August 2017
Source:Materials Today
Author(s): David Bradley




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Additive Manufacturing Technologies Used for 3D Metal Printing in Dentistry

Abstract

Purpose of Review

Compared to conventional casting methods used for processing different alloys for dental applications, additive manufacturing technologies reduce manufacturing time and costs, minimize human errors and prevent possible defects in the cast objects. This review highlights working mechanisms, possible advantages and drawbacks of recent additive manufacturing technologies used for metal processing in dentistry.

Recent Findings

The literature reviewed indicated that powder-based fusion mainly based on selective laser sintering, selective laser melting and electro beam melting are the most commonly used technologies for 3D metal printing in dentistry for dental appliances made of CoCr and Ti6Al4V. Although mechanical properties of 3D printed alloys could be considered satisfactory, accuracy and reproducibility data do not present consistent results.

Summary

There appears room for improvement between 3D printed metals and ceramic interfaces and precision before such technologies could be favoured over conventional cast methods.

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Scholar : These new articles for Journal of Natural History are available online

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The online platform for Taylor & Francis Online content New for Journal of Natural History and online now on Taylor & Francis Online: Article Microhabitat selection in the sand recluse spider (Sicarius thomisoides): the effect of rock size and temperature Andrés Taucare-Ríos, Claudio Veloso & Ramiro O. Bustamante Pages: 1-12 | DOI: 10.1080/00222933.2017.1367046 ARTICLE The morphological and functional variability of pleon-holding mechanisms in selected Eubrachyura (Crustacea: Decapoda) Stephanie Köhnk , Stanislav Gorb & Dirk Brandis Pages: 1-46 | DOI: 10.1080/00222933.2017.1355076 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.