bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of novel recombinants of hepatitis B virus genotypes F and G in human immunodeficiency virus-positive patients from Argentina and Brazil
Authors: Araujo Natalia M. , Araujo Oscar C. , Silva Edinete M. , Villela-Nogueira Cristiane A. , Nabuco Letícia C. , Parana Raymundo , Bessone Fernando , Gomes Selma A. , Trepo Christian , Kay Alan
Published: October 2012

Hepatitis B virus (HBV) genotype G (HBV/G) infection is almost always detected along with a co-infecting HBV strain that can supply HBeAg, typically HBV/A2. In this study we describe, in two human immunodeficiency virus (HIV)-positive patients from Argentina and Brazil, the first report of HBV/G infection in Argentina and co-circulation of HBV/G, HBV/F and G/F recombinants in the American continent. HBV isolates carrying the 36 bp insertion of HBV/G were the most prevalent in both patients, with >99 % of colonies hybridizing to a probe specific for this insertion. Phylogenetic analyses of full-length genomes and precore/core fragments revealed that F4 and F1b were the co-infecting subgenotypes in the Brazilian and Argentinian patients, respectively. Bootscanning analysis provided evidence of recombination in several clones from both patients, with recombination breakpoints located mainly at the precore/core region. These data should encourage further investigations on the clinical implications of HBV/G recombinants in HBV/HIV co-infected patients.
Summer Watering Patterns of Mule Deer in the Great Basin Desert, USA: Implications of Differential Use by Individuals and the Sexes for Management of Water Resources
Authors: Shields Andrew V. , Larsen Randy T. , Whiting Jericho C.
Published: October 2012

Changes in the abundance and distribution of free water can negatively influence wildlife in arid regions. Free water is considered a limiting factor for mule deer (Odocoileus hemionus) in the Great Basin Desert. Consequently, a better understanding of differential use of water by individuals and the sexes could influence the conservation and management of mule deer and water resources in their habitats. We deployed remote cameras at all known water sources (13 wildlife water developments and 4 springs) on one mountain range in western Utah, USA, during summer from 2007 to 2011 to document frequency and timing of water use, number of water sources used by males and females, and to estimate population size from individually identified mule deer. Male and female mule deer used different water sources but visited that resource at similar frequencies. Individual mule deer used few water sources and exhibited high fidelity to that resource. Wildlife water developments were frequently used by both sexes. Our results highlight the differing use of water sources by sexes and individual mule deer. This information will help guide managers when siting and reprovisioning wildlife water developments meant to benefit mule deer and will contribute to the conservation and management of this species.
Natural Variation for Seed Longevity and Seed Dormancy Are Negatively Correlated in Arabidopsis
Authors: Nguyen Thu-Phuong , Keizer Paul , van Eeuwijk Fred , Smeekens Sjef , Bentsink Leónie
Published: October 2012

Dormancy is a state of metabolic arrest that facilitates the survival of organisms during environmental conditions incompatible with their regular course of life. Many organisms have deep dormant stages to promote an extended life span (increased longevity). In contrast, plants have seed dormancy and seed longevity described as two traits. Seed dormancy is defined as a temporary failure of a viable seed to germinate in conditions that favor germination, whereas seed longevity is defined as seed viability after dry storage (storability). In plants, the association of seed longevity with seed dormancy has not been studied in detail. This is surprising given the ecological, agronomical, and economic importance of seed longevity. We studied seed longevity to reveal its genetic regulators and its association with seed dormancy in Arabidopsis (Arabidopsis thaliana). Integrated quantitative trait locus analyses for seed longevity, in six recombinant inbred line populations, revealed five loci: Germination Ability After Storage1 (GAAS1) to GAAS5. GAAS loci colocated with seed dormancy loci, Delay Of Germination (DOG), earlier identified in the same six recombinant inbred line populations. Both GAAS loci and their colocation with DOG loci were validated by near isogenic lines. A negative correlation was observed, deep seed dormancy correlating with low seed longevity and vice versa. Detailed analysis on the collocating GAAS5 and DOG1 quantitative trait loci revealed that the DOG1-Cape Verde Islands allele both reduces seed longevity and increases seed dormancy. To our knowledge, this study is the first to report a negative correlation between seed longevity and seed dormancy.
X-(Diiodoarsanyl)benzoic acid (X= 3 and 4)
Authors: Ilyin Igor Yu. , Pushkarevsky Nikolay A. , Kuratieva Natalia V. , Naumov Dmitry Yu. , Konchenko Sergey N.
Published: October 2012

The title compounds, 4-(diiodoarsanyl)benzoic acid, (I), and 3-(diiodoarsanyl)benzoic acid, (II), both [As(C7H5O2)I2], which possess a –COOH coordinating group, form molecular crystal structures composed of hydrogen-bonded dimers, the packing differences of which are caused by the relative position of the diiodoarsanyl groups. Theparaisomer, withZ′ = 1, crystallizes in a layered structure with shortened contacts of the As atoms to only the arene rings of adjacent molecules. In contrast, themetaisomer, withZ′ = 3, forms separate rectangular blocks of three ribbons, each composed of dimeric molecular units positioned almost directly above each other and with the As atoms possessing only two As...I contacts to the I atoms of neighbouring molecules.
A new two-dimensional cadmium metal–organic framework: poly[bis(4,7-diphenyl-1,10-phenanthroline)(μ3-5-nitroisophthalato)cadmium(II)]
Authors: Ye Jun-Wei , Zhao Li-Mei , Li Wei , Ning Gui-Ling
Published: October 2012

In the title cadmium metal–organic framework complex, [Cd(C8H3NO6)(C24H16N2)]nor [Cd(NIPH)(dpphen)] (NIPH is nitroisophthalate and dpphen is 4,7-diphenyl-1,10-phenanthroline), the unique CdIIcation in a general position is coordinated by four carboxy O atoms from three symmetry-related NIPH anions and two N atoms from a dpphen ligand. The CdIIcations are bridged by pairs of NIPH anions to generate a dinuclear molecular building block, [Cd2N4(CO2R)4], with a Cd...Cd separation of 4.0936 (10) Å. Each such building block is connected to four adjacent dinuclear building blocks by NIPH anions, resulting in a two-dimensional layer framework in thebcplane. The dpphen ligands occupy the space between these layers and are linked by π–π interactions, with a separation of 3.4541 (6) Å between the central aromatic rings of inversion-related dpphen ligands. The thermogravimetric and photoluminescent properties of the complex have also been investigated.
Endo-β-D-1,4-mannanase fromChrysonilia sitophiladisplays a novel loop arrangement for substrate selectivity
Authors: Gonçalves Ana Maria D. , Silva Catarina S. , Madeira Tânia I. , Coelho Ricardo , de Sanctis Daniele , San Romão Maria Vitória , Bento Isabel
Published: October 2012

The crystal structure of wild-type endo-β-D-1,4-mannanase (EC 3.2.1.78) from the ascomyceteChrysonilia sitophila(CsMan5) has been solved at 1.40 Å resolution. The enzyme isolated directly from the source shows mixed activity as both an endo-glucanase and an endo-mannanase. CsMan5 adopts the (β/α)8-barrel fold that is well conserved within the GH5 family and has highest sequence and structural homology to the GH5 endo-mannanases. Superimposition with proteins of this family shows a unique structural arrangement of three surface loops of CsMan5 that stretch over the active centre, promoting an altered topography of the binding cleft. The most relevant feature results from the repositioning of a long loop at the extremity of the binding cleft, resulting in a shortened glycone-binding region with two subsites. The other two extended loops flanking the binding groove produce a narrower cleft compared with the wide architecture observed in GH5 homologues. Two aglycone subsites (+1 and +2) are identified and a nonconserved tryptophan (Trp271) at the +1 subsite may offer steric hindrance. Taken together, these findings suggest that the discrimination of mannan substrates is achieved through modified loop length and structure.
Alteration of fluorescent protein spectroscopic properties upon cryoprotection
Authors: von Stetten David , Batot Gaëlle O. , Noirclerc-Savoye Marjolaine , Royant Antoine
Published: October 2012

Cryoprotection of a protein crystal by addition of small-molecule compounds may sometimes affect the structure of its active site. The spectroscopic and structural effects of the two cryoprotectants glycerol and ethylene glycol on the cyan fluorescent protein Cerulean were investigated. While glycerol had almost no noticeable effect, ethylene glycol was shown to induce a systematic red shift of the UV–vis absorption and fluorescence emission spectra. Additionally, ethylene glycol molecules were shown to enter the core of the protein, with one of them binding in close vicinity to the chromophore, which provides a sound explanation for the observed spectroscopic changes. These results highlight the need to systematically record spectroscopic data on crystals of light-absorbing proteins and reinforce the notion that fluorescent proteins must not been seen as rigid structures.
Nanoflow electrospinning serial femtosecond crystallography
Authors: Sierra Raymond G. , Laksmono Hartawan , Kern Jan , Tran Rosalie , Hattne Johan , Alonso-Mori Roberto , Lassalle-Kaiser Benedikt , Glöckner Carina , Hellmich Julia , Schafer Donald W. , Echols Nathaniel , Gildea Richard J. , Grosse-Kunstleve Ralf W. , Sellberg Jonas , McQueen Trevor A. , Fry Alan R. , Messerschmidt Marc M. , Miahnahri Alan , Seibert M. Marvin , Hampton Christina Y. , Starodub Dmitri , Loh N. Duane , Sokaras Dimosthenis , Weng Tsu-Chien , Zwart Petrus H. , Glatzel Pieter , Milathianaki Despina , White William E. , Adams Paul D. , Williams Garth J. , Boutet Sébastien , Zouni Athina , Messinger Johannes , Sauter Nicholas K. , Bergmann Uwe , Yano Junko , Yachandra Vittal K. , Bogan Michael J.
Published: October 2012

An electrospun liquid microjet has been developed that delivers protein microcrystal suspensions at flow rates of 0.14–3.1 µl min−1to perform serial femtosecond crystallography (SFX) studies with X-ray lasers. Thermolysin microcrystals flowed at 0.17 µl min−1and diffracted to beyond 4 Å resolution, producing 14 000 indexable diffraction patterns, or four per second, from 140 µg of protein. Nanoflow electrospinning extends SFX to biological samples that necessitate minimal sample consumption.
Severe diffraction anisotropy, rotational pseudosymmetry and twinning complicate the refinement of a pentameric coiled-coil structure of NSP4 of rotavirus
Authors: Chacko Anita R. , Zwart Peter H. , Read Randy J. , Dodson Eleanor J. , Rao C. D. , Suguna Kaza
Published: October 2012

The crystal structure of the region spanning residues 95–146 of the rotavirus nonstructural protein NSP4 from the asymptomatic human strain ST3 was determined at a resolution of 2.5 Å. Severe diffraction anisotropy, rotational pseudosymmetry and twinning complicated the refinement of this structure. A systematic explanation confirming the crystal pathologies and describing how the structure was successfully refined is given in this report.
Age Estimation Using Foot Radiographs from a Modern Scottish Population
Authors: Hackman Lucina , Davies Catriona M. , Black Sue
Published: October 2012

The Hoerr et al. atlas was published in 1962 and provides a standard for the age estimation of juveniles through radiographs of the feet. This study examines the accuracy of this atlas when used as an age estimation method on a modern Scottish population. A total of 403 left foot/ankle radiographs (175 female, 228 male) were age assessed using the Hoerr et al. atlas method. Analysis showed that there was a strong correlation between chronological age and estimated age (female R² = 0.952, male R² = 0.962). The atlas had a tendency to underage all ages of females and to underage males up to the age of 10 years after which point the pattern is one of both over and underaging. This study showed that the Hoerr et al. atlas method can be applied to a modern population.
Calculating the Weight of Evidence in Low‐Template Forensic DNA Casework
Authors: Lohmueller Kirk E. , Rudin Norah
Published: October 2012

Interpreting and assessing the weight of low‐template DNA evidence presents a formidable challenge in forensic casework. This report describes a case in which a similar mixed DNA profile was obtained from four different bloodstains. The defense proposed that the low‐level minor profile came from an alternate suspect, the defendant's mistress. The strength of the evidence was assessed using a probabilistic approach that employed likelihood ratios incorporating the probability of allelic drop‐out. Logistic regression was used to model the probability of drop‐out using empirical validation data from the government laboratory. The DNA profile obtained from the bloodstain described in this report is at least 47 billion times more likely if, in addition to the victim, the alternate suspect was the minor contributor, than if another unrelated individual was the minor contributor. This case illustrates the utility of the probabilistic approach for interpreting complex low‐template DNA profiles.
Local depletion of two larger Duikers in the Oban Hills Region, Nigeria
Authors: Jimoh Saka O. , Ikyaagba Emmanuel T. , Alarape Abideen A. , Adeyemi Adesoji A. , Waltert Matthias
Published: October 2012

Across West and Central Africa, duikers are important for trade and consumption; their populations are expected to become depleted. Reliable data on their status are scanty in Nigeria. We assessed duiker populations in the Oban Sector of Cross River National Park through diurnal and nocturnal surveys along 32 transects of 2 km each. After 508‐km survey effort, only Ogilby's duiker (Cephalophus ogilbyi) and blue duiker (Philantomba monticola) were recorded. Using habitat as a covariate in modelling detection probability in DISTANCE 6.0, we estimated densities for the blue duiker ranging from 15.5 (95% CI: 7.8–30.9) in the core, 5.8 (CI: 2.6–12.9) in the buffer and 0.9 (CI: 0.09–10.1) km² in farm fallow to no duikers in the plantation. For Ogilby's duiker, densities ranged from 1.6 (95% CI: 0.7–3.7) km² in the core, 2.0 (CI: 0.8–5.1) in buffer to no duikers in farm fallow and plantation. The apparent absence of yellow‐backed and Bay duikers may indicate local depletion. We call on all stakeholders to rise up to the challenge of rescuing this biological hotspot in Nigeria from further degradation and species loss through improved funding for well‐equipped field staff and institutionalized community wildlife management.
Rotavirus genotype distribution in Kyrgyzstan and Kazakhstan, 2007–2009
Authors: Vainio Kirsti , Latipov Renat , Utegenova Elmira , Kasymbekova Kaliya , Juraev Rivojiddin , Asilova Mukhayyo , Flem Elmira
Published: October 2012

This is the first study to present rotavirus genotype distribution in children admitted to a hospital with acute gastroenteritis in Kyrgyzstan and Kazakhstan from January 2007 through December 2009. In total, 858 rotavirus ELISA‐positive samples were characterized by RT‐PCR, with a considerable geographical and seasonal variation in genotype distribution observed during the study. The globally common genotypes (G1P[8], G2P[4], G3P[8], G4P[8], G9P[8], G12P[8] and G12P[6]) accounted for 81.5–88.2% of the infections in Kyrgyzstan and 72.3–79.3% of the infections in Kazakhstan. The predominant genotypes were G1P[8], G2P[4] and G3P[8]. G1P[8] was the dominating genotype in Kyrgyzstan, detected in 51–64.7% of the samples. A similar predominance was not seen for G1P[8] in Kazakhstan, with a shift to G2P[4] predominance being seen in 2008. G9P[8] was a rare genotype in both countries, whereas G12 was detected in between 2.2% and 7.6% of the samples. The surveillance period was characterized by many co‐circulating genotypes, and eight unusual combinations (G1P[4], G2P[8], G2P[6], G3P[4], G9P[4], G12P[4], G9P[9] and G10P[4]) were detected. This study provides important baseline data on rotavirus genotypes in Kyrgyzstan and Kazakhstan in the pre‐vaccine era, and the results may indicate that the two licensed vaccines can be expected to prevent rotavirus disease in these countries.
Clinical pharmacology of analgesics assessed with human experimental pain models: bridging basic and clinical research
Authors: Oertel Bruno Georg , Lötsch Jörn
Published: October 2012

The medical impact of pain is such that much effort is being applied to develop novel analgesic drugs directed towards new targets and to investigate the analgesic efficacy of known drugs. Ongoing research requires cost‐saving tools to translate basic science knowledge into clinically effective analgesic compounds. In this review we have re‐examined the prediction of clinical analgesia by human experimental pain models as a basis for model selection in phase I studies. The overall prediction of analgesic efficacy or failure of a drug correlated well between experimental and clinical settings. However, correct model selection requires more detailed information about which model predicts a particular clinical pain condition. We hypothesized that if an analgesic drug was effective in an experimental pain model and also a specific clinical pain condition, then that model might be predictive for that particular condition and should be selected for development as an analgesic for that condition. The validity of the prediction increases with an increase in the numbers of analgesic drug classes for which this agreement was shown. From available evidence, only five clinical pain conditions were correctly predicted by seven different pain models for at least three different drugs. Most of these models combine a sensitization method. The analysis also identified several models with low impact with respect to their clinical translation. Thus, the presently identified agreements and non‐agreements between analgesic effects on experimental and on clinical pain may serve as a solid basis to identify complex sets of human pain models that bridge basic science with clinical pain research.
ARF6 and GASP‐1 are post‐endocytic sorting proteins selectively involved in the intracellular trafficking of dopamine D2 receptors mediated by GRK and PKC in transfected cells
Authors: Cho DI , Zheng M , Min C , Kwon KJ , Shin CY , Choi HK , Kim KM
Published: October 2012

Background and Purpose

GPCRs undergo both homologous and heterologous regulatory processes in which receptor phosphorylation plays a critical role. The protein kinases responsible for each pathway are well established; however, other molecular details that characterize each pathway remain unclear. In this study, the molecular mechanisms that determine the differences in the functional roles and intracellular trafficking between homologous and PKC‐mediated heterologous internalization pathways for the dopamine D2 receptor were investigated.

Experimental Approach

All of the S/T residues located within the intracellular loops of D2 receptor were mutated, and the residues responsible for GRK‐ and PKC‐mediated internalization were determined in HEK‐293 cells and SH‐SY5Y cells. The functional role of receptor internalization and the cellular components that determine the post‐endocytic fate of internalized D2 receptors were investigated in the transfected cells.

Key Results

T134, T225/S228/S229 and S325 were involved in PKC‐mediated D2 receptor desensitization. S229 and adjacent S/T residues mediated the PKC‐dependent internalization of D2 receptors, which induced down‐regulation and desensitization. S/T residues within the second intracellular loop and T225 were the major residues involved in GRK‐mediated internalization of D2 receptors, which induced receptor resensitization. ARF6 mediated the recycling of D2 receptors internalized in response to agonist stimulation. In contrast, GASP‐1 mediated the down‐regulation of D2 receptors internalized in a PKC‐dependent manner.

Conclusions and Implications

GRK‐ and PKC‐mediated internalizations of D2 receptors occur through different intracellular trafficking pathways and mediate distinct functional roles. Distinct S/T residues within D2 receptors and different sorting proteins are involved in the dissimilar regulation of D2 receptors by GRK2 and PKC.
Benzimidazolones enhance the function of epithelial Na+ transport
Authors: Laube M , Kimpel SU , Dietl P , Thome UH , Wittekindt OH
Published: October 2012

Background and Purpose

Pharmacological enhancement of vectorial Na+ transport may be useful to increase alveolar fluid clearance. Herein, we investigated the influence of the benzimidazolones 1‐ethyl‐1,3‐dihydro‐2‐benzimidazolone (1‐EBIO), 5,6‐dichloro‐1‐EBIO (DC‐EBIO) and chlorzoxazone on vectorial epithelial Na+ transport.

Experimental Approach

Effects on vectorial Na+ transport and amiloride‐sensitive apical membrane Na+ permeability were determined by measuring short‐circuit currents (ISC) in rat fetal distal lung epithelial (FDLE) monolayers. Furthermore, amiloride‐sensitive membrane conductance and the open probability of epithelial Na+ channels (ENaC) were determined by patch clamp experiments using A549 cells.

Key Results

ISC was increased by approximately 50% after addition of 1‐EBIO, DC‐EBIO and chlorzoxazone. With permeabilized basolateral membranes in the presence of a 145:5 apical to basolateral Na+ gradient, the benzimidazolones markedly increased amiloride‐sensitive ISC. 5‐(N‐Ethyl‐N‐isopropyl)amiloride‐induced inhibition of ISC was not affected. The benzamil‐sensitive ISC was increased in benzimidazolone‐stimulated monolayers. Pretreating the apical membrane with amiloride, which inhibits ENaC, completely prevented the stimulating effects of benzimidazolones on ISC. Furthermore, 1‐EBIO (1 mM) and DC‐EBIO (0.1 mM) significantly increased (threefold) the open probability of ENaC without influencing current amplitude. Whole cell measurements showed that DC‐EBIO (0.1 mM) induced an amiloride‐sensitive increase in membrane conductance.

Conclusion and Implications

Benzimidazolones have a stimulating effect on vectorial Na+ transport. The antagonist sensitivity of this effect suggests the benzimidazolones elicit this action by activating the highly selective ENaC currents. Thus, the results demonstrate a possible new strategy for directly enhancing epithelial Na+ transport.
Small ubiquitin‐like modifier 1–3 is activated in human astrocytic brain tumors and is required for glioblastoma cell survival
Authors: Yang Wei , Wang Liangli , Roehn Gabriele , Pearlstein Robert D. , Ali‐Osman Francis , Pan Hongjie , Goldbrunner Roland , Krantz Matthew , Harms Christoph , Paschen Wulf
Published: October 2012

Small ubiquitin‐like modifier (SUMO1–3) constitutes a group of proteins that conjugate to lysine residues of target proteins thereby modifying their activity, stability, and subcellular localization. A large number of SUMO target proteins are transcription factors and other nuclear proteins involved in gene expression. Furthermore, SUMO conjugation plays key roles in genome stability, quality control of newly synthesized proteins, proteasomal degradation of proteins, and DNA damage repair. Any marked increase in levels of SUMO‐conjugated proteins is therefore expected to have a major impact on the fate of cells. We show here that SUMO conjugation is activated in human astrocytic brain tumors. Levels of both SUMO1‐ and SUMO2/3‐conjugated proteins were markedly increased in tumor samples. The effect was least pronounced in low‐grade astrocytoma (WHO Grade II) and most pronounced in glioblastoma multiforme (WHO Grade IV). We also found a marked rise in levels of Ubc9, the only SUMO conjugation enzyme identified so far. Blocking SUMO1–3 conjugation in glioblastoma cells by silencing their expression blocked DNA synthesis, cell growth, and clonogenic survival of cells. It also resulted in DNA‐dependent protein kinase‐induced phosphorylation of H2AX, indicative of DNA double‐strand damage, and G2/M cell cycle arrest. Collectively, these findings highlight the pivotal role of SUMO conjugation in DNA damage repair processes and imply that the SUMO conjugation pathway could be a new target of therapeutic intervention aimed at increasing the sensitivity of glioblastomas to radiotherapy and chemotherapy. (Cancer Sci 2013; 104: 70–77)
Child Care Quality and Cognitive Development: Trajectories Leading to Better Preacademic Skills
Authors: Côté Sylvana M. , Mongeau Chantal , Japel Christa , Xu Qian , Séguin Jean R. , Tremblay Richard E.
Published: October 2012

The associations between trajectories of child care quality from ages 2 to 4 years and children's cognitive performance at 4 years (n = 250) were tested. Distinct quality trajectories were identified: low and high ascending Teaching and Interactions trajectory; low and high Provision for Learning trajectory. Membership in the high ascending Teaching and Interactions trajectory was associated with better numeracy (effect size [ES] = .39, confidence interval [CI] = .21–.66), receptive vocabulary (ES = .41, CI = .14–.68), and school readiness (ES = .32, CI = .06–.58). The results suggest that a pattern of increasing quality of teacher–child interactions during the preschool years, particularly with regard to supporting the development of language, has a moderate impact on children's cognitive development.
Heterogeneity in the responses of human lung mast cells to stem cell factor
Authors: Lewis A. , Wan J. , Baothman B. , Monk P. N. , Suvarna S. K. , Peachell P. T.
Published: October 2012

Background

Stem cell factor (SCF) is a growth factor that is involved in mast cell differentiation and proliferation. SCF primes human lung mast cells for enhanced responses to IgE‐directed activation but is not generally recognized as a direct activator. SCF mediates its effects through c‐kit.

Objective

The aim of this study was to reappraise the effects of SCF on human lung mast cells.

Methods

Mast cells were isolated from human lung. Mast cells were challenged with anti‐IgE or SCF and the generation of histamine, cysteinyl‐leukotrienes (cys‐LTs) and prostaglandin D2 (PGD2) was assessed as was expression of the activation marker, CD63. The effects of c‐kit inhibitors on mediator release were evaluated.

Results

Stem cell factor (10 ng/mL) alone was unable to induce mediator release but primed mast cells for enhanced IgE‐dependent secretion. At higher concentrations (≥ 30 ng/mL), SCF had more varied effects and even when used alone was able to drive substantial levels of histamine release in about a third of all preparations studied. Similarly, SCF (100 ng/mL) alone was effective in stimulating the generation of cys‐LTs in half of the preparations studied. SCF (100 ng/mL) was even more effective at stimulating PGD2 generation as almost all preparations generated substantial quantities of the prostanoid. Mediator release induced by SCF was accompanied by the up‐regulation of the activation marker, CD63. There was a positive correlation between the extent of mediator release induced by SCF and c‐kit receptor expression. The effects of SCF on mediator release from mast cells were reversed by the c‐kit inhibitor imatinib.

Conclusions and clinical relevance

These data demonstrate that the responses of mast cells to SCF are heterogeneous. SCF can drive much greater levels of mediator release from mast cells, especially of PGD2, than hitherto appreciated and this could be important in the context of respiratory diseases.
Visual outcomes of cataract surgery performed by supervised novice surgeons during training in rural China
Authors: Huang Wenyong , Ye Ronghua , Liu Bin , Chen Qianyun , Huang Guofu , Liu Yizhi , Friedman David S , Congdon Nathan G , Ling Jin , He Mingguang
Published: October 2012

Background 

To assess the outcomes of cataract surgery performed by novice surgeons during training in a rural programme.

Design 

Retrospective study.

Participants 

Three hundred thirty‐four patients operated by two trainees under supervision at rural Chinese county hospitals.

Methods 

Two trainees performed surgeries under supervision. Visual acuity, refraction and examinations were carried out 3 months postoperatively.

Main Outcome Measures 

Postoperative uncorrected visual acuity, pinhole visual acuity, causes of visual impairment (postoperative uncorrected visual acuity < 6/18)

Results 

Among 518 operated patients, 426 (82.2%) could be contacted and 334 (64.4% of operated patients) completed the examinations. The mean age was 74.1 ± 8.8 years and 62.9% were women. Postoperative uncorrected visual acuity was available in 372 eyes. Among them, uncorrected visual acuity was ≥6/18 in 278 eyes (74.7%) and <6/60 in 60 eyes (16.1%), and 323 eyes (86.8%) had pinhole visual acuity ≥ 6/18 and 38 eyes (10.2%) had pinhole visual acuity < 6/60. Main causes of visual impairment were uncorrected refractive error (63.9%) and comorbid eye disease (24.5%). Comorbid eye diseases associated with pinhole visual acuity < 6/60 (n = 23, 6.2%) included glaucoma, other optic nerve atrophy, vitreous haemorrhage and retinal detachment.

Conclusions 

The findings suggest that hands‐on training remains safe and effective even when not implemented in centralized training centres. Further refinement of the training protocol, providing postoperative refractive services and more accurate preoperative intraocular lens calculations, can help optimize outcomes.
Trachoma in Australia: an update
Authors: Taylor Hugh R , Anjou Mitchell D
Published: October 2012

In 2001, one of the authors wrote in the Medical Journal of Australia about trachoma explaining that Australia is the only developed country in the world where blinding trachoma still exists. Ten years later, the same is still true, but there is some progress and the situation in Australia is starting to change. However, this progress has been somewhat glacial, especially compared with the rapid changes being made in other ‘undeveloped’ parts of the world.
Assessment of adequate removal of ophthalmic viscoelastic device with irrigation/aspiration by quantifying intraocular lens ‘Judders’
Authors: Sim Benjamin WC , Amjadi Shahriar , Singh Ravjit , Bhardwaj Gaurav , Dubey Rahul , Francis Ian C
Published: October 2012

Background

To assess the efficacy of ‘Judders’ as a technique reflecting adequacy of removal of ophthalmic viscoelastic device in cataract surgery.

Design

Prospective, consecutive, single surgeon study.

Participants

Cohort of 223 patients undergoing phacoemulsification.

Methods

‘Judders’ are periodic, abrupt, horizontal displacements of the intraocular lens causing balanced salt solution to displace retropseudophakic ophthalmic viscoelastic device. The number of ‘Judders’ was correlated with axial length, anterior chamber depth, and preoperative and postoperative intraocular pressure.

Main Outcome Measures

Number of ‘Judders’, axial length, anterior chamber depth, day 1 postoperative intraocular pressure.

Results

The mean number of ‘Judders’ was 3.2. There was a positive association between the number of ‘Judders’ and axial length, but not between number of ‘Judders’ and anterior chamber depth. Mean preoperative intraocular pressure was 14.5 mmHg; mean day 1 postoperative intraocular pressure was 15.6 mmHg. Intraocular pressure rose in 47% of cases. In six cases (5%), intraocular pressure rose greater than 10 mmHg (range 11–23 mmHg) from the preoperative level.

Conclusions

Aspirating ophthalmic viscoelastic device with the irrigation/aspiration tip posterior to the intraocular lens may be associated with the risk of a posterior capsule tear. Maintaining the irrigation/aspiration tip anterior to the intraocular lens may offer a significant safety advantage. The number of ‘Judders’, usually 3–4, appears to be a safe and reliable end‐point of complete ophthalmic viscoelastic device removal. There were significantly more ‘Judders’ in eyes with a longer axial length. The safety and efficacy of ‘Judders’ are reflected by the stable mean postoperative intraocular pressure.
In vivo evaluation of bioactive glass‐based coatings on dental implants in a dog implantation model
Authors: van Oirschot Bart A. J. A. , Alghamdi Hamdan S. , Närhi Timo O. , Anil Sukumaran , Al Farraj Aldosari Abdullah , van den Beucken Jeroen J. J. P. , Jansen John A.
Published: October 2012

Objectives

Although titanium is commonly used as a favorable bone implant material due to its mechanical properties, its bioactive and osteoconductive capacity is relatively low. Calcium phosphate ceramics, predominantly hydroxyapatite (HA), have been frequently used for coating purposes to improve the bioactive properties. In view of the suggested osteopromotive capacity of bioactive glasses (BGs), this study aimed to evaluate the effect of BG incorporation into HA coatings on implant performance in terms of bone contact and bone area.

Materials and Methods

A total of 48 screw‐type titanium implants with magnetron sputter coatings containing different ratios of HA and BG (HA, HABGLow, and HABGHigh; n = 8) were placed into the mandible of 16 Beagle dogs. After 4 and 12 weeks, their performance was evaluated histologically and histomorphometrically. Peri‐implant bone area percentage (BA%) was determined in three zones (inner, 0–500 μm; middle, 500–1000 μm; and outer, 1000–1500 μm). Additionally, bone‐to‐implant contact (BIC%) and first bone–implant contact (1st BIC) were assessed for each sample.

Results

After 4 weeks, bone‐to‐implant contact for the HA‐ and HABGLow‐coated groups was significantly higher (P < 0.05) than for the HABGHigh coatings. Mean values for overall BA% showed comparable values for both the HABGLow (58.3%)‐ and HABGHigh (56.3%)‐coated groups. Data suggest that the relative BA around the HA‐coated implants (67.8%) was higher, although this was only significant compared to the HABGHigh group. After 12 weeks, all three groups showed similar bone‐to‐implant contact and no differences in BA were found.

Conclusions

The incorporation of BG into HA sputter coatings did not enhance the performance of a dental implant in implantations sites with good bone quality and quantity. On the contrary, coatings containing high concentrations of BG resulted in inferior performance during the early postimplantation healing phase.
Surgery Upregulates High Mobility Group Box‐1 and Disrupts the Blood–Brain Barrier causing Cognitive Dysfunction in Aged Rats
Authors: He Hui‐Juan , Wang Yi , Le Yuan , Duan Kai‐Ming , Yan Xue‐Bin , Liao Qin , Liao Yan , Tong Jian‐Bin , Terrando Niccolò , Ouyang Wen
Published: October 2012

Aim

Postoperative cognitive dysfunction (POCD) is a growing and largely underestimated problem without defined etiology. Herein, we sought to determine the relationship between cognitive decline, blood–brain barrier (BBB) permeability, and inflammation, namely high mobility group box‐1 (HMGB1), after surgery in aged rats.

Methods

Aged rats were randomly assigned as surgery group (n = 45, splenectomy under general anesthesia), anesthesia (n = 45, 2% isoflurane for 2 h), and naïve control (n = 15). Markers of inflammation were measured in plasma and brain. Blood–brain barrier ultrastructure and permeability were measured by transmission electron microscope (TEM) and IgG immunohistochemistry. Cognitive function was assessed in a reversal learning version of the Morris water maze (MWM).

Results

Surgical trauma under general anesthesia caused distinct changes in systemic and central proinflammatory cytokines. Levels of HMGB1 and the receptor for advanced glycation end products (RAGE) were significantly upregulated in the hippocampus of operated animals. Immunohistochemistry and TEM showed BBB disruption induced by surgery and anesthesia. These molecular changes were associated with cognitive impairment in latency with the MWM up to postoperative day 3.

Conclusions

HMGB1 and RAGE signaling appear pivotal mediators of surgery‐induced cognitive decline and may contribute to the changes in BBB permeability after peripheral surgical trauma.
Laparoscopic colectomy for transverse colon carcinoma: a surgical challenge but oncologically feasible
Authors: Fernández‐Cebrián J. M. , Gil Yonte P. , Jimenez‐Toscano M. , Vega L. , Ochando F.
Published: October 2012

Aim

The aim of the study was to assess the safety and feasibility of laparoscopic surgery for transverse colon cancer and to compare the clinicopathological outcome with that of conventional open surgery.

Method

From March 1998 to December 2009, 1253 patients with colorectal tumours were operated on, 564 laparoscopically. There were 154 cases of transverse colon cancer, 86 of which were included in the study. Details were collected on age, sex, body mass index (BMI), operation time, blood loss, time to first flatus, time to resume a liquid diet, postoperative length of hospital stay, complications, TNM stage, tumour size, distal resection margin, proximal resection margin, number of nodes harvested and surgical procedure. Laparoscopic and open surgical removal was compared.

Results

No significant differences were found between laparoscopic and conventional groups in age, sex, BMI, operation time or postoperative length of hospital stay. The mean blood loss during the operations was significantly less in the laparoscopic group (105.9 ± 140.9 ml vs 305.7 ± 325.3 ml; P = 0.05). The time to the first flatus was shorter (2.1 ± 0.3 days vs 3.8 ± 3.0 days; P = 0.043) and diet was started earlier (3.1 ± 1.4 days vs 3.4 ± 1.5 days) in the laparoscopic group. No significant differences in tumour size, proximal resection margin or number of lymph nodes were observed. The mean distal resection margin was not statistically different (10.3 ± 4.5 cm vs 8.8 ± 4.9 cm). At a mean follow up of 33 ± 2.3 months, nonport‐site metastases occurred in eight patients and locoregional recurrence occurred in three, with no significant difference between the groups. The 3‐year cumulative overall survival rate was 78%, and the disease‐free survival rate was 69%.

Conclusion

There was no difference in the outcome of laparoscopic and open surgery for transverse colon cancer, including the cancer‐specific outcome.
The differential anti‐inflammatory effects of exercise modalities and their association with early carotid atherosclerosis progression in patients with Type 2 diabetes
Authors: Kadoglou N. P. E. , Fotiadis G. , Kapelouzou A. , Kostakis A. , Liapis C. D. , Vrabas I. S.
Published: October 2012

Objective

Adipokines, visfatin, apelin, vaspin and ghrelin have emerged as novel cardiovascular risk factors. We aimed to evaluate the effects of different exercise modalities on the aforementioned novel adipokines and carotid intima‐media thickness in patients with Type 2 diabetes mellitus.

Methods

One hundred patients with Type 2 diabetes were equivalently (n = 25) randomized into four groups: (1) a control group with patients encouraged to perform self‐controlled exercise; (2) a supervised aerobic exercise group (exercise four times/week, 60 min/session, 60–75% of maximum heart rate); (3) a resistance training group (60–80% baseline maximum load achieved in one repetition); and (4) a combined aerobic exercise plus resistance training group, as in groups 2 and 3. All participants had HbA1c levels ≥ 48 mmol/mol (≥ 6.5%), without overt diabetic vascular complications. Blood samples, clinical characteristics, peak oxygen uptake and carotid intima‐media thickness measurements were obtained at baseline and at the end of the study, after 6 months.

Results

At baseline, there were non‐significant differences between groups. All active groups significantly ameliorated glycaemic profile, insulin sensitivity and triglycerides levels compared with the control group (P < 0.05). Aerobic training further improved lipids, systolic blood pressure and exercise capacity compared with the resistance training and the control groups (P < 0.05). Moreover, high‐sensitivity C‐reactive protein and visfatin decreased, while vaspin and apelin circulating levels increased within the aerobic exercise group and the aerobic exercise plus resistance training group, and compared with the other groups (P < 0.05). Within‐ and between‐group comparisons showed negligible alterations in ghrelin serum levels and body weight after all exercise modalities. Finally, aerobic training attenuated the carotid intima‐media thickness progression (0.017 ± 0.006 mm) compared with the control subjects (0.129 ± 0.042 mm, P < 0.001). That effect was independently associated with visfatin and amelioration of peak oxygen uptake.

Conclusions

In subjects with Type 2 diabetes, all exercise training modalities improved metabolic profile. Importantly, aerobic training predominantly ameliorated adipokines concentrations and carotid intima‐media thickness progression.
Exenatide once weekly improved glycaemic control, cardiometabolic risk factors and a composite index of an HbA1c < 7%, without weight gain or hypoglycaemia, over 52 weeks
Authors: Bergenstal R. M. , Li Y. , Porter T. K. Booker , Weaver C. , Han J.
Published: October 2012

Aims

Type 2 diabetes mellitus (T2DM) is often associated with cardiovascular (CV) risk factors such as obesity, hypertension and dyslipidemia. The objective of this analysis was to evaluate potential effects of exenatide once weekly (ExQW), a GLP‐1 receptor agonist, on glycaemic control and CV risk factors.

Methods

This analysis included 675 Intent‐to‐Treat patients with T2DM [baseline (mean ± SD) HbA1c, 8.1 ± 1.2%; fasting blood glucose (FBG), 166 ± 48 mg/dl; weight, 94.3 ± 19.4 kg; systolic/diastolic blood pressure (SBP/DBP), 129 ± 15/78 ± 9 mm Hg; total cholesterol, 178.5 ± 41.9 mg/dl; low‐density lipoprotein (LDL), 100.1 ± 35.0 mg/dl; high‐density lipoprotein (HDL), 44.5 ± 11.6 mg/dl; triglycerides, 155.6 ± 3.3 mg/dl; alanine aminotransferase (ALT), 32.1 ± 19.5 U/l] treated with diet and exercise alone or in combination with metformin, sulfonylurea, and/or thiazolidinedione who received 52 weeks of ExQW in four clinical trials.

Results

At 52 weeks, ExQW significantly improved HbA1c [mean (SE) change from baseline, −1.3 (0.05)%], FBG [−36.3 (2.02) mg/dl], body weight [−2.6 (0.19) kg], SBP/DBP [−3.6 (0.56) mm Hg/−1.2 (0.34) mm Hg], total cholesterol, −4.4 (1.33) mg/dl; LDL, −2.6 (1.08) mg/dl; HDL, 1.1 (0.31) mg/dl; triglycerides, −7 (1.6)%], and ALT [−4.3 (0.71) IU/l] concentrations, with greater improvements in patients with elevated analyte levels at baseline. Improvements were observed across a range of background antihyperglycaemia therapies. Of patients completing 52 weeks, 19% achieved the composite American Diabetes Association goal (HbA1c < 7.0%, BP < 130/80 mm Hg, LDL < 100 mg/dl), compared to 1% at baseline. Nearly half (48%) achieved HbA1c < 7.0% without weight gain or major/minor hypoglycaemia. Nausea was the most frequent adverse event and was predominantly mild. Hypoglycaemia was infrequent, and more common with a sulfonylurea.

Conclusions

With 52 weeks of ExQW, patients experienced sustained improvements in glycaemic control and CV risk factors, with an increased likelihood of achieving both a clinically relevant composite outcome (HbA1c < 7% without weight gain or increased risk of hypoglycaemia) and a composite of key therapeutic goals (HbA1c < 7%, BP < 130/80 mm Hg, LDL < 100 mg/dl).
Fabricated Illness: Working within the Family System to Find a Pathway to Health
Authors: Kozlowska Kasia , Foley Sue , Savage Blanche
Published: October 2012

The term medically unexplained symptoms refers to a clinical presentation where the child's symptoms and impairment cannot be explained by any known organic pathology, and may include conversion disorders, somatoform pain disorders, factitious disorder, and factitious disorder by proxy. In this case study, we present our treatment of a 9‐year‐old girl with a 2‐year history of medically unexplained abdominal cramping and vaginal discharge. During the 9 months that we worked with this family, we were never able to clarify in our own minds the source of the child's symptoms—that is, who was responsible for their induction or who was the instigator or maintainer of the exaggerated symptoms. Nor did we come to fully understand the function of the symptoms in the family system. Our case report does not answer either of these questions. Instead, we describe how we worked with the family despite the ongoing ambiguities as to why the symptoms were occurring and who was inducing them. The functional outcome was disappearance of symptoms, return to full school attendance, and improved parenting behavior.
The Influence of Mothers' and Fathers' Parenting Stress and Depressive Symptoms on Own and Partner's Parent‐Child Communication
Authors: Ponnet Koen , Wouters Edwin , Mortelmans Dimitri , Pasteels Inge , De Backer Charlotte , Van Leeuwen Karla , Van Hiel Alain
Published: October 2012

This study examines how parenting stress and depressive symptoms experienced by mothers and fathers influence their own (actor effects) and the partner's (partner effects) parent–child communication. Based on the Actor‐Partner Interdependence Model, data from 196 families were analyzed, with both parents rating their parenting stress and depressive feelings, and parents as well as children rating the open parent–child communication. Actor effects were found between parenting stress and open parent–child communication, whereas partner effects were prominent between depressive symptoms and open parent–child communication. The results provide no evidence for gender differences in the strength of the pathways to open parent–child communication. Our findings demonstrate the need to include both parents in studies on parent–child communication to enhance our understanding of the mutual influence among family members.
Burden, Interdependence, Ethnicity, and Mental Health in Caregivers of Patients with Schizophrenia
Authors: Suro Giulia , Weisman de Mamani Amy G.
Published: October 2012

Caring for a patient with schizophrenia often results in high levels of perceived burden and poorer overall mental health. Using a sample of 176 caregivers of patients with schizophrenia, the present study examined how two components of burden (objective and subjective) interacted with interdependence and ethnicity to influence relatives' overall mental health. In line with study hypotheses, and with the stress‐appraisal‐coping model developed by Lazurus and Folkman (1984), we found that subjective burden mediated the relationship between objective burden and mental health. In other words, subjective appraisals of caregiving appeared to partially underlie the association between the concrete costs of caregiving and psychological outcomes in schizophrenia caregivers. Also as hypothesized, we found that interdependence, or the perceived interconnectedness of individuals within a group, moderated the relationship between objective burden and subjective burden. In other words, when levels of interdependence were high, the objective components of burden appeared to have a weaker relationship with subjective burden. When interdependence was low, on the other hand, objective burden was more likely to be associated with subjective burden. This finding suggests that helping caregivers to value harmony and connection with others over individual self‐interests may reduce the likelihood that objective stressors (which are often inevitable in schizophrenia) will result in subjective distress. On the basis of prior research, we also tested several hypotheses regarding the role of ethnicity and its association with burden, interdependence, and mental health. However, contrary to expectations, no ethnic patterns were observed.