bluuebunny/crossref_metadata_2025 huggingface dataset:
Central‐local Relations and Renewable Energy Policy Implementation in a Developing Country
Authors: Marquardt Jens
Published: May 2017

Implementing renewable energy policies is a complex governance challenge that involves numerous jurisdictional levels. Transforming an energy system towards renewables requires not only top‐down activities from the central government, but also bottom‐up developments at subnational jurisdictions. This article investigates how complex multi‐level governance arrangements affect renewable energy policy implementation in a developing country. Speaking to current conceptual debates in multi‐level governance research, insights from pluralist power theories are incorporated into a multi‐level governance framework to investigate the role of governance structures, resources and capacities. The approach is applied exemplarily to discuss the implementation of the Philippine Renewable Energy Act. The national government struggles to implement this law due to powerful local authorities. Political factors such as unclear responsibilities, conflicting regulations, weak local capacity, a lack of awareness for national intentions and missing consultation are identified as major obstacles for renewable energy policy implementation. Results are primarily derived from documents and qualitative expert interviews. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
On the Necessity of an Integrated, Participative and Adaptive Approach to Sustainable Urban Environmental Quality Planning
Authors: van Stigt Rien , Driessen Peter , Spit Tejo
Published: May 2017

Based on a review of recent literature, this paper addresses the question of how urban planners can steer urban environmental quality, given the fact that it is multidimensional in character, is assessed largely in subjective terms and varies across time. A novel perspective of urban environmental quality is proposed, simultaneously exploring three questions that are at the core of planning and designing cities: ‘quality of what?’, ‘quality for whom?’ and ‘quality at what time?’. The dilemmas that urban planners face in answering these questions are illustrated using secondary material. This approach provides perspectives for action. Rather than further detailing the exact nature of urban quality, it calls for sustainable urban environmental quality planning that is integrated, participative and adaptive. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
NK cells generate memory‐type responses to human cytomegalovirus‐infected fibroblasts
Authors: Newhook Nicholas , Fudge Neva , Grant Michael
Published: May 2017

Natural killer (NK) cells are cytotoxic lymphocytes that selectively respond against abnormal cells. Human cytomegalovirus (HCMV) infection causes expansion of NKG2C+CD57+ NK cells in vivo and NKG2C+ NK cells proliferate when cultured with HCMV‐infected cells. This raises the possibility of an NK‐cell subset selectively responding against a specific pathogen and accruing memory. To test this possibility, we compared proliferation, natural cytotoxicity and interferon‐γ (IFN‐γ) production of NK cells from HCMV‐seropositive and HCMV‐seronegative individuals co‐cultured with HCMV‐infected or uninfected MRC‐5 cells. There was no significant difference in proliferation of NK cells from HCMV‐seropositive or seronegative individuals against uninfected MRC‐5 cells, but significantly more NK cells from the HCMV‐seropositive group proliferated in response to HCMV‐infected MRC‐5 cells. Natural cytotoxicity of NK cells against K562 cells increased following co‐culture with HCMV‐infected versus uninfected MRC‐5 only for the HCMV‐seropositive group. After co‐culture with HCMV‐infected MRC‐5 cells, proliferating NK cells from HCMV‐seropositive donors selectively produced IFN‐γ when re‐exposed to HCMV‐infected MRC‐5 cells. Both NKG2C+ and NKG2C− NK cells proliferated in co‐culture with HCMV‐infected MRC‐5 cells, with the fraction of proliferating NKG2C+ NK cells directly correlating with the circulating NKG2C+ fraction. These data illustrate an at least partly NKG2C‐independent human NK‐cell memory‐type response against HCMV.
Gram‐Negative Extremophile Lipopolysaccharides: Promising Source of Inspiration for a New Generation of Endotoxin Antagonists
Authors: Di Lorenzo Flaviana , Billod Jean‐Marc , Martín‐Santamaría Sonsoles , Silipo Alba , Molinaro Antonio
Published: May 2017

Extremophiles are microorganisms exhibiting the fascinating capability to thrive in habitats that are considered clearly inhospitable. Extreme‐loving microorganisms have acquired ever‐increasing importance in the biomedical and pharmaceutical fields, with many of their bioactive products having long been used as life‐saving drugs. In this context, extremophile Gram‐negative bacterial lipopolysaccharides (LPSs) and their analogues offer many promising opportunities for a variety of biomedical and therapeutic applications. The structure‐dependent capability to elicit and to modulate host immune responses is surely the most intriguing feature of LPSs in the context of new drug discovery and design. This review offers an overview of the chemical peculiarities of LPSs isolated from extremophile bacteria, providing the most promising results relating to their biological activity. We discuss the pharmacologically important potential of extremophile LPSs as fundamental immunomodulatory compounds from the perspective of drug synthesis and development.
Croconaine Dyes – the Lesser Known Siblings of Squaraines
Authors: Lynch Daniel E. , Hamilton Darren G.
Published: May 2017

In the 50+ years since the first squaraine dye, made by using 3,4‐dihydroxycyclobut‐3‐ene‐1,2‐dione (squaric acid), was reported, numerous analogues have not only been made and published, but similarly, a number of good review articles on squaraine dyes has also been published. In contrast, for the majority of this time, reports of croconaine dyes, made by using 4,5‐dihydroxy‐4‐cyclopentene‐1,2,3‐trione (croconic acid), have also been published, but they have not received the same attention as squaraine dyes. Furthermore, the only known review of croconaine dyes, which was recently published, is written in Chinese. This current review aims to document the history of croconaine dyes since their first report in a German patent in 1970. This review sources both the scientific literature and published patents, and attention is given to both synthesis and spectroscopic details.
Synthesis of Functionalised 3‐Isochromanones by Silylcarbocyclisation/Desilylation Reactions
Authors: Albano Gianluigi , Morelli Martina , Aronica Laura Antonella
Published: May 2017

A new protocol for the synthesis of 3‐isochromanone derivatives based on rhodium‐promoted silylcarbocyclisation reactions of ethynylbenzyl alcohol with different arylsilanes is described. The structure of the isochromanone depends upon the reaction conditions used: when the reaction is carried out without base, (Z)‐4‐[(aryldimethylsilyl)methylene]isochroman‐3‐ones are obtained as major products. These compounds can be submitted to a desilylation/aryl migration reaction to give 4‐(arylmethyl)isochroman‐3‐ones in high yields. In contrast, in the presence of DBU (1,8‐diazabicyclo[5.4.0]undec‐7‐ene), hydrogenation of methyleneisochroman‐3‐ones takes place, and the corresponding β‐(silylmethyl)‐3‐isochromanones are formed. Moreover, when internal alkynes are treated with hydrosilanes under silylcarbocyclisation reaction conditions, alcoholysis of the hydrosilanes occurs exclusively.
Diastereoselective Hydrolysis of Branched Malonate Diesters by Porcine Liver Esterase: Synthesis of 5‐Benzyl‐Substituted Cα‐Methyl‐β‐proline and Catalytic Evaluation
Authors: Kotapati Hari Kiran , Robinson Jamarii D. , Lawrence Daniel R. , Fortner Kimberly R. , Stanford Caleb W. , Powell Douglas R. , Wardenga Rainer , Bornscheuer Uwe T. , Masterson Douglas S.
Published: May 2017

Malonate diesters with highly branched side chains containing a preexisting chiral center were prepared from optically pure amino alcohols and subjected to asymmetric enzymatic hydrolysis by Porcine Liver Esterase (PLE). Recombinant PLE isoenzymes have been utilized in this work to synthesize diastereomerically enriched malonate half‐esters from enantiopure malonate diesters. The diastereomeric excess of the product half‐esters was further improved in the later steps of synthesis either by simple recrystallization or flash column chromatography. The diastereomerically enriched half‐ester was transformed into a novel 5‐substituted Cα‐methyl‐β‐proline analogue (3R,5S)‐1c, in high optical purity employing a stereoselective cyclization methodology. This β‐proline analogue was tested for activity as a catalyst of the Mannich reaction. The β‐proline analogue derived from the hydrolysis reaction by the crude PLE appeared to catalyze the Mannich reaction between an α‐imino ester and an aldehyde providing decent to good diastereoselectivities. However, the enantioselectivities in the reaction was low. The second diastereomer of the 5‐benzyl‐substituted Cα‐methyl‐β‐proline, (3S,5S)‐1cwas prepared by enzymatic hydrolysis using PLE isoenzyme 3 and tested for its catalytic activity in the Mannich reaction. Amino acid, (3S,5S)‐1ccatalyzed the Mannich reaction between isovaleraldehyde and an α‐imino ester yielding the “anti” selective product with an optical purity of 99 %ee.
Combination of large‐volume sample stacking with an electroosmotic flow pump with field‐amplified sample injection on cross‐channel chips
Authors: Kitagawa Fumihiko , Ishiguro Tatsuya , Tateyama Misaki , Nukatsuka Isoshi , Sueyoshi Kenji , Kawai Takayuki , Otsuka Koji
Published: May 2017

A combination of two online sample concentration techniques, large‐volume sample stacking with an electroosmotic flow (EOF) pump (LVSEP) and field‐amplified sample injection (FASI), was investigated in microchip electrophoresis (MCE) to achieve highly sensitive analysis. By applying reversed‐polarity voltages on a cross‐channel microchip, anionic analytes injected throughout a microchannel were first concentrated on the basis of LVSEP, followed by the electrokinetic stacking injection of the analytes from a sample reservoir by the FASI mechanism. As well as the voltage application, a pressure was also applied to the sample reservoir in LVSEP‐FASI. The applied pressure generated a counter‐flow against the EOF to reduce the migration velocity of the stacked analytes, especially around the cross section of the microchannel, which facilitated the FASI concentration. At the hydrodynamic pressure of 15 Pa, 4520‐fold sensitivity increase was obtained in the LVSEP‐FASI analysis of a standard dye, which was 33‐times higher than that obtained with a normal LVSEP. Furthermore, the use of the sharper channel was effective for enhancing the sensitivity, e.g., 29 100‐fold sensitivity increase was achieved with the 75‐μm wide channel. The developed method was applied to the chiral analysis of amino acids in MCE, resulting in the sensitivity enhancement factor of 2920 for the separated d‐leucine.
How lethal concentration changes over time: Toxicity of cadmium, copper, and lead to the freshwater isopod Asellus aquaticus
Authors: Van Ginneken Marjolein , Blust Ronny , Bervoets Lieven
Published: May 2017

Metal pollution is a serious threat to environmental health. While the aquatic isopod Asellus aquaticus L. (Isopoda) is an important decomposer of freshwater ecosystems, very little research has reported its long-term or incipient lethal concentrations for metals. Moreover, the lethal concentrations at a certain percentage (LCxs) that can be found in the literature are often based on unmeasured concentrations, which could lead to a severe underestimation of the actual toxicity. In the present exploratory study, the 1-, 4-, 7-, and 14-d LC10, LC20, and LC50 values of copper, cadmium, and lead for adult A. aquaticus were determined. The LCx values were calculated using the nominal concentrations, the effective concentrations, and the free ion activities. Incipient lethal values were determined as well. In general, surprisingly lower lethal concentrations were found than in other studies. Furthermore, the present study shows that lethal concentrations based on free ion activities were generally much lower than nominal and effective concentrations. Although almost all LC values were higher than the environmental quality standards (EQS), the Cu 14-d LC10 and several (incipient) Pb LC10 and LC20 values, all calculated with free ion activities, were lower than the EQS. We conclude that lethal or effective concentrations based on free ion activities provide a more realistic view, which is vital for environmental policy making. Environ Toxicol Chem 2017;36:2849–2854. © 2017 SETAC
Heavy metal–induced toxicity in the Indian green frog: Biochemical and histopathological alterations
Authors: Jayawardena Uthpala Apekshani , Angunawela Preethika , Wickramasinghe Deepthi Devika , Ratnasooriya Wanigasekara Daya , Udagama Preethi Vidya
Published: May 2017

Heavy metal contamination may have adverse effects on wetland biota, particularly on amphibians. Severe immunotoxic effects elicited in Euphlyctis hexadactylus (Indian green frog) because of metal exposure (Cd, Cr, Cu, Pb, and Zn) in the Bellanwila-Attidiya Sanctuary, a polluted urban wetland in Sri Lanka, provided the rationale for the present study. We evaluated the biochemical and histopathological effects of this metal contamination with a reference E. hexadactylus population and a laboratory exposure group that was subjected to 28 d of exposure to a mixture of Cd, Cr, Cu, Pb, and Zn (5 ppm in each mixture). A histopathological scoring for the semiquantification of tissue damage was established. Results of the biochemical and histopathological markers were remarkably consistent between the 2 exposure scenarios, providing validation for the heavy metal exposure hypothesis. Damage to liver, kidney, lung, and skin of metal-exposed E. hexadactylus quantified multiple impairments absent in the reference frogs. Liver injuries complemented significantly elevated aspartate transaminase (AST), alanine transaminase (ALT), γ-glutamyl transferase (γ-GT), and alkaline phosphatases in frog liver homogenate, indicating hepatocellular leakage and loss of functional and structural integrity of the hepatocyte membrane in both field- and laboratory-exposed frogs. Significant elevation of Kupffer cell hypertrophy, pigmentation, inflammatory cell infiltrates and hepatic inflammation, extramedullary hematopoiesis, karyocytomegaly of hepatocytes (p < 0.05) of the liver, and degeneration of epithelia and necrosis of the lung, manifested as impairments in both metal exposure scenarios. Significantly reduced serum total protein and albumin and significantly elevated urea and creatinine in metal-exposed frogs were indicative of hepatic and renal dysfunction, respectively. The present study affirms histopathology-related biochemical alterations as potential biomarkers for heavy metal toxicity in amphibians. Environ Toxicol Chem 2017;36:2855–2867. © 2017 SETAC
Subcortical hyperintensities in the cholinergic system are associated with improvements in executive function in older adults with coronary artery disease undergoing cardiac rehabilitation
Authors: Santiago Calvin , Herrmann Nathan , Swardfager Walter , Saleem Mahwesh , Oh Paul I. , Black Sandra E. , Bradley Janelle , Lanctôt Krista L.
Published: May 2017

Objective

Coronary artery disease (CAD) is frequently accompanied by white matter hyperintensities and executive dysfunction. Because acetylcholine is important in executive function, these symptoms may be exacerbated by subcortical hyperintensities (SH) located in cholinergic (CH) tracts. This study investigated the effects of SH on cognitive changes in CAD patients undergoing a 48‐week cardiac rehabilitation program.

Methods

Fifty patients (age 66.5 ± 7.1 years, 84% male) underwent the National Institute of Neurological Disorders and Stroke – Canadian Stroke Network neurocognitive battery at baseline and 48 weeks. Patients underwent a 48‐week cardiac program and completed neuroimaging at baseline. Subcortical hyperintensities in CH tracts were measured using Lesion Explorer. Repeated measures general linear models were used to examine interactions between SH and longitudinal cognitive outcomes, controlling for age, education, and max VO2 change as a measure of fitness.

Results

In patients with SH in CH tracts, there was a significant interaction with the Trail Making Test (TMT) part A and part B over time. Patients without SH improved on average 16.6 and 15.0% on the TMT‐A and TMT‐B, respectively. Patients with SH on average showed no improvements in either TMT‐A or TMT‐B over time. There were no significant differences in other cognitive measures.

Conclusion

These results suggest that CAD patients with SH in CH tracts improve less than those without SH in CH tracts, over 48 weeks of cardiac rehabilitation. Thus, SH in CH tracts may contribute to longitudinal cognitive decline following a cardiac event and may represent a vascular risk factor of cognitive decline. © 2017 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.
Disrupted topological organization of structural networks revealed by probabilistic diffusion tractography in Tourette syndrome children
Authors: Wen Hongwei , Liu Yue , Rekik Islem , Wang Shengpei , Zhang Jishui , Zhang Yue , Peng Yun , He Huiguang
Published: May 2017

Tourette syndrome (TS) is a childhood‐onset neurobehavioral disorder. Although previous TS studies revealed structural abnormalities in distinct corticobasal ganglia circuits, the topological alterations of the whole‐brain white matter (WM) structural networks remain poorly understood. Here, we used diffusion MRI probabilistic tractography and graph theoretical analysis to investigate the topological organization of WM networks in 44 drug‐naive TS children and 41 age‐ and gender‐matched healthy children. The WM networks were constructed by estimating inter‐regional connectivity probability and the topological properties were characterized using graph theory. We found that both TS and control groups showed an efficient small‐world organization in WM networks. However, compared to controls, TS children exhibited decreased global and local efficiency, increased shortest path length and small worldness, indicating a disrupted balance between local specialization and global integration in structural networks. Although both TS and control groups showed highly similar hub distributions, TS children exhibited significant decreased nodal efficiency, mainly distributed in the default mode, language, visual, and sensorimotor systems. Furthermore, two separate networks showing significantly decreased connectivity in TS group were identified using network‐based statistical (NBS) analysis, primarily composed of the parieto‐occipital cortex, precuneus, and paracentral lobule. Importantly, we combined support vector machine and multiple kernel learning frameworks to fuse multiple levels of network topological features for classification of individuals, achieving high accuracy of 86.47%. Together, our study revealed the disrupted topological organization of structural networks related to pathophysiology of TS, and the discriminative topological features for classification are potential quantitative neuroimaging biomarkers for clinical TS diagnosis.Hum Brain Mapp 38:3988–4008, 2017. ©2017 Wiley Periodicals, Inc.
Clinical perineural invasion of the trigeminal and facial nerves in cutaneous head and neck squamous cell carcinoma: Outcomes and prognostic implications of multimodality and salvage treatment
Authors: Erkan Serkan , Savundra James M. , Wood Bradley , Acharya Aanand N. , Rajan Gunesh P.
Published: May 2017

Background

Clinical perineural invasion (PNI) of the trigeminal and facial nerves from cutaneous head and neck squamous cell carcinoma (cutaneous HNSCC) is a rare clinical entity that poses unique therapeutic challenges.

Methods

A retrospective chart review of a skull base oncology database was performed of patients with the diagnosis of clinical PNI from a cutaneous HNSCC. Patients who were previously untreated underwent multimodal treatment entailing surgical resection and postoperative radiotherapy (PORT) and patients who were previously treated with radiotherapy underwent salvage surgical resection between the years 2006 and 2012. Survival outcomes, such as disease‐free survival (DFS) and overall survival (OS), were analyzed and correlated with surgical factors, such as margin status, previous treatment, zone involvement, and trigeminal involvement (branch‐specific), as well as the pretreatment and posttreatment pain scores.

Results

Of 21 patients with clinical PNI from cutaneous HNSCC, 7 patients (33%) were previously treated for their disease with primary radiotherapy. Negative tumor margins were achieved in 18 patients (86%). Three of the 7 patients (43%) undergoing salvage surgery had positive margins. One‐year and 3‐year DFS for previously untreated patients was 91% and 67%, respectively, whereas 1‐year and 3‐year DFS was 72% and 28%, respectively, for the previously treated patients. Previous radiotherapy, ophthalmic nerve involvement, and positive margins portended poorer survival outcomes in this study.

Conclusion

The retrospective study of this rare clinical entity demonstrates that multimodal treatment can achieve favorable survival outcomes. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1280–1286, 2017
Robotic thyroidectomy and parathyroidectomy: An initial experience with retroauricular approach
Authors: Alshehri Mohammed , Mohamed Hossam Eldin , Moulthrop Thomas , Kandil Emad
Published: May 2017

Background

New approaches for robotic‐assisted thyroidectomy were recently described. The purpose of this study was to present the report of our initial experience using a retroauricular approach for thyroid and parathyroid surgeries.

Methods

This is a prospective study that was conducted under institutional review board approval and all surgeries were performed by a single surgeon at a North American academic institution. Some patients underwent an additional concomitant neck lift surgery in addition to the thyroid surgery. Some cases were performed without the use of the robot and they have been evaluated compared with the robotic cases. Clinical characteristics, total operative time, blood loss, surgical outcome, and length of hospital stay were evaluated.

Results

Forty cases representing thirty‐eight female patients were included in this study, which includes 37 thyroid lobectomies and 3 parathyroid surgeries. Mean age was 44 ± 13 years, and mean body mass index (BMI) was 26.9 ± 5.31. Mean thyroid nodule size was 2.01 ± 0.94 cm. All cases were completed successfully via a single retroauricular incision. There was no conversion to an open approach. Six of 38 patients underwent additional neck lift surgery with a mean total operative time of 189 ± 45 minutes. The mean operative time for the remaining 34 patients who underwent retroauricular robotic‐assisted hemithyroidectomy without neck lift surgery was 156 ± 39 minutes. Five patients underwent an endoscopic, retroauricular approach to the thyroid and parathyroid without using the robot. Two of 38 patients developed postoperative hematoma, in whom one of them needed a surgical evacuation. There were no cases of permanent vocal cord paralysis or permanent hypoparathyroidism. However, 2 patients developed transient hoarseness, which resolved 9 weeks and 10 weeks postoperatively, respectively. Mean blood loss was 19.0 ± 30.93 mL. Twenty‐one patients were discharged on the same day of surgery, 17 patients were discharged after an overnight stay, and the remaining 2 patients were discharged after 2 days.

Conclusion

Single‐incision retroauricular robotic hemithyroidectomy and parathyroidectomy can be safe and feasible and concomitant neck lift surgery can be offered in a select group of patients. In addition, the nonrobotic retroauricular approach can be performed safely; however, future studies are warranted to further evaluate the benefits and limitations of this novel robotic retroauricular surgical approach.
Delayed platelet recovery after allogeneic hematopoietic stem cell transplantation: Association with chronic graft‐versus‐host disease and survival outcome
Authors: Akahoshi Yu , Kimura Shun‐ichi , Gomyo Ayumi , Hayakawa Jin , Tamaki Masaharu , Harada Naonori , Kusuda Machiko , Kameda Kazuaki , Ugai Tomotaka , Wada Hidenori , Ishihara Yuko , Kawamura Koji , Sakamoto Kana , Sato Miki , Terasako‐Saito Kiriko , Kikuchi Misato , Nakasone Hideki , Kako Shinichi , Kanda Yoshinobu
Published: May 2017

Delayed platelet recovery (DPR) despite prompt neutrophil engraftment is frequently observed after allogeneic hematopoietic stem cell transplantation (HSCT). However, few studies have evaluated the risk factors and long‐term outcome. Therefore, we retrospectively analysed 219 adult patients who underwent their first allogenic HSCT with neutrophil engraftment. Of these 219 patients, 50 (22.8%) had DPR that was defined as relapse‐free survival at day 60 after HSCT without primary platelet recovery despite neutrophil engraftment. The results of a multivariate analysis showed that a high‐risk underlying disease (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.04‐5.48; P = .041) and human leukocyte antigen–mismatched HSCT (OR, 2.63; 95% CI, 1.28‐5.43; P = .009) were associated with an increased risk of DPR. In univariate analyses, the occurrence of DPR was significantly associated with inferior overall survival, high nonrelapse mortality, and a low incidence of chronic graft‐versus‐host disease (GVHD), despite a comparable relapse rate. In multivariate analyses, DPR was associated with inferior overall survival (hazard ratio [HR], 2.00; 95% CI, 1.23‐3.27; P = .005) and a low incidence of chronic GVHD (HR, 0.42; 95% CI, 0.22‐0.78; P = .002). In conclusion, DPR was a strong predictor of shorter survival but also less frequent chronic GVHD.
Impact of comorbidity on survival in peripheral T‐cell lymphomas: A Swedish Lymphoma Registry study
Authors: Ellin Fredrik , Jerkeman Mats , Törnqvist Jenny , Brudin Lars , Relander Thomas
Published: May 2017

Comorbidity impacts survival in B‐cell lymphoma patients, but the influence in peripheral T‐cell lymphomas (PTCLs) has been little studied. To investigate the impact of comorbidity on outcome in PTCL, we identified adult patients with newly diagnosed PTCL from 2000 to 2009 in the Swedish Lymphoma Registry. Data on comorbidity at diagnosis were retrospectively collected according to the Charlson Comorbidity Index (CCI). Comorbid conditions were present in 263 out of 694 (38%) patients. A CCI score of ≥2 was associated with inferior overall survival (OS) (hazard ratio [HR] 1.63, P < .001) and progression‐free survival (HR 1.54, P < .001) in multivariate analysis. In patients undergoing front‐line autologous stem cell transplantation (auto SCT), CCI >0 was associated with inferior OS (HR 2.40, P = .013). Chemotherapy regimens were classified as curative or low‐intensity treatments. Among patients aged ≥75 years (n = 214), low‐intensity and curative treatment groups had similar OS (HR 0.8, P = .6), also when adjusted for CCI. In summary, our results demonstrate CCI to be independently associated with survival in PTCLs. Even limited comorbidity impacted survival after front‐line auto SCT, which needs to be considered in treatment decisions. Intensive anthracycline‐based chemotherapy in elderly PTCL patients might be of limited benefit.
The use and design of the BSC in the health care sector: A systematic literature review for Italy, Spain, and Portugal
Authors: Gonzalez‐Sanchez Maria Beatriz , Broccardo Laura , Martins Pires Amélia Maria
Published: May 2017

The aim of this paper is to gain a better understanding of how the balanced scorecard (BSC) has evolved in Spain, Italy, and Portugal. It reviews all the articles on the BSC in the health care sector written between 1992 and 2015 by Spanish, Italian, or Portuguese authors and published in Spanish, Italian, or Portuguese as well as in English.

Our study first shows the state of knowledge on BSC in health care for a homogeneous group of Southern European countries. Second, it uncovers the perspectives, indicators, and generation used in the countries under observation to reveal the extent to which this management tool has evolved. Third, it analyses international variations in design and use within the health care context, especially in the United States. Moreover, it also highlights a number of important issues. The BSC is in its early stage of development in these 3 countries, which do not use it as a tool to implement strategy and align all of the elements that help integrate the organization.
A trial of oral corticosteroids for persistent systemic and airway inflammation in severe asthma
Authors: Oishi Keiji , Hirano Tsunahiko , Suetake Ryo , Ohata Syuichiro , Yamaji Yoshikazu , Ito Kosuke , Edakuni Nobutaka , Matsunaga Kazuto
Published: May 2017

Introduction

The fraction of exhaled nitric oxide (FeNO) and blood eosinophils, markers of local and systemic eosinophilic inflammation, respectively, are increased in asthmatic patients. Little is known concerning the relationship between the FeNO levels and blood eosinophils in asthmatics.

Methods

Twenty severe asthmatics with persistent FeNO elevation (≥40 ppb) and blood eosinophilia (≥3%) despite maintenance therapy including high‐daily‐dose inhaled corticosteroids were analyzed. We investigated the response of FeNO and blood eosinophils to systemic corticosteroids treatment and the change in Asthma Control Questionnaire (ACQ) according to differences in the response of FeNO and blood eosinophils to steroid.

Results

The changes in blood eosinophils were not correlated with the changes in FeNO levels by systemic steroid treatment (r = 0.37, P = 0.11). 50% of the subjects showed both ≥20% reductions in FeNO levels and blood eosinophils. There were significant differences in the ACQ score between the steroid response group and poor response group (P < 0.005). The group in which both FeNO and blood eosinophils were suppressed fulfilled the change in score of ≥0.5 on the ACQ.

Conclusions

In the patients with severe asthma, responses to systemic corticosteroids were variable in terms of FeNO and blood eosinophils. It was necessary to suppress both persistent eosinophilia and high FeNO for the improvement of asthma control.
Iron Metabolism and the Inflammatory Response
Authors: Martins Ana C. , Almeida Joana I. , Lima Illyane S. , Kapitão Antonino S. , Gozzelino Raffaella
Published: May 2017

Iron (Fe) is essential to almost all organisms, as required by cells to satisfy metabolic needs and accomplish specialized functions. Its ability to exchange electrons between different substrates, however, renders it potentially toxic. Fine tune‐mechanisms are necessary to maintain Fe homeostasis and, as such, to prevent its participation into the Fenton reaction and generation of oxidative stress. These are particularly important in the context of inflammation/infection, where restricting Fe availability to invading pathogens is one, if not, the main host defense strategy against microbial growth. The ability of Fe to modulate several aspects of the immune response is associated with a number of “costs” and “benefits”, some of which have been described in this review. © 2017 IUBMB Life, 69(6):442–450, 2017
Modulation of surface stiffness and cell patterning on polymer films using micropatterns
Authors: Sunami Hiroshi , Shimizu Yusuke , Denda Junko , Yokota Ikuko , Yoshizawa Tomokazu , Uechi Yukiko , Nakasone Hitoshi , Igarashi Yasuyuki , Kishimoto Hidehiro , Matsushita Masayuki
Published: May 2017

Here, a new technology was developed to selectively produce areas of high and low surface Young's modulus on biomedical polymer films using micropatterns. First, an elastic polymer film was adhered to a striped micropattern to fabricate a micropattern‐supported film. Next, the topography and Young's modulus of the film surface were mapped using atomic force microscopy. Contrasts between the concave and convex locations of the stripe pattern were obvious in the Young's modulus map, although the topographical map of the film surface appeared almost flat. The concave and convex locations of a polymer film supported by a different micropattern also contrasted clearly. The resulting Young's modulus map showed that the Young's modulus was higher at convex locations than at concave locations. Hence, regions of high and low stiffness can be locally generated based on the shape of the micropattern supporting the film. When cells were cultured on the micropattern‐supported films, NIH3T3 fibroblasts preferentially accumulated in convex regions with high Young's moduli. These findings demonstrate that this new technology can regulate regions of high and low surface Young's modulus on a cellular scaffold with high planar resolution, as well as providing a method for directing cellular patterning. © 2017 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 976–985, 2018.
An Anti‐Cancer Drug Candidate OSI‐027 and its Analog as Inhibitors of mTOR: Computational Insights Into the Inhibitory Mechanisms
Authors: Rehan Mohd
Published: May 2017

The mammalian target of rapamycin (mTOR) is a serine‐threonine kinase, which regulates cellular metabolism and growth, and is a validated therapeutic target in various cancers. Recently, OSI‐027, a selective ATP competitive inhibitor of mTOR, has been developed. The OSI‐027 is an orally bioavailable compound whose anti‐cancer activities were observed in various cancer cell lines and tumor xenograft models. The current study is the first attempt to explore the binding mode and the molecular‐interactions of OSI‐027 with mTOR using molecular docking and (un)binding simulation approaches. The study identified various interacting residues and their extent of involvement in binding was emphasized using different methods. The (un)binding simulation analyses provided snapshots of various phases in OSI‐027 binding and identified residues important for binding but away from the catalytic site. Further, to explore a better binder for mTOR among OSI‐027 analogs, the virtual screening led to propose an OSI‐027 analog with CID: 73294902 as a better inhibitor than the OSI‐027 and the native ligand PI‐103. The binding mode of the proposed compound is compared with those of OSI‐027 and other native inhibitors. The comparison of (un)binding simulation phases of proposed compound with that of OSI‐027 revealed that both, bound to the same catalytic site, follow different (un)binding path. Thus, the current study presents computational insights into the OSI‐027 mediated inhibition of mTOR kinase and proposed an OSI‐027 analog as better mTOR inhibitor, and thus, a good drug for further research in experimental laboratories. J. Cell. Biochem. 118: 4558–4567, 2017. © 2017 Wiley Periodicals, Inc.
Associations of muscle force, power, cross‐sectional muscle area and bone geometry in older UK men
Authors: Zengin Ayse , Pye Stephen R. , Cook Michael J. , Adams Judith E. , Rawer Rainer , Wu Frederick C.W. , O'Neill Terence W. , Ward Kate A.
Published: May 2017

Background

Ageing is associated with sarcopenia, osteoporosis, and increased fall risk, all of which contribute to increased fracture risk. Mechanically, bone strength adapts in response to forces created by muscle contractions. Adaptations can be through changes in bone size, geometry, and bending strength. Muscle mass is often used as a surrogate for muscle force; however, force can be increased without changes in muscle mass. Increased fall risk with ageing has been associated with a decline in muscle power—which is a measure of mobility. The aims of this study were as follows: (i) to investigate the relationship between muscle parameters in the upper and lower limbs with age in UK men and the influence of ethnicity on these relationships; (ii) to examine the relationships between jump force/grip strength/cross‐sectional muscle area (CSMA) with bone outcomes at the radius and tibia.

Methods

White European, Black Afro‐Caribbean, and South Asian men aged 40–79 years were recruited from Manchester, UK. Cortical bone mineral content, cross‐sectional area, cortical area, cross‐sectional moment of inertia, and CSMA were measured at the diaphysis of the radius and tibia using peripheral quantitative computed tomography. Lower limb jump force and power were measured from a single two‐legged jump performed on a ground‐reaction force platform. Grip strength was measured using a dynamometer. Associations between muscle and bone outcomes was determined using linear regression with adjustments for age, height, weight, and ethnicity.

Results

Three hundred and one men were recruited. Jump force was negatively associated with age; for every 10 year increase in age, there was a 4% reduction in jump force (P < 0.0001). There was a significant age–ethnicity interaction for jump power (P = 0.039); after adjustments, this was attenuated (P = 0.088). For every 10 year increase in age, grip strength decreased by 11%. Jump force was positively associated with tibial bone outcomes: a 1 standard deviation greater jump force was associated with significantly higher cortical bone mineral content 3.1%, cross‐sectional area 4.2%, cortical area 3.4%, and cross‐sectional moment of inertia 6.8% (all P < 0.001). Cross‐sectional muscle area of the lower leg was not associated with tibial bone outcomes. Both grip strength and CSMA of the arm were positively associated, to a similar extent, with radius diaphyseal bone outcomes.

Conclusions

Jump force and power are negatively associated with age in UK men. In the lower limb, the measurement of jump force is more strongly related to bone outcomes than CSMA. It is important to consider jump force and power when understanding the aetiology of bone loss and mobility in ageing men.
Thymol feed supplementation in quail alters the percentages of nutritionally relevant egg yolk fatty acids: effects throughout incubation
Authors: Fernandez Maria E , Marin Raul H , Luna Agustin , Zunino Maria P , Labaque Maria C
Published: May 2017

BACKGROUND

Polyunsaturated fatty acids (PUFA) are crucial components of egg yolk and particularly prone to oxidative damage, generating losses of nutrients for embryonic development and influencing the quality of eggs for human consumption. The aim of this study was to evaluate whether dietary thymol (a natural antioxidant) is related to changes in quail egg yolk total (T), triglyceride (TG) and phospholipid (PL) fatty acid composition at different stages of embryo development. Thus female Japanese quail (100 days of age) were assigned to one of two dietary treatments (12 individuals each): CON (basal diet) or THY (0.0016 mol thymol day−1 per bird). After 2 weeks of supplementation, eggs were incubated and samples were obtained at 0, 4 and 16 days of embryonic development.

RESULTS

In 0 day THY eggs, α‐linolenic acid and n‐3 PUFA in T and TG, docosahexaenoic acid and PUFA in T and arachidonic acid in TG were increased, while saturated fatty acids (SFA) in T were reduced. From 4 days on, PUFA, n‐3 PUFA and SFA from T and TG in THY eggs were found to be similar to those of CON eggs. The changes in PL throughout incubation were similar in both dietary treatments.

CONCLUSION

Thymol would provide the embryo with PUFA for synthesis/deposition in membranes and/or assign to supply energy. Additionally, thymol supplementation would be advisable for the production of healthier table eggs. © 2017 Society of Chemical Industry
Antioxidant activity and bioactive compound contents before and after in vitro digestion of new tomato hybrids
Authors: Tommonaro Giuseppina , Speranza Giovanna , De Prisco Rocco , Iodice Carmine , Crudele Egle , Abbamondi Gennaro Roberto , Nicolaus Barbara
Published: May 2017

BACKGROUND

The antioxidant properties and bioactive compound contents of fresh new tomato hybrids before and after in vitro digestion were investigated. To this aim, the antioxidant activities of lipophilic, hydrophilic and polyphenolic extracts of tomato hybrids were determined by ABTS (2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid)), DMPD (N,N‐dimethyl‐p‐phenylenediamine dihydrochloride) and DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) methods respectively, while the bioactive compound contents were estimated via Folin–Ciocalteu (polyphenols), pH differential (anthocyanins) and high‐performance liquid chromatography (lycopene and β‐carotene) methods.

RESULTS

After the digestion process, a marked loss (ranging from 37 to 77%) of antioxidant capacity linked to the hydrophilic fraction was observed. In contrast, the lipophilic and methanolic fractions showed an increase in antioxidant activity (ranging from 9 to 40%) after gastric digestion, and a rapid decrease was observed after total digestion. Moreover, the presence of anthocyanins and carotenoids after simulated digestion was a notable result.

CONCLUSION

The bioavailability of bioactive metabolites from nutraceutical food and their healthful properties in humans are strictly dependent on the digestion process. © 2017 Society of Chemical Industry
Memory Effect Canceling and Novel Driving Scheme of Twisting‐ball Display via Space‐charge Polarization
Authors: Komazaki Yusuke , Torii Toru
Published: May 2017

In this paper, characteristics of memory effect cancelling method for twisting‐ball display utilizing space‐charge polarization were examined. Response speed of the display to voltage removal became slow with increasing resistance value of resistors connected in parallel to the display. Memory effect canceling was effective with the resistance value at least up to 1 GΩ. Polarization and depolarization of space‐charges in a twisting‐ball display were completed in 60 s at 50 V and space‐charge polarization was induced under 1 Hz. The strength of space‐charge polarization can be controlled by the extent of progress of polymerization of the silicone rubber sheet, which means unpolymerized silicone rubber molecules or cross‐linker molecules can be charge careers in the display. Also, we proposed and demonstrated a novel driving scheme for the twisting‐ball display utilizing space‐charge polarization, which achieved simple structure, fast response and low energy consumption.
RFamide‐related peptide 3 and gonadotropin‐releasing hormone‐II are autocrine–paracrine regulators of testicular function in the boar
Authors: Lents Clay A. , Thorson Jennifer F. , Desaulniers Amy T. , White Brett R.
Published: May 2017

Widespread use of artificial insemination in swine requires millions of doses of boar semen each year. Subfertility of boars remains a major constraint, which can impact the reproductive efficiency of thousands of sows, so a better understanding of testicular function is needed in order to develop methods to improve semen production. With this in mind, the effects of RFamide‐related peptide 3 (RFRP3) and Gonadotropin‐releasing hormone‐II (GnRH‐II) on gonadotropin secretion and testicular function of pigs are reviewed here. Receptors for RFRP3 are present in the pig hypothalamus, adenohypophysis, and testis. Evidence from in vitro studies indicates that RFRP3 could be a hypophysiotropic hormone in the pig by suppressing secretion of GnRH‐I from the hypothalamus and luteinizing hormone (LH) from the pituitary gland; however, effects of RFRP3 on in vivo secretion of LH in pigs are minimal. Within the pig testis, RFRP3 suppresses testosterone secretion by inhibiting steroidogenic enzymes. GnRH‐II and its receptor (GnRHR‐II) are abundant in pig testes. Interstitial cells express GnRHR‐II, and exogenous GnRH‐II robustly stimulates secretion of testosterone in boars, despite minimal secretion of LH. Data illustrate that GnRH‐II directly stimulates secretion of testosterone from the testes of mature boars. Thus, the primary function of RFRP3 and GnRH‐II in the boar appears to be autocrine–paracrine inhibition and stimulation, respectively, of testosterone secretion within the testis. A better understanding of changes in the RFRP3 and GnRH‐II systems within the testis during development will provide important clues about how to improve the testicular function of boars.
Dynamic 1H imaging of hyperpolarized [1‐13C]lactate in vivo using a reverse INEPT experiment
Authors: Wang Jiazheng , Kreis Felix , Wright Alan J. , Hesketh Richard L. , Levitt Malcolm H. , Brindle Kevin M.
Published: May 2017

Purpose

Dynamic magnetic resonance spectroscopic imaging of hyperpolarized 13C‐labeled cell substrates has enabled the investigation of tissue metabolism in vivo. Currently observation of these hyperpolarized substrates is limited mainly to 13C detection. We describe here an imaging pulse sequence that enables proton observation by using polarization transfer from the hyperpolarized 13C nucleus to spin‐coupled protons.

Methods

The pulse sequence transfers 13C hyperpolarization to 1H using a modified reverse insensitive nuclei enhanced by polarization transfer (INEPT) sequence that acquires a fully refocused echo. The resulting hyperpolarized 1H signal is acquired using a 2D echo‐planar trajectory. The efficiency of polarization transfer was investigated using simulations with and without T1 and T2 relaxation of both the 1H and 13C nuclei.

Results

Simulations showed that 1H detection of the hyperpolarized 13C nucleus in lactate should increase significantly the signal‐to‐noise ratio when compared with direct 13C detection at 3T. However the advantage of 1H detection is expected to disappear at higher fields. Dynamic 1H images of hyperpolarized [1‐13C]lactate, with a spatial resolution of 1.25 × 1.25 mm2, were acquired from a phantom injected with hyperpolarized [1‐13C]lactate and from tumors in vivo following injection of hyperpolarized [1‐13C]pyruvate.

Conclusions

The sequence allows 1H imaging of hyperpolarized 13C‐labeled substrates in vivo. Magn Reson Med 79:741–747, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Exploring genetic susceptibility to obesity through genome functional pathway analysis
Authors: Gabrielli Alexander P. , Manzardo Ann M. , Butler Merlin G.
Published: May 2017

Objective

Obesity has been reaching epidemic levels in recent decades, with a growing body of research identifying predisposing genetic components. To explore the relationship of genetic factors contributing to obesity, an analytical computer‐based gene‐profiling approach utilizing an updated list of clinically relevant and known obesity‐related genes was undertaken.

Methods

An updated list of 494 genes reportedly associated with obesity was compiled, and the GeneAnalytics profiling software was utilized to interrogate genomic databases from GeneCards® to cross‐reference obesity gene sets against tissues and cells, diseases, genetic pathways, gene ontology (GO)‐biological processes and GO‐molecular functions, phenotypes, and compounds.

Results

Obesity‐related fields identified by GeneAnalytics algorithms included 8 diseases, 46 pathways, 62 biological processes, 22 molecular functions, 148 phenotypes, and 286 compounds impacting adipogenesis, signal transduction by G‐protein coupled receptors, and lipid metabolism involving insulin‐related genes (IGF1, INS, IRS1). GO‐biological processes identified feeding behavior, cholesterol metabolic process, and glucose and cholesterol homeostasis pathways, while GO‐molecular processes pertained to receptor binding, affecting glucose homeostasis, body weight, and circulating insulin and triglyceride levels.

Conclusions

The gene‐profiling model suggests that pathogenesis of obesity relates to the coordination of biological responses to glucose and intracellular lipids possibly through a disruption of biochemical cascades and cellular signaling arising from affected receptors.