bluuebunny/crossref_metadata_2025 huggingface dataset:
A sulfated carbohydrate epitope inhibits axon regeneration after injury
Authors: Brown Joshua M. , Xia Jiang , Zhuang BinQuan , Cho Kin-Sang , Rogers Claude J. , Gama Cristal I. , Rawat Manish , Tully Sarah E. , Uetani Noriko , Mason Daniel E. , Tremblay Michel L. , Peters Eric C. , Habuchi Osami , Chen Dong F. , Hsieh-Wilson Linda C.
Published: March 2012

Chondroitin sulfate proteoglycans (CSPGs) represent a major barrier to regenerating axons in the central nervous system (CNS), but the structural diversity of their polysaccharides has hampered efforts to dissect the structure-activity relationships underlying their physiological activity. By taking advantage of our ability to chemically synthesize specific oligosaccharides, we demonstrate that a sugar epitope on CSPGs, chondroitin sulfate-E (CS-E), potently inhibits axon growth. Removal of the CS-E motif significantly attenuates the inhibitory activity of CSPGs on axon growth. Furthermore, CS-E functions as a protein recognition element to engage receptors including the transmembrane protein tyrosine phosphatase PTPσ, thereby triggering downstream pathways that inhibit axon growth. Finally, masking the CS-E motif using a CS-E-specific antibody reversed the inhibitory activity of CSPGs and stimulated axon regeneration in vivo. These results demonstrate that a specific sugar epitope within chondroitin sulfate polysaccharides can direct important physiological processes and provide new therapeutic strategies to regenerate axons after CNS injury.
Structure of the ZU5-ZU5-UPA-DD tandem of ankyrin-B reveals interaction surfaces necessary for ankyrin function
Authors: Wang Chao , Yu Cong , Ye Fei , Wei Zhiyi , Zhang Mingjie
Published: March 2012

Ankyrin-R/B/G (encoded by
ANK1/2/3
, respectively) are a family of very large scaffold proteins capable of anchoring numerous receptors and ion channels to specific, spectrin-containing membrane micro-domains. Hereditary mutations of ankyrins are known to be associated with diseases including spherocytosis, cardiac arrhythmia, and bipolar disorder in humans, although the underlying molecular bases are poorly understood. The middle spectrin-binding domain of ankyrins contains highly conserved ZU5-ZU5-UPA-DD domains arranged into the ZZUD tandem. Curiously, most of the disease-causing mutations in the tandem have no apparent impact on the spectrin binding of ankyrins. The high resolution structure of the ankyrin-B ZZUD tandem determined here reveals that the ZU5-ZU5-UPA domains form a tightly packed structural supramodule, whereas DD is freely accessible. Although the formation of the ZZU supramodule does not influence the spectrin binding of ankyrins, mutations altering the interdomain interfaces of ZZU impair the functions of ankyrin-B&G. Our structural analysis further indicates that the ZZU supramodule of ankyrins has two additional surfaces that may bind to targets other than spectrin. Finally, the structure of the ankyrin ZZUD provides mechanistic explanations to many disease-causing mutations identified in ankyrin-B&R.
Supernova-driven outflows and chemical evolution of dwarf spheroidal galaxies
Authors: Qian Yong-Zhong , Wasserburg G. J.
Published: March 2012

We present a general phenomenological model for the metallicity distribution (MD) in terms of [Fe/H] for dwarf spheroidal galaxies (dSphs). These galaxies appear to have stopped accreting gas from the intergalactic medium and are fossilized systems with their stars undergoing slow internal evolution. For a wide variety of infall histories of unprocessed baryonic matter to feed star formation, most of the observed MDs can be well described by our model. The key requirement is that the fraction of the gas mass lost by supernova-driven outflows is close to unity. This model also predicts a relationship between the total stellar mass and the mean metallicity for dSphs in accord with properties of their dark matter halos. The model further predicts as a natural consequence that the abundance ratios [E/Fe] for elements such as O, Mg, and Si decrease for stellar populations at the higher end of the [Fe/H] range in a dSph. We show that, for infall rates far below the net rate of gas loss to star formation and outflows, the MD in our model is very sharply peaked at one [Fe/H] value, similar to what is observed in most globular clusters. This result suggests that globular clusters may be end members of the same family as dSphs.
Genetics.
Authors: Stommel J. R. , Albrecht E.
Published: March 2012

This chapter presents recent advances in research on the genetics of pepper (Capsicum spp.), mainly discussing molecular taxonomy, phylogenetics, male sterility, interspecific hybridization, and genetic improvement of colour, capsaicinoid content, morphology, and resistance to abiotic stress (drought, flooding, salinity, heat stress and cold stress), diseases (fungal, bacterial and viral diseases) and pests (insects, mites and nematodes). Quantitative trait loci and genetic markers associated with economically important traits of pepper are extensively covered.
Stand establishment.
Authors: Leskovar D. I. , Kahn B. A.
Published: March 2012

This chapter describes the impact of physiological, chemical and biological agents (including plant growth regulators, endophytes, and vesicular arbuscular mycorrhizas) on key morphological and physiological adaptive mechanisms that peppers (Capsicum spp.) use to cope with abiotic stress (heat and cold stress, drought, nutrition-related stress, salinity, and transplant shock). A comparison of direct sowing and transplanting methods of sweet and hot peppers based on root and shoot growth and yield is presented.
Salt tolerance in pepper (Capsicum spp.).
Authors: Niu G. H.
Published: March 2012

This chapter summarizes recent research findings on salt tolerance in Capsicum species and genotypes. Factors influencing salt tolerance (environmental conditions, nutrient management, plant age, and cultural methods), the effects of salinity and soil type on seedling emergence of pungent peppers, salt tolerance in pungent peppers during early vegetative growth under greenhouse and field conditions, and physiological responses of peppers to salinity.
Organic pepper production.
Authors: Ozores-Hampton M. , Roberts P. , Stansly P. A.
Published: March 2012

This chapter discusses the following aspects of organic pepper (Capsicum spp.) production: transplant production, soil fertility management and nutrient budgeting (establishment of cover crops, compost application and composting, and manure application), weed management, disease management, arthropod pest management, and postharvest handling.
Crown and root diseases of pepper.
Authors: Huang C. H. , Vallad G. E.
Published: March 2012

This chapter describes the symptoms, disease cycle and epidemiology, and control (cultural, chemical, biological and integrated control methods) of the following crown and root diseases of pepper (Capsicum spp.): charcoal rot (Macrophomina phaseolina); damping-off and root rot (Rhizoctonia solani [Thanatephorus cucumeris], and various species of Fusarium, Phytophthora and Pythium); Fusarium stem and fruit rot (Nectria haematococca [Haematonectria haematococca]); Fusarium wilt (various Fusarium species, including F. oxysporum f.sp. vasinfectum, F. redolens and F. oxysporum f.sp. capsici); Phytophthora blight and root, crown and fruit rot (Phytophthora capsici); southern blight (Sclerotium rolfsii [Athelia rolfsii]); Verticillium wilt (Verticillium albo-atrum and V. dahliae); white mould (Sclerotinia sclerotiorum and S. minor); and bacterial wilt (Ralstonia solanacearum).
Fine‐Scale Population Genetic Structure and Dispersal of Juvenile Steelhead in the Bulkley‐Morice River, British Columbia
Authors: Wellband Kyle W. , Atagi Dana Y. , Koehler Rachel A. , Heath Daniel D.
Published: March 2012

A knowledge of fine‐scale population genetic structure and patterns of dispersal is an essential component of any action to conserve genetic diversity and maintain population viability. We genotyped 417 juvenile steelhead Oncorhynchus mykiss from the main stem and tributaries of the Bulkley–Morice River, British Columbia, at 10 microsatellite loci to assess fine‐scale population structure and the patterns and magnitude of juvenile dispersal and mixing. We detected significant genetic structuring among juvenile steelhead from seven tributaries of the Bulkley–Morice River (pairwise FST: 0.008–0.156) and found significant isolation by distance among the tributary populations (R2 = 0.198, P = 0.038). These results reflect the homing behavior of spawning adults as well as the temporal stability of those populations. Genotype assignment of tributary‐caught juveniles showed that rates of juvenile dispersal varied among tributaries. The assignment of juveniles sampled from the main stem of the river to source tributary populations suggested that long‐distance movement in juvenile steelhead is common and that juveniles are well mixed in the main stem. Dispersal and fine‐scale genetic structure in pristine steelhead populations are more complex than previously thought. Therefore, actions to conserve Bulkley–Morice River steelhead must strive to maintain the genetic diversity of tributary populations.
Selective disruption of high sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations
Authors: Cui Yuanyuan , Yang Fan , Cao Xu , Yarov-Yarovoy Vladimir , Wang KeWei , Zheng Jie
Published: March 2012

The capsaicin receptor transient receptor potential vanilloid (TRPV)1 is a highly heat-sensitive ion channel. Although chemical activation and heat activation of TRPV1 elicit similar pungent, painful sensation, the molecular mechanism underlying synergistic activation remains mysterious. In particular, where the temperature sensor is located and whether heat and capsaicin share a common activation pathway are debated. To address these fundamental issues, we searched for channel mutations that selectively affected one form of activation. We found that deletion of the first 10 amino acids of the pore turret significantly reduced the heat response amplitude and shifted the heat activation threshold, whereas capsaicin activation remained unchanged. Removing larger portions of the turret disrupted channel function. Introducing an artificial sequence to replace the deleted region restored sensitive capsaicin activation in these nonfunctional channels. The heat activation, however, remained significantly impaired, with the current exhibiting diminishing heat sensitivity to a level indistinguishable from that of a voltage-gated potassium channel, Kv7.4. Our results demonstrate that heat and capsaicin activation of TRPV1 are structurally and mechanistically distinct processes, and the pore turret is an indispensible channel structure involved in the heat activation process but is not part of the capsaicin activation pathway. Synergistic effect of heat and capsaicin on TRPV1 activation may originate from convergence of the two pathways on a common activation gate.
VUV Photoionization and Dissociation of Tyramine and Dopamine: the Joint Experimental and Theoretical Studies
Authors: Guo Hui-jun , Ye Li-li , Jia Liang-yuan , Zhang Li-dong , Qi Fei
Published: March 2012

Photon induced dissociation investigations of neutral tyramine and dopamine are carried out with synchrotron vacuum ultraviolet photoionization mass spectrometry and theoretical calculations. At low photon energy only molecular ions are measured by virtue of nearthreshold photoionization. While increasing photon energy to 11.7 eV or more, four distinct fragment ions are obtained for tyramine and dopamine, respectively. Besides, the ionization energies of tyramine and dopamine are determined to be 7.98±0.05 and 7.67±0.05 eV by measuring the photoionization efficiency curves of corresponding molecular ions. With help of density function theory calculations, the detailed fragmentation pathways are established as well. These two molecular cations have similar aminoethyl group elimination pathways, C7H8O2+· (m/z=124) and C7H8O+· (m/z=108) are supposed to be generated by the McLafferty rearrangement via γ-hydrogen (γ-H) shift inducing β-fission. And CH2NH2+ is proposed to derive from the direct fission of C7-C8 bond. Besides, the McLafferty rearrangement and the C7-C8 bond fission are validated to be dominant dissociation pathways for tyramine and dopamine cations.
Raman Scattering at Resonant or Near-Resonant Conditions: A Generalized Short-Time Approximation
Authors: Mohammed Abdelsalam , Sun Yu-Ping , Miao Quan , Ågren Hans , Gel'mukhanov Faris
Published: March 2012

We investigate the dynamics of resonant Raman scattering in the course of the frequency detuning. The dephasing in the time domain makes the scattering fast when the photon energy is tuned from the absorption resonance. This makes frequency detuning to act as a camera shutter with a regulated scattering duration and provides a practical tool of controlling the scattering time in ordinary stationary measurements. The theory is applied to resonant Raman spectra of a couple of few-mode model systems and to trans-1,3,5-hexatriene and guanine-cytosine (G-C) Watson-Crick base pairs (DNA) molecules. Besides some particular physical effects, the regime of fast scattering leads to a simplification of the spectrum as well as to the scattering theory itself. Strong overtones appear in the Raman spectra when the photon frequency is tuned in the resonant region, while in the mode of fast scattering, the overtones are gradually quenched when the photon frequency is tuned more than one vibrational quantum below the first absorption resonance. The detuning from the resonant region thus leads to a strong purification of the Raman spectrum from the contamination by higher overtones and soft modes and purifies the spectrum also in terms of avoidance of dissociation and interfering fluorescence decay of the resonant state. This makes frequency detuning a very useful practical tool in the analysis of the resonant Raman spectra of complex systems and considerably improves the prospects for using the Raman effect for detection of foreign substances at ultra-low concentrations.
First-principles Study on Neutral Nitrogen Impurities in Zinc Oxide
Authors: Li Ping , Deng Sheng-hua , Li Yi-bao , Zhang Li , Liu Guo-hong , Huang Jing
Published: March 2012

The atomic geometries, electronic structures, and formation energies of neutral nitrogen impurities in ZnO have been investigated by first-principles calculations. The nitrogen impurities are always deep acceptors, thus having no contributions to p-type conductivity. Among all the neutral nitrogen impurities, nitrogen substituting on an oxygen site has the lowest formation energy and the shallowest acceptor level, while nitrogen substituting on a zinc site has the second-lowest formation energy in oxygen-rich conditions. Nitrogen interstitials are unstable at the tetrahedral site and spontaneously relax into a kick-out configuration. Though nitrogen may occupy the octahedral site, the concentrations will be low for the high formation energy. The charge density distributions in various doping cases are discussed, and self-consistent results are obtained.
B12N12 Nano-cage as Potential Sensor for NO2 Detection
Authors: Beheshtian Javad , Kamfiroozi Mohammad , Bagheri Zargham , Peyghan Ali Ahmadi
Published: March 2012

The NO2 molecule adsorption on B12N12 nano-cage was investigated using density functional theory calculations in terms of adsorption energy, HOMO/LUMO energy gap (Eg) changes, charge transfer, structural deformation, etc. Furthermore, some aspects of stability and properties of B12N12 including calculation of binding electronic and Gibbs free energies, density of states, and molecular electrostatic potential surfaces are investigated. Three possible configurations for NO2 adsorption on the B12N12 nano-cage are energetically found. Interestingly, the results reveals that the Eg of B12N12 cluster is very sensitive to the presence of NO2 molecules as its value reduces from 6.84 eV in free cluster to 3.23 eV in the most stable configuration of NO2/cluster complex. This phenomenon dramatically increases the electrical conductivity of the cluster, suggesting that the B12N12 nano-cluster may be potential sensor for NO2 gaseous molecule detection.
Left ventricular discoordination index measured by speckle tracking strain rate imaging predicts reverse remodelling and survival after cardiac resynchronization therapy
Authors: Wang Chun‐Li , Powell Brian D. , Redfield Margaret M. , Miyazaki Chinami , Fine Nowell M. , Olson Lyle J. , Cha Yong‐Mei , Espinosa Raul E. , Hayes David L. , Hodge David O. , Lin Grace , Friedman Paul A. , Oh Jae K.
Published: March 2012

Aims

This study aimed to evaluate the predictive value of a baseline speckle tracking strain rate imaging‐derived discoordination index for response to cardiac resynchronization therapy (CRT).

Methods and results

Ninety‐seven patients with QRS ≥120 ms and left ventricular (LV) ejection fraction ≤35% were prospectively followed after CRT in the Mayo CRT Registry. The LV discoordination index (stretch/shortening or thinning/thickening during ejection) was calculated from three types of deformation, radial, circumferential, and longitudinal, using two‐dimensional speckle tracking strain rate imaging. The benefit of CRT was evaluated by reverse remodelling (i.e. reduction of LV end‐systolic volume ≥15% at 6‐month follow‐up) and survival. The optimal cut‐off value of the baseline discoordination index in discriminating responders from non‐responders was determined by receiver operating characteristic curve analysis. Significant differences in baseline indices between responders and non‐responders were noted for radial and circumferential discoordination indices. A mid‐ventricular radial discoordination index (RDI‐M) >38% best predicted responders, especially in patients with ischaemic cardiomyopathy (area under the curve 0.86 for all patients, sensitivity 80%, and specificity 91%). Death occurred in 28 patients over a median follow‐up of 3.2 years. When adjusted for confounding variables, lack of significant discoordination (RDI‐M <38%) before CRT was associated with a particularly high mortality (hazard ratio 7.05, 95% confidence interval 2.45–26.0).

Conclusion

LV discoordination assessed by speckle tracking RDI‐M imaging was able to predict reverse remodelling at 6 months and survival of patients who received CRT.
Global Health and Primary Care: Building Capacity
Authors: Greenhalgh Trisha
Published: March 2012

Primary health care and global health are linked for four reasons. Firstly, the principles of good primary health care are the same the world over. Secondly, primary health care is particularly appropriate for meeting the challenges of a ‘globalized’ society. Thirdly, in our globalized world, the needs of migrants often form a significant component of primary care workload. Finally, capacity building for primary health care in low- and middle-income countries is a moral imperative and one of the most cost-effective ways of improving global health outcomes. This article will consider these issues in turn.
What the Numbers Say: A Digit-Based Test for Election Fraud
Authors: Beber Bernd , Scacco Alexandra
Published: March 2012

Is it possible to detect manipulation by looking only at electoral returns? Drawing on work in psychology, we exploit individuals' biases in generating numbers to highlight suspicious digit patterns in reported vote counts. First, we show that fair election procedures produce returns where last digits occur with equal frequency, but laboratory experiments indicate that individuals tend to favor some numerals over others, even when subjects have incentives to properly randomize. Second, individuals underestimate the likelihood of digit repetition in sequences of random integers, so we should observe relatively few instances of repeated numbers in manipulated vote tallies. Third, laboratory experiments demonstrate a preference for pairs of adjacent digits, which suggests that such pairs should be abundant on fraudulent return sheets. Fourth, subjects avoid pairs of distant numerals, so those should appear with lower frequency on tainted returns. We test for deviations in digit patterns using data from Sweden's 2002 parliamentary elections, Senegal's 2000 and 2007 presidential elections, and previously unavailable results from Nigeria's 2003 presidential election. In line with observers' expectations, we find substantial evidence that manipulation occurred in Nigeria as well as in Senegal in 2007.
Noninvasive Continuous Arterial Blood Pressure Monitoring with Nexfin®
Authors: Martina Jerson R. , Westerhof Berend E. , van Goudoever Jeroen , de Beaumont Edouard M. F. H. , Truijen Jasper , Kim Yu-Sok , Immink Rogier V. , Jöbsis Dorothea A. , Hollmann Markus W. , Lahpor Jaap R. , de Mol Bas A. J. M. , van Lieshout Johannes J.
Published: March 2012

Background

If invasive measurement of arterial blood pressure is not warranted, finger cuff technology can provide continuous and noninvasive monitoring. Finger and radial artery pressures differ; Nexfin® (BMEYE, Amsterdam, The Netherlands) measures finger arterial pressure and uses physiologic reconstruction methodologies to obtain values comparable to invasive pressures.

Methods

Intra-arterial pressure (IAP) and noninvasive Nexfin arterial pressure (NAP) were measured in cardiothoracic surgery patients, because invasive pressures are available. NAP-IAP differences were analyzed during 30 min. Tracking was quantified by within-subject precision (SD of individual NAP-IAP differences) and correlation coefficients. The ranges of pressure change were quantified by within-subject variability (SD of individual averages of NAP and IAP). Accuracy and precision were expressed as group average ± SD of the differences and considered acceptable when smaller than 5 ± 8 mmHg, the Association for the Advancement of Medical Instrumentation criteria.

Results

NAP and IAP were obtained in 50 (34-83 yr, 40 men) patients. For systolic, diastolic, mean arterial, and pulse pressure, median (25-75 percentiles) correlation coefficients were 0.96 (0.91-0.98), 0.93 (0.87-0.96), 0.96 (0.90-0.97), and 0.94 (0.85-0.98), respectively. Within-subject precisions were 4 ± 2, 3 ± 1, 3 ± 2, and 3 ± 2 mmHg, and within-subject variations 13 ± 6, 6 ± 3, 9 ± 4, and 7 ± 4 mmHg, indicating precision over a wide range of pressures. Group average ± SD of the NAP-IAP differences were -1 ± 7, 3 ± 6, 2 ± 6, and -3 ± 4 mmHg, meeting criteria. Differences were not related to mean arterial pressure or heart rate.

Conclusion

Arterial blood pressure can be measured noninvasively and continuously using physiologic pressure reconstruction. Changes in pressure can be followed and values are comparable to invasive monitoring.
The episodic nature of episodic-like memories
Authors: Easton Alexander , Webster Lisa A.D. , Eacott Madeline J.
Published: March 2012

Studying episodic memory in nonhuman animals has proved difficult because definitions in humans require conscious recollection. Here, we assessed humans’ experience of episodic-like recognition memory tasks that have been used with animals. It was found that tasks using contextual information to discriminate events could only be accurately performed using recollection, not familiarity. However, tasks using temporal information to discriminate events could be accurately performed using either recollection or familiarity. The results strengthen the position that some episodic-like recognition memory tasks are a valid model of episodic memory. However, tasks that rely on temporal information may be susceptible to nonepisodic strategies.
A one-dimensional coordination polymer based on a di-Schiff base supported trinuclear CuIIsubunit
Authors: Zhang Liangliang , Liu Fuling , Yuan Shuai , Wang Xiaoyang , Sun Di
Published: March 2012

A novel one-dimensional CuIIcoordination polymer,catena-poly[bis(μ4-3-{[2-(3-hydroxy-2-oxidobenzylidene)hydrazinylidene]methyl}benzene-1,2-diolato)dimethanoltricopper(II)], [Cu3(C14H10N2O4)2(CH3OH)2]n, (I), was constructed with a di-Schiff base supported centrosymmetric trinuclear CuIIsubunit. In the subunit, two peripheral symmetry-related CuIIcations have square-pyramidal CuNO4geometry and the central third CuIIcation lies on an inversion centre with octahedral CuN2O4geometry. In (I), each partially deprotonated di-Schiff base 3-{[2-(3-hydroxy-2-oxidobenzylidene)hydrazinylidene]methyl}benzene-1,2-diolate ligand (Hbcaz3−) acts as a heptadentate ligand to bind the CuIIcentres into chains along theaaxis. A centrosymmetric Cu2O2unit containing an asymmetrically bridging O atom, being axial at one Cu atom and equatorial at the other Cu atom, links the trinuclear CuIIsubunit into a one-dimensional chain, which is reinforced by intramolecular phenol–methanol O—H...O and methanol–phenolate O—H...O hydrogen bonds. Interchain π–π stacking interactions between pyrocatechol units, with a distance of 3.5251 (18) Å, contribute to the stability of the crystal packing.
3β-Chloro-6-[2-(2-cyanoacetyl)hydrazin-1-ylidene]-5α-cholestane
Authors: Yusufzai Samina Khan , Osman Hasnah , Abdul Rahim Aisyah Saad , Arshad Suhana , Razak Ibrahim Abdul
Published: March 2012

The asymmetric unit of the title compound, C30H48ClN3O, contains two molecules,AandB. In both molecules, the three cyclohexane rings in the steroid fused ring systems adopt chair conformations, while the cyclopentane rings adopt envelope and twist conformations in moleculesAandB, respectively. In moleculeB, the cyano group is disordered over two orientations with refined site-occupancies of 0.593 (8) and 0.407 (8). An intramolecular C—H...N interaction forms anS(10) ring in both molecules. In the crystal, molecules are linked by N—H...O, C—H...O and C—H...N interactions, resulting is chains propagating along thea-axis direction.
Diphenyl[2-(phenylsulfonyl)propan-2-yl]-λ5-phosphanethione
Authors: Gessner Viktoria H.
Published: March 2012

The title compound, C21H21O2PS2, was obtained from the corresponding dilithio methandiide by treatment with iodomethane. The bond lengths and angles deviate considerably from those in the dimetallated compound. These differences are most pronounced in the PCS backbone. While the title compound features C—P and C—S distances of 1.9082 (17) and 1.8348 (17) Å, respectively, the dianion showed C—Pavdistances shortened by 11% [1.710 (4) Å] and C—S distances shortened by 12% [1.614 (3) Å]. Additionally, the P—C—S angle experiences a contraction by methylation of the dianion from 121.4 (2) to 111.96 (9)° in the title compound.
3-(4-Chloroanilino)-5,5-dimethylcyclohex-2-en-1-one
Authors: Anthal Sumati , Sambyal Ambika , Bamzai R. K. , Kant Rajni , Gupta Vivek K.
Published: March 2012

The asymmetric unit of the title compound, C14H16ClNO, contains two independent molecules, both with the cyclohexene ring in a sofa conformation. In the crystal, N—H...O hydrogen bonds link the molecules related by translation along theaaxis into two crystallographically independent chains. Weak C—H...π interactions are also observed.
Impact of ustekinumab on health‐related quality of life in Japanese patients with moderate‐to‐severe plaque psoriasis: Results from a randomized, double‐blind, placebo‐controlled phase 2 / 3 trial
Authors: NAKAGAWA Hidemi , SCHENKEL Brad , KATO Mai , KATO Takeshi , IGARASHI Atsuyuki ,   The Japanese Ustekinumab Study Group
Published: March 2012

This study evaluates the effect of ustekinumab on health‐related quality of life (HRQoL) in Japanese patients with moderate‐to‐severe plaque psoriasis through 64 weeks. A total of 158 patients were randomized to receive subcutaneous injections of ustekinumab 45 mg (n = 64) or 90 mg (n = 62) at weeks 0, 4, and every‐12‐weeks, or placebo (n = 32) with crossover to ustekinumab at week 12. Secondary study endpoints included change in Dermatology Life Quality Index (DLQI) at week 12. Other assessments included the 36‐item Short Form health survey to assess Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, and Psoriasis Disability Index (PDI), a psoriasis‐specific instrument to assess HRQoL. Baseline demographic and disease characteristics were similar across randomized treatment groups. Ustekinumab‐treated patients had significantly greater mean improvements in DLQI from baseline to week 12 (45 mg: 8.0 ± 6.5; 90 mg: 7.4 ± 6.5) than placebo‐treated patients (0.3 ± 5.3; P < 0.0001 for each), and these improvements were maintained through week 64. Also at week 12, significant improvements from baseline in PDI scores were observed in ustekinumab‐treated patients (45 mg: 8.6 ± 9.6; 90 mg: 12.0 ± 11.8) compared with placebo‐treated patients (−0.1 ± 4.2). Improvements in the PCS (45 mg: 7.8 ± 14.5; 90 mg: 5.1 ± 12.0) and MCS (45 mg: 5.3 ± 9.8; 90 mg: 5.8 ± 10.5) scores were also observed in ustekinumab‐treated patients at week 12. Placebo‐treated patients who crossed‐over to ustekinumab achieved improvements in HRQoL comparable to those observed in patients originally randomized to ustekinumab. Ustekinumab significantly improves HRQoL in Japanese patients with moderate‐to‐severe plaque psoriasis through week 64.
Renal iron load in sickle cell disease is influenced by severity of haemolysis
Authors: Vasavda Nisha , Gutiérrez Lucía , House Michael J. , Drašar Emma , St Pierre Tim G. , Thein Swee L.
Published: March 2012

Spin density projection‐assisted R2‐magnetic resonance imaging (R2‐MRI; FerriScan®) scans from 40 chelation‐naïve sickle cell patients were used to assess renal iron load by measuring renal R2 (R‐R2). Clinical data were collected retrospectively for the 2‐year period preceding the scan. R‐R2 showed no significant correlation with transfusional iron load (assessed by liver iron concentration), but correlated significantly with serum bilirubin (R = 0·61, P < 0·0001) and lactate dehydrogenase (R = 0·58, P < 0·0001). Mean (±standard deviation) R‐R2 was higher (P = 0·02) in patients with renal hyperfiltration (29·8 ± 10·3/s) than those without (23·11 ± 6·6/s). Five patients had significantly lower signal intensity in the renal cortex, as compared to the medulla. These patients had a significantly higher (P < 0·0001) mean R‐R2 than those showing no cortico‐medullary difference. We postulate that the increased R‐R2 is associated with haemolysis rather than transfusional iron load in sickle cell disease.
Soil respiration under climate change: prolonged summer drought offsets soil warming effects
Authors: Schindlbacher Andreas , Wunderlich Steve , Borken Werner , Kitzler Barbara , Zechmeister‐Boltenstern Sophie , Jandl Robert
Published: March 2012

Climate change may considerably impact the carbon (C) dynamics and C stocks of forest soils. To assess the combined effects of warming and reduced precipitation on soil CO2 efflux, we conducted a two‐way factorial manipulation experiment (4 °C soil warming + throughfall exclusion) in a temperate spruce forest from 2008 until 2010. Soil was warmed by heating cables throughout the growing seasons. Soil drought was simulated by throughfall exclusions with three 100 m2 roofs during 25 days in July/August 2008 and 2009. Soil warming permanently increased the CO2 efflux from soil, whereas throughfall exclusion led to a sharp decrease in soil CO2 efflux (45% and 50% reduction during roof installation in 2008 and 2009, respectively). In 2008, CO2 efflux did not recover after natural rewetting and remained lowered until autumn. In 2009, CO2 efflux recovered shortly after rewetting, but relapsed again for several weeks. Drought offset the increase in soil CO2 efflux by warming in 2008 (growing season CO2 efflux in t C ha−1: control: 7.1 ± 1.0; warmed: 9.5 ± 1.7; warmed + roof: 7.4 ± 0.3; roof: 5.9 ± 0.4) and in 2009 (control: 7.6 ± 0.8; warmed + roof: 8.3 ± 1.0). Throughfall exclusion mainly affected the organic layer and the top 5 cm of the mineral soil. Radiocarbon data suggest that heterotrophic and autotrophic respiration were affected to the same extent by soil warming and drying. Microbial biomass in the mineral soil (0–5 cm) was not affected by the treatments. Our results suggest that warming causes significant C losses from the soil as long as precipitation patterns remain steady at our site. If summer droughts become more severe in the future, warming induced C losses will likely be offset by reduced soil CO2 efflux during and after summer drought.
Influence of exercise on mood in postmenopausal women
Authors: Villaverde Gutiérrez Carmen , Torres Luque Gema , Ábalos Medina Gracia M , Argente del Castillo Maria J , Guisado Isabel M , Guisado Barrilao Rafael , Ramírez Rodrigo Jesús
Published: March 2012

Aim and objective.  To evaluate the influence of an exercise programme on postmenopausal women with symptoms of anxiety and depression.

Background.  The menopause is a period of hormonal changes when mood variations are probably more severe than at any other period of women’s lives.

Design.  Prospective study with control group and pre‐ and post‐treatment measures, after six months treatment. Conducted at two healthcare clinics, in the province of Granada (Spain).

Methods.  A convenience sample of 60 postmenopausal women aged 60–70 years, with symptoms of depression and anxiety, was recruited. The women were randomly divided into two groups: (1) control group, no treatment (n = 30); (2) exercise group, which carried out a programme of mixed physical exercises with musical support (n = 30). All subjects answered questionnaires for the Hamilton Anxiety Scale and the Brink and Yesavage Geriatric Depression Scale before and after treatment.

Results.  In the exercise group, statistically significant improvements were observed in subjects with moderate and severe depression (18 and 22%, respectively) and in those with symptoms of anxiety. No such changes were observed in the control group.

Conclusions.  A controlled programme of physical exercise for postmenopausal women alleviates symptoms of anxiety and depression, and its inclusion in primary healthcare programmes should be considered.

Relevance to clinical practice.  Menopausal women may benefit from physical exercise, which attenuates the effects of the physiological and psychological changes associated with the menopause and prevents pathologic changes.
Dangling conversations: reflections on the process of creating digital stories during a workshop with people with early‐stage dementia
Authors: STENHOUSE R. , TAIT J. , HARDY P. , SUMNER T.
Published: March 2012

Accessible summary

Digital stories provide a creative way for people to tell their stories using an amalgamation of voice, image and music, and can be used to engage nurses with others' experiences in the classroom setting.

Seven people with early‐stage dementia and one carer participated in making their own stories during a digital storytelling workshop.

These participants experienced particular and varied challenges relating to telling a story and engaging with the technical process of digital storytelling. They were supported in overcoming these challenges through person‐centred relationships with facilitators, allowing them to negotiate the help required.

During the workshop a number of positive changes were observed in the participants: increased confidence, improved speech, a sense of purpose and increased connection.

Care and compassion are key features of the NHS Constitution. Recent reports have identified a lack of compassion in the care and treatment of older people. Nurses draw on aesthetic knowledge, developed through engagement with the experience of others, when providing compassionate care. Patient Voices reflective digital stories are used in healthcare education to facilitate student engagement with the patient experience. Digital stories were made with seven people with early‐stage dementia as part of a learning package for student nurses. In this paper the authors reflect on their experience and observations from facilitating the 4‐day digital story‐making workshop. Social theories of dementia provide a theoretical framework for understanding these reflections. Despite considerable challenges in developing a story, and anxiety about using the technology, reading and speaking, all participants engaged in creating their own digital stories. Positive changes in the participants' interactions were observed. These improvements appeared to be the product of the person‐centred facilitation and the creative process which supported self‐expression and a sense of identity. Nurses working in this way could facilitate ability of the person with dementia to participate in their care, and improve their sense of well‐being by supporting self‐expression.
Drug solubility classification in the dog
Authors: MARTINEZ M. N. , PAPICH M. G.
Published: March 2012

Martinez, M. N., Papich, M. G. Drug solubility classification in the dog. J. vet. Pharmacol. Therap. 35 (Suppl. 1), 87–91.

Similar to human drugs, oral drug delivery is a major route of drug administration in dogs. Therefore, it is important to consider how the physiological characteristics of the dog may influence the considerations that go into the classification of drug solubility. In this manuscript, we discuss the impact of body size vs. administered dose and gastric volume on the estimated gastric drug concentration that needs to be considered. However, when using a dose number (Do) paradigm, there are very few drugs for which the different methods of estimating gastric volume will alter the drug solubility classification. We also evaluate the range of pH values under which a solubility assessment should be generated and conclude that despite specific differences in the pH values of the gastrointestinal environment of people and dogs, the human pH criteria for evaluating drug solubility can be used when evaluating drug solubility of oral medications in dogs.
Should licking behavior be considered in the bioavailability evaluation of transdermal products?
Authors: TOUTAIN P.‐L. , MODRIC S. , BOUSQUET‐MÉLOU A. , SALLOVITZ J. M. , LANUSSE C.
Published: March 2012

Toutain, P.‐L., Modric, S., Bousquet‐Mélou, A., Sallovitz, J. M., Lanusse, C. Should licking behavior be considered in the bioavailability evaluation of transdermal products? J. vet. Pharmacol. Therap.35 (Suppl. 1), 39–43.

Antiparasitic drugs, and especially macrocyclic lactones (MLs), are often formulated as pour‐on products because of their ease of administration, convenience, and reduction of stress in treated animals. However, because of self‐ and allo‐grooming, much of a drug administered transdermally may be systemically absorbed via the oral route, creating highly variable pharmacokinetic and pharmacodynamic response in treated (and untreated) animals. Testing bioequivalence (BE) of pour‐on drugs in cattle under laboratory conditions (with restricted licking) ignores a major factor of drug disposition of these drugs and thus fails to predict therapeutic equivalence in the target population under clinical conditions of use. Therefore, the interanimal and intra‐animal variability associated with licking behavior should be considered as a biological fact, rather than a noise that needs to be reduced or eliminated. As a result, it is recommended that the BE testing for pour‐on products in cattle be conducted by evaluating both the mean and distribution of bioavailability parameters between the reference and test products when animals are not prevented from allo‐ and self‐licking.
Challenges obtaining a biowaiver for topical veterinary dosage forms
Authors: BAYNES R. , RIVIERE J. , FRANZ T. , MONTEIRO‐RIVIERE N. , LEHMAN P. , PEYROU M. , TOUTAIN P.‐L.
Published: March 2012

Baynes, R., Riviere, J., Franz, T., Monteiro‐Riviere, N., Lehman, P., Peyrou, M., Toutain, P.‐L. Challenges obtaining a biowaiver for topical veterinary dosage forms.J. vet. Pharmacol. Therap.35(Suppl. 1), 103–114.

Obtaining a biowaiver for topical drugs used in veterinary species faces many of the same challenges associated with human topicals. However, the skin of domestic animals varies anatomically and biochemically and experimental approaches to assess bioequivalence (BE) in veterinary species have challenges that are not often encountered with human skin. This is especially the situation with locally acting drugs. The focus of this paper is to address several of the challenges associated with (i) determining the BE of these locally acting drugs and (ii) critically examine the current technological advances that can act as a surrogate for clinical trials.
The photoprotective protein PsbS exerts control over CO2 assimilation rate in fluctuating light in rice
Authors: Hubbart Stella , Ajigboye Olubukola O. , Horton Peter , Murchie Erik H.
Published: March 2012

A direct impact of chloroplastic protective energy dissipation (qE) on photosynthetic CO2 assimilation has not been shown directly in plants in the absence of photoinhibition. To test this empirically we transformed rice to possess higher (overexpressors, OE) and lower (RNA interference, RNAi) levels of expression of the regulatory psbS gene and analysed CO2 assimilation in transformants in a fluctuating measurement light regime. Western blots showed a several‐fold difference in levels of PsbS protein between RNAi and OE plants with the wild type (WT) being intermediate. At a growth light intensity of 600 μmol m−2 sec−1, the carboxylation capacity, electron transport capacity and dark adapted Fv/Fm (ratio of variable to maximum fluorescence) were inhibited in RNAi plants compared with WT and OE. The PsbS content had a significant impact on qE (measured here as non‐photochemical quenching, NPQ) but the strongest effect was observed transiently, immediately following the application of light. This capacity for qE was several‐fold lower in RNAi plants and significantly higher in OE plants during the first 10 min of illumination. At steady state the differences were reduced: notably at 500 μmol m−2 sec−1 all plants had the same NPQ values regardless of PsbS content. During a series of light–dark transitions the induction of CO2 assimilation was inhibited in OE plants, reducing integrated photosynthesis during the light period. We conclude that the accumulation of PsbS and the resultant qE exerts control over photosynthesis in fluctuating light, showing that optimization of photoprotective processes is necessary for maximum photosynthetic productivity even in the absence of photoinhibitory stress.
Chinese Americans' views of prenatal genetic testing in the genomic era: a qualitative study
Authors: Chen Lei‐Shih , Zhao Mei , Zhou Qiong , Xu Lei
Published: March 2012

Prenatal genetic testing (PGT) for early and accurate diagnosis of complex genomic diseases and traits, along with relatively rare and severe genetic disorders, is a growing trend in genomic medicine. To address the ethical, legal, and social issues regarding PGT use, the voices of racial/ethnic minorities should be heard. This first‐of‐its‐kind qualitative study examined Chinese Americans' perspectives regarding PGT to diagnose their fetuses for various genetic/genomic diseases and traits. We conducted semi‐structural, hypothetical‐scenario‐based interviews with 49 participants from two major Chinese‐American communities in the South. Although approximately one fifth of participants refused to test their fetuses, most tended to favor PGT. The four most frequently identified diseases/traits mentioned by participants included family‐history‐related diseases, genetic disorders, intelligence quotient (IQ), and psychological/mental disorders. A few respondents, regardless of socio‐demographic status, indicated they might terminate their pregnancies if their fetuses carried genes for family‐history‐related diseases, genetic disorders, low IQ, psychological/mental disorders, and/or physical defects. Participants' attitudes might reflect lack of genetic/genomic knowledge and unawareness of available resources for families with special needs. Moreover, some participants' attitudes appeared related to their cultural beliefs. Our findings represent an initial window to understand Chinese Americans' views regarding PGT. Additional quantitative studies on large samples are needed.
Selection strategies for dairy buffaloes: economic and genetic consequences
Authors: Seno L.O. , Fernández J. , Cardoso V.L. , García‐Cortes L.A. , Toro M. , Santos D.O. , Albuquerque L.G. , de Camargo G.M.F. , Tonhati H.
Published: March 2012

Buffaloes are generally raised in Brazil without milk‐recording programs, and thus without genetic evaluations of any of their traits. This study evaluated the economic impacts of three different selection strategies on buffalo populations and the evolution of genetic trends, genetic variances and inbreeding coefficients resulting from each of them. The selection strategies used were as follows: (i) random selection; (ii) phenotypic selection; and (iii) progeny testing (PT). As the numbers of herds enrolled in milk‐recording programs increased, phenotypic selection and PT strategies increased both monetary benefits and genetic trends. The extra costs of implementing milk recording (MR) and PT procedures were exceeded by the income resulting from better buffalo performance. Progeny testing is known to result in beneficial genetic trends and the use of artificial insemination promoted better distributions of genetic material into herds that were not enrolled in milk‐recording programs. Phenotypic selection and PT increased mean milk production ‐ a key factor in profitability. Inbreeding levels remained stable with phenotypic selection, even as the numbers of MR herds increased. Increases in the numbers of sires that were evaluated reduced the mean inbreeding coefficient in PT. Increasing the number of herds enrolled in milk‐recording programs resulted in increased numbers of sires needed for PT, but this did not increase the inbreeding coefficient. In summary, phenotypic selection and PT strategies appear to be economically viable for buffalo husbandry in south‐eastern Brazil under current (2007–2008) economic conditions and should be encouraged.
Wire assisted transpancreatic septotomy, needle knife precut or both for difficult biliary access
Authors: Chan Calvin HY , Brennan Frank N , Zimmerman Matthew J , Ormonde Donald G , Raftopoulos Spiro Costa , Yusoff Ian F
Published: March 2012

Background and Aims:  Pre‐cut techniques, the most commonly described being needle knife papillotomy (NK), have been used to facilitate biliary access in failed standard biliary cannulation (BC). Transpancreatic septotomy (TS) is a pre‐cut technique with limited outcome data. We aim to assess the outcomes of wire assisted transpancreatic septotomy (WTS) as the primary pre‐cut technique after initial failed attempted BC and to compare these with outcomes of primary NK.

Methods:  We retrospectively reviewed all endoscopic retrograde cholangiopancreatographies (ERCPs) performed by endoscopists who performed WTS over a 3‐year period. We selected cases where WTS and/or NK were performed, and these cases were reviewed to assess for procedure related complications and BC success.

Results:  During the study period 1336 ERCPs were performed. WTS was performed in 53 cases. In seven cases WTS and NK were performed sequentially (resulting in immediate cannulation in all these cases). Immediate BC was achieved on first attempt in 36 (68%) WTS cases and in a further 14 cases on a repeat attempt (cumulative BC rate 94%). During the same period 66 (5%) patients underwent primary NK. In these cases initial cannulation was achieved in 50 (76%) cases and cannulation on repeat attempt in six cases (cumulative success rate 85%). Complications occurred in three WTS patients (5.6%) and seven NK patients (10.6%). The differences were not statistically significant.

Conclusions:  Wire assisted transpancreatic septotomy is a safe and effective alternative technique to traditional NK in patients who have failed standard BC techniques. It also allows other pre‐cut techniques such as NK to be used should initial WTS be unsuccessful.