bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of sense of duty on brand community outcomes
Authors: Goellner Katharina , Mark Tanya , Alvarado Jennifer
Published: February 2016

Research suggests that three markers are essential for a successful brand community: a sense of belonging, rituals and tradition, and a sense of duty toward the community. The first two of these markers have been empirically validated; however, the third marker, sense of duty, has yet to be empirically investigated. From a marketing perspective, this is important because there is a need to understand the marketing levers that influence favourable behavioural outcomes. We find that sense of duty is a decisive mediator of brand community behaviours and social identity. In addition, we find that sense of duty is a multidimensional construct consisting of three distinct components: new member integration, mentorship, and member retention. Copyright © 2016 ASAC. Published by John Wiley & Sons, Ltd.
Lipoprotein(a) and Increased Cardiovascular Risk in Women
Authors: Costello Briana T. , Silverman Eric R. , Doukky Rami , Braun Lynne T. , Aggarwal Neelum T. , Deng Youping , Li Yan , Lundberg Gina , Williams Kim A. , Volgman Annabelle S.
Published: February 2016

Background

Approximately 20% of the population has elevated circulating levels of lipoprotein(a) (Lp[a]), one of the most robust predictors of cardiovascular disease risk. This is particularly true for women.

Hypothesis

Many female patients with “normal” traditional risk factors or low atherosclerotic cardiovascular disease (ASCVD) risk scores may harbor high risk related to elevated levels of Lp(a).

Methods

A retrospective, cross‐sectional study of consecutive female patients presenting to Heart Centers for Women was performed. Discordance between low‐density lipoprotein cholesterol (LDL‐C) and Lp(a) was determined. The ASCVD risk and Reynolds Risk Score models A (RRS‐A) and B (RRS‐B) were calculated, and level of agreement in patients meeting treatment threshold (≥7.5% for ASCVD, ≥10% for RRS‐A and RRS‐B) were compared.

Results

Among 713 women, 290 (41%) had elevated Lp(a); however, LDL‐C and Lp(a) were weakly correlated (r = 0.08). Significant discordance was observed between abnormal LDL‐C and Lp(a) levels (McNemar P = 0.03). There was moderate correlation between RRS‐A and ASCVD risk (r = 0.71, P < 0.001), and Bland‐Altman plot showed diminished correlation with increased risk. More patients met treatment threshold by ASCVD risk estimation, but nearly 1 out of 20 patients met treatment threshold by RRS‐A but not ASCVD score.

Conclusions

There is high prevalence of elevated Lp(a) among women presenting to Heart Centers for Women. Although traditional risk markers such as elevated LDL‐C or high ASCVD risk may be absent in some women, elevated Lp(a) may identify patients who may benefit from aggressive risk‐factor modification and pharmacologic therapy.
Clinical Outcome of First‐ vs Second‐Generation DES According to DAPT Duration: Results of ARCTIC‐Generation
Authors: Collet Jean‐Philippe , Silvain Johanne , Kerneis Mathieu , Cuisset Thomas , Meneveau Nicolas , Boueri Ziad , Barthélémy Olivier , Rangé Grégoire , Cayla Guillaume , Belle Eric Van , Elhadad Simon , Carrié Didier , Caussin Christophe , Rousseau Hélène , Aubry Pierre , Monségu Jacques , Sabouret Pierre , O'Connor Stephen A. , Abtan Jérémie , Saint‐Etienne Christophe , Beygui Farzin , Vicaut Eric , Montalescot Gilles ,   for the ARCTIC Investigators
Published: February 2016

There is an apparent benefit with extension of dual antiplatelet therapy (DAPT) beyond 1 year after implantation of drug‐eluting stents (DES). Assessment by a Double Randomization of a Conventional Antiplatelet Strategy vs a Monitoring‐Guided Strategy for Drug‐Eluting Stent Implantation, and of Treatment Interruption vs Continuation One Year After Stenting (ARCTIC)‐Generation assessed whether there is a difference of outcome between first‐ vs second‐generation DES and if there is an interaction with DAPT duration in the ARCTIC‐Interruption study. ARCTIC‐Interruption randomly allocated 1259 patients 1 year after stent implantation to a strategy of interruption of DAPT (n = 624), in which aspirin antiplatelet treatment only was maintained, or DAPT continuation (n = 635) for 6 to 18 additional months. The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization. A total of 520 and 722 patients received a first‐ and a second‐generation DES, respectively. After a median follow‐up of 17 months (interquartile range, 15–18 months) after randomization, the primary endpoint occurred in 32 (6.2%) and 19 (2.6%) patients with first‐ and second‐generation DES, respectively (hazard ratio: 2.31, 95% confidence interval: 1.31‐4.07, P = 0.004). This was observed irrespective of the strategy of interruption or continuation of DAPT and timing of study recruitment. Major bleeding events occurred in 4 (0.8%) and 3 patients (0.4%) with first‐ and second‐generation DES, respectively (hazard ratio: 1.79, 95% confidence interval: 0.40‐8.02, P = 0.44). Results did not change after multiple adjustments for potential confounding variables. ARCTIC‐Generation showed worse clinical outcome with first‐ vs second‐generation DES, a difference that appeared to persist even with prolonged DAPT.
Response to Association Between Preinfarction Angina and Angiographic Findings in Non–ST‐Segment Elevation Myocardial Infarction
Authors: Bajka Balazs , Benedek Theodora , Molnar Călin
Published: February 2016

Misumida N et al. Clin Cardiol. 2015;38:535–541.
Young investigator challenge: Validation and optimization of immunohistochemistry protocols for use on cellient cell block specimens
Authors: Sauter Jennifer L. , Grogg Karen L. , Vrana Julie A. , Law Mark E. , Halvorson Jennifer L. , Henry Michael R.
Published: February 2016

BACKGROUND

The objective of the current study was to establish a process for validating immunohistochemistry (IHC) protocols for use on the Cellient cell block (CCB) system.

METHODS

Thirty antibodies were initially tested on CCBs using IHC protocols previously validated on formalin‐fixed, paraffin‐embedded tissue (FFPE). Cytology samples were split to generate thrombin cell blocks (TCB) and CCBs. IHC was performed in parallel. Antibody immunoreactivity was scored, and concordance or discordance in immunoreactivity between the TCBs and CCBs for each sample was determined. Criteria for validation of an antibody were defined as concordant staining in expected positive and negative cells, in at least 5 samples each, and concordance in at least 90% of the samples total. Antibodies that failed initial validation were retested after alterations in IHC conditions.

RESULTS

Thirteen of the 30 antibodies (43%) did not meet initial validation criteria. Of those, 8 antibodies (calretinin, clusters of differentiation [CD] 3, CD20, CDX2, cytokeratin 20, estrogen receptor, MOC‐31, and p16) were optimized for CCBs and subsequently validated. Despite several alterations in conditions, 3 antibodies (Ber‐EP4, D2‐40, and paired box gene 8 [PAX8]) were not successfully validated.

CONCLUSIONS

Nearly one‐half of the antibodies tested in the current study failed initial validation using IHC conditions that were established in the study laboratory for FFPE material. Although some antibodies subsequently met validation criteria after optimization of conditions, a few continued to demonstrate inadequate immunoreactivity. These findings emphasize the importance of validating IHC protocols for methanol‐fixed tissue before clinical use and suggest that optimization for alcohol fixation may be needed to obtain adequate immunoreactivity on CCBs. Cancer (Cancer Cytopathol) 2016;124:89‐99. © 2016 American Cancer Society.
FNA smears as a potential source of DNA for targeted next‐generation sequencing of lung adenocarcinomas
Authors: Treece Amanda L. , Montgomery Nathan D. , Patel Nirali M. , Civalier Chris J. , Dodd Leslie G. , Gulley Margaret L. , Booker Jessica K. , Weck Karen E.
Published: February 2016

BACKGROUND

Diff‐Quik–stained fine‐needle aspiration (FNA) smears and touch preparations from biopsies represent alternative specimens for molecular testing when cell block or biopsy material is insufficient. This study describes the use of these samples for targeted next‐generation sequencing (NGS) of primary and metastatic lung adenocarcinoma and reports the DNA quality and success rates of FNA smears versus other specimens from 1 year of clinical use.

METHODS

A validation set of 10 slides from 9 patients with prior clinical epidermal growth factor receptor (EGFR) Sanger sequencing and KRAS pyrosequencing (5 KRAS‐positive/EGFR‐negative and 4 KRAS‐negative/EGFR‐negative) underwent DNA extraction, quality assessment, and targeted NGS. Subsequently, lung adenocarcinoma specimens submitted for NGS solid tumor mutation panel testing in 1 calendar year (60 biopsies, 57 resections, 33 FNA cell blocks, 12 FNA smears, and 10 body fluid cell blocks) were reviewed for specimen adequacy, sequencing success, and DNA quality.

RESULTS

All 10 validation samples met the DNA quality threshold (delta Ct threshold < 8; range, –2.2 to 4.9) and yielded 0.5 to 22 μg of DNA. The KRAS and EGFR mutation status from FNA smears according to NGS was concordant with previous clinical testing for all 10 samples. In the 1‐year review, FNA smears were 100% successful, and this suggested a performance equivalent to or better than the performance of established specimen types, including FNA cell blocks. DNA quality according to ΔCt was significantly better with FNA smears versus biopsies, resections, and FNA cell blocks.

CONCLUSIONS

FNA smears of lung adenocarcinomas are high‐quality alternative specimens for a targeted NGS panel with a high success rate in clinical practice. Cancer Cytopathol 2016;124:406–14. © 2016 American Cancer Society.
Tuning Charge Transfer in Ion–Surface Collisions at Hyperthermal Energies
Authors: Yao Yunxi , Giapis Konstantinos P.
Published: February 2016

Charge exchange in ion–surface collisions may be influenced by surface adsorbates to alter the charge state of the scattered projectiles. We show here that the positive‐ion yield, observed during ion scattering on metal surfaces at low incident energies, is greatly enhanced by adsorbing electronegative species onto the surface. Specifically, when beams of N+ and O+ ions are scattered off of clean Au surfaces at hyperthermal energies, no positive ions are observed exiting. Partial adsorption of F atoms on the Au surface, however, leads to the appearance of positively charged primary ions scattering off of Au, a direct result of the increase in the Au work function. The inelastic energy losses for positive‐ion exits are slightly larger than the corresponding ionization energies of the respective N and O atoms, which suggest that the detected positive ions are formed by surface reionization during the hard collision event.
Dye‐Sensitized Cu2XSnS4 (X=Zn, Ni, Fe, Co, and Mn) Nanofibers for Efficient Photocatalytic Hydrogen Evolution
Authors: Gonce Mehmet Kerem , Aslan Emre , Ozel Faruk , Hatay Patir Imren
Published: February 2016

The photocatalytic hydrogen evolution activities of low‐cost and noble‐metal‐free Cu2XSnS4 (X=Zn, Ni, Fe, Co, and Mn) nanofiber catalysts have been investigated using triethanolamine as an electron donor and eosin Y as a photosensitizer under visible‐light irradiation. The rates of hydrogen evolution by Cu2XSnS4 (X=Zn, Ni, Fe, Co, and Mn) nanofibers have been compared with each other and with that of the noble metal Pt. The hydrogen evolution rates for the nanofibers change in the order Cu2NiSnS4>Cu2FeSnS4>Cu2CoSnS4>Cu2ZnSnS4>Cu2MnSnS4 (2028, 1870, 1926, 1420, and 389 μmol g−1 h−1, respectively). The differences between the hydrogen evolution rates of the nanofibers could be attributed to their energy levels. Moreover, Cu2NiSnS4, Cu2FeSnS4, and Cu2CoSnS4 nanofibers show higher and more stable photocatalytic hydrogen production rates than that of the noble metal Pt under long‐term irradiation with visible light.
Glandular epithelial abnormalities on thinprep® pap tests: Clinical and cytohistologic correlation
Authors: Selvaggi Suzanne M.
Published: February 2016

Background

Although the incidence of glandular epithelial abnormalities on cervical cytology is low, the clinical and histologic findings are often significant. The laboratory's 12‐year experience is reported.

Methods

from January 1, 2003 to December 31, 2014, the Cytopathology Laboratory of the University of Wisconsin Hospital and Clinics processed 191,087 ThinPrep® Pap Tests of which 184 (0.1%) were reported as glandular epithelial abnormalities. One hundred forty‐three (78%) of these cases had histologic follow‐up and form the basis of this study. Of the 143 women (mean age, 52; median, 50), 45% presented with vaginal bleeding and 55% were asymptomatic. The cytologic groups included atypical glandular cells, atypical glandular cells; favor a neoplastic process, atypical endocervical cells, atypical endocervical cells; favor a neoplastic process, endocervical adenocarcinoma in situ, atypical endometrial cells and adenocarcinoma, NOS.

Results

Overall, the histologic follow‐up showed epithelial abnormalities including endometrial and endocervical carcinoma, endocervical adenocarcinoma in situ, CIN 3 involving endocervical glands and metastatic carcinoma in 78% of the cases. The diagnoses were age‐dependent and influenced by clinical symptomatology.

Conclusion

Glandular epithelial abnormalities on Pap tests warrant further clinical investigation. Diagn. Cytopathol. 2016;44:389–393. © 2016 Wiley Periodicals, Inc.
Development of a Probe for Detecting Magnetic Fluid in Lymph Nodes
Authors: OOKUBO TETSU , INOUE YUSUKE , KIM DONGMIN , OHSAKI HIROYUKI , MASHIKO YUSUKE , KUSAKABE MORIAKI , SEKINO MASAKI
Published: February 2016

Lymph nodes are selectively removed in order to diagnose cancer metastases. In this investigation, we developed a magnetic probe for intraoperatively detecting the accumulation of magnetic fluid. We built a magnetic probe consisting of a permanent magnet and a Hall effect sensor, and investigated its sensitivity. The results agreed well with the numerical results. In addition, a prototype probe detected 1.6 mL of magnetic fluid located 30 mm from the probe head.
Calculation of Local Bifurcation Points in Piecewise Nonlinear Discrete‐Time Dynamical Systems
Authors: TONE YUSUKE , ASAHARA HIROYUKI , ITO DAISUKE , UETA TETSUSHI , AIHARA KAZUYUKI , KOUSAKA TAKUJI
Published: February 2016

This paper proposes a method for calculation of local bifurcation points in discrete‐time dynamical systems with piecewise nonlinear characteristics (PNDDS). First, an ‐dimensional PNDDS, which has two piecewise nonlinear maps, is shown and its variational equation is derived. Next, a calculation method for the local bifurcation points that utilizes the conditional equation for the periodic solution and the characteristic equation is proposed. It is essential to calculate the derivatives of the map with an initial value and with a bifurcation parameter to obtain the bifurcation points continuously in the parameter space. The above calculation process is a key component of the proposed method, and is explained in detail. Finally, we apply the proposed method to a two‐dimensional PNDDS and calculate the local bifurcation points in order to confirm the validity of the proposed method.
Accuracy Improvement of Low‐Invasive Temperature Measurement for Hyperthermia Treatment Using a Ferromagnetic Implant with Low Curie Temperature
Authors: MIYAMOTO RYUHEI , SAITO HAJIME , SUZUKI MASAFUMI , YOSHIMURA NOBORU , MITOBE KAZUTAKA
Published: February 2016

We investigated a hyperthermia treatment method in which a ferromagnetic implant with a low Curie temperature (FILCT) is implanted into a malignant tumor and then a high‐frequency magnetic field is applied outside the body. In earlier studies, we confirmed that the target temperature of the tumor can be noninvasively monitored by detecting changes in the magnetic field caused by changes in magnetic permeability. It was very difficult, however, to detect the FILCT temperature if the applied magnetic field was in an unstable state. Additionally, if the initial bias is higher, it is more difficult to detect the FILCT temperature because the resolution of the lock‐in amplifier is reduced. In order to improve the accuracy of low‐invasive temperature measurement, we formulated a method that reduces the drift in the pickup coil voltage caused by instability from the applied magnetic field. In addition, we experimentally confirmed that the influence of fluctuations in the applied magnetic field can be reduced by adjusting the initial bias value to close to 0 V.
Review of Low‐Temperature Bonding Technologies and Their Application in Optoelectronic Devices
Authors: HIGURASHI EIJI , SUGA TADATOMO
Published: February 2016

Low‐temperature bonding is an important fabrication technique for advanced microelectronics, microelectromechanical systems (MEMS), and optoelectronic devices. Recently, many low‐temperature bonding techniques such as surface activated bonding have been studied in order to create unique device structures for a wide range of photonics applications. This paper focuses on low‐temperature bonding techniques and reviews the state‐of‐the‐art applications involving optoelectronic devices.
BH4–‐Promoted, Radical‐Initiated, Catalytic Oxidation of (CH3)2SO by N2O in Aqueous Solution
Authors: Yanus Rinat Levy , Yardeni Guy , Maimon Eric , Saphier Magal , Zilbermann Israel , Meyerstein Dan
Published: February 2016

Methyl radicals react with BH4– to form BH3·–/BH4· (k ≈ 5 × 103 M–1 s–1. BH3·–/BH4· reacts with N2O to form OH· radicals, which react with (CH3)2SO to form methyl radicals and thus initiate a chain oxidation process. It is suggested that analogous reactions can be initiated by the reaction of OH· radicals with other organic substrates. Thus, BH4– promotes oxidation processes.
Diacylglycerol‐enriched oil production using chemical glycerolysis
Authors: Satriana  , Arpi Normalina , Lubis Yanti Meldasari , Adisalamun  , Supardan Muhammad Dani , Mustapha Wan Aida Wan
Published: February 2016

Diacylglycerol (DAG)‐enriched oils have been drawing increased global attention from researchers and food manufacturers. The production of DAG‐enriched oils have been investigated extensively because of its health benefit. DAG is commonly produced chemically through glycerolysis processes. This paper attempts to review and summarize the chemical glycerolysis methods for DAG‐enriched oils production. The critical process parameters of the DAG synthesis are also presented and discussed. In addition, a process intensification for DAG‐enriched oils production has been developed with an objective of reducing required temperature with better reaction yields, and also lowering energy requirement and cost of processing.

Practical applications: Diacylglycerol (DAG) has been widely used at different purity levels as an additive for enhancing fats’ plasticity, an emulsifier and stabilizer in food as well as in medicine and cosmetic industries. DAG can be produced chemically through a glycerolysis process. Chemical production of DAG oil avoids a number of complex steps required in the enzymatic method. Important parameters in chemical glycerolysis must be fully considered to gain a better performance of chemical glycerolysis.

Diacylglycerol (DAG) is ester of glycerol in which two of the hydroxyl group are esterified with fatty acids. DAG‐enriched oil is commonly produced chemically through a glycerolysis process. Important process parameters in chemical glycerolysis as well as process intensification for DAG‐enriched oil production are summarized in this review article.
Quasi‐Solid‐State Dye‐Sensitized Solar Cells Based on Ru(II) Polypyridine Sensitizers
Authors: ElBatal Hany S. , Aghazada Sadig , Al‐Muhtaseb Shaheen A. , Grätzel Michael , Nazeeruddin Mohammad Khaja
Published: February 2016

The Ru(II) polypyridine complexes SA22 and SA25 consisting of anchoring and light harvesting moieties and possessing broad light absorption spectra were used to fabricate and optimize dye‐sensitized solar cells (DSSCs). The highly efficient Z960 electrolyte was used as redox‐mediator, and the J–V characteristics and incident photon‐to‐current conversion efficiency (IPCE) data were measured. The solar cells based on these dyes and electrolyte yielded power conversion efficiencies (PCE) of 7 % using SA22 and 5 % with SA25. The higher‐performance sensitizer SA22 was selected to build solar‐cell devices, using either the high‐thermal‐stability Z946 electrolyte or a gel‐electrolyte composed of Z946 electrolyte and 2 wt % low‐molecular‐mass organogelator (LMOG) NME‐5. The quasi‐solid‐state electrolyte produced a DSSC with a PCE of 4.7 %, whereas that made using Z946 showed 5 % efficiency. The quasi‐solid‐state DSSC was sealed and a stability study was performed using accelerated thermal aging conditions at 70 °C for 7 days, by which the cell parameters (including PCE, Jsc, Voc, and FF) retained more than 90 % of their original values.
Polyvinyl Alcohol Functionalized Solid Acid Catalyst DICAT‐1 for Microwave‐Assisted Synthesis of 5‐Hydroxymethylfurfural in Green Solvent
Authors: Pawar Hitesh S. , Lali Arvind M.
Published: February 2016

Microwave‐assisted cyclodehydration of fructose to 5‐hydroxymethylfurfural (5‐HMF) was studied herein over polyvinyl alcohol (PVA)‐functionalized solid acid catalyst DICAT‐1 in low‐boiling green solvents. Of the tested solvent systems [isopropanol (IPA), tert‐butyl alcohol, THF, acetone, CH3CN, DMF, and DMSO], IPA was the preferred low boiling point (LBP) reaction medium, resulting in 95 % fructose conversion and 85 % 5‐HMF yield in 120 s. The characteristic dispersibility and swelling properties of DICAT‐1 in IPA had a significant effect on 5‐HMF yield. The catalyst DICAT‐1 was stable and robust under the reaction conditions and easily recycled. The structural and morphological characteristics of the catalyst were elucidated by FTIR spectroscopy, SEM/energy‐dispersive X‐ray spectroscopy, X‐ray fluorescence spectroscopy, XRD, and N2 sorption analysis. DICAT‐1 has covalently bonded −SO3H active sites, an amorphous nature, and mesoporous surface morphology; these features result in excellent performance in IPA. Estimated values of turnover number, turnover frequency, E‐factor, and process mass intensity categorize the overall process as environmentally safe for the production of 5‐HMF. A catalytic mechanism for 5‐HMF formation on DICAT‐1 is proposed.
Structure‐reactivity relationships between the fluorescent chromophores and antioxidant activity of grain and sweet sorghum seeds
Authors: Uchimiya Minori , Ni Xinzhi , Wang Ming Li
Published: February 2016

Polyphenolic structures are the putative cause of a variety of seed functions including bird/insect resistance and antioxidant activity. Structure‐reactivity relationships are necessary to understand the influence of polyphenolic chromophore structures on the tannin content and free radical quenching ability determined by the traditional calorimetric methods. This study investigated the relationships between the structural attributes of fluorescent chromophore and the following seed characterization methods: procyanidin (by acid‐butanol assay) and flavonoid (by vanillin assay) contents, radical quenching (by DPPH assay), electron‐donating capacity (by FeIII reduction), and λmax (by UV/visible spectrophotometry). Distinctively different response was observed for different seed categories: U.S. grain sorghum hybrids, African grain sorghum, and sweet sorghum. The U.S. grain sorghum varieties (low‐tannin to maximize the livestock digestion) responded only to the DPPH assay. For sweet sorghum and African grain sorghum, linear correlation was observed between (1) the antioxidant activity (2) the amounts of procyanidins and flavonoids, and (2) the aromaticity of fingerprint fluorescent structures.
Tuftsin‐driven experimental autoimmune encephalomyelitis recovery requires neuropilin‐1
Authors: Nissen Jillian C. , Tsirka Stella E.
Published: February 2016

Experimental autoimmune encephalomyelitis (EAE) is an animal model of demyelinating autoimmune disease, such as multiple sclerosis (MS), which is characterized by central nervous system white matter lesions, microglial activation, and peripheral T‐cell infiltration secondary to blood–brain barrier disruption. We have previously shown that treatment with tuftsin, a tetrapeptide generated from IgG proteolysis, dramatically improves disease symptoms in EAE. Here, we report that microglial expression of Neuropilin‐1 (Nrp1) is required for tuftsin‐driven amelioration of EAE symptoms. Nrp1 ablation in microglia blocks microglial signaling and polarization to the anti‐inflammatory M2 phenotype, and ablation in either the microglia or immunosuppressive regulatory T cells (Tregs) reduces extended functional contacts between them and Treg activation, implicating a role for microglia in the activation process, and more generally, how immune surveillance is conducted in the CNS. Taken together, our findings delineate the mechanistic action of tuftsin as a candidate therapeutic against immune‐mediated demyelinating lesions. GLIA 2016;64:923–936
Contributions of Ernest Wenkert to the Use of Cyclopropanes in Synthesis – Impact, Reflections, and Recollections
Authors: Hudlicky Tomas
Published: February 2016

This essay describes Ernest Wenkert's contributions to the chemistry of cyclopropanes and their use in synthesis. The impact of his work on the careers of others, especially including the development of cyclopropane‐based research in the Hudlicky group, is addressed, along with reflections on his mentorship. Personal recollections from some of his past students are provided at the end of the article.
Synthetic Applications of Aroyl‐ and Nitro‐substituted 2‐Aryl‐Cyclopropane‐1,1‐Dicarboxylates
Authors: Selvi Thangavel , Srinivasan Kannupal
Published: February 2016

The synthetic applications of aroyl‐ and nitro‐substituted D‐A cyclopropanes probed in the authors’ laboratory are reviewed. These cyclopropanes, though looking similar, exhibit markedly different reactivity patterns. Lewis acid‐mediated transformations of these cyclopropanes (in the presence or absence of a reaction partner) afford a variety of carbocycles and heterocycles. Mechanistic aspects of the reactions are discussed for clear understanding of the transformations.
Quantitative evaluation of local pulmonary distribution of TiO2 in rats following single or multiple intratracheal administrations of TiO2 nanoparticles using X‐ray fluorescence microscopy
Authors: Zhang Guihua , Shinohara Naohide , Kano Hirokazu , Senoh Hideki , Suzuki Masaaki , Sasaki Takeshi , Fukushima Shoji , Gamo Masashi
Published: February 2016

Uneven pulmonary nanoparticle (NP) distribution has been described when using single‐dose intratracheal administration tests. Multiple‐dose intratracheal administrations with small quantities of NPs are expected to improve the unevenness of each dose. The differences in local pulmonary NP distribution (called microdistribution) between single‐ and multiple‐dose administrations may cause differential pulmonary responses; however, this has not been evaluated. Here, we quantitatively evaluated the pulmonary microdistribution (per mesh: 100 μm × 100 μm) of TiO2 in lung sections from rats following one, two, three, or four doses of TiO2 NPs at a same total dosage of 10 mg kg−1 using X‐ray fluorescence microscopy. The results indicate that: (i) multiple‐dose administrations show lower variations in TiO2 content (ng mesh−1) for sections of each lobe; (ii) TiO2 appears to be deposited more in the right caudal and accessory lobes located downstream of the administration direction of NP suspensions, and less so in the right middle lobes, irrespective of the number of doses; (iii) there are not prominent differences in the pattern of pulmonary TiO2 microdistribution between rats following single and multiple doses of TiO2 NPs. Additionally, the estimation of pulmonary TiO2 deposition for multiple‐dose administrations imply that every dose of TiO2 would be randomly deposited only in part of the fixed 30–50% of lung areas. The evidence suggests that multiple‐dose administrations do not offer remarkable advantages over single‐dose administration on the pulmonary NP microdistribution, although multiple‐dose administrations may reduce variations in the TiO2 content for each lung lobe. Copyright © 2016 John Wiley & Sons, Ltd.
Stereoselectivity and the potential endocrine disrupting activity of di‐(2‐ethylhexyl)phthalate (DEHP) against human progesterone receptor: a computational perspective
Authors: Sheikh Ishfaq Ahmad
Published: February 2016

Di‐(2‐ethylhexyl)phthalate (DEHP) is a phthalate plasticizer and is one of the very common endocrine‐disrupting chemicals (EDCs) contaminating our ecosystem. It is used for imparting flexibility to plastics and frequently used in personal and industrial products. Clinical and experimental studies have indicated that exposure to DEHP is associated with developmental abnormalities of the reproductive system particularly of male neonates, endometriosis and miscarriage in women, low sperm counts and lower sperm motility and DNA integrity in men, and placental problems with higher rates of low birth weight, premature birth, and fetal loss in laboratory animals. Binding of DEHP to progesterone receptor (PR) represents a potential mechanism of interference in the reproductive functions. DEHP is a chiralmolecule and is available commercially as a racemic mixture of RR, SS and RS stereoisomers. The ability of individual stereoisomers of DEHP to interfere with the reproductive functions of humans and animals is not known and molecular interactions of DEHP stereoisomers with PR are not available. In the present study, in silico approaches were adopted for molecular simulation studies of the three stereoisomers of DEHP with PR. The study suggested that all three stereoisomers of DEHP have the potential to compete with the normal substrate binding of PR. However, the binding of DEHP to PR was stereoselective with RR stereoisomer of DEHP having the best binding characteristics compared with SS, and RS stereoisomers. It has been suggested that stereoselectivity may be employed for improving the safety of the commercial compounds using pure stereoisomers instead of racemic mixtures. Copyright © 2016 John Wiley & Sons, Ltd.
Toxicity and dosimetric analysis of non–small cell lung cancer patients undergoing radiotherapy with 4DCT and image‐guided intensity modulated radiotherapy: a regional centre's experience
Authors: Livingston Gareth C. , Last Andrew J. , Shakespeare Thomas P. , Dwyer Patrick M. , Westhuyzen Justin , McKay Michael J. , Connors Lisa , Leader Stephanie , Greenham Stuart
Published: February 2016

Introduction

For patients receiving radiotherapy for locally advance non–small cell lung cancer (NSCLC), the probability of experiencing severe radiation pneumonitis (RP) appears to rise with an increase in radiation received by the lungs. Intensity modulated radiotherapy (IMRT) provides the ability to reduce planned doses to healthy organs at risk (OAR) and can potentially reduce treatment‐related side effects. This study reports toxicity outcomes and provides a dosimetric comparison with three‐dimensional conformal radiotherapy (3DCRT).

Methods

Thirty curative NSCLC patients received radiotherapy using four‐dimensional computed tomography and five‐field IMRT. All were assessed for early and late toxicity using common terminology criteria for adverse events. All plans were subsequently re‐planned using 3DCRT to the same standard as the clinical plans. Dosimetric parameters for lungs, oesophagus, heart and conformity were recorded for comparison between the two techniques.

Results

IMRT plans achieved improved high‐dose conformity and reduced OAR doses including lung volumes irradiated to 5–20 Gy. One case each of oesophagitis and erythema (3%) were the only Grade 3 toxicities. Rates of Grade 2 oesophagitis were 40%. No cases of Grade 3 RP were recorded and Grade 2 RP rates were as low as 3%.

Conclusion

IMRT provides a dosimetric benefit when compared to 3DCRT. While the clinical benefit appears to increase with increasing target size and increasing complexity, IMRT appears preferential to 3DCRT in the treatment of NSCLC.
Divergent genes in potential inoculant Sinorhizobium strains are related to DNA replication, recombination, and repair
Authors: Penttinen Petri , Greco Dario , Muntyan Victoria , Terefework Zewdu , De Lajudie Philippe , Roumiantseva Marina , Becker Anke , Auvinen Petri , Lindström Kristina
Published: February 2016

To serve as inoculants of legumes, nitrogen‐fixing rhizobium strains should be competitive and tolerant of diverse environments. We hybridized the genomes of symbiotically efficient and salt tolerant Sinorhizobium inoculant strains onto the Sinorhizobium meliloti Rm1021 microarray. The number of variable genes, that is, divergent or putatively multiplied genes, ranged from 503 to 1556 for S. meliloti AK23, S. meliloti STM 1064 and S. arboris HAMBI 1552. The numbers of divergent genes affiliated with the symbiosis plasmid pSymA and related to DNA replication, recombination and repair were significantly higher than expected. The variation was mainly in the accessory genome, implying that it was important in shaping the adaptability of the strains.
SpxB‐mediated H2O2 induces programmed cell death in Streptococcus sanguinis
Authors: Li Ting , Zhai Shuheng , Xu Mengya , Shang Mengmeng , Gao Yu , Liu Gangshan , Wang Qingxuan , Zheng Lanyan
Published: February 2016

Streptococcus sanguinis (S. sanguinis) is a commensal oral streptococci that produces hydrogen peroxide (H2O2), and this production is dependent on pyruvate oxidase (SpxB) activity. In addition to its well‐known role in intraspecies or interspecies competitions, recent studies have shown that H2O2 produced by S. sanguinis under aerobic conditions not only upregulates biofilm formation and eDNA release but also regulates cell death without obvious cell lysis. Here, we report that S. sanguinis exhibits characteristic hallmarks of eukaryotic apoptosis when it encounters endogenous and exogenous H2O2. As the most common mode of programmed cell death (PCD), apoptosis is accompanied by a series of biochemical and morphological events, including DNA fragmentation, chromosome condensation, membrane potential depolarization, phosphatidylserine (PS) exposure, and caspase substrate binding protein activity changes. In addition, we also provide genetic evidence that there is decreased expression of the related DNA repair genes comEA, recA, dnaC, dinG, and pcrA in the wild‐type compared to the isogenic spxB mutant in S. sanguinis. Our data suggest that endogenous H2O2 is the most important agent in this development process in S. sanguinis.
The Use of Intelligence in Tourism Destination Management: An Emerging Role for DMOs
Authors: Sheehan Lorn , Vargas‐Sánchez Alfonso , Presenza Angelo , Abbate Tindara
Published: February 2016

Over time, the acronym DMO has evolved from a meaning centered on marketing (i.e. Destination Marketing Organization) to a meaning centered on management (i.e. Destination Management Organization). Expanding the role of DMOs to one of management implies a greater need to engage stakeholders both within the destination and external to the destination. We assert that this places the DMO in a fundamentally unique position of being a boundary spanner between the internal destination environment and the external competitive environment. This boundary‐spanning role requires higher capabilities in knowledge management. The successful DMO of the future will be an intelligent agent of the destination that is able to identify, engage and learn from disparate stakeholders both within and outside the destination. It must acquire, filter, analyze and prioritize data and information from various sources to create knowledge that can be used to fulfill its role in destination management.

Our paper is conceptual in nature, advocating an organizing framework to help understand the DMO's role as an intelligent agent that acts as a boundary spanner between the destination and the external competitive environment generating and disseminating knowledge. Outside the destination, the DMO must gain knowledge about the competitive environment, opportunities and threats, and trends that will change the future competitive landscape. Within the destination, the DMO must use this knowledge to strategically assess the strengths and weaknesses of the destination, align the resources of stakeholders and develop adequate competencies to formulate a strategy that is both competitive and sustainable. We conclude with a set of prescriptions for destination managers seeking to create an intelligent DMO that maximizes their knowledge management capabilities. Copyright © 2016 John Wiley & Sons, Ltd.
Alterations of putaminal shape in de novo Parkinson's disease
Authors: Caligiuri Maria Eugenia , Nisticò Rita , Arabia Gennarina , Morelli Maurizio , Novellino Fabiana , Salsone Maria , Barbagallo Gaetano , Lupo Angela , Cascini Giuseppe Lucio , Galea Domenico , Cherubini Andrea , Quattrone Aldo
Published: February 2016

Introduction

Several neuroimaging studies have been carried out to gain insight on the pathological processes that cause PD, but literature findings are inconsistent. The aim of this study was to combine information carried by functional imaging with DA transporter ligands and structural MRI.

Methods

Forty‐two untreated, de novo‐PD patients and 30 control subjects were involved in this study. Patients were divided in subgroups according to the presence of uni‐ or bilateral reduction of ligand uptake in the putamen, as observed on DA transporter single‐photon emission tomography: 12 patients had abnormal uptake in the right putamen and 11 in the left, whereas 19 had bilateral abnormal uptake. Voxel‐based morphometry and shape analysis were used to compare healthy subjects to all de novo‐PD or to patients with either right or left abnormal uptake.

Results

Shape analysis identified significant differences between de novo‐PD and controls in putaminal regions. In patients with unilateral abnormal uptake, only the medial surface of the structure was involved. When patients with bilateral uptake reduction were also considered, changes extended from the medial to the lateral surface of putamina. Voxel‐based morphometry showed similar results to those detected with shape analysis, but it failed to identify the putaminal subfield involved in patients with asymmetric or symmetric damage on DA transporter single‐photon emission tomography.

Conclusions

Shape analysis in de novo‐PD patients suggested a progressive medial‐to‐lateral involvement of the putamina that paralleled an asymmetric‐to‐bilateral distribution of DA transporter depletion. © 2016 International Parkinson and Movement Disorder Society
Long‐term effect of epoetin alfa on clinical and biochemical markers in friedreich ataxia
Authors: Saccà Francesco , Puorro Giorgia , Marsili Angela , Antenora Antonella , Pane Chiara , Casali Carlo , Marcotulli Christian , Defazio Giovanni , Liuzzi Daniele , Tatillo Chiara , Cambriglia Donata Maria , Schiano di Cola Giuseppe , Giuliani Luigi , Guardasole Vincenzo , Salzano Andrea , Ruvolo Antonio , De Rosa Anna , Cittadini Antonio , De Michele Giuseppe , Filla Alessandro
Published: February 2016

Background

Friedreich ataxia is an autosomal recessive disease with no available therapy. Clinical trials with erythropoietin in Friedreich ataxia patients have yielded conflicting results, and the long‐term effect of the drug remains unknown.

Methods

We designed a double‐blind, placebo‐controlled, multicenter trial to test the efficacy of epoetin alfa on 56 patients with Friedreich ataxia. The primary endpoint of the study was the effect of epoetin alfa on peak oxygen uptake (VO2 max) at the cardiopulmonary exercise test. Secondary endpoints were frataxin levels in peripheral blood mononuclear cells, improvement in echocardiography findings, vascular reactivity, neurological progression, upper limb dexterity, safety, and quality of life. Epoetin alfa or placebo (1:1 ratio) was administered subcutaneously at a dose of 1200 IU/Kg of body weight every 12 weeks for 48 weeks.

Results

A total of 56 patients were randomized; 27 completed the study in the active treatment group, and 26 completed the study in the placebo group[KG1]. VO2 max was not modified after treatment (0.01 [−0.04 to 0.05]; P = .749), as well as most of the secondary endpoint measures, including frataxin. The 9‐hole peg test showed a significant amelioration in the treatment group (−17.24 sec. [−31.5 to −3.0]; P = .018). The treatment was safe and well tolerated.

Conclusions

Although results are not in favor of an effect of epoetin alfa in Friedreich ataxia, this is the largest trial testing its effect. It is still possible that epoetin alfa may show some symptomatic effect on upper‐limb performance. This study provides class I evidence that erythropoietin does not ameliorate VO2 max in patients with Friedreich ataxia. © 2016 International Parkinson and Movement Disorder Society
The Use of Avoidance, Adjustment, Interaction and Acceptance Strategies to Handle Participation Restrictions Among Swedish Men with Early Rheumatoid Arthritis
Authors: Östlund Gunnel , Thyberg Ingrid , Valtersson Eva , Björk Mathilda , Annette Sverker
Published: February 2016

Objectives

Living with a chronic disease means learning to live under new circumstances and involves a continuous adaptation to new ways of living. There is increasing knowledge about how people cope with stressful life events and adapt to new life situations. Approximately a third of patients diagnosed with rheumatoid arthritis (RA) are men; however, few studies have described the needs and experiences of men living with RA. The aim of the present study was to explore men's strategies for handling challenges related to participation in everyday life.

Methods

The present study was associated with the prospective Swedish multicentre early arthritis project (given the Swedish acronym TIRA), which, in 2006–2009, included patients with early RA, contemporarily treated, with a mean disease duration of three years. From this cohort, 25 men, aged 20–63 years, were recruited consecutively. Data were collected in individual interviews, using the critical incident technique. The strategies for dealing with the challenges of RA in everyday life were analysed and categorized using content analysis.

Results

Men with RA described four types of strategy for dealing with participation restrictions in everyday life: (i)Adjustment strategies– adjust behaviour, movements, medication, equipment and clothing to find new ways to conduct tasks or activities; (ii)Avoidance strategies– avoid activities, movements, social contacts and sometimes medication; (iii)Interaction strategies– say no, ask for help and work together to handle participation restrictions; and (iv)Acceptance strategies– learn to accept RA, with the pain, the slower work pace and the extended time needed.

Conclusions

According to men's lived experiences, a combination of strategies was used to deal with RA, depending on the situation and the experienced restriction. The results provided an understanding of how men with RA manage their disease, to reduce physical, social and emotional challenges. This knowledge may be used further to develop multi‐professional interventions and patient education tailored to men with RA.
Bladder telemetry: A new approach to evaluate micturition behavior under physiological and inflammatory conditions
Authors: Monjotin Nicolas , Farrié Martine , Vergnolle Nathalie , Le Grand Bruno , Gillespie James , Junquero Didier
Published: February 2016

Aims

To establish a new approach to cystometry using telemetry in conscious rats and to use this technique to determine the role of conscious decision making processes with respect to the initiation of voiding in physiological, inflammatory, and painful conditions.

Methods

The pressure transducer of a telemetric transmitter was implanted in the dome of the urinary bladder. After a recovery period of at least 1 month, several investigations of urodynamic parameters were performed after diuresis activation by a pulse of furosemide. The model was characterized by tolterodine and mirabegron under physiological conditions and same animals were reused to evaluate the modification of the voiding pattern under bladder inflammation induced by cyclophosphamide.

Results

The quality of traces and measurement of parameters recorded telemetrically were comparable to those with conventional cystometry. Furosemide induced a reproducible transient increase of urine production and a series of voids that persisted for 60 min. Tolterodine reduced the amplitude of micturition contractions although mirabegron was devoid of any effect. Seven hours after injection of CYP, voiding frequency increased significantly and the micturition amplitude contraction was not altered. However, the mean volume voided during individual micturitions and the total voided volume decreased. During a second exposure to furosemide 24H after CYP injection, the micturition pattern returned to control, however, the micturition volume was still lower than in control.

Conclusion

This telemetric model appears to be as accurate as previously described in conscious conventional cystometry, and allows the repeated evaluation of compounds which may modulate the voiding patterns. Neurourol. Urodynam. 36:308–315, 2017. © 2016 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.
The effect of combined treatment with a β3AR agonist and a ROCK inhibitor on detrusor overactivity
Authors: Wróbel Andrzej , Rechberger Tomasz
Published: February 2016

Aims

The objective of the study was to evaluate the efficacy and safety of the combined treatment with the β3AR agonist and ROCK inhibitor in the rat model of detrusor overactivity induced by retinyl acetate instillation.

Methods

The ROCK inhibitor (GSK 269962) and/or the β3AR agonist (BRL 37344) were administered in single doses and a cystometry was carried out, along with a 24 hr measurement of cardiovascular parameters and diuresis.

Results

The combined use of GSK 269962 and BRL 37344 in doses ineffective in monotherapies, ameliorated DO. An increase was found in voided volume, voiding efficiency, volume threshold, intercontraction interval, bladder compliance, and volume threshold to elicit nonvoiding contractions, accompanied by a decrease in basal pressure, threshold pressure, detrusor overactivity index, nonvoiding contractions amplitude, and frequency. The combination therapy in question proved to have no effect on micturition voiding pressure, post‐void residual, bladder contraction duration, or relaxation time. A 24 hr observation of female rats who received GSK 269962 and/or BRL 37344 did not show any significant changes in urine production. BRL 37344 increased heart rate and blood pressure proportionately to the applied dose. The assessment of the combined treatment with GSK 269962 and BRL 37344 revealed a significant drop of cardiovascular parameters when compared to the rats which only received BRL 37344.

Discussion

The combined use of β3AR agonists and ROCK inhibitors may improve overactive bladder treatment efficacy and minimize side effects.

Conclusion

This polytherapy appears to improve urine storage with no impairment of voiding function. Neurourol. Urodynam. 36:580–588, 2017. © 2016 Wiley Periodicals, Inc.