bluuebunny/crossref_metadata_2025 huggingface dataset:
Interkalationsverbindungen als Referenzelektroden für reproduzierbare und robuste ionenselektive Festkontaktelektroden
Authors: Ishige Yu , Klink Stefan , Schuhmann Wolfgang
Published: March 2016

Ionenselektive Elektroden (ISE) werden jedes Jahr millionenfach zur routinemäßigen klinischen Analyse von Blutelektrolyten eingesetzt. Die Entwicklung von preiswerten, Chip‐integrierten Sensoren erfordert bisher jedoch einen Kompromiss zwischen Größe, Robustheit und Reproduzierbarkeit der Elektroden, da die Grenzflächenpotentiale zwischen ionenselektiver Membran und innerer Referenzelektrode bei der Miniaturisierung häufig in Mitleidenschaft gezogen werden. In dieser Arbeit zeigen wir, wie sich kationenselektive Interkalationsverbindungen wie halbgeladenes Lithiumeisenphosphat als innere Referenzelektrode quasi‐erster Art für ISEs verwenden lassen. Das symmetrische Ansprechverhalten der Membran und der Referenzelektrode gegenüber Kationen resultiert dabei sowohl in einer hohen Robustheit gegenüber Konzentrationsschwankungen der Innenfüllung (≈5 mV pro Konzentrationsdekade) als auch in einer robusten miniaturisierbaren Festkontakt‐ISE ohne Innenfüllung. Beide Arten von ISE weisen ein definiertes und stabiles Potential auf, welches sich aus dem Gleichgewichtspotential des LiFePO4/FePO4‐Redoxpaares (97.0±1.5 mV nach 42 Tagen) ableitet und mit −1.1±1.4 μV h−1 keine statistisch signifikante Drift bei einer durchschnittlichen Standardabweichung jeder Elektrode von weniger als ±0.7 mV nach 50 Tagen aufweist.
Structural Characterization of N‐Alkylated Twisted Amides: Consequences for Amide Bond Resonance and N−C Cleavage
Authors: Hu Feng , Lalancette Roger , Szostak Michal
Published: March 2016

Herein, we describe the first structural characterization of N‐alkylated twisted amides prepared directly by N‐alkylation of the corresponding non‐planar lactams. This study provides the first experimental evidence that N‐alkylation results in a dramatic increase of non‐planarity around the amide N−C(O) bond. Moreover, we report a rare example of a molecular wire supported by the same amide C=O‐Ag bonds. Reactivity studies demonstrate rapid nucleophilic addition to the N−C(O) moiety of N‐alkylated amides, indicating the lack of nN to π*C=O conjugation. Most crucially, we demonstrate that N‐alkylation activates the otherwise unreactive amide bond towards σ N−C cleavage by switchable coordination.
Construction of Vicinal Quaternary Stereogenic Centers by Enantioselective Direct Mannich‐Type Reaction Using a Chiral Bis(guanidino)iminophosphorane Catalyst
Authors: Takeda Tadahiro , Kondoh Azusa , Terada Masahiro
Published: March 2016

A novel asymmetric direct Mannich‐type reaction of α‐iminophenylacetate esters with thionolactones, bearing a substituent at the α‐position, as a less acidic pronucleophile was developed. Using bis(guanidino)iminophosphorane as the chiral organosuperbase catalyst, the reaction afforded densely functionalized amino‐acid derivatives having vicinal quaternary stereogenic centers, one of which is an all‐carbon quaternary stereogenic center, in good yield with high diastereo‐ and enantioselectivities.
Effect of temperature on the release of volatile and odorous compounds in flax fibers
Authors: Savary Géraldine , Morel Aurélie , Picard Céline , Grisel Michel
Published: March 2016

The behavior of flax fibers was investigated at temperatures of 80 °C, 200 °C, 215 °C, and 230 °C for a period of 60 min. First, thermogravimetric and colorimetric analyzes were carried out to characterize the impact of the temperature on the weight loss and the color of the fibers. Then, the release of volatile and odorous compounds from flax fibers was studied using both chemical and sensory approaches. Solid phase micro extraction was done to isolate the volatile organic compounds (VOCs) from the headspace of the sample while gas chromatography‐mass spectrometry (GC‐MS) and olfactometry (O) were used to determine the volatile and odorous compounds released at each temperature. About 24 VOCs were identified in the volatile fraction of flax fibers with a high occurrence of aliphatic aldehydes, phenols, and furans. Quantification by GC‐MS and by the aroma extract dilution analysis method was implemented. The results point to a critical temperature between 215 °C and 230 °C from which the odor of flax fibers becomes more intense, more complex, and with unpleasant features. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43497.
Fast‐Response Turn‐on Fluorescent Probes Based on Thiolysis of NBD Amine for H2S Bioimaging
Authors: Wang Runyu , Li Zhifei , Zhang Changyu , Li Yanyan , Xu Guoce , Zhang Qiang‐Zhe , Li Lu‐Yuan , Yi Long , Xi Zhen
Published: March 2016

Hydrogen sulfide (H2S) is an important endogenous signaling molecule with multiple biological functions. New selective fluorescent turn‐on probes based on fast thiolyling of NBD (7‐nitro‐1,2,3‐benzoxadiazole) amine were explored for sensing H2S in aqueous buffer and in living cells. The syntheses of both probes are simple and quite straightforward. The probes are highly sensitive and selective toward H2S over other biologically relevant species. The fluorescein‐NBD‐based probe showed 65‐fold green fluorescent increase upon H2S activation. The rhodamine‐NBD‐based probe reacted rapidly with H2S (t1/2≈1 min) to give a 4.5‐fold increase in red fluorescence. Moreover, both probes were successfully used for monitoring H2S in living cells and in mice. Based on such probe‐based tools, we could observe H2O2‐induced H2S biogenesis in a concentration‐dependent and time‐dependent fashion in living cells.
New Insights into the Diels–Alder Reaction of Graphene Oxide
Authors: Brisebois Patrick P. , Kuss Christian , Schougaard Steen B. , Izquierdo Ricardo , Siaj Mohamed
Published: March 2016

Graphene oxide is regarded as a major precursor for graphene‐based materials. The development of graphene oxide based derivatives with new functionalities requires a thorough understanding of its chemical reactivity, especially for canonical synthetic methods such as the Diels–Alder cycloaddition. The Diels–Alder reaction has been successfully extended with graphene oxide as a source of diene by using maleic anhydride as a dienophile, thereby outlining the presence of the cis diene present in the graphene oxide framework. This reaction provides fundamental information for understanding the exact structure and chemical nature of graphene oxide. On the basis of high‐resolution 13C‐SS NMR spectra, we show evidence for the formation of new sp3 carbon centers covalently bonded to graphene oxide following hydrolysis of the reaction product. DFT calculations are also used to show that the presence of a cis dihydroxyl and C vacancy on the surface of graphene oxide are promoting the reaction with significant negative reaction enthalpies.
New Chiral Reagent for Installation of Pharmacophoric (S)‐ or (R)‐2‐(Alkoxyphosphono)‐1‐amino‐2,2‐difluoroethyl Groups
Authors: Xie Chen , Zhang Lijun , Mei Haibo , Pajkert Romana , Ponomarenko Maksym , Pan Yi , Röschenthaler Gerd‐Volker , Soloshonok Vadim A. , Han Jianlin
Published: March 2016

A new chiral reagent has been developed for generalized installation of pharmacophoric (S)‐ or (R)‐2‐(alkoxyphosphono)‐1‐amino‐2,2‐difluoroethyl group into organic compounds. The original synthetic application of this new reagent is exemplified by Friedel–Crafts reactions with indoles, which proceed efficiently with excellent diastereoselectivity to give enantiomerically pure products.
Physicochemical properties of cellulose nanocrystals treated by photo‐initiated chemical vapour deposition (PICVD)
Authors: Javanbakht Taraneh , Raphael Wendell , Tavares Jason Robert
Published: March 2016

Cellulose nanocrystals (CNCs) are novel nanomaterials produced by the pulp and paper industry. The surface properties of CNCs are key factors for their dispersion in solvents. These polar materials disperse readily in water, but not in organic solvents. The ability to disperse into typically non‐polar organic matrices is an indispensable requirement to exploit the growing market for nanocomposite materials. We present an innovative approach for modifying the surface of CNCs through scalable, gas‐phase photo‐initiated chemical vapour deposition (PICVD). Using syngas as a treatment precursor, we demonstrate the effectiveness of this technique to render the surface of the CNCs compatible with mildly polar and non‐polar solvents, evidenced by contact angle measurements. Further proof of this successful modification is given through dispersion assays, showing for example the ability to disperse treated CNC in toluene (whereas untreated samples do not disperse). Suspensions in organic solvents remain stable in excess of two weeks. Chemical characterization through XPS and FTIR confirms the presence of an oxygen‐containing coating on the CNC surface.
Cationic Supramolecular Vesicular Aggregates for Pulmonary Tissue Selective Delivery in Anticancer Therapy
Authors: Licciardi Mariano , Paolino Donatella , Mauro Nicolò , Cosco Donato , Giammona Gaetano , Fresta Massimo , Cavallaro Gennara , Celia Christian
Published: March 2016

The biopharmaceutical properties of supramolecular vesicular aggregates (SVAs) were characterized with regard to their physicochemical features and compared with cationic liposomes (CLs). Neutral and cationic SVAs were synthesized using two different copolymers of poly(aspartyl hydrazide) by thin‐layer evaporation and extrusion techniques. Both copolymers were self‐assembled in pre‐formulated liposomes and formed neutral and cationic SVAs. Gemcitabine hydrochloride (GEM) was used as an anticancer drug and loaded by a pH gradient remote loading procedure, which significantly increased drug loading inside the SVAs. The resulting average size of the SVAs was 100 nm. The anticancer activity of GEM‐loaded neutral and cationic SVAs was tested in human alveolar basal epithelial (A549) and colorectal cancer (CaCo‐2) cells. GEM‐loaded cationic SVAs increased the anticancer activity in A549 and CaCo‐2 cells relative to free drug, neutral SVAs, and CLs. In vivo biodistribution in Wistar rats showed that cationic SVAs accumulate at higher concentrations in lung tissue than neutral SVAs and CLs. Cationic SVAs may therefore serve as an innovative future therapy for pulmonary carcinoma.
In‐depth characterization of the salivary adenoid cystic carcinoma transcriptome with emphasis on dominant cell type
Authors: Bell Diana , Bell Achim H. , Bondaruk Jolanta , Hanna Ehab Y. , Weber Randall S.
Published: March 2016

BACKGROUND

Adenoid cystic carcinoma (ACC), 1 of the most common salivary gland malignancies, arises from the intercalated ducts, which are composed of inner ductal epithelial cells and outer myoepithelial cells. The objective of this study was to determine the genomic subtypes of ACC with emphasis on dominant cell type to identify potential specific biomarkers for each subtype and to improve the understanding of this disease.

METHODS

A whole‐genome expression study was performed based on 42 primary salivary ACCs and 5 normal salivary glands. RNA from these specimens was subjected to expression profiling with RNA sequencing, and results were analyzed to identify transcripts in epithelial‐dominant ACC (E‐ACC), myoepithelial‐dominant ACC (M‐ACC), and all ACC that were expressed differentially compared with the transcripts in normal salivary tissue.

RESULTS

In total, the authors identified 430 differentially expressed transcripts that were unique to E‐ACC, 392 that were unique to M‐ACC, and 424 that were common to both M‐ACC and E‐ACC. The sets of E‐ACC–specific and M‐ACC–specific transcripts were sufficiently large to define and differentiate E‐ACC from M‐ACC. Ingenuity pathway analysis identified known cancer‐related genes for 60% of the E‐ACC transcripts, 69% of the M‐ACC transcripts, and 68% of the transcripts that were common in both E‐ACC and M‐ACC. Three sets of highly expressed candidate genes—distal‐less homeobox 6 (DLX6) for E‐ACC; protein keratin 16 (KRT16), SRY box 11 (SOX11), and v‐myb avian myeloblastosis viral oncogene homolog (MYB) for M‐ACC; and engrailed 1 (EN1) and statherin (STATH), which are common to both E‐ACC and M‐ACC)—were further validated at the protein level.

CONCLUSIONS

The current results enabled the authors to identify novel potential therapeutic targets and biomarkers in E‐ACC and M‐ACC individually, with the implication that EN1, DLX6, and OTX1 (orthodenticle homeobox 1) are potential drivers of these cancers. Cancer 2016;122:1513–22. © 2016 American Cancer Society.
The developmental biogeography of hawksbill sea turtles in the North Pacific
Authors: Van Houtan Kyle S. , Francke Devon L. , Alessi Sarah , Jones T. Todd , Martin Summer L. , Kurpita Lauren , King Cheryl S. , Baird Robin W.
Published: March 2016

High seas oceanic ecosystems are considered important habitat for juvenile sea turtles, yet much remains cryptic about this important life‐history period. Recent progress on climate and fishery impacts in these so‐called lost years is promising, but the developmental biogeography of hawksbill sea turtles (Eretmochelys imbricata) has not been widely described in the Pacific Ocean. This knowledge gap limits the effectiveness of conservation management for this globally endangered species. We address this with 30 years of stranding observations, 20 years of bycatch records, and recent simulations of natal dispersal trajectories in the Hawaiian Archipelago. We synthesize the analyses of these data in the context of direct empirical observations, anecdotal sightings, and historical commercial harvests from the insular Pacific. We find hawksbills 0–4 years of age, measuring 8–34 cm straight carapace length, are found predominantly in the coastal pelagic waters of Hawaii. Unlike other species, we find no direct evidence of a prolonged presence in oceanic habitats, yet satellite tracks of passive drifters (simulating natal dispersal) and our small sample sizes suggest that an oceanic phase for hawksbills cannot be dismissed. Importantly, despite over 600 million hooks deployed and nearly 6000 turtle interactions, longline fisheries have never recorded a single hawksbill take. We address whether the patterns we observe are due to population size and gear selectivity. Although most sea turtle species demonstrate clear patterns of oceanic development, hawksbills in the North Pacific may by contrast occupy a variety of ecosystems including coastal pelagic waters and shallow reefs in remote atolls. This focuses attention on hazards in these ecosystems – entanglement and ingestion of marine debris – and perhaps away from longline bycatch and decadal climate regimes that affect sea turtle development in oceanic regions.
Photoluminescence, Unconventional‐Range Temperature Sensing, and Efficient Catalytic Activities of Lanthanide Metal–Organic Frameworks
Authors: Gomez Germán E. , Kaczmarek Anna M. , Van Deun Rik , Brusau Elena V. , Narda Griselda E. , Vega Daniel , Iglesias Marta , Gutierrez‐Puebla Enrique , Monge M. Ángeles
Published: March 2016

A luminescent lanthanide metal–organic framework (MOF) based on Eu3+ and Tb3+ ions with 2‐phenylsuccinate (EuTb‐psa) was obtained solvothermally to explore its behavior as a temperature sensor in an unconventional temperature range through the study of the thermal evolution of the hypersensitive 4f–4f 5D0→7F2 transition and the luminescence lifetime. The efficiency of the luminescence process was evaluated through the europium intrinsic quantum yield (QEu), and its variation as a function of temperature is also reported. The optical properties of four isostructural compounds (Pr‐psa, Nd‐psa, Gd‐psa, and Tb‐psa) were investigated and compared with those of related compounds. The energy of the triplet state of the ligand was also estimated. The samples were fully characterized by single‐crystal and powder X‐ray diffraction, thermal analysis, and vibrational spectroscopy. The heterogeneous catalytic activities of a series of Ln‐psa MOFs (with Ln = Sm, Eu, Gd, Tb, EuGd, and EuTb) were evaluated in a one‐pot cyanosilylation with benzaldehyde as the substrate.
seco‐Casbanes from the Australian Rainforest: ECD Predictions Key for Determining Remote Absolute Configuration
Authors: Maslovskaya Lidia A. , Savchenko Andrei I. , Gordon Victoria A. , Reddell Paul W. , Pierce Carly J. , Parsons Peter G. , Williams Craig M.
Published: March 2016

The seco‐casbane framework, first isolated from Croton insularis, is surprisingly rare. Further evaluation of this Australian rainforest plant unearthed two additional members, EBC‐328 and EBC‐363. TD DFT predicted electronic circular dichroism (ECD) spectra were critical for remote absolute stereochemical determination. EBC‐328 displayed cytotoxic activity towards leukemia cells (K562). Potential biosynthetic relationships are discussed.
Glutaric Acid Assisted Fabrication of CuO Nanostructures and their Application in Development of Highly Sensitive Electrochemical Sensor System for Carbamates
Authors: Soomro Razium Ali , Hallam Keith Richard , Ibupoto Zafar Hussain , Tahira Aneela , Sherazi Syed Tufail Hussain , Juddin Siraj , Jawaid Sana , Willander Magnus
Published: March 2016

This work describes the fabrication of unique arrow head shaped CuO nanostructures using simple hydrothermal treatment method. The highly attractive features were obtained by the application of glutaric acid utilised simultaneous as template and functionalising agent. The functionalised nanostructures were known to possess excellent potential towards the electro‐catalytic oxidation of carbofuran pesticide. The generated intense electrochemical signal with lower potential value enabled sensitive and selective determination of carbofuran up to 1×10−3 µM with wide sensing window in range of 0.01 to 0.16 µM. The feasibility of the developed sensor system for the practical application was also studied by testing its potential in real sample extracts of various vegetables. The excellent recoveries demonstrated the analytical robustness of the developed sensor system. The sensor system utilises a new and simple approach towards sensitive determination of toxic pesticides reflecting its wide spectrum application in various fields.
Remote sensing estimates and measures of uncertainty for forest variables at different aggregation levels
Authors: Mauro F. , Molina I. , García‐Abril A. , Valbuena R. , Ayuga‐Téllez E.
Published: March 2016

Empirical best linear unbiased predictors (EBLUPs) based on auxiliary information are efficient for estimating means or totals of environmental attributes in small domains. In small area estimation, the EBLUPs and their approximately unbiased mean square error (MSE) estimators are obtained under the premise of having a large number of population units in the target domain. In remote sensing, single pixels are regarded as population units, and EBLUPs and MSE estimators may also be required for subdomains containing a low number of pixels or even single pixels. In this study, EBLUPs, their MSE, and an unbiased estimator of the MSE are derived when predicting linear parameters for subdomains with a small number of population units that do not intersect with the training sample. In these situations, an additional MSE component should be considered to prevent MSE underestimation. A case study illustrates the applicability of the obtained results in the context of a Light Detection and Ranging‐based forest inventory, where estimates are provided for areas of interest sizing from single pixels or population units to thousands of hectares. Based on our results, we recommend to consider the additional component in the MSE estimator when estimating in pixels and domains of interest sizing few hectares. Copyright © 2016 John Wiley & Sons, Ltd.
Comparison of Two ELISA Methods and Mass Spectrometry for Measurement of Vitamin D-Binding Protein: Implications for the Assessment of Bioavailable Vitamin D Concentrations Across Genotypes
Authors: Denburg Michelle R , Hoofnagle Andrew N , Sayed Samir , Gupta Jayanta , de Boer Ian H , Appel Lawrence J , Durazo-Arvizu Ramon , Whitehead Krista , Feldman Harold I , Leonard Mary B ,   on behalf of the Chronic Renal Insufficiency Cohort study investigators
Published: March 2016

Studies using vitamin D-binding protein (DBP) concentrations to estimate free and bioavailable vitamin D have increased dramatically in recent years. Combinations of two single-nucleotide polymorphisms (SNPs) produce three major DBP isoforms (Gc1f, Gc1s, and Gc2). A recent study showed that DBP concentrations quantified by liquid chromatography–tandem mass spectrometry (LC-MS/MS) did not differ by race, whereas a widely used monoclonal enzyme-linked immunosorbent assay (ELISA) quantified DBP differentially by isoform, yielding significantly lower DBP concentrations in black versus white individuals. We compared measurements of serum DBP using a monoclonal ELISA, a polyclonal ELISA, and LC-MS/MS in 125 participants in the Chronic Renal Insufficiency Cohort (CRIC). Serum free and bioavailable 25OHD were calculated based on DBP concentrations from these three assays in homozygous participants, and race differences were compared. We confirmed that the monoclonal ELISA quantifies DBP differentially by isoform and showed that the polyclonal ELISA is not subject to this bias. Whereas ≤9% of the variability in DBP concentrations quantified using either LC-MS/MS or the polyclonal ELISA was explained by genotype, 85% of the variability in the monoclonal ELISA-based measures was explained by genotype. DBP concentrations measured by the monoclonal ELISA were disproportionately lower than LC-MS/MS-based results for Gc1f homozygotes (median difference –67%; interquartile range [IQR] –71%, –64%), 95% of whom were black. In contrast, the polyclonal ELISA yielded consistently and similarly higher measurements of DBP than LC-MS/MS, irrespective of genotype, with a median percent difference of +50% (IQR +33%, +65%). Contrary to findings using the monoclonal ELISA, DBP concentrations did not differ by race, and free and bioavailable 25OHD were significantly lower in black versus white participants based on both the polyclonal ELISA and LC-MS/MS, consistent with their lower total 25OHD. Future studies of DBP and free or bioavailable vitamin D metabolites should employ DBP assays that are not biased by DBP genotype. © 2016 American Society for Bone and Mineral Research.
Finite Element Analysis of Denosumab Treatment Effects on Vertebral Strength in Ovariectomized Cynomolgus Monkeys
Authors: Lee David C , Varela Aurore , Kostenuik Paul J , Ominsky Michael S , Keaveny Tony M
Published: March 2016

Finite element analysis has not yet been validated for measuring changes in whole-bone strength at the hip or spine in people after treatment with an osteoporosis agent. Toward that end, we assessed the ability of a clinically approved implementation of finite element analysis to correctly quantify treatment effects on vertebral strength, comparing against direct mechanical testing, in cynomolgus monkeys randomly assigned to one of three 16-month-long treatments: sham surgery with vehicle (Sham-Vehicle), ovariectomy with vehicle (OVX-Vehicle), or ovariectomy with denosumab (OVX-DMAb). After treatment, T12 vertebrae were retrieved, scanned with micro-CT, and mechanically tested to measure compressive strength. Blinded to the strength data and treatment codes, the micro-CT images were coarsened and homogenized to create continuum-type finite element models, without explicit porosity. With clinical translation in mind, these models were then analyzed for strength using the U.S. Food and Drug Administration (FDA)-cleared VirtuOst software application (O.N. Diagnostics, Berkeley, CA, USA), developed for analysis of human bones. We found that vertebral strength by finite element analysis was highly correlated (R2 = 0.97; n = 52) with mechanical testing, independent of treatment (p = 0.12). Further, the size of the treatment effect on strength (ratio of mean OVX-DMAb to mean OVX-Vehicle, as a percentage) was large and did not differ (p = 0.79) between mechanical testing (+57%; 95% CI [26%, 95%]) and finite element analysis (+51% [20%, 88%]). The micro-CT analysis revealed increases in cortical thickness (+45% [19%, 73%]) and trabecular bone volume fraction (+24% [8%, 42%]). These results show that a preestablished clinical finite element analysis implementation—developed for human bone and clinically validated in fracture-outcome studies—correctly quantified the observed treatment effects of denosumab on vertebral strength in cynomolgus monkeys. One implication is that the treatment effects in this study are well explained by the features contained within these finite element models, namely, the bone geometry and mass and the spatial distribution of bone mass. © 2016 American Society for Bone and Mineral Research.
Suberoylanilide Hydroxamic Acid Restores Estrogen Reduced‐cTnI Expression in Neonatal Hearts of Mice
Authors: Peng Chang , Luo Xiaomei , Xing Qianlu , Sun Huichao , Huang Xupei
Published: March 2016

Diastolic cardiac dysfunction can be caused by abnormality in cTnI expression during cardiogenesis. In this study, we investigated the effects of estrogen on the abnormal expression of cTnI in the hearts of neonatal mice and its potential epigenetic mechanisms. We then evaluated suberoylanilide hydroxamic acid (SAHA), a HDAC inhibitor, as a new target treatment of diastolic cardiac dysfunction. Postnatal day 0.5 C57BL/6 mice were injected with estrogen for 1 week, then the hearts of 7‐day‐old neonatal mice were retrieved for examination. The activities of HDAC and HAT were assayed by colorimetry, and the interaction of cTnI with HDAC5 in mice hearts were examined using chromatin immunoprecipitation assays. The expression of cTnI was tested by quantitative real‐time RT‐PCR and Western blot. Estrogen treated groups displayed a significantly increased HDAC activity in the hearts of neonatal mice while HAT activity remained unchanged. Additionally, HDAC5 was higher at the cTnI promoter, as compared to the saline treated control groups. The acetylation of histone H3K9ac on cTnI promoter significantly decreased in the hearts of neonatal mice treated with estrogen, and the expression of cTnI at transcriptional and protein levels also decreased. SAHA was shown to increase the acetylation of histone H3K9ac and upregulate the expression of cTnI. The data demonstrated that SAHA can correct cTnI expression abnormality caused by estrogen through inhibiting the binding of HDAC5 to the promoter of cTnI. J. Cell. Biochem. 117: 2377–2384, 2016. © 2016 Wiley Periodicals, Inc.
Reference Intervals of Fibrosis Index Based on Four Indicators in Healthy Elderly Chinese
Authors: Zhang Guo‐Ming , Xia Yong‐Jie
Published: March 2016

Background

The establishment of reference intervals of total bilirubin, Alanine aminotransferase (ALT), aspartate aminotransferases (AST), and creatinine provided necessary reference in screening and diagnosis of various kidney and liver diseases. However, these reference intervals were not available to estimate liver fibrosis degree. The purpose of this study is to establish the reference intervals of fibrosis index based on the four indicators (FIB‐4) in apparently healthy elderly Chinese.

Methods

A total of 24,949 blood specimens were collected by the standard procedures, and ALT, AST, and PLT were determined. FIB‐4 were calculated by the following formula: FIB‐4 = (age [years] × AST [U/l])/((PLT [109/l]) × (ALT [U/l])1/2).The elderly's FIB‐4 were analyzed between the same age of different sexes and different ages of the same sex. Statistical data were analyzed by SPSS18.0 software.

Results

Reference intervals of FIB‐4 index, established for the healthy elderly, were 0.9923–4.5424 for males and 0.9007–4.1934 for females.

Conclusion

We established reference intervals of FIB‐4 index. This research provided reference value that can be used by relevant clinicians and inspection officers.
Alternative Start Codon Connects eIF5A to Mitochondria
Authors: Pereira Karina Danielle , Tamborlin Letícia , Meneguello Letícia , de Proença André Ricardo Gomes , Almeida Isadora Cristina de Paula Andrade , Lourenço Rogério Ferreira , Luchessi Augusto Ducati
Published: March 2016

Eukaryotic translation initiation factor 5A (eIF5A), a protein containing the amino acid residue hypusine required for its activity, is involved in a number of physiological and pathological cellular processes. In humans, several EIF5A1 transcript variants encode the canonical eIF5A1 isoform B, whereas the hitherto uncharacterized variant A is expected to code for a hypothetical eIF5A1 isoform, referred to as isoform A, which has an additional N‐terminal extension. Herein, we validate the existence of eIF5A1 isoform A and its production from transcript variant A. In fact, variant A was shown to encode both eIF5A1 isoforms A and B. Mutagenic assays revealed different efficiencies in the start codons present in variant A, contributing to the production of isoform B at higher levels than isoform A. Immunoblotting and mass spectrometric analyses showed that isoform A can undergo hypusination and acetylation at specific lysine residues, as observed for isoform B. Examination of the N‐terminal extension suggested that it might confer mitochondrial targeting. Correspondingly, we found that isoform A, but not isoform B, co‐purified with mitochondria when the proteins were overproduced. These findings suggest that eIF5A1 isoform A has a role in mitochondrial function. J. Cell. Physiol. 231: 2682–2689, 2016. © 2016 Wiley Periodicals, Inc.
Pharmacological Management of Challenging Behaviours in People with Dementia
Authors: Peisah Carmelle , Brodaty Henry
Published: March 2016

Behavioural and psychological signs and symptoms in hospitalised demented patients pose problems for sufferers, staff and fellow patients alike. Guidelines are provided for managing these difficult behaviours in the hospital setting. Pharmacotherapy should only be implemented after consideration of underlying causes, the need for treatment and the appropriateness of nonpharmacological measures. When choosing drug type and dose, clinicians should be mindful of altered pharmacokinetics in the elderly, the variable efficacy and toxicity of different psychotropic drugs and, importantly, issues of consent. Pharmacological strategies for treating specific symptoms are outlined, with recommendations regarding drug dosage, monitoring and review.
Who Can Read Consumer Product Information?
Authors: Baker Stuart J
Published: March 2016

Aim:To assess the readability of a sample of Consumer Product Information (CPI) leaflets for Australian pharmaceutical products.

Method: 30 CPIs were randomly selected from a total of 83 supplied from the Australian Pharmaceutical Manufacturers Association (90%) and the remainder from a community pharmacy. The CPIs were scanned as a computer file or typed into WordPerfect 6.1 and analysed for readability using the Flesch Reading Ease (FRE) formula. CPIs were also assessed for good design features using a newly created measure — the Baker Able Leaflet Design (BALD).

Results: The mean FRE score was 51 (SD, 6.8; range 37—60) so the sampled CPIs could be understood by 40% or less of the population. The mean BALD score was 17 (SD, 3.6; range 10– 22) out of a maximum of 32. This compared favourably to a few overseas leaflets but not to some non‐CPIs produced in Australia and there were many features that could be easily remedied to make CPIs easier to use.

Conclusion: CPIs are pitched at a level beyond the comprehension of most of the population. People who have English as their second language would have even more difficulty.

Aust J Hosp Pharm 1997; 27: 126–31.
Guidelines for Drug Administration During Enteral Feeding
Authors: Gilbar Peter J , Kam Fanny SF
Published: March 2016

Objective: The purpose of this article is to highlight the factors that must be considered when administering medications via an enteral feeding tube and to provide recommendations for safe and effective drug administration by this route.

Data Sources: A variety of literature sources, including manual and on‐line (Medline, IDIS) searching, were used. Gastrointestinal drug administration linked with a variety of enteral feeding terminologies and individual drug names were used as the primary search terms. Study Selection: Any articles relevant to drug administration during enteral feeding were considered.

Conclusion: With the increasing use of the enteral route as a means of drug delivery, it is important for health professionals to be aware of the potential complications of this method. Factors including dosage forms, compatibility, drug absorption and clearance must be considered before medication can be successfully administered via an enteral feeding tube. Improved drug bioavailability can be achieved by following the recommended administration guidelines, but regular monitoring of patients is needed to ensure an optimal clinical response.

Aust J Hosp Pharm 1997; 27: 214–20.
Optimisation of Drug Delivery I. Principles of Oral Absorption and Limitations of Conventional Oral Dosage Forms
Authors: Benson Heather AE , Prankerd Richard J
Published: March 2016

This review presents the main physiological and physicochemical aspects of oral drug absorption. These include absorption processes, drug dissolution, acid‐base equilibria, transit time, presence of food, enterohepatic cycling and colonic absorption. Some of the limitations of oral drug delivery are then reviewed, including unacceptable taste, drug instability in the gastrointestinal tract, gastrointestinal irritation, first‐pass metabolism, onset of action, poor absorption, side effects, limited absorption capacity, drug interactions, formulation effects on bioavailability, variable absorption and disease effects. Approaches to circumventing some of these limitations are discussed.
A Preliminary Study of the Effects of Venlafaxine on 24‐Hour Urinary Catecholamine Excretion Profile
Authors: Alderman Christopher P
Published: March 2016

Objective: To investigate the effects of venlafaxine on the 24‐hour urinary catecholamine excretion profile in patients treated with this drug for depression.

Method: Patients to be treated with venlafaxine for the management of a depressive illness were requested to provide a 24‐hour urine sample immediately before the commencement of therapy. The urinary concentrations of adrenaline and noradrenaline were determined, and the 24‐hour urinary catecholamine excretion profile was calculated. This procedure was repeated after treatment with venlafaxine for 14 days.

Results: Eight patients were enrolled in the study, but three patients did not complete the protocol because of adverse drug reactions. The effects of venlafaxine treatment on the profile of urinary catecholamine excretion were assessable in five patients. The mean 24‐hour excretion of noradrenaline appeared to be decreased after venlafaxine treatment, but this decrease failed to attain statistical significance. The 24‐hour urinary excretion of adrenaline was unchanged after venlafaxine, but the ratio of noradrenaline:adrenaline urinary excretion decreased significantly after treatment.

Conclusions: This small prospective study demonstrates an altered profile of urinary catecholamine excretion in patients treated with venlafaxine for depression for two weeks. Further research is needed to determine whether there is a correlation between the effects of venlafaxine on urinary noradrenaline excretion and the therapeutic and/or adverse effects of this antidepressant.

Aust J Hosp Pharm 1997; 27: 232–3.
Opportunities in Coordinated Care
Authors: McCrudden Elizabeth A
Published: March 2016

The 1997 Pharmacy Leadership and Development Program (PLDP) explored some of the issues and opportunities facing pharmacists as the Australian coordinated care trials begin. Pharmacists are in a unique position to assist in the management of patients with complex care needs. Pharmacists are the most frequently accessed primary healthcare professionals, have established and extensive liaison networks and are computerised so as to be able to provide appropriate and timely information. However, a unified and proactive approach is necessary for the role of pharmacists to be acknowledged by funding bodies. Coordinated care provides opportunities to move the pharmacy profession towards a significant role in the modern delivery of health care.
Compatibility of Paclitaxel in 5% Glucose and 0.9% Sodium Chloride Injections with EVA Minibags
Authors: Xu Quanyun A , Trissel Lawrence A , Davis Melvyn R
Published: March 2016

Aim: To evaluate the compatibility of a paclitaxel formulation (Anzatax, Paulding) at concentrations of 0.3 and 1.2 mg/mL in 5% glucose injection and 0.9% sodium chloride injection with Baxter ethylene vinyl acetate (EVA) solution containers. We evaluated the potential for leachable materials to be extacted from the EVA bag by the paclitaxel formulation and the potential for paclitaxelloss due to sorption to the plastic.

Method: The paclitaxel admixtures at both concentrations were prepared and stored at 25 and 32°C, protected from light, for 72 hours. All admixtures were prepared in triplicate in the EVA minibags; samples were drawn from the containers initially upon preparation and after 24 and 72 hours of storage. The paclitaxel concentrations of the samples and the extractable content from the container were determined using separate high performance liquid chromatographic methods. Leached material was analysed by mass spectrometer.

Results: Paclitaxel was chemically stable throughout the 72‐hour study period exhibiting no loss due to decomposition or sorption in any of the admixtures. However,
an unknown material was leached from the EVA containers, appearing in both the 24‐ and 72‐hour samples. The unknown material chromatographed very similarly to an unknown that was extracted by contact of the plastic with pure acetonitrile. The unknown primarily consisted of three entities having masses of 888.69, 932.68, and 976.73 daltons and may be leached polymeric material varying in the number of associated acetate groups.

Conclusion: Paclitaxel is chemically stable at 0.3 and 1.2 mg/mL in 5% glucose injection and in 0.9% sodium chloride injection in EVA containers for up to 72 hours at 25 and 32°C. However, some material of unknown identity was leached into the drug admixture from the container within 24 hours.
Perhexiline‐Paroxetine Drug Interaction
Authors: Alderman Christopher P
Published: March 2016

Objective: To document a case of perhexiline toxicity associated with concurrent treatment with paroxetine.

Clinical Features: An 86‐year‐old woman was admitted to hospital when she was unable to cope at home and because of ataxia, falls, lethargy and nausea. She had started on paroxetine 20 mg daily five weeks before presentation. Investigations revealed elevations in both liver function and serum perhexiline concentration (2.02 mg/L, range 0.15‐0.6 mg/L).

Conclusion: Perhexiline toxicity may occur as a result of concurrent treatment with a selective serotonin reuptake inhibitor.
Strategies to Attract Locum Pharmaciststo Hospital Practice
Authors: Linsley Ross F , Gregory Debbie
Published: March 2016

Uncompetitive wages, inflexible work conditions, and scarce graduate positions in hospital each year have contributed to a shortage of locum hospital pharmacists in New South Wales (NSW). Therefore, the NSW Branch of SHPA introduced a self‐funding, fee‐paying placement service coordinated by a locum pharmacist. Twenty‐two known locums were surveyed to identify their needs, motivation, and the barriers to working in hospital.

Most locums were newly registered pharmacists or were returning to hospital pharmacy after an extended absence. Hospital pharmacy was attractive because of a clinical and supportive environment, plus contact with patients and physicians. The barriers were locums' perceived gap in clinical knowledge, the absence of entry level clinical courses, inflexible work hours, illogical procedures, and a bureaucratic mentality.

Consequently, an Introduction to Hospital Pharmacy course is being offered by SHPA (NSW), with an emphasis on mentoring locums back into the workforce through entry‐level clinical teaching and an explanation of policies and procedures. Since this initiative, two pharmacists who had been out of work for many years are now keenly sought as locums,some locums have worked in other hospitals and are enjoying the variety, UK pharmacists have telephoned in advance for placement, and the locums have appreciated information about a job from an independent source.
Polypharmacy in a Major Australian Teaching Hospital
Authors: Pellizzer Anne‐Marie , O'Callaghan Christopher J , Branley Pauline , Thomson Bill , Krum Henry
Published: March 2016

We sought to determine the extent of polypharmacy and the incidence of potentially clinically significant drug‐drug interactions in discharge medication.
Management of Peptic Ulcer Disease in Older People
Authors: Lockrey Gregory J
Published: March 2016

Peptic ulcer disease is common in older people, and they bear much of the impact of its complications. Improved understanding of the principal causes of ulcers ‐ Helicobacter pylori and non‐steroidal anti‐inflammatory drugs ‐ has recently led to significant advances in drug treatment for ulcer disease. These new treatments offer the prospect of better symptom relief and improved mortality in the elderly.
Surgical Antibiotic Prophylaxis in a Private Hospital Compliance with Guidelines
Authors: McConachy Kerri A , Cuell Sylvia , Kent Paschal J , McDonald Malcolm I
Published: March 2016

Objective: To prospectively evaluate the appropriateness of prophylactic surgical antibiotic use and the cost of inappropriate surgical antibiotic prophylaxis in a 115‐bed private hospital.

Method: Details of prophylactic antibiotic administration were recorded by operating theatre nursing staff and the clinical pharmacists assessed the appropriateness of the indication, antibiotic choice and dose. Surgical antibiotic prophylaxis was considered appropriate if it met either the in‐house Surgical Antimicrobial Protocol or the Antibiotic Guidelines 96/97 9th edition. We assessed the timing of administration and analysed the cost of inappropriate drug use and laboratory monitoring.

Results: Surgical antibiotic prophylaxis was indicated in 92% of procedures (230/251) and used, or not used, appropriately in 86% of procedures (215/251). In the 197 cases in which antibiotics were indicated and used: only 62% of doses (122/197) were administered at or less than two hours before induction; and the correct antibiotic was chosen in 90% of cases (178/197). Dosage was correct in 77% of cases overall (192/251), but in 98% of cases when the appropriate antibiotic was chosen (174/178). Single doses were employed in only 68% of procedures (133/197). There was compliance with all five criteria in only 35% of cases. The annual cost to this hospital of inappropriate antibiotic prophylaxis was estimated at over $40 000.

Conclusion: This study demonstrated modest compliance with current recommendations for surgical antimicrobial prophylaxis. As a result, the in‐house protocol is being revised to include ENT procedures and a new anaesthetic record form is being developed. Further education is being targeted to anaesthetists, urologists, orthopaedic, colorectal and ENT surgeons.
Survey of Pharmacy Resources Needed to Implement Hospital Antibiotic Policies
Authors: Adu Ammishaddai , Simpson Judy M , Armour Carol L
Published: March 2016

We surveyed directors of pharmacy in New South Wales (NSW) public hospitals to identify the resources they considered essential or needed to implement and evaluate antibiotic policies.
Monitoring Thyroxine Dosage with Serum Concentrations of Thyroid Stimulating Hormone
Authors: McConachy Kerri A , Brien Jo‐anne E
Published: March 2016

To prospectively review thyroxine replacement therapy at The Geelong Hospital and evaluate the relationship between thyroxine dose and measured thyroid stimulating hormone (TSH) concentration in this population.
Pindolol Augmentation of Antidepressant Therapy
Authors: Alderman Christopher P , Colarco Tania
Published: March 2016

To review the safety and efficacy of pindolol in augmenting the response to antidepressant drugs.
Low Levels of Adherence to Antibiotic Prescribing Guidelines within Emergency Departments
Authors: To Nancy NL , Khan Zhora , Chiu Felix , Jordan Margaret , Koller Lorraine , Daly Genevieve , Armour Carol L
Published: March 2016

To assess the adherence of antibiotic prescribing in emergency departments (ED) to hospital guidelines.
Inpatients' Satisfaction with Clinical Pharmacists' Counselling
Authors: Robinson Maxine KF , Connolly Jennifer
Published: March 2016

To evaluate the satisfaction of inpatients with hospital pharmacists' counselling.
Destabilisation of Fat Emulsion in Total Nutrient Admixtures by Concentrated Albumin 20% Infusion
Authors: Ambados Fotios
Published: March 2016

To demonstrate the disruptive effect of albumin on fat emulsion homogeneity in total nutrient admixtures (TNAs) stored at room temperature.
Cytotoxic Manufacturing: What a Load of Rubbish
Authors: Bayles Maryann , Siderov Jim
Published: March 2016

To review the amount of waste generated from the cytotoxic production unit (CPU), to implement procedures to minimise landfill waste and encourage recycling, and to reduce costs associated with cytotoxic waste disposal.
Community Liaison Pharmacy Working with the Illawarra Division of General Practice and the Illawarra Area Health Service in 1998
Authors: Mullan Judy R
Published: March 2016

To describe the role of a community liaison pharmacist working with general practitioners, community pharmacists and other healthcare professionals to improve medication management.
ICD‐10‐AM Activity Codes: An Opportunity for Standardisation
Authors: McLennan Danielle N , Dooley Michael J , Brien Jo‐anne E
Published: March 2016

To implement the pharmacy‐specific ICD‐10‐AM codes into clinical practice and to evaluate their applicability to the classification and documentation of clinical pharmacy activities.
Concurrent Frusemide‐Theophylline Dosing Reduces Serum Vancomycin Concentrations in Preterm Infants
Authors: Yeung Melinda Y , Smyth John P
Published: March 2016

To document serum vancomycin concentrations in preterm infants on concurrent frusemide‐theophylline therapy and to observe the effect of this drug combination on serum creatinine concentrations.
Drugs in Ambulatory Infusion Devices The Appropriate Temperature for Stability Testing
Authors: Poole Susan G , Doole Michael J
Published: March 2016

To determine the temperature of an infusion solution during simulated ambulatory infusion and recommend temperatures for stability assessment of drugs in this setting.
Cytochrome P450 1. Multiplicity and Function
Authors: McKinnon Ross A
Published: March 2016

This article updates pharmacists on the cytochrome P450 superfamily of drug metabolising enzymes. It comprises a brief history of P450 research, the standard P450 nomenclature system, an outline of recent advances in P450 identification, and an estimate of the total number of human P450 enzymes.
Azathioprine Hepatotoxicity Confirmed by Rechallenge
Authors: Eaton Vaughn S , Casanova Jenny M , Kupa Ann
Published: March 2016

To document a case of azathioprine hepatotoxicity confirmed by rechallenge.
Cytochrome P450 2. Pharmacogenetics
Authors: McKinnon Ross A , Evans Allan M
Published: March 2016

Inter‐individual variability in drug metabolism results from the
influence of a myriad of factors including genetic factors and
concurrent drug therapy. Advances in recombinant DNA technology
have greatly enhanced our understanding of the extent
of genetic variation in the P450 superfamily, clarifying the
molecular basis of many clinically observed variations in drug
response. This second article in the cytochrome P450 series
describes our current understanding of genetic variability in
the major drug‐metabolising P450s, the nomenclature used to
describe variant P450 genes, and the clinical significance of
such variability.