Epoxy hybrid networks with high mass fraction molecular-level dispersion of pendant polyhedral oligomeric silsesquioxane (POSS)

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Amit K. Sharma, Reese Sloan, Jeffrey S. Wiggins
A novel high shear continuous reactor method was developed to obtain molecular level incorporation of polyhedral oligomeric silsesquioxane (POSS) containing one amine group and seven isobutyl groups into epoxy network as pendant cage. The method consisted of optimizing reaction time and temperature for the synthesis of POSS-epoxy precursor in a high shear continuous reactor. A full conversion of POSS into POSS-epoxy precursor was achieved within 30–40 s of reaction time in a continuous reactor for all molar compositions from 1:140 to 1:1.05 in comparison to a batch process with the reaction time of 18 h. The structure of this precursor at the end of the reaction, determined by silicon Nuclear Magnetic Resonance spectroscopy (²⁹Si NMR), was close to the ideal one. The distribution of reaction product was determined by size exclusion chromatography (SEC). The reaction product containing up to 1:3-mol ratio of POSS: epoxy molecules showed 'epoxy-POSS-epoxy' precursor as a primary product in comparison to 1:2 and 1:1.05-mol ratios with higher molecular weight precursor as the primary product. Hybrid networks containing up to 50 wt % POSS were prepared by curing these precursors with an aromatic amine curative 4, 4'diamino diphenyl methane (DDM). The resulting networks are completely transparent and no phase separation was observed by SEM and TEM in the course of polymerization despite the incompatibility of the isobutyl groups attached to the POSS with the aromatic epoxy-amine networks. In addition to that, DMA and TGA results prove that the introduction of high shear continuous reactor promotes the dispersion of pendant POSS to a molecular level into epoxy networks.

Graphical abstract

http://ift.tt/2njEdHv

Investigation of strain-induced crystallization of carbon black and silica filled natural rubber composites based on mechanical and temperature measurements

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): T. Spratte, J. Plagge, M. Wunde, M. Klüppel
Strain-induced crystallization (SIC) in unfilled and carbon black or silica filled Natural Rubber (NR) with and without silane is investigated. The method introduced in this paper is based on measurements of the surface temperature during tensile test, whereby SIC is quantified by dividing the produced heat into different contributions, namely the dissipative heat, entropy-related reversible heat and crystallization enthalpy. It turns out that there is pronounced SIC in unfilled and carbon black filled NR, while silica/silane systems show less SIC. The degree of crystallinity correlates with the tensile strength of the samples. For silica/silane systems at the same strain level self-reinforcement by SIC is less pronounced possibly due to a lower crosslink density or strain amplification factor. Because of its simplicity, the method developed here is a promising option to investigate SIC on a broad experimental scale and provides an alternative access next to well-established methods like WAXS.

Graphical abstract

http://ift.tt/2njEeLz

An asymmetrical thieno[2,3-f]benzofuran (TBF)-based conjugated polymer for organic solar cells with high fill factor

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Dingjun He, Lixia Qiu, Jun Yuan, Zhi-Guo Zhang, Yongfang Li, Yingping Zou
An asymmetrical building block-TBF modified with alkylthio phenyl as the side chain, polymerization with 4, 7-di (5-bromothiophen-2-yl)-5, 6-dioctyloxybenzo[c] [1,2,5]thiadiazole (BT), a new polymer-TBFPS-BT was obtained. As described in the UV-Vis spectrum, TBFPS-BT exhibited good absorption covering from 300 to 750 nm. Benefited from the alkylthio phenyl substitution, the polymer possessed deep HOMO level of −5.39 eV. The photoluminescence (PL) spectra indicated the generated excitons could be almost completely dissociation at the polymer/PC71BM interface. Furthermore, the high and balanced mobility (1.49 × 10⁻⁴ cm² V⁻¹ s⁻¹ for hole and 1.07 × 10⁻⁴ cm² V⁻¹ s⁻¹ for electron) greatly contributed to enhance the fill factor (FF) and short-circuit current density (Jsc) of device. PSC with different electron transporting layers (ETLs) were investigated, the results showed that when using perylene diimide (PDI) derivative with amino terminal substituent (PDIN) as ETL companied with 2% 1,8-Diiodooctane (DIO), the device delivered a best PCE of 6.55% (Voc = 0.8 V, Jsc = 11.93 mA cm⁻² and FF = 0.69). It is worth noting that all of the devices with ETLs and 2% DIO have shown high FFs over 0.65. So, the suitable modification on TBF and selection of ETLs were valid methods to improve device efficiency.

Graphical abstract

http://ift.tt/2njBFZI

Liquid-crystal self-assembly of lipid membranes on solutions: A dissipative particle dynamic simulation study

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): Xiaowei Qiang, Xianghong Wang, Yongyun Ji, Shiben Li, Linli He
The self-assembly of the amphiphilic lipid molecules in aqueous solution is investigated via dissipative particle dynamic simulation. Lipid bilayer and perforated bilayer membranes, together with the micelles and vesicles, which couple the spatial inhomogeneity and orientation ordering, are observed in equilibrium states and dynamics processes. For the equilibrium states, the phase diagrams are arranged by the lengths of head and tail chains in various lipid-water mixtures, where the influence of chain length and water composition on formation of bilayer and perforated bilayer membranes is carefully analyzed. In the dynamic processes, we investigate the bilayer membranes by analyzing the energies of systems, which indicates that the formations of bilayers and perforated bilayers strongly depended on the initial chain distributions and lipid types. Moreover, we also investigate the dependence of elastic modulus on the chain lengths for the bilayer membranes and the tension for the perforated pores in the perforated bilayer membranes. The observations on these liquid-crystalline self-assembly provided a promising approach that could be used to design and understand the biomembrane based on the lipid molecules.

Graphical abstract

http://ift.tt/2njxhtM

Compatibilization and toughening of co-continuous ternary blends via partially wet droplets at the interface

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Ali M. Zolali, Basil D. Favis
This work reports that a partially wet phase can compatibilize and toughen a co-continuous PLA/PA11 blend. Four different polymers: PBS, PBAT, EMA and EMA-GMA are examined for their capacity to partially wet the PLA/PA11 interface in a melt-blending process. All the blends exhibit a partial wetting morphology, but offer very different compatibilization efficacies and toughening effects. EMA-GMA demonstrates the best compatibilization effect as it reduces the co-continuous thickness to 5–6 μm, which is about half that of the original binary PLA/PA11 blend, followed by EMA while PBS and PBAT result in the least changes in morphology and properties. Despite the enhanced compatibilization effect obtained with EMA-GMA, it is the self-assembled droplets of EMA at the PLA/PA11 interface which result in a major increase in the ductility of the blend with an elongation at break of 260% as compared to 4% for the binary blend. A substantial increase in the notched Izod impact strength is also achieved with partially wet droplets of EMA with a value of 73 J/m, a four-fold increase as compared to the impact strength of the pure PLA and the PLA/PA11 binary blend. This difference is attributed to the limited internal cavitation of the very fine droplets of EMA-GMA at the interface whereas the blends with partially wet EMA demonstrate significant interfacial cavitation after the impact fracture test. This work shows that self-assembled rubbery EMA droplets at a co-continuous PLA/PA11 interface combine to compatibilize the system, improve interfacial adhesion and interfacially cavitate through the continuous system upon fracture. The percolation of the stress field around these interfacially cavitated partially wet droplets results in the shear yielding of the matrix and a significant toughening effect ensues. These results indicate the potential of partially wet droplets to compatibilize and toughen co-continuous structures.

Graphical abstract

http://ift.tt/2njJcry

Eugenol as renewable comonomer compared to 4-penten-1-ol in ethylene copolymerization using a palladium aryl sulfonate catalyst

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): L.R. Parisi, D.M. Scheibel, S. Lin, E.M. Bennett, J.M. Lodge, M.J. Miri
A series of binary copolymerizations of ethylene with two comonomers, eugenol and 4-penten-1-ol, were conducted with a single-component palladium aryl phosphine sulfonate catalyst in toluene solution. Eugenol showed a much a higher tolerance by the catalyst than 4-penten-1-ol. Peak assignments for ¹H NMR and ¹³C NMR spectra of both types of copolymers were established. Eugenol was incorporated into the copolymer at a higher rate compared to 4-penten-1-ol. Both comonomers were mainly inserted into the polymer chains rather than added as end groups. An end group analysis was performed, based on which some conclusions about the polymerization mechanisms were made. The molecular weight properties of the polymers were measured by GPC. The effects of each comonomer on the polymer crystallinity and melting temperature were determined. Antibacterial efficiency tests showed that copolymers containing more than 3.1 % eugenol resulted in a reduction of bacteria exceeding 90 %.

Graphical abstract

http://ift.tt/2njJb6Y

Graphical Contents list & Author index

Publication date: 24 March 2017
Source:Polymer, Volume 113





http://ift.tt/2njtk8e

Intrinsic high-barrier polyimide with low free volume derived from a novel diamine monomer containing rigid planar moiety

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Yiwu Liu, Jie Huang, JingHua Tan, Yi Zeng, JunJie Liu, Hailiang Zhang, Yong Pei, XianWei Xiang, YueJun Liu
An intrinsic high-barrier and thermally stable polyimide (2,7-CPPI) was prepared by the polymerization of pyromellitic dianhydride (PMDA) and novel diamine (2,7-CPDA), which consists of rigid planar carbazole moiety. The resulted 2,7-CPPI exhibits excellent barrier properties, with oxygen transmission rate and water vapor transmission rate low to 0.2 cm³ m⁻²·day⁻¹ and 0.1 g m⁻²·day⁻¹, respectively. Wide angle X-ray diffractograms (WAXD), positron annihilation lifetime spectroscopy (PALS) and molecular dynamics simulations reveal that the excellent barrier properties of 2,7-CPPI are mainly ascribed to the crystallinity, high chain rigidity and low free volume, which are resulted from the rigid planar structure and strong hydrogen bonding among molecular chains. Meanwhile, 2,7-CPPI also presents outstanding thermal stability and mechanical properties with a glass transition temperature of 437 °C, 5 wt % loss temperature of 556 °C under N2, coefficient of thermal expansion of 2.89 ppm/K and tensile strength of 143.8 MPa. The polyimide shows attractive potential applications in flexible electronics and high-grade packaging area, especially using as the substrates for top-emitting OLEDs display.

Graphical abstract

http://ift.tt/2nOQUqe

Poly(tetrafluoroethylene-hexafluoropropylene) films with high energy density and low loss for high-temperature pulse capacitors

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Xiaomeng Zhang, Yifei Zhao, Yuhao Wu, Zhicheng Zhang
As the most important material of metalized capacitors, dielectric polymers with large energy density (Ue), promising discharging efficiency (η), and elevated breakdown strength (Eb) are dreadfully requested for energy storage purpose. During the charging and discharging circles, the Joule heat could cause significant temperature rising and undesirable early failure in the capacitors. Few of the known polymeric dielectrics are able to work functionally at temperature over 100 °C, especially under high electric field. In present contribution, poly(tetrafluoroethylene-hexafluoropropylene) (P(TFE-HFP)) is fabricated into thin films via hot-pressing followed by uniaxially stretching. At ambient temperature, P(TFE-HFP) films exhibit linear dielectric behaviour like biaxially orientated polypropylene (BOPP). The high Tm and Young's modulus allow P(TFE-HFP) films to work functionally at temperature up to 110 °C, whose Eb is over 500 MV/m, Ue is more than 6 J/cm³ and η is larger than 80%, respectively. The excellent performance suggests that P(TFE-HFP) films may substitute BOPP films to work as dielectric materials at elevated temperature.

Graphical abstract

http://ift.tt/2nOKAz4

Molecular dynamics modeling of PPTA crystallite mechanical properties in the presence of defects

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Brian Mercer, Edward Zywicz, Panayiotis Papadopoulos
The mechanical properties of PPTA crystallites, the fundamental building blocks of aramid polymer fibers such as Kevlar^® and Twaron^®, are studied here using molecular dynamics simulations. The ReaxFF interatomic potential is employed to study crystallite failure via covalent and hydrogen bond rupture in constant strain-rate tensile loading simulations. Emphasis is placed on analyzing how chain-end defects in the crystallite influence its mechanical response and fracture strength. Chain-end defects are found to affect the behavior of nearby chains in a region of the PPTA crystallite that is small relative to the typical crystallite size in manufactured aramid fibers. The central CN bond along the backbone chain is identified as the weakest in the PPTA polymer chain backbone in dynamic strain-to-failure simulations of the crystallite. It is found that clustering of chain-ends leads to reduced crystallite strength and crystallite failure via hydrogen bond rupture and chain sliding, whereas randomly scattered defects impact the strength less and failure is by covalent bond rupture and chain scission. The axial crystallite modulus increases with increasing chain length and is independent of chain-end defect locations. On the basis of these findings, a theoretical model is proposed to predict the axial modulus as a function of chain length.

Graphical abstract

http://ift.tt/2nOKA22

Editorial board

Publication date: 24 March 2017
Source:Polymer, Volume 113





http://ift.tt/2nOO9oG

A cross-sectional comparison of ethanol-related cytokine expression in the hippocampus of young and aged Fischer 344 rats

Publication date: June 2017
Source:Neurobiology of Aging, Volume 54
Author(s): Anny Gano, Tamara L. Doremus-Fitzwater, Terrence Deak
Our work in Sprague Dawley rats has shown rapid alterations in neuroimmune gene expression (RANGE) in the hippocampus and paraventricular nucleus of the hypothalamus (PVN). These manifest as increased interleukin (IL)-6 and IκBα, and suppressed IL-1β and tumor necrosis factor alpha during acute ethanol intoxication. The present studies tested these effects across the lifespan (young adulthood at 2–3 months; senescence at 18 and 24 months), as well as across strain (Fischer 344) and sex. The hippocampus revealed age-dependent shifts in cytokine expression (IL-6, IL-1β, and monocyte chemoattractant protein 1), but no changes were observed in the PVN at baseline or following ethanol. RANGE in adults was similar across sex and comparable with effects seen in Sprague Dawley rats. Plasma corticosterone levels increased with age, whereas the blood ethanol concentrations and loss of righting reflex were similar in all groups older than 2 months. These findings indicate that the RANGE effect is largely conserved across strain and is durable across age, even in the face of a shifting neuroimmune profile that emerges during immunosenescence.



http://ift.tt/2n8hKfY

Fe(III)-based metal–organic framework-derived core–shell nanostructure: Sensitive electrochemical platform for high trace determination of heavy metal ions

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Zhihong Zhang, Hongfei Ji, Yingpan Song, Shuai Zhang, Minghua Wang, Changchang Jia, Jia-Yue Tian, Linghao He, Xiaojing Zhang, Chun-Sen Liu
A new core–shell nanostructured composite composed of Fe(III)-based metal–organic framework (Fe-MOF) and mesoporous Fe3O4@C nanocapsules (denoted as Fe-MOF@mFe3O4@mC) was synthesized and developed as a platform for determining trace heavy metal ions in aqueous solution. Herein, the mFe3O4@mC nanocapsules were prepared by calcining the hollow Fe3O4@C that was obtained using the SiO2 nanoparticles as the template, followed by composing the Fe-MOF. The Fe-MOF@mFe3O4@mC nanocomposite demonstrated excellent electrochemical activity, water stability and high specific surface area, consequently resulting in the strong biobinding with heavy-metal-ion-targeted aptamer strands. Furthermore, by combining the conformational transition interaction, which is caused by the formation of the G-quadruplex between a single-stranded aptamer and high adsorbed amounts of heavy metal ions, the developed aptasensor exhibited a good linear relationship with the logarithm of heavy metal ion (Pb²⁺ and As³⁺) concentration over the broad range from 0.01 to 10.0nM. The detection limits were estimated to be 2.27 and 6.73 pM toward detecting Pb²⁺ and As³⁺, respectively. The proposed aptasensor showed good regenerability, excellent selectivity, and acceptable reproducibility, suggesting promising applications in environment monitoring and biomedical fields.



http://ift.tt/2mZm5kV

A new amplified π-shape electrochemical aptasensor for ultrasensitive detection of aflatoxin B1

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Khalil Abnous, Noor Mohammad Danesh, Mona Alibolandi, Mohammad Ramezani, Ahmad Sarreshtehdar Emrani, Reza Zolfaghari, Seyed Mohammad Taghdisi
There is a prompt need for determination of aflatoxin B1 (AFB1) in food products to avoid distribution and consumption of contaminated food products. In this study, an accurate electrochemical sensing strategy was presented for detection of AFB1 based on aptamer (Apt)-complementary strands of aptamer (CSs) complex which forms a π-shape structure on the surface of electrode and exonuclease I (Exo I). The presence of π-shape structure as a double-layer physical barrier allowed detection of AFB1 with high sensitivity. In the absence of AFB1, the π-shape structure remained intact, so only a weak peak current was recorded. Upon the addition of AFB1, the π-shape structure was disassembled and a strong current was recorded following the addition of Exo I. Under optimal conditions, the electrochemical signals enhanced as AFB1 concentrations increased with a dynamic range of 7–500pg/mL and a limit of detection (LOD) of 2pg/mL. The developed aptasensor was also used to analyze AFB1 spiked human serum and grape juice samples and the recoveries were 95.4–108.1%.



http://ift.tt/2mFy1Wt

Sensitivity enhancement of graphene/zinc oxide nanocomposite-based electrochemical impedance genosensor for single stranded RNA detection

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Sze Shin Low, Hwei-San Loh, Jian Sheng Boey, Poi Sim Khiew, Wee Siong Chiu, Michelle T.T. Tan
An efficient electrochemical impedance genosensing platform has been constructed based on graphene/zinc oxide nanocomposite produced via a facile and green approach. Highly pristine graphene was synthesised from graphite through liquid phase sonication and then mixed with zinc acetate hexahydrate for the synthesis of graphene/zinc oxide nanocomposite by solvothermal growth. The as-synthesised graphene/zinc oxide nanocomposite was characterised with scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopy and X-ray diffractometry (XRD) to evaluate its morphology, crystallinity, composition and purity. An amino-modified single stranded DNA oligonucleotide probe synthesised based on complementary Coconut Cadang-Cadang Viroid (CCCVd) RNA sequence, was covalently bonded onto the surface of graphene/zinc oxide nanocomposite by the bio-linker 1-pyrenebutyric acid N-hydroxysuccinimide ester. The hybridisation events were monitored by electrochemical impedance spectroscopy (EIS). Under optimised sensing conditions, the single stranded CCCVd RNA oligonucleotide target could be quantified in a wide range of 1.0×10^–11M to 1.0×10⁻⁶ with good linearity (R =0.9927), high sensitivity with low detection limit of 4.3×10^–12M. Differential pulse voltammetry (DPV) was also performed for the estimation of nucleic acid density on the graphene/zinc oxide nanocomposite-modified sensing platform. The current work demonstrates an important advancement towards the development of a sensitive detection assay for various diseases involving RNA agents such as CCCVd in the future.



http://ift.tt/2mZhRda

Functional characterization of Gram-negative bacteria from different genera as multiplex cadmium biosensors

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Lara Bereza-Malcolm, Sanja Aracic, Ruban Kannan, Gülay Mann, Ashley E. Franks
Widespread presence of cadmium in soil and water systems is a consequence of industrial and agricultural processes. Subsequent accumulation of cadmium in food and drinking water can result in accidental consumption of dangerous concentrations. As such, cadmium environmental contamination poses a significant threat to human health. Development of microbial biosensors, as a novel alternative method for in situ cadmium detection, may reduce human exposure by complementing traditional analytical methods. In this study, a multiplex cadmium biosensing construct was assembled by cloning a single-output cadmium biosensor element, cadRgfp, and a constitutively expressed mrfp1 onto a broad-host range vector. Incorporation of the duplex fluorescent output [green and red fluorescence proteins] allowed measurement of biosensor functionality and viability. The biosensor construct was tested in several Gram-negative bacteria including Pseudomonas, Shewanella and Enterobacter. The multiplex cadmium biosensors were responsive to cadmium concentrations ranging from 0.01 to 10µgml⁻¹, as well as several other heavy metals, including arsenic, mercury and lead at similar concentrations. The biosensors were also responsive within 20–40min following exposure to 3µgml⁻¹ cadmium. This study highlights the importance of testing biosensor constructs, developed using synthetic biology principles, in different bacterial genera.



http://ift.tt/2mFp8w6

Ventilation with high versus low peep levels during general anaesthesia for open abdominal surgery does not affect postoperative spirometry: A randomised clinical trial.

BACKGROUND: Invasive mechanical ventilation during general anaesthesia for surgery typically causes atelectasis and impairs postoperative lung function. OBJECTIVE: We investigated the effect of intraoperative ventilation with high positive end-expiratory pressure (PEEP) and recruitment manoeuvres (RMs) on postoperative spirometry. DESIGN: This was a preplanned, single-centre substudy of an international multicentre randomised controlled trial, the PROVHILO trial. SETTING: University hospital from November 2011 to January 2013. PATIENTS: Nonobese patients scheduled for major abdominal surgery at a high risk of postoperative pulmonary complications (PPCs). INTERVENTION: Intraoperative low tidal volume ventilation with PEEP levels of 12 cmH2O and RM (the high PEEP group) or with PEEP levels of 2 cmH2O or less without RM (the low PEEP group). MAIN OUTCOME MEASURES: Time-weighted averages (TWAs) of the forced expiratory volume in 1 s (FEV1) and the forced vital capacity (FVC) up to postoperative day five. RESULTS: Thirty-one patients were allocated to the high PEEP group and 32 to the low PEEP group. No postoperative spirometry test results were available for 6 patients. In both groups, TWA of FEV1 and FVC until postoperative day five were lower than preoperative values. Postoperative spirometry test results were not different between the high and low PEEP group; Data are median [interquartile range], TWA FVC 1.8 [1.6 to 2.4] versus 1.7 [1.2 to 2.4] l (P = NS) and TWA FEV1 1.2 [1.1 to 2.5] versus 1.2 [0.9 to 1.9] l (P = NS). Patients who developed PPCs had lower FEV1 and FVC on postoperative day five; 1.1 [0.9 to 1.6] versus 1.6 [1.4 to 1.9] l (P = 0.001) and 1.6 [1.2 to 2.6] versus 2.3 [1.7 to 2.6] l (P = 0.036), respectively. CONCLUSION: Postoperative spirometry is not affected by PEEP and RM during intraoperative ventilation for open abdominal surgery in nonobese patients at a high risk of PPCs, but rather is associated with the development of PPCs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01441791. (C) 2017 European Society of Anaesthesiology

http://ift.tt/2mSVqom

Oxford Textbook of Obstetric Anaesthesia.

No abstract available

http://ift.tt/2mdcdFm

The use of dipyrone in the ICU is associated with acute kidney injury: A retrospective cohort analysis.

BACKGROUND: Use of dipyrone (metamizole) in perioperative and ICU pain therapy remains controversial due to a lack of solid evidence weighing dipyrone benefit against its potential life-threatening complications. Although dipyrone has known analgesic and antipyretic properties, its mechanisms of actions are incompletely understood. Although dipyrone effects on renal vasodilator prostaglandin synthesis are documented, little is known about its potential renal side effects, especially in the critical care environment. OBJECTIVE: Investigation of the perioperative nephrotoxic potential of dipyrone in patients prone to acute kidney injury (AKI). DESIGN: Retrospective cohort study. SETTING: Single centre study in a tertiary referral hospital from January 2013 until June 2013. PATIENTS: A total of 500 consecutive patients aged 18 years and older referred to the anaesthesia ICU. Patients were excluded if admitted from or discharged to other ICUs, if referred for post resuscitation care, or if repeatedly admitted to the ICU. MAIN OUTCOME MEASURES: Incidence of AKI, as defined by the Kidney Disease: Improving Global Outcomes Acute Kidney Injury Work Group criteria, and duration of vasopressor therapy. RESULTS: Use of dipyrone was associated with an increased incidence of AKI in a dose-dependent manner with a 1.6-fold increase in the incidence of AKI with each additional gram of intravenous dipyrone per day. Dipyrone dose of more than 2.5 g day-1 was the best risk predictive cut-off for AKI. Patients receiving dipyrone on the ICU presented with a prolonged duration of vasopressor therapy. CONCLUSION: Increasing dipyrone dosage is a potential independent risk factor for AKI in adult ICU patients and may prolong vasopressor therapy. Clinical evidence for a benefit of dipyrone therapy in the ICU is insufficient and needs further critical evaluation. (C) 2017 European Society of Anaesthesiology

http://ift.tt/2mSXay5

On the Interpretation of the Hazard Ratio and Communication of Survival Benefit

This brief communication will clarify the difference between a relative hazard and a relative risk. We highlight the importance of this difference, and demonstrate in practical terms that 1 minus the hazard ratio should not be interpreted as a risk reduction in the commonly understood sense of the term. This article aims to provide a better understanding of the type of risk reduction that a hazard ratio implies, thereby clarifying the intent in the communication among practitioners and researchers and establishing an accurate and realistic foundation for communicating with patients. The Oncologist 2017;22:1–3

http://ift.tt/2mSM4ZC

Academic Cancer Center Phase I Program Development

Multiple factors critical to the effectiveness of academic phase I cancer programs were assessed among 16 academic centers in the U.S. Successful cancer centers were defined as having broad phase I and I/II clinical trial portfolios, multiple investigator-initiated studies, and correlative science. The most significant elements were institutional philanthropic support, experienced clinical research managers, robust institutional basic research, institutional administrative efforts to reduce bureaucratic regulatory delays, phase I navigators to inform patients and physicians of new studies, and a large cancer center patient base. New programs may benefit from a separate stand-alone operation, but mature phase I programs work well when many of the activities are transferred to disease-oriented teams. The metrics may be useful as a rubric for new and established academic phase I programs. The Oncologist 2017;22:1–6

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Risk-Reducing Strategies for Ovarian Cancer in BRCA Mutation Carriers: A Balancing Act

Objective.

The objective of this study was to review the role of bilateral salpingo-oophorectomy in BRCA mutation (mBRCA) carriers and alternative interventions in risk reduction of ovarian cancer (OC).

Materials and Methods.

A systematic review using PubMed, MEDLINE, EMBASE, and the Cochrane library was conducted to identify studies of different strategies to prevent OC in mBRCA carriers, including bilateral salpingo-oophorectomy, prophylactic salpingectomy with delayed oophorectomy, intensive surveillance, and chemoprevention.

Results.

Risk-reducing bilateral salpingo-oophorectomy is an effective intervention, but its associated morbidity is substantial and seems to curtail uptake rates among the target population. Although there is much interest and a strong theoretical basis for salpingectomy with delayed oophorectomy, data on its clinical application are scarce with regard to screening, the use of an algorithmic protocol has recently shown favorable albeit indefinite results in average-risk postmenopausal women. Its incorporation into studies focused on high-risk women might help solidify a future role for screening as a bridge to surgery. The use of oral contraceptives for chemoprevention is well supported by epidemiologic studies. However, there is a lack of evidence for advocating any of the other agents proposed for this purpose, including nonsteroidal anti-inflammatory drugs, vitamin D, and retinoids.

Conclusion.

Further studies are needed before salpingectomy with delayed oophorectomy or intensive surveillance can be offered as acceptable, less morbid alternatives to upfront oophorectomy for mBRCA carriers. The Oncologist 2017;22:1–10

Implications for Practice: Risk-reducing bilateral salpingo-oophorectomy is currently the most effective method for reducing the risk of ovarian cancer in BRCA mutation (mBRCA) carriers. Unfortunately, it is associated with significant short- and long-term morbidity, stemming from reduced circulating estrogen. In recent years, much research has been devoted to evaluating less morbid alternatives, especially multimodal cancer screening and prophylactic salpingectomy with delayed oophorectomy. This review describes the present state of the art, with the aim of informing the counseling provided to mBRCA carriers on this complicated issue and encouraging additional research to facilitate the incorporation of such alternatives into routine practice.

http://ift.tt/2mSSDLU

End-of-Life Care Matters: Palliative Cancer Care Results in Better Care and Lower Costs

http://ift.tt/2mcY7UC

Performance of Mid-Treatment Breast Ultrasound and Axillary Ultrasound in Predicting Response to Neoadjuvant Chemotherapy by Breast Cancer Subtype

Background.

The primary objective was to determine whether mid-treatment ultrasound measurements of index breast tumors and index axillary nodes of different cancer subtypes associate with residual cancer burden (RCB).

Methods.

Patients with invasive breast cancer who underwent neoadjuvant chemotherapy and had pre-treatment and mid-treatment breast and axillary ultrasound were included in this single-institution, retrospective cohort study. Linear regression analysis assessed associations between RCB with (a) change in index breast tumor size, (b) change in index node size, and (c) absolute number of abnormal nodes at mid-treatment. Multivariate linear regression was used to calculate best-fit models for RCB.

Results.

One hundred fifty-nine patients (68 triple negative breast cancer [TNBC], 45 hormone receptor [HR]+/human epidermal growth factor receptor 2 [HER2]–, and 46 HR–/HER2+) were included. Median age at diagnosis was 50 years, range 30–76. Median tumor size was 3.4 cm, range 0.9–10.4. Pathological complete response/RCB-I rates were 36.8% (25/68) for TNBC patients, 24.4% (11/45) for HR+/HER2– patients, and 71.7% (33/46) for HR–/HER2+ patients. Linear regression analyses demonstrated associations between percent change in tumor ultrasound measurements at mid-treatment with RCB index score in TNBC and HR+/HER2– (p < .05) but not in HR–/HER2+ (p > .05) tumors and an association between axillary ultrasound assessment of number of abnormal nodes at mid-treatment with RCB index score across all subtypes (p < .05).

Conclusion.

Performance characteristics of breast ultrasound associated with RCB vary by cancer subtype, whereas the performance characteristics of axillary ultrasound associated with RCB are consistent across cancer subtype. Breast and axillary ultrasound may be valuable in monitoring response to neoadjuvant therapy. The Oncologist 2017;22:1–8

Implications for Practice: The differential performance characteristics of breast ultrasound by molecular subtype and the consistent performance characteristics of axillary ultrasound across molecular subtypes can have clinical utility in monitoring response to neoadjuvant therapy.

http://ift.tt/2mSJgvE

A Phase I Study of Abiraterone Acetate Combined with BEZ235, a Dual PI3K/mTOR Inhibitor, in Metastatic Castration Resistant Prostate Cancer

Lessons Learned.

The combination of standard dose abiraterone acetate and BEZ235, a pan-class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC.

Although the clinical development of BEZ235 has been discontinued in prostate cancer, agents that more selectively target PI3K-AKT-mTOR signaling may have a more favorable therapeutic index and should continue to be explored.

Background.

Androgen receptor (AR) and phosphatidylinositol-3 kinase (PI3K) signaling are two commonly perturbed pathways in prostate cancer. Preclinical data have shown that the two pathways compensate for each other when one is inhibited, and combined inhibition of AR and PI3K signaling may be a viable strategy to prevent or overcome castration resistance.

Methods.

This phase I study evaluated the safety and tolerability of abiraterone acetate and prednisone combined with BEZ235, a dual PI3K and mTORC1/2 inhibitor, in men with progressive metastatic castration resistant prostate cancer (mCRPC) who have not received prior chemotherapy.

Results.

Six patients (n = 6) were treated at the starting dose level of abiraterone acetate 1,000 mg with prednisone 5 mg twice daily and BEZ235 200 mg twice daily in a 3 + 3 dose escalation design. The study was terminated early because three of the six patients (50%) experienced dose-limiting toxicities: grade 3 mucositis, grade 3 hypotension, and grade 4 dyspnea and pneumonitis. All six patients had previously progressed on abiraterone/prednisone. The median treatment duration was 27 days (range: 3–130 days). No prostate-specific antigen (PSA) decline or objective response were observed.

Conclusion.

The combination of standard-dose abiraterone/prednisone with BEZ235 200 mg twice daily was poorly tolerated in patients with mCRPC. The on-target and off-target effects of dual PI3K and mTORC inhibition likely contributed to the unacceptable toxicity profile. The Oncologist 2017;22:1–8

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SAFE-HEaRt: Rationale and Design of a Pilot Study Investigating Cardiac Safety of HER2 Targeted Therapy in Patients with HER2-Positive Breast Cancer and Reduced Left Ventricular Function

Background.

Human epidermal growth receptor 2 (HER2) targeted therapies have survival benefit in adjuvant and metastatic HER2 positive breast cancer but are associated with cardiac dysfunction. Current U.S. Food and Drug Administration recommendations limit the use of HER2 targeted agents to patients with normal left ventricular (LV) systolic function.

Methods.

The objective of the SAFE-HEaRt study is to evaluate the cardiac safety of HER2 targeted therapy in patients with HER2 positive breast cancer and mildly reduced left ventricular ejection fraction (LVEF) with optimized cardiac therapy. Thirty patients with histologically confirmed HER2 positive breast cancer (stage I–IV) and reduced LVEF (40% to 49%) who plan to receive HER2 targeted therapy for ≥3 months will be enrolled. Prior to initiation on study, optimization of heart function with beta-blockers and angiotensin converting enzyme inhibitors will be initiated. Patients will be followed by serial echocardiograms and cardiac visits during and 6 months after completion of HER2 targeted therapy. Myocardial strain and blood biomarkers, including cardiac troponin I and high-sensitivity cardiac troponin T, will be examined at baseline and during the study.

Discussion.

LV dysfunction in patients with breast cancer poses cardiac and oncological challenges and limits the use of HER2 targeted therapies and its oncological benefits. Strategies to prevent cardiac dysfunction associated with HER2 targeted therapy have been limited to patients with normal LVEF, thus excluding patients who may receive the highest benefit from those strategies. SAFE-HEaRt is the first prospective pilot study of HER2 targeted therapies in patients with reduced LV function while on optimized cardiac treatment that can provide the basis for clinical practice changes. The Oncologist 2017;22:1–8

Implications for Practice: Human epidermal growth receptor 2 (HER2) targeted therapies have survival benefit in adjuvant and metastatic HER2 positive breast cancer but are associated with cardiac dysfunction. To our knowledge, SAFE-HEaRt is the first clinical trial that prospectively tests the hypothesis that HER2 targeted therapies may be safely administered in patients with mildly reduced cardiac function in the setting of ongoing cardiac treatment and monitoring. The results of this study will provide cardiac safety data and inform consideration of clinical practice changes in patients with HER2 positive breast cancer and reduced cardiac function, as well as provide information regarding cardiovascular monitoring and treatment in this population.

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Endocrine Therapy in the Current Management of Postmenopausal Estrogen Receptor-Positive Metastatic Breast Cancer

Metastatic breast cancer (MBC) results in substantial morbidity and mortality for women afflicted with this disease. A majority of MBCs are hormone-responsive and estrogen receptor-positive, making endocrine therapy (ET) an integral component of systemic therapy. With a primary goal of minimizing the effects of estrogen on hormone-responsive MBC, ETs are among the first targeted treatments that aim to inhibit the influence of estrogen receptor activation on tumor proliferation. Several biochemical mechanisms have been the focus of drug development for treatment, including selective estrogen-receptor modulation, aromatase inhibition, and selective estrogen-receptor degradation. Treatments that exploit these mechanisms have improved survival and quality of life for women with MBC. However, in many cases, resistance to ET limits their effectiveness. Elucidation of the complex cellular signal cascades involved in the development of acquired resistance to ET and the interrelationship of growth factor signaling and estrogen responsiveness have characterized components of these pathways as attractive targets for drug development. Based on these insights and with the aim of overcoming hormone resistance, targeted therapies are emerging as useful treatments for MBC. This article reviews current endocrine treatments of MBC as well as recent and ongoing study of combination treatments and targeted therapies that interfere with cellular proliferation pathways as means of overcoming resistance. The Oncologist 2017;22:1–11

Implications for Practice: This review provides medical oncologists and other oncology health care providers with a current understanding of the rationale for endocrine therapy in estrogen receptor-positive metastatic breast cancer and the efficacy and safety profile of available treatment options. Additionally, current concepts regarding the development of treatment resistance and the treatment strategies for overcoming resistance are discussed. Enhancing the current information and the understanding of these topics will assist clinicians in evaluating optimal treatment options for their patients.

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Comprehensive proteomic characterization of stem cell-derived extracellular matrices

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Héloïse Ragelle, Alexandra Naba, Benjamin L. Larson, Fangheng Zhou, Miralem Prijić, Charles A. Whittaker, Amanda Del Rosario, Robert Langer, Richard O. Hynes, Daniel G. Anderson
In the stem-cell niche, the extracellular matrix (ECM) serves as a structural support that additionally provides stem cells with signals that contribute to the regulation of stem-cell function, via reciprocal interactions between cells and components of the ECM. Recently, cell-derived ECMs have emerged as in vitro cell culture substrates to better recapitulate the native stem-cell microenvironment outside the body. Significant changes in cell number, morphology and function have been observed when mesenchymal stem cells (MSC) were cultured on ECM substrates as compared to standard tissue-culture polystyrene (TCPS). As select ECM components are known to regulate specific stem-cell functions, a robust characterization of cell-derived ECM proteomic composition is critical to better comprehend the role of the ECM in directing cellular processes. Here, we characterized and compared the protein composition of ECM produced in vitro by bone marrow-derived MSC, adipose-derived MSC and neonatal fibroblasts from different donors, employing quantitative proteomic methods. Each cell-derived ECM displayed a specific and unique matrisome signature, yet they all shared a common set of proteins. We evaluated the biological response of cells cultured on the different matrices and compared them to cells on standard TCPS. The matrices lead to differential survival and gene-expression profiles among the cell types and as compared to TCPS, indicating that the cell-derived ECMs influence each cell type in a different manner. This general approach to understanding the protein composition of different tissue-specific and cell-derived ECM will inform the rational design of defined systems and biomaterials that recapitulate critical ECM signals for stem-cell culture and tissue engineering.

Graphical abstract

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Supramolecular biofunctional materials

Publication date: June 2017
Source:Biomaterials, Volume 129
Author(s): Jie Zhou, Jie Li, Xuewen Du, Bing Xu
This review discusses supramolecular biofunctional materials, a novel class of biomaterials formed by small molecules that are held together via noncovalent interactions. The complexity of biology and relevant biomedical problems not only inspire, but also demand effective molecular design for functional materials. Supramolecular biofunctional materials offer (almost) unlimited possibilities and opportunities to address challenging biomedical problems. Rational molecular design of supramolecular biofunctional materials exploit powerful and versatile noncovalent interactions, which offer many advantages, such as responsiveness, reversibility, tunability, biomimicry, modularity, predictability, and, most importantly, adaptiveness. In this review, besides elaborating on the merits of supramolecular biofunctional materials (mainly in the form of hydrogels and/or nanoscale assemblies) resulting from noncovalent interactions, we also discuss the advantages of small peptides as a prevalent molecular platform to generate a wide range of supramolecular biofunctional materials for the applications in drug delivery, tissue engineering, immunology, cancer therapy, fluorescent imaging, and stem cell regulation. This review aims to provide a brief synopsis of recent achievements at the intersection of supramolecular chemistry and biomedical science in hope of contributing to the multidisciplinary research on supramolecular biofunctional materials for a wide range of applications. We envision that supramolecular biofunctional materials will contribute to the development of new therapies that will ultimately lead to a paradigm shift for developing next generation biomaterials for medicine.



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Monitoring and visualizing microRNA dynamics during live cell differentiation using microRNA-responsive non-viral reporter vectors

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Hideyuki Nakanishi, Kenji Miki, Kaoru R. Komatsu, Masayuki Umeda, Megumi Mochizuki, Azusa Inagaki, Yoshinori Yoshida, Hirohide Saito
MicroRNA (miRNA) activity differs with cell type, suggesting it can be used as a cell marker. In this study, we developed novel miRNA–responsive non-viral reporter vectors to continuously monitor and visualize miRNA dynamics during differentiation and to efficiently purify target living cells. Each vector codes miRNA-responsive and reference reporter genes in a single mRNA. These two genes are independent modules but transcribed by a single promoter, which enables us to distinguish miRNA-mediated post-transcriptional repression from transcriptional repression. We generated stable, miRNA-responsive vector-containing human induced pluripotent stem cells (hiPSCs) using the piggyBac transposon or episomal vectors. We could continuously monitor the differentiation status of living hiPSCs by detecting the activity of hiPSC-specific miRNA (miR-302a*). In addition, we could selectively sort hiPSC-derived cardiomyocytes using cardiomyocyte-specific miRNA (miR-208a or miR-1)-reporter vectors. Our miRNA reporter system provides a simple way to quantitatively and continuously monitor and visualize changes in the cellular state and should facilitate a broad range of studies that depend on cellular changes including drug discovery and cell-fate conversion.



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A positive feedback strategy for enhanced chemotherapy based on ROS-triggered self-accelerating drug release nanosystem

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Jing-Jing Hu, Qi Lei, Meng-Yun Peng, Di-Wei Zheng, Yi-Xuan Chen, Xian-Zheng Zhang
Here, a positive feedback strategy was utilized to amplify the concentration of intracellular reactive oxygen species (ROS) and a ROS-triggered self-accelerating drug release nanosystem (defined as T/D@RSMSNs) was demonstrated for enhanced tumor chemotherapy. The mesoporous silica nanoparticles (MSNs) based nanocarriers were gated by β-cyclodextrin (β-CD) through the ROS-cleavable thioketal (TK) linker to encapsulate the anticancer drug doxorubicin hydrochloride (DOX) and ROS producing agent α-tocopheryl succinate (α-TOS), whose surface was further anchored with adamantane conjugated poly(ethylene glycol) chain (AD-PEG) via host-guest interaction. It was found that in human breast cancer (MCF-7) cells, T/D@RSMSNs could not only release DOX and α-TOS initiatively, but also lead to increased concentration of intracellular ROS, which could be used as new trigger to cut away TK linkage and then in turn facilitate the further release of DOX for enhanced chemotherapy. Both in vitro and in vivo experiments demonstrated that T/D@RSMSNs exhibited more significant antitumor activity in the human breast cancer than the traditional single-DOX loaded ROS-responsive nanocarrier. This novel ROS-triggered self-accelerating drug release nanosystem with remarkably improved therapeutic effects could provide a general strategy to branch out the applications of existing ROS-responsive drug delivery systems (DDSs).

Graphical abstract

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The Phonological Unit of Japanese Kanji Compounds: A Masked Priming Investigation.

Author: Yoshihara, Masahiro; Nakayama, Mariko; Verdonschot, Rinus G.; Hino, Yasushi

DOI: 10.1037/xhp0000374

Publication Date: POST AUTHOR CORRECTIONS, 16 March 2017

http://ift.tt/2mZ2GAN

The Role of Error Processing in the Contextual Interference Effect During the Training of Perceptual-Cognitive Skills.

Author: Broadbent, David P.; Causer, Joe; Williams, A. Mark; Ford, Paul R.

DOI: 10.1037/xhp0000375

Publication Date: POST AUTHOR CORRECTIONS, 16 March 2017

http://ift.tt/2nBlNiF

Embodied Memory Allows Accurate and Stable Perception of Hidden Objects Despite Orientation Change.

Author: Pan, Jing Samantha; Bingham, Ned; Bingham, Geoffrey P.

DOI: 10.1037/xhp0000392

Publication Date: POST AUTHOR CORRECTIONS, 16 March 2017

http://ift.tt/2mYZSDS

Physical activity alters limb bone structure but not entheseal morphology

Publication date: June 2017
Source:Journal of Human Evolution, Volume 107
Author(s): Ian J. Wallace, Julia M. Winchester, Anne Su, Doug M. Boyer, Nicolai Konow
Studies of ancient human skeletal remains frequently proceed from the assumption that individuals with robust limb bones and/or rugose, hypertrophic entheses can be inferred to have been highly physically active during life. Here, we experimentally test this assumption by measuring the effects of exercise on limb bone structure and entheseal morphology in turkeys. Growing females were either treated with a treadmill-running regimen for 10 weeks or served as controls. After the experiment, femoral cortical and trabecular bone structure were quantified with μCT in the mid-diaphysis and distal epiphysis, respectively, and entheseal morphology was quantified in the lateral epicondyle. The results indicate that elevated levels of physical activity affect limb bone structure but not entheseal morphology. Specifically, animals subjected to exercise displayed enhanced diaphyseal and trabecular bone architecture relative to controls, but no significant difference was detected between experimental groups in entheseal surface topography. These findings suggest that diaphyseal and trabecular structure are more reliable proxies than entheseal morphology for inferring ancient human physical activity levels from skeletal remains.



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Evolutionary anatomy of the Neandertal ulna and radius in the light of the new El Sidrón sample

Publication date: May 2017
Source:Journal of Human Evolution, Volume 106
Author(s): Laura Pérez-Criado, Antonio Rosas
This paper aims to improve our understanding of the phylogenetic trait polarity related to hominin forearm evolution, in particular those traits traditionally defined as "Neandertal features." To this aim, twelve adult and adolescent fragmented forelimb elements (including ulnae and radii) of Homo neanderthalensis recovered from the site of El Sidrón (Asturias, Spain) were examined comparatively using three-dimensional geometric and traditional morphometrics. Mean centroid size and shape comparisons, principal components analysis, and phylogenetic signal analysis were undertaken. Our investigations revealed that the proximal region of the ulna discriminated best between Neandertals and modern humans, with fewer taxonomically-informative features in the distal ulna and radius. Compared to modern humans, the divergent features in the Neandertal ulna are an increase in olecranon breadth (a derived trait), lower coronoid length (primitive), and anterior orientation of the trochlear notch (primitive). In the Neandertal radius, we observe a larger neck length (primitive), medial orientation of the radial tubercle (secondarily primitive), and a curved diaphysis (secondarily primitive). Anatomically, we identified three units of evolutionary change: 1) the olecranon and its fossa, 2) the coronoid–radius neck complex, and 3) the tubercle and radial diaphysis. Based on our data, forearm evolution followed a mosaic pattern in which some features were inherited from a pre-Homo ancestor, others originated in some post-ergaster and pre-antecessor populations, and other characters emerged in the specific Homo sapiens and H. neanderthalensis lineages, sometimes appearing as secondarily primitive. Future investigations might consider the diverse phylogenetic origin of apomorphies while at the same time seeking to elucidate their functional meaning.



http://ift.tt/2n7r1Vi

An updated age for the Xujiayao hominin from the Nihewan Basin, North China: Implications for Middle Pleistocene human evolution in East Asia

Publication date: May 2017
Source:Journal of Human Evolution, Volume 106
Author(s): Hong Ao, Chun-Ru Liu, Andrew P. Roberts, Peng Zhang, Xinwen Xu
The Xujiayao site in the Nihewan Basin (North China) is one of the most important Paleolithic sites in East Asia. Twenty Homo fossils, which were previously assigned to an archaic Homo sapiens group, have been excavated along with more than 30,000 lithic artifacts and ∼5000 mammalian fossil specimens. Dating of the Xujiayao hominin has been pursued since its excavation in the 1970s, but its age has remained controversial because of limitations of the dating techniques that have been applied to available materials. Here, we report new ages for the Xujiayao hominin based on combined electron spin resonance (ESR) dating of quartz in the sediments and high-resolution magnetostratigraphy of the fluvio-lacustrine sequence. The magnetostratigraphy suggests that the upper Matuyama and Brunhes polarity chrons are recorded at Xujiayao. The ESR dating results indicate a pooled average age of 260–370 ka for the Homo-bearing layer, which is consistent with its position within the middle Brunhes normal polarity chron indicated by magnetostratigraphy. This age estimate makes the Xujiayao hominin among the oldest mid-Pleistocene hominins with derived Neanderthal traits in East Asia. This age is consistent with the time when early Denisovans, a sister group of Neanderthals, appeared and colonized eastern Eurasia. Our updated age and the Neanderthal-like traits of the Xujiayao Homo fossils, particularly the Denisovan-like molar teeth, make it possible that the Xujiayao hominin could represent an early Denisovan.



http://ift.tt/2mS2cKU

Another look at the foramen magnum in bipedal mammals

Publication date: April 2017
Source:Journal of Human Evolution, Volume 105
Author(s): Gabrielle A. Russo, E. Christopher Kirk
A more anteriorly positioned foramen magnum evolved in concert with bipedalism at least four times within Mammalia: once in macropodid marsupials, once in heteromyid rodents, once in dipodid rodents, and once in hominoid primates. Here, we expand upon previous research on the factors influencing mammalian foramen magnum position (FMP) and angle with four new analyses. First, we quantify FMP using a metric (basioccipital ratio) not previously examined in a broad comparative sample of mammals. Second, we evaluate the potential influence of relative brain size on both FMP and foramen magnum angle (FMA). Third, we assess FMP in an additional rodent clade (Anomaluroidea) containing bipedal springhares (Pedetes spp.) and gliding/quadrupedal anomalures (Anomalurus spp.). Fourth, we determine the relationship between measures of FMP and FMA in extant hominoids and an expanded mammalian sample. Our results indicate that bipedal/orthograde mammals have shorter basioccipitals than their quadrupedal/non-orthograde relatives. Brain size alone has no discernible effect on FMP or FMA. Brain size relative to palate size has a weak influence on FMP in some clades, but effects are not evident in all metrics of FMP and are inconsistent among clades. Among anomaluroids, bipedal Pedetes exhibits a more anterior FMP than gliding/quadrupedal Anomalurus. The relationship between FMA and FMP in hominoids depends on the metric chosen for quantifying FMP, and if modern humans are included in the sample. However, the relationship between FMA and FMP is nonexistent or weak across rodents, marsupials, and, to a lesser extent, strepsirrhine primates. These results provide further evidence that bipedal mammals tend to have more anteriorly positioned foramina magna than their quadrupedal close relatives. Our findings also suggest that the evolution of FMP and FMA in hominins may not be closely coupled.



http://ift.tt/2n7ow5B

A newly discovered galagid fossil from Nakali, an early Late Miocene locality of East Africa

Publication date: Available online 17 March 2017
Source:Journal of Human Evolution
Author(s): Yutaka Kunimatsu, Masato Nakatsukasa, Tetsuya Sakai, Mototaka Saneyoshi, Yoshihiro Sawada, Hideo Nakaya




http://ift.tt/2mS7iXC

Editorial Board

Publication date: March 2017
Source:Journal of Human Evolution, Volume 104





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Molecular defects identified by whole exome sequencing in a child with atypical mucopolysaccharidosis IIIB

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2n7cd9c

Leptin and adiponectin levels in discordant dichorionic twins at 72 hours of age-associations with anthropometric parameters and insulin resistance

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2mS0ARv

Clinical features of girls with short stature among inv (9), Turner (45, X) and control individuals

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2n7cBoj

Increase of body mass index (BMI) from 1.5 to 3 years of age augments the degree of insulin resistance corresponding to BMI at 12 years of age

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2n7cA3J

A cross-sectional survey of the nature and correlates of sleep disturbance in people with psoriasis

Abstract

Background

Research suggests that sleep disturbance is common in psoriasis. Despite 32 studies conducted in sleep, many demonstrate methodological flaws, often using unvalidated measurement, with no study examining multiple dimensions of sleep-wake functioning. Moreover, research has yet to comprehensively examine the range of physical and psychological factors that may affect sleep in people with psoriasis.

Objective

To characterise sleep disturbance using validated measures and identify physical and psychological predictors of sleep quality in people with psoriasis.

Methods

An online survey was conducted (n=186;M_age=39.2) comprising validated measures assessing sleep (Pittsburgh Sleep Quality Index [PSQI], Berlin Questionnaire, Pre-Sleep Arousal Scale), chronotype (Morningness-Eveningness Questionnaire), mood (Hospital Anxiety and Depression Scale), itch (5-D Itch Scale) and psoriasis severity (Simplified Psoriasis Index). Group comparisons and regression analyses were used to examine predictors of poor sleep.

Results

Mean PSQI score was 9.24 (SD=4.32), with 76.3% scoring above the threshold for poor sleep (≥ 6 on the PSQI) and 32.5% scoring 'positive' for probable obstructive sleep apnoea. Poor sleep and high likelihood of OSA was associated with more severe psoriasis (p<.05; η²=.07; η²=.005). Cognitive arousal (β=.264, p=.001), itch (β=.260, p<.001) and depression (β=.236, p=.001) were the most robust predictors of poor sleep quality which, together with somatic arousal (β=.168, p=.022), accounted for 43% of variance in PSQI scores.

Conclusions

Poor sleep is common in psoriasis and associated with psychological and physical factors. Rates of probable obstructive sleep apnoea are also high. Given the importance of restorative sleep for health, sleep complaints should receive greater clinical attention in the management of psoriasis.

This article is protected by copyright. All rights reserved.

http://ift.tt/2mECM2B

A chronic recurrent disease course of dermatomyositis is associated with autoantibodies against TIF1γ

Abstract

Dermatomyositis (DM) is a rare autoimmune disease with high clinical variability in terms of cutaneous and muscle involvement as well as disease duration. DM severely impacts the quality of life of the patients and may be life threatening. This is primarily due to lung involvement and the 3.0 to 7.7 fold increased relative risk for cancer compared to the general adult population^1;2.

This article is protected by copyright. All rights reserved.

http://ift.tt/2mc3cfQ

Sorption and desorption of silver ions by bentonite clays

Abstract

Anthropogenic activities have increased the concentration of metal species in the environment. The toxicity of silver ions to aquatic and terrestrial organisms has required monitoring by analytical methods, besides actions to promote its control as pollutant. Sorption and desorption processes are directly related to the mobility and availability of metal ions in the environment. In this context, clay minerals can be used for pre-concentration, removal and recovery of silver ions from aqueous solution. Herein, two bentonite clays (BaVC-1 and SWy-2) were characterised and applied to investigate the sorption and desorption of silver ions. Isotherms were fitted to the dual-mode Langmuir-Freundlich model to qualify and quantify sorption sites and evaluate the mobilisation process. The maximum sorption capacity was 743 and 849 meq kg⁻¹ for BaVC-1 and SWy-2, respectively. Hysteresis index (HI) and mobilisation factor (MF) suggest that the desorption of silver ions in BaVC-1 is about four times more conducive compared to that in SWy-2, although both materials have demonstrated a great potential for Ag⁺ pre-concentration from aqueous solutions.

http://ift.tt/2mc1TNY

Dynamics of biochemical properties associated with soil nitrogen mineralization following nitrification inhibitor and fungicide applications

Abstract

Agrochemical applications may have side effects on soil biochemical properties related to soil nitrogen (N) mineralization and thus affect N cycling. The present study aimed to evaluate the effects of nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) and fungicide iprodione on soil neutral protease (NPR), alkaline protease (APR), chitinase (CHI), and their functional genes (nprA, aprA, and chiA) related to soil N mineralization. The following four treatments were included: blank control (CK), single DMPP application (DAA), weekly iprodione applications (IPR), and the combined applications of DMPP and iprodione (DI). Compared with the CK treatment, DMPP application significantly inhibited the CHI activity in the first 14 days of incubation, and iprodione applications, particularly when applied alone, decreased the NPR, APR, and CHI activities. Relative to the IPR treatment, extra DMPP application had the potential to alleviate the inhibitory effects of iprodione on the activities of these enzymes. DMPP application significantly increased aprA gene abundances after 14 days of incubation. However, repeated iprodione applications, alone or with the DMPP, decreased nprA and chiA gene abundances. Relative to the CK treatment, DMPP application generated negligible effects on the positive/negative correlations between soil enzyme activities and the corresponding functional gene abundances. However, the positive correlation between the CHI activity and chiA gene abundance was changed to negative correlation by repeated iprodione applications, alone or together with the DMPP. Our results demonstrated that agrochemical applications, particularly repeated fungicide applications, can have inadvertent effects on enzyme activities and functional gene abundances associated with soil N mineralization.

http://ift.tt/2mEwJuZ

A preliminary investigation of noise impact within metro stations in the urban city of Guangzhou, China

Abstract

The noise in the metro station is synthesized from a variety of different noise sources. Excessive noise exposure will bring serious impacts on humans' health. To alleviate the shortage of the urban land, most metro stations are planning to develop convenience stores and shopping malls. In order to evaluate the potential noise impact on humans' comfort in the metro stations, this study selected four representative stations of Guangzhou Metro Line 1 to carry out a preliminary questionnaire survey of 226 respondents for the perception and perform a noise measurement. Additionally, platform screen doors as a potential method for noise mitigation were examined. The results show that the noise caused by trains was dominant in the metro stations; however, the noise impact by public broadcast and passengers cannot be ignored. The noise levels of the transfer stations were obviously greater than the normal stations, especially during the peak hours. In addition, people in the metro stations have potential exposure to noise that the noise levels exceed the criteria limit of China, which would bring discomfort for humans; however, the normal activities of people would not be impacted. The platform screen doors should be further improved or relevant noise mitigation methods should be taken into account to reduce the noise level within the criteria limit.

http://ift.tt/2mbIzAA

Degradation of n -alkanes and PAHs from the heavy crude oil using salt-tolerant bacterial consortia and analysis of their catabolic genes

Abstract

In the present study, salt-tolerant strains, Dietzia sp. HRJ2, Corynebacterium variabile HRJ4, Dietzia cinnamea HRJ5 and Bacillus tequilensis HRJ6 were isolated from the Dagang oil field, China. These strains degraded n-alkanes and polycyclic aromatic hydrocarbons (PAHs) aerobically from heavy crude oil (HCO) in an experiment at 37 °C and 140 rpm. The GC/MS investigation for degradation of different chain lengths of n-alkanes (C8–C40) by individual strains showed the highest degradation of C8–C19 (HRJ5), C20–C30 (HRJ4) and C31–C40 (HRJ5), respectively. Moreover, degradation of 16 PAHs with individual strains demonstrated that the bicyclic and pentacyclic aromatic hydrocarbons (AHs) were mostly degraded by HRJ5, tricyclic and tetracyclic AHs by HRJ6 and hexacyclic AHs by HRJ2. However, the highest degradation of total petroleum hydrocarbons (TPHs), total saturated hydrocarbons (TSH), total aromatic hydrocarbons (TAH), n-alkanes (C8–C40) and 16 PAHs was achieved by a four-membered consortium (HRJ2 + 4 + 5 + 6) within 12 days, with the predominance of HRJ4 and HRJ6 strains which was confirmed by denaturing gradient gel electrophoresis. The abundance of alkB and nah genes responsible for catabolism of n-alkanes and PAHs was quantified using the qPCR. Maximum copy numbers of genes were observed in HRJ2 + 4 + 5 + 6 consortium (gene copies l⁻¹) 2.53 × 10⁴ (alkB) and 3.47 × 10³ (nah) at 12 days, which corresponded to higher degradation rates of petroleum hydrocarbons. The superoxide dismutase (SOD) (total SOD (T-SOD), Cu²⁺Zn²⁺-SOD), catalase (CAT) and ascorbate peroxidase (APX) activities in Allium sativum and Triticum aestivum were lower in the HRJ2 + 4 + 5 + 6-treated HCO as compared to the plantlets exposed directly to HCO. The present results revealed the effective degradation of HCO-contaminated saline medium using the microbial consortium having greater metabolic diversity.

http://ift.tt/2mEEbGz

Exploiting fruit byproducts for eco-friendly nanosynthesis: Citrus × clementina peel extract mediated fabrication of silver nanoparticles with high efficacy against microbial pathogens and rat glial tumor C6 cells

Abstract

Process byproducts from the fruit industry may represent a cheap and reliable source of green reducing agents to be used in current bio-nanosynthesis. This study reports the use of orange (Citrus × clementina) peel aqueous extract (OPE) for one-pot green synthesis of silver nanoparticles (AgNPs) with high effectiveness against various microbial pathogens as well as rat glial tumor C6 cells. The effects of various operational parameters on the synthesis of AgNPs were systematically investigated. The morphology, particle size, and properties of synthesized AgNPs were characterized using UV–visible spectroscopy, x-ray diffraction, x-ray photoelectron spectroscopy, field emission scanning electron microscopy, energy-dispersive x-ray spectroscopy, and Fourier transform infrared spectroscopy. High-resolution transmission electron microscopy shows that the nanoparticles are mostly spherical in shape and monodispersed, with an average particle size of 15–20 nm. Notably, the OPE-synthesized AgNPs were stable up to 6 months without change in their properties. Low doses of OPE-AgNPs inhibited the growth of human pathogens Escherichia coli, Bacillus cereus, and Staphylococcus aureus. The minimum inhibitory concentration and minimum bactericidal concentration of AgNPs against selected pathogenic bacteria were determined. OPE-AgNPs exhibited strong antioxidant activity in terms of ABTS (2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)) radical scavenging (IC₅₀ 49.6 μg/mL) and DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging (IC₅₀ 63.4 μg/mL). OPE-AgNPs showed dose-dependent response against rat glial tumor C6 cells (LD₅₀ 60 μg/mL) showing a promising potential as anticancer agents. Overall, the current investigation highlighted a cheap green technology route to synthesize AgNPs using OPE byproducts and could potentially be utilized in biomedical, cosmetic, and pharmaceutical industry.

http://ift.tt/2mbOPZe

Determination of heavy metals in muscle tissue of six fish species with different feeding habits from the Danube River, Belgrade—public health and environmental risk assessment

Abstract

The aim of this study was to investigate the presence of heavy metals/metalloids (Pb, Cd, Hg, Cu, Fe, Zn, As) in the muscle tissue of fish from the Danube River (two locations: Zemun and Grocka). For the purpose of heavy metal determination in fish muscle, 120 samples of six different fish species, Prussian carp, barbel, bream, carp, pike perch, and catfish were collected. For determining heavy metals, we used microwave oven digestion and atomic absorption spectrometer methods. The highest average content of Pb (0.084 ± 0.004 mg kg⁻¹), Cd (0.082 ± 0.003 mg kg⁻¹), Hg (0.466 ± 0.006 mg kg⁻¹), and As (0.333 ± 0.007 mg kg⁻¹) was found in the muscle of carp (an omnivorous fish) from Grocka, while the highest average level of Fe (13.60 ± 0.03 mg kg⁻¹) was deposited in bream (also omnivorous) from Zemun. Also, the average Cu level (1.62 ± 0.13 mg kg⁻¹) was the highest in catfish muscle (a carnivorous fish) from Grocka, while the highest Zn content (11.16 ± 0.17 mg kg⁻¹) was determined in muscle of Prussian carp (an omnivorous fish) from Zemun. The highest content of heavy metals (Cu, Fe, and Zn, respectively) in muscle of the six different types of fish from both locations was symmetrically arranged by species (catfish, barbel, and Prussian carp, respectively). Concentrations of Pb, Hg, and As in the Danube River fish muscle were under the maximum residual levels prescribed by the European Union (EU) and the maximum allowed concentrations (MAC) for Serbia. On the other hand, in all fish muscle from both locations (Zemun and Grocka), higher concentrations of Cd than prescribed (MAC) were found, with the exception of bream and pike perch.

http://ift.tt/2mbRCS1

Spatial distribution, ecological risk assessment, and potential sources of heavy metal(loid)s in surface sediments from the Huai River within the Bengbu section, China

Abstract

The Huai River is one of the major drinking water resources in Bengbu City of China's eastern Anhui Province. The study focused on extracting information for spatial distributions of heavy metal(loid)s (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) based on the contents of pollutants in 20 surface sediments. Geoaccumulation index and Hakanson potential ecological index were used to calculate the ecological risk of sediment environment in this paper. The I _geo results indicated that the sediments were moderately contaminated by Hg and Pb. The potential ecological risk sequence of the metals was Hg > Cd > Pb > Cu > Ni > Cr > Zn > As. Among the metal(loid)s, Hg was the main source of pollution that contributed ∼76% towards the potential ecological risk, followed by Cd. Finally, multivariate statistical analysis methods were conducted to identify the potential causes of pollution and provide basis for environment treatment in Bengbu Reach. The results depicted that Pb may be mainly derived from the traffic emission and manufacturing industry, while Hg may be originated from agricultural emissions.

http://ift.tt/2mEBhBv

Spatiotemporal variability in salinity and hydraulic relationship with salt intrusion in the tidal reaches of the Minjiang River, Fujian Province, China

Abstract

Salinity is one of the most important factors for tidal-affected water bodies including estuaries and tidal river reaches. However, due to the limitations of simultaneous manual monitoring in long-distance areas, studies of estuaries are preferred to tidal reaches. Hence, in this study, we investigated the tidal reach of the Minjiang River and five sets of field observations were used to determine the influence of saltwater intrusion in different seasons. During the dry and wet season with low discharge, the longitudinal salinity profiles showed that a station located about 45 km from the river mouth still suffered from saltwater intrusion especially when the upstream discharge was under 754 m³ s⁻¹, where the periodical fluctuation in the salinity remained the same with the water level, but there was a time lag of approximately 4 h compared with the discharge process. However, during the wet season in April and May 2016, the monitored salinity was approximately at the detectable limit of 0.02–0.04 ppt at the station close to the river mouth, which indicated that there was no saltwater exchange into the river, although dual flow directions were observed in the survey periods. The major differences among five survey periods were mainly related to upstream discharge rather than the seasons, the tidal range, and tidal excursion. The conclusions of this study have strategic importance for protecting water sources by guiding the government to assess the optimal freshwater release time and discharge rate to prevent saltwater entering the important tidal-affected river reaches.

http://ift.tt/2mbTwlF

Nipple reconstruction with complementary triangular flaps

Abstract

Background

Nipple reconstruction is a surgical procedure often performed after total breast reconstruction. The main limitation of all techniques is premature or excessive flattening of the reconstructed nipple. Over the past few years, we have modified the CV flap technique in order to increase the reconstructed nipple size and reduce premature flattening.

Methods

The modified technique proposes the addition of lateral and medial flaps which are drawn as two right triangles disposed symmetrically in a mirror-like fashion along the longitudinal axis. The symmetry between the two triangles allows the use of all the available height during creation of the new nipple. Once raised, flaps are rearranged into the shape of a nipple, trimmed only if necessary, and sutured. Diameter and projection of the reconstructed nipple were measured at 1 and 2 years and compared to immediate postoperative standard measures.

Results

Twenty-two patients underwent nipple reconstruction with this technique. Patients were followed up for 2 years. No complications were reported. Immediate postoperative standard measures of the reconstructed nipple were on average 1.3 cm in projection and 1.3 cm in diameter. After 1-year follow-up, the average projection was 0.61 cm ± 0.14 cm and the diameter was 1.13 ± 0.18 cm. After the 2-year follow-up, the average projection was 0.53 ± 0.16 and the diameter was 1.12 ± 0.18.

Conclusions

The modified nipple reconstruction technique herein presented is easy to perform and provides long-lasting results with a low risk of postoperative complications. Further studies to compare this technique with the traditional CV flap are warranted.

Level of Evidence: Level IV, therapeutic study.

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Effect of acidity of in-office bleaching gels on tooth sensitivity and whitening: a two-center double-blind randomized clinical trial

Abstract

Objectives

The study aimed to compare the tooth sensitivity (TS) and bleaching efficacy of two hydrogen peroxide gels with different pHs (acid pH [Pola Office, SDI] and the neutral pH [Pola Office+, SDI]) used for in-office bleaching.

Materials and methods

Fifty-four patients from Brazil and Chile, with right superior incisor darker than A2, were selected for this double-blind, split-mouth randomized trial. Teeth were bleached in two sessions, with 1-week interval. Each session had three applications of 8 min each, according to the manufacturer's instructions. The color changes were evaluated by subjective (Vita Classical and Vita Bleachedguide) and objective (Easy shade spectrophotometer) methods. Participants recorded TS with 0–10 visual analog scale. Color change in shade guide units (SGU) and ΔE was analyzed by Student's t test (α = 0.05). The absolute risk and intensity of TS were evaluated by McNemar's test and Wilcoxon-paired test, respectively (α = 0.05).

Results

All groups achieved the same level of whitening after 30 days of clinical evaluation. The use of a neutral in-office bleaching gel significantly decreases the absolute risk of TS (28%, 95% CI 18–41) and intensity of TS when compared to the acid bleaching gel (absolute risk of 50%, 95% CI 37–63).

Conclusion

The use of a neutral in-office bleaching agent gel produced the same whitening degree than an acid bleaching gel but with reduced risk and intensity of tooth sensitivity.

Clinical significance

Clinicians should opt to use in-office bleaching with a neutral gel than an acid product because the former causes a significant lower risk and intensity of tooth sensitivity.

http://ift.tt/2mDv3Sh

Fully automated VMAT treatment planning for advanced-stage NSCLC patients

Abstract

Purpose

To develop a fully automated procedure for multicriterial volumetric modulated arc therapy (VMAT) treatment planning (autoVMAT) for stage III/IV non-small cell lung cancer (NSCLC) patients treated with curative intent.

Materials and methods

After configuring the developed autoVMAT system for NSCLC, autoVMAT plans were compared with manually generated clinically delivered intensity-modulated radiotherapy (IMRT) plans for 41 patients. AutoVMAT plans were also compared to manually generated VMAT plans in the absence of time pressure. For 16 patients with reduced planning target volume (PTV) dose prescription in the clinical IMRT plan (to avoid violation of organs at risk tolerances), the potential for dose escalation with autoVMAT was explored.

Results

Two physicians evaluated 35/41 autoVMAT plans (85%) as clinically acceptable. Compared to the manually generated IMRT plans, autoVMAT plans showed statistically significant improved PTV coverage (V_95% increased by 1.1% ± 1.1%), higher dose conformity (R₅₀ reduced by 12.2% ± 12.7%), and reduced mean lung, heart, and esophagus doses (reductions of 0.9 Gy ± 1.0 Gy, 1.5 Gy ± 1.8 Gy, 3.6 Gy ± 2.8 Gy, respectively, all p < 0.001). To render the six remaining autoVMAT plans clinically acceptable, a dosimetrist needed less than 10 min hands-on time for fine-tuning. AutoVMAT plans were also considered equivalent or better than manually optimized VMAT plans. For 6/16 patients, autoVMAT allowed tumor dose escalation of 5–10 Gy.

Conclusion

Clinically deliverable, high-quality autoVMAT plans can be generated fully automatically for the vast majority of advanced-stage NSCLC patients. For a subset of patients, autoVMAT allowed for tumor dose escalation.

http://ift.tt/2mb3m7e

Cooperative inhibitory effects of uremic toxins and other serum components on OATP1B1-mediated transport of SN-38

Abstract

Purpose

Half-life of SN-38, an active metabolite of irinotecan, remarkably increases in patients with end-stage kidney disease (ESKD), even though SN-38 is excreted in bile. Uremic toxins (UTs), which accumulate in the serum of ESKD patients, were reported to inhibit organic anion-transporting polypeptide (OATP) 1B1-mediated uptake of SN-38; however, the relevance of this finding in a clinical setting is unknown. This study focused on cooperative effects of serum components and UTs on OATP1B1-mediated transport of SN-38.

Methods

Uptake of SN-38 by OATP1B1 was evaluated using cells stably expressing OATP1B1. Serum was obtained from > 400 ESKD patients undergoing hemodialysis. Deproteinized serum was combined with human serum albumin (HSA) to explore the effects of albumin-bound and unbound serum compounds.

Results

Uptake clearance of SN-38 in OATP1B1 cells decreased by 40% in the presence of uremic serum residue with albumin compared to that in the presence of normal serum residue. Additional UTs (3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, hippuric acid, indole-3-acetic acid, and 3-indoxyl sulfate) combined with normal serum residue in HSA decreased OATP1B1-mediated SN-38 transport by 32.1% compared to that in the presence of normal serum residue. The inhibitory effect of albumin-unbound fraction with UTs and normal serum residue was comparable to that of uremic serum residue, with an uptake decrease of 17.2% compared to that reported in the presence of normal serum residue.

Conclusions

Hepatic uptake of SN-38 via OATP1B1 decreases in ESKD patients through cooperative inhibitory effects of UTs and serum components.

http://ift.tt/2niuOQ9

Polymeric micelles as mighty nanocarriers for cancer gene therapy: a review

Abstract

Purpose

Gene therapy has shown extensive potential to treat human diseases occurring from the defection of genes like various types of cancers. The cationic polymers, as non-viral gene carriers, offer the ability to engineer carrier systems having customized features that can be adapted to suit any system. Upon polymeric micelle systems' core–shell structure, micelles can create the capacity to load genes/gene-drugs into the different micelle compartments, respectively.

Methods

The search will be managed in Pubmed, Medline, Cochrane library, Embase and Proquest for articles related to polymeric micelle-based gene delivery in order to cancer gene therapy using the accommodative search terms. A database of the first search of all search engines results will be made and repeated articles will be removed. After that, the related articles will be selected, and also the references of selected articles will be searched in order to find any other articles to complete the search database.

Results

This study reviews kinds of polymeric nanomicelles, which have been used in gene therapy, critical parameters for micelle-based gene delivery, challenges and advantages/disadvantages as well as biosafety of nanomicelles in gene delivery systems. Furthermore, the discussion has focused on stimuli-responsive polymers and strategy and mechanisms regarding tumor-selective gene delivery.

Conclusions

This study provides an overview of the advantages/disadvantages of polymeric-based nanocarriers for cancer gene therapy.

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A phase I study of SAR405838, a novel human double minute 2 (HDM2) antagonist, in patients with solid tumours

Publication date: May 2017
Source:European Journal of Cancer, Volume 76
Author(s): Maja de Jonge, Vincent A. de Weger, Mark A. Dickson, Marlies Langenberg, Axel Le Cesne, Andrew J. Wagner, Karl Hsu, Wei Zheng, Sandrine Macé, Gilles Tuffal, Koruth Thomas, Jan H.M. Schellens
PurposeIn tumours with wild-type TP53, the tumour-suppressive function of p53 is frequently inhibited by HDM2. This phase I, dose-escalating study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics and pharmacodynamics of SAR405838, an HDM2 inhibitor, in patients with advanced solid tumours (NCT01636479).MethodsIn dose escalation, patients with any locally advanced/metastatic solid tumour with TP53 mutation prevalence below 40%, or documented as TP53 wild-type, were eligible. In the MTD expansion cohort, only patients with de-differentiated liposarcoma were included. Primary end-points were MTD and efficacy in the MTD expansion cohort. Secondary end-points included safety, pharmacokinetics and pharmacodynamics biomarkers.ResultsSeventy-four patients were treated with SAR405838 (50–800 mg once daily [QD], 800–1800 mg weekly and 1800 mg twice weekly). Two patients treated with SAR405838 400 mg QD had thrombocytopaenia as a dose-limiting toxicity (DLT). The MTD for the QD schedule of SAR405838 was 300 mg QD. No DLTs were observed with the weekly schedule; one patient had a DLT of nausea with the 1800 mg twice-weekly dose. Treatment with SAR405838 was associated with increased plasma MIC-1, reflecting p53 pathway activation. In the de-differentiated liposarcoma MTD cohort, 89% of the patients had HDM2 amplification at baseline and no TP53 mutations were observed; best response was stable disease in 56% and progression-free rate at 3 months was 32%.ConclusionSAR405838 had an acceptable safety profile with limited activity in patients with advanced solid tumours. The MTD of SAR405838 was 300 mg QD; MTD was not reached with the weekly schedule.



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Optimal dose reduction of FOLFIRINOX for preserving tumour response in advanced pancreatic cancer: Using cumulative relative dose intensity

Publication date: May 2017
Source:European Journal of Cancer, Volume 76
Author(s): Jong-chan Lee, Jin Won Kim, Soyeon Ahn, Hyoung Woo Kim, Jongchan Lee, Young Hoon Kim, Kyu-hyun Paik, Jaihwan Kim, Jin-Hyeok Hwang
BackgroundFOLFIRINOX has increased efficacy but also toxicity. Despite various modified FOLFIRINOX regimens, how much reduction is acceptable remains unclear. This study aimed to find the optimal relative dose intensity (RDI, %) of FOLFIRINOX that preserves tumour responses in patients with advanced pancreatic cancer (PC).MethodsWe reviewed 201 patients with PC treated with first-line FOLFIRINOX during 2012–2015. We established a modified Hryniuk model (http://www.rdicalc.com) and defined cumulative RDI (cRDI, %). The optimal cRDI thresholds for response rate (RR) and disease control rate (DCR) were assessed using receiver operating characteristic (ROC) analysis. Relationships between cRDI and haematologic toxicities (neutropenia and febrile neutropenia [FN]) were also analysed according to use of granulocyte colony-stimulating factor (G-CSF).ResultsAmong 156 eligible patients, 133 (48 locally advanced PC and 85 metastatic PC) completed initial treatment plan prior to the first radiological evaluation (median 58 days; 71.8% cRDI). For optimal cRDI thresholds, ROC curves showed a 71.2% cRDI for RR (83.3% sensitivity, 64.7% specificity, and 0.746 area under the curve [AUC]) and a 55.3% cRDI for DCR (93.6% sensitivity, 62.5% specificity and 0.805 AUC). Among 96 patients who did not receive prophylactic G-CSF, cRDI ≥80.1% was a significant predictor for frequent FN (73.7% sensitivity, 72.7% specificity and 0.793 AUC). There was no correlation between cRDI and haematologic toxicities in patients receiving prophylactic G-CSF.ConclusionTo preserve optimal RR and DCR in advanced PC, cRDI values for FOLFIRINOX >70% and >55%, respectively, are recommended. If cRDI is >80%, primary G-CSF prophylaxis is needed.



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Denosumab in advanced/unresectable giant-cell tumour of bone (GCTB): For how long?

Publication date: May 2017
Source:European Journal of Cancer, Volume 76
Author(s): E. Palmerini, N.S. Chawla, S. Ferrari, M. Sudan, P. Picci, E. Marchesi, M. Piccinni Leopardi, I. Syed, K.K. Sankhala, P. Parthasarathy, W.E. Mendanha, M. Pierini, A. Paioli, S.P. Chawla
BackgroundGiant-cell tumours of bone (GCTB) are RANK/RANK-ligand (RANKL) positive, aggressive and progressive osteolytic tumours. Denosumab, a RANKL inhibitor, was FDA-approved for adults and skeletally mature adolescents with unresectable GCTB or when surgical resection is likely to result in severe morbidity. Data on long-term toxicity and activity of denosumab monthly 'GCTB-schedule' (120 mg per 12/year, 1440 mg total dose/year) are lacking.MethodsPatients with GCTB receiving denosumab, 120 mg on days 1, 8, 15, 29 and every 4 weeks thereafter, from 2006 to 2015 treated in two centres were included. Long-term toxicity was evaluated.Results: Ninety-seven patients were identified. 43 patients underwent resection of the tumour with a median time on denosumab treatment of 12 months (range 6–45 months). Fifty-four patients had unresectable GCTB's (male/female 23/31, median age 35 years [range: 13–76 years], 26% presented with lung metastases, 31% had primary tumor located to the spine, 63% were relapsed after previous surgery) with a median time on denosumab of 54 months (9–115 months). In the unresectable GCTB group, tumour control and clinical benefits were observed in all patients undergoing denosumab, whereas 40% of patients discontinuing denosumab had tumour progression after a median of 8 months (range 7–15 months).Adverse eventsOverall, six (6%) patients developed osteonecrosis of jaw (ONJ): 1/43 (2%) in the resectable group, 5/54 (9%) in the unresectable group, with a 5-year ONJ-free survival of 92% (95% CI 84–100). Only patients with prolonged treatment experienced mild peripheral neuropathy (6/54, 11%), skin rash (5/54, 9%), hypophosphataemia (2/54, 4%) and atypical femoral fracture (2/54, 4%).ConclusionsProlonged treatment with denosumab has sustained activity in GCTB, with a mild toxicity profile. The dose-dependent toxicity observed recommends a careful and strict monitoring of patients who need prolonged treatment. Decreased dose-intensity schedules should be further explored in unresectable GCTB.



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Influenza vaccination in adult patients with solid tumours treated with chemotherapy

Publication date: May 2017
Source:European Journal of Cancer, Volume 76
Author(s): Albert Vollaard, Imke Schreuder, Lizzy Slok-Raijmakers, Wim Opstelten, Guus Rimmelzwaan, Hans Gelderblom
Patients with solid tumours receiving chemotherapy are at risk for influenza complications. Yearly influenza vaccination is recommended to patients treated with chemotherapy. However, adherence to vaccination is low, most likely due to lack of data on efficacy, optimal timing and safety of vaccination. There is scarce evidence for the effectiveness of the influenza vaccine in adult patients with solid tumours and chemotherapy on reduction of pneumonia, decreased mortality and fewer interruptions of oncological treatment. A review of 20 non-randomised serological studies in adult patients with different cancer types and chemotherapy provides insight in general trends of response to vaccination. Overall, the magnitude of the antibody response after influenza vaccination (i.e. seroconversion) can be lower than in healthy controls, but the majority of patients with solid tumours is able to mount a timely, protective immunological response (i.e. seroprotection) regardless of chemotherapy schedule, similar to healthy controls. Small sample sizes, patient heterogeneity and lack of comparable study designs limit more specific recommendations related to cancer type and optimal timing of vaccination. The inactivated influenza vaccine is safe to administer to immunosuppressed patients; side-effects are similar to those in healthy individuals. Although vaccination before start of chemotherapy is preferred to ensure optimal protection in adults with solid tumours, also vaccination during chemotherapy can reduce influenza-related complications considering the overall trends in serological response. Given the increased morbidity and mortality of influenza, influenza vaccination should be advocated as an inexpensive and safe preventive measure in patients with solid tumours receiving chemotherapy.



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Immune cells and mediators involved in the inflammatory responses induced by a P-I metalloprotease and a phospholipase A2 from Bothrops atrox venom

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Danilo L. Menaldo, Carolina P. Bernardes, Karina F. Zoccal, Anna L. Jacob-Ferreira, Tássia R. Costa, Maria P.F.M. Del Lama, Rose M.Z.G. Naal, Fabiani G. Frantz, Lúcia H. Faccioli, Suely V. Sampaio
Bothrops envenomations can promote severe inflammatory responses by inducing edema, pain, leukocyte recruitment and release of chemical mediators by local cells. In the present study, two toxins from Bothrops atrox venom (the P-I metalloprotease Batroxase and the acidic phospholipase A2 BatroxPLA2) were evaluated in relation to their inflammatory effects induced in vivo and in vitro, mainly focusing on the participation of different immune cells and inflammatory mediators. Both toxins mainly promoted acute inflammatory responses with significant recruitment of neutrophils in the early hours (1–4h) after administration into the peritoneal cavity of C57BL/6 mice, and increased infiltration of mononuclear cells especially after 24h. Among the mediators induced by both toxins are IL-6, IL-10 and PGE2, with Batroxase also inducing the release of L-1β, and BatroxPLA2 of LTB4 and CysLTs. These responses pointed to possible involvement of immune cells such as macrophages and mast cells, which were then evaluated in vitro. Mice peritoneal macrophages stimulated with Batroxase produced significant levels of IL-6, IL-1β, PGE2 and LTB4, whereas stimulus with BatroxPLA2 induced increases of IL-6, PGE2 and LTB4. Furthermore, both toxins were able to stimulate degranulation of RBL-2H3 mast cells, but with distinct concentration-dependent effects. Altogether, these results indicated that Batroxase and BatroxPLA2 promoted local and acute inflammatory responses related to macrophages and mast cells and to the production of several mediators. Our findings should contribute for better understanding the different mechanisms of toxicity induced by P-I metalloproteases and phospholipases A2 after snakebite envenomations.



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JAK inhibitors in dermatology: The promise of a new drug class

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): William Damsky, Brett A. King
New molecularly targeted therapeutics are changing dermatologic therapy. Janus kinase–signal transducer and activator of transcription (JAK-STAT) is an intracellular signaling pathway upon which many different proinflammatory signaling pathways converge. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators, which rely on JAK-STAT signaling, and inhibition of this pathway using JAK inhibitors might be a useful therapeutic strategy for these diseases. Growing evidence suggests that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis, and vitiligo. Additional evidence suggests that JAK inhibition might be broadly useful in dermatology, with early reports of efficacy in several other conditions. JAK inhibitors can be administered orally or used topically and represent a promising new class of medications. The use of JAK inhibitors in dermatology is reviewed here.



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Infraorbital cutaneous horn

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): Divya Shenoy, Joy King, Julie P. Wyatt, Robert T. Brodell




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Table of Contents

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4





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Antimalarial therapy for granuloma annulare: Results of a retrospective analysis

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): Sungat K. Grewal, Courtney Rubin, Misha Rosenbach




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Information for Readers

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4





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JAAD Case Reports Article List

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4





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Can mindfulness-based interventions improve the quality of life of patients with moderate/severe alopecia areata? A prospective pilot study

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): Rosella Gallo, Carlo Chiorri, Giulia Gasparini, Alessio Signori, Anna Burroni, Aurora Parodi




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Journal Based CME Instructions and Information

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4





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Beyond JAAD April 2017: Articles of interest to dermatologists from the nondermatologic literature

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): Andrew Bronin, Robert Phelps, Robert Sidbury




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The role of imaging in the management of patients with nonmelanoma skin cancer

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): Deborah MacFarlane, Komal Shah, Ashley Wysong, Ximena Wortsman, Tatyana R. Humphreys
While uncomplicated cases of nonmelanoma skin cancer can be treated with surgery, destruction, or topical therapy alone, advanced or neglected cases require more complex management decisions. Dermatologists and dermatologic surgeons should be familiar with the imaging techniques relevant to cutaneous oncology and their value in different clinical scenarios. Herein we review imaging modalities used in management of nonmelanoma skin cancer.



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Editorial Board

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4





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CME examination

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4





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Clinicopathologic analysis of atypical hand, foot, and mouth disease in adult patients

Publication date: April 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 4
Author(s): Julie Second, Charles Velter, Sophie Calès, François Truchetet, Dan Lipsker, Bernard Cribier
BackgroundHand, foot, and mouth disease is a contagious viral infection usually affecting children. A resurgence of cases in adults, mainly caused by coxsackievirus A6 and with an atypical and more severe presentation, has taken place.ObjectiveThe goal was to examine the clinical, histologic, and immunohistochemical features of this disease in adults.MethodsThis is a retrospective study on documented cases of adult hand, foot, and mouth disease from France's Dermatology Department of Strasbourg University Hospital and Bel-Air Hospital in Thionville.ResultsSix patients with severe and atypical presentation were included, 4 caused by coxsackievirus A6. The histologic features were: spongiosis, neutrophilic exocytosis, massive keratinocyte necrosis, shadow cells in the upper epidermis, vacuolization of basal cells, necrotic cells in follicles and sweat glands, dense superficial dermal infiltrate of CD3⁺ lymphocytes, and strong granulysin expression.LimitationsThis is a retrospective case series.ConclusionIn adult patients presenting with atypical hand, foot, and mouth disease caused by coxsackievirus A6, biopsy specimens show distinctive changes in the epidermis but also in adnexal structures. The inflammatory infiltrate is made of T cells with a cytotoxic profile, with numerous granulysin-positive cells, as observed in severe drug-induced eruption with necrosis of keratinocytes.



http://ift.tt/2mRHs68