bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemokine receptor CXCR3 facilitates CD8+ T cell differentiation into short-lived effector cells leading to memory degeneration
Authors: Kurachi Makoto , Kurachi Junko , Suenaga Fumiko , Tsukui Tatsuya , Abe Jun , Ueha Satoshi , Tomura Michio , Sugihara Kei , Takamura Shiki , Kakimi Kazuhiro , Matsushima Kouji
Published: July 2011

Strength of inflammatory stimuli during the early expansion phase plays a crucial role in the effector versus memory cell fate decision of CD8+ T cells. But it is not known how early lymphocyte distribution after infection has an impact on this process. We demonstrate that the chemokine receptor CXCR3 is involved in promoting CD8+ T cell commitment to an effector fate rather than a memory fate by regulating T cell recruitment to an antigen/inflammation site. After systemic viral or bacterial infection, the contraction of CXCR3−/− antigen-specific CD8+ T cells is significantly attenuated, resulting in massive accumulation of fully functional memory CD8+ T cells. Early after infection, CXCR3−/− antigen-specific CD8+ T cells fail to cluster at the marginal zone in the spleen where inflammatory cytokines such as IL-12 and IFN-α are abundant, thus receiving relatively weak inflammatory stimuli. Consequently, CXCR3−/− CD8+ T cells exhibit transient expression of CD25 and preferentially differentiate into memory precursor effector cells as compared with wild-type CD8+ T cells. This series of events has important implications for development of vaccination strategies to generate increased numbers of antigen-specific memory CD8+ T cells via inhibition of CXCR3-mediated T cell migration to inflamed microenvironments.
RNAG: a new Gibbs sampler for predicting RNA secondary structure for unaligned sequences
Authors: Wei Donglai , Alpert Lauren V. , Lawrence Charles E.
Published: July 2011

Motivation: RNA secondary structure plays an important role in the function of many RNAs, and structural features are often key to their interaction with other cellular components. Thus, there has been considerable interest in the prediction of secondary structures for RNA families. In this article, we present a new global structural alignment algorithm, RNAG, to predict consensus secondary structures for unaligned sequences. It uses a blocked Gibbs sampling algorithm, which has a theoretical advantage in convergence time. This algorithm iteratively samples from the conditional probability distributions P(Structure | Alignment) and P(Alignment | Structure). Not surprisingly, there is considerable uncertainly in the high-dimensional space of this difficult problem, which has so far received limited attention in this field. We show how the samples drawn from this algorithm can be used to more fully characterize the posterior space and to assess the uncertainty of predictions.

Results: Our analysis of three publically available datasets showed a substantial improvement in RNA structure prediction by RNAG over extant prediction methods. Additionally, our analysis of 17 RNA families showed that the RNAG sampled structures were generally compact around their ensemble centroids, and at least 11 families had at least two well-separated clusters of predicted structures. In general, the distance between a reference structure and our predicted structure was large relative to the variation among structures within an ensemble.

Availability: The Perl implementation of the RNAG algorithm and the data necessary to reproduce the results described in Sections 3.1 and 3.2 are available at http://ccmbweb.ccv.brown.edu/rnag.html

Contact:  charles_lawrence@brown.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Homoarginine, heart failure, and sudden cardiac death in haemodialysis patients
Authors: Drechsler Christiane , Meinitzer Andreas , Pilz Stefan , Krane Vera , Tomaschitz Andreas , Ritz Eberhard , März Winfried , Wanner Christoph
Published: July 2011

Aims

Sudden cardiac death (SCD) is a major contributor to the excess mortality of patients on maintenance dialysis. Homoarginine deficiency may lead to decreased nitric oxide availability and endothelial dysfunction. Based on this rationale we assessed whether homoarginine deficiency is a risk factor for SCD in dialysis patients.

Methods and results

This study examined the association of homoarginine with cardiovascular outcomes in 1255 diabetic haemodialysis patients from the German diabetes and dialysis study. During a median of 4 years of follow‐up, hazard ratios (HR) (95% CI) for reaching the following pre‐specified, adjudicated endpoints were determined: SCD, myocardial infarction, stroke, death due to heart failure, and combined cardiovascular events. There was a strong association of low homoarginine concentrations with the presence of congestive heart failure and left ventricular hypertrophy as well as increased levels of brain natriuretic peptide. Per unit decrease in homoarginine, the risk of SCD increased three‐fold (HR 3.1, 95% CI 2.0–4.9), attenuating slightly in multivariate models (HR 2.4; 95% CI 1.5–3.9). Patients in the lowest homoarginine quintile experienced a more than two‐fold increased risk of SCD, and more than three‐fold increased risk of heart failure death than patients in the highest quintile, which accounted for the high incidence of combined cardiovascular events. Low homoarginine showed a trend towards increased risk of stroke, however, myocardial infarction was not meaningfully affected.

Conclusion

Low homoarginine is a strong risk factor for SCD and death due to heart failure in haemodialysis patients. Further studies are needed to elucidate the underlying mechanisms, offering the potential to develop new interventional strategies.
A Guide to Preoperative Assessment
Authors: Dodwell Hannah
Published: July 2011

As part of their training, Associates-in-Training (AiTs) will spend time in hospital within surgical specialties. Most hospitals have dedicated clinics for the preoperative assessment of patients scheduled for elective surgery, which are usually run by specialist nurses. However, sometimes, the responsibility for preoperative assessment will fall to the AiT. If you have not done this before, it can be daunting and it may be difficult to know which investigations patients need. Most hospitals will have preoperative assessment guidelines and proformas for you to use but here are some basics to get you started.
Botryosphaeriaceae Species Associated with Avocado Branch Cankers in California
Authors: McDonald Virginia , Eskalen Akif
Published: July 2011

Members of the family Botryosphaeriaceae cause branch cankers and dieback on California avocado trees. More intensive pruning, a practice associated with high-density planting that is becoming more common in the California avocado industry, may increase the occurrence of branch canker. This study was undertaken to identify and characterize the Botryosphaeriaceae spp. involved in the branch canker disease complex in order to develop future management strategies. From 2008 to 2009, branch cankers were sampled from four or five trees from each of eight avocado groves in five California counties. Six Botryosphaeriaceae spp. were identified based on morphology as well as phylogenetic analysis of the internal transcribed spacer region (ITS1-5.8S-ITS2) and a partial sequence of the β-tubulin gene. These six species included Neofusicoccum australe, N. luteum, N. parvum, an unknown Neofusicoccum sp., Fusicoccum aesculi, and Dothiorella iberica. Members of the Botryosphaeriaceae were isolated from all avocado-growing regions sampled in California; however, incidence and distribution of species varied. This report is the first description of the isolation of D. iberica from avocado branch cankers in California.
First Report of Root Rot Caused by Fusarium proliferatum on Blueberry in Argentina
Authors: Pérez B. A. , Berretta M. F. , Carrión E. , Wright E. R.
Published: July 2011

In 2009, a highbush blueberry (Vaccinium corymbosum L. ‘O'Neal’) field located in Rojas, Buenos Aires Province showed 30% of plants with dry or dead branches. Disinfected root pieces were placed on water agar and incubated at 24°C. A fungal colony was obtained and purified by successive transfers of an individual hyphal tip from a sparsely growing colony. Colony color and growth rate were evaluated in potato dextrose agar where the fungus produced white-to-pale pink colonies and grew 3.5 cm after 5 days. The fungus was studied on Spezieller Nährstoffarmer agar (2), carnation leaf-piece agar, and KCl agar where it produced abundant single-celled hyaline microconidia in moderate-length chains and in false heads originated from monophialides and polyphialides. Microconidia measured 6 to 12 × 2 to 3 μm (average 8 × 2.3 μm). On KCl, chains of microconidia and tan-to-light cream sporodochia with 3- to 5-septate, slender, relatively straight macroconidia were easily observed after 4 and 10 days, respectively. Macroconidia measured 38 to 48 × 3.5 to 4 μm (average 43.9 × 3.9 μm). Chlamydospores and sclerotia were not present. Data coincided with the description for Fusarium proliferatum (Matsush.) Niremberg ex Gerlach & Niremberg. The isolate was deposited in the IMYZA Microbial Collection as INTA-IMC 144. The fungus was cultured in 100 ml of Czapek-Dox supplemented with sucrose, peptone, yeast extract, sodium nitrate, and vitamins for 4 days. Genomic DNA was obtained with a DNA extraction kit, PCR amplified with primers ITS1 and ITS4 for the internal transcribed spacer (ITS) region of ribosomal genes, and sequenced. The nucleotide sequence (Accession No JF913468) was compared with GenBank records. The sequence shared 99% identity with Accession No HQ113948 for F. proliferatum. Pathogenicity was confirmed in 1-year-old ‘O'Neal’ plants. A 10-ml suspension (2.4 × 106 conidia/ml in sterile distilled water) was applied to six potted plants grown in sterilized potting mix. Roots were superficially wounded with a needle. Control plants were treated with sterile distilled water. Plants were incubated at 24°C and a 12-h photoperiod. After 90 days, plants showed root rot, leaf chlorosis, and branch necrosis followed by plant death. Control plants remained healthy. F. proliferatum was reisolated from diseased roots of inoculated plants. This fungus was previously cited in Argentina on asparagus (1), corn (1,3), and oat (4). To our knowledge, this is the first report of F. proliferatum as a root pathogen of highbush blueberry in Argentina.

References: (1) G. Lori et al. Plant Dis. 82:1405, 1998. (2) H. I. Nirenberg. Releases Fed. Biol. Res. Ctr. Agric. For. (Berlin-Dahlem) 169:1, 1976. (3) D. A. Sampietro et al. Fung. Biol. 114:74, 2010. (4) S. A. Stenglein et al. Plant Dis. 94:783, 2010.
Advances in therapies for acute promyelocytic leukemia
Authors: Kamimura Tomohiko , Miyamoto Toshihiro , Harada Mine , Akashi Koichi
Published: July 2011

Acute promyelocytic leukemia (APL), a distinct subtype of acute myelogenous leukemia (AML), results from the arrest of the maturation of hematopoietic progenitors at the promyelocyte stage. It has been shown that APL is associated with a reciprocal chromosomal translocation, involving chromosomes 15 and 17, which fuses the gene encoding the retinoic acid receptor α (RARα) and the promyelocytic leukemia (PML) gene. The resultant PML‐RARα fusion protein plays a critical role in the pathogenesis of APL. Although there are many subtypes of AML, all are typically managed using a standard chemotherapy regimen of an anthracycline plus cytarabine arabinoside (CA). Despite high rates of complete remission following standard chemotherapy, most patients relapse and long‐term disease‐free survival is only 30–40%. The introduction of drugs such as all‐trans retinoic acid (ATRA) that promote progenitor differentiation by directly inhibiting the PML‐RARα fusion protein has changed the treatment paradigm for APL and markedly improved patient survival. The purposes of the present review are to provide the latest results and future directions of clinical research into APL and to illustrate how new therapies, such as ATRA plus anthracycline‐based induction and consolidation therapy, risk‐adapted therapy, salvage therapy containing arsenic trioxide‐based regimens, and hematopoietic stem cell transplantation, have improved the treatment outcomes for APL patients. (Cancer Sci 2011; 102: 1929–1937)
The determinants of periorbital skin ageing in participants of a melanoma case–control study in the U.K.
Authors: Suppa M. , Elliott F. , Mikeljevic J.S. , Mukasa Y. , Chan M. , Leake S. , Karpavicius B. , Haynes S. , Bakker E. , Peris K. , Barrett J.H. , Bishop D.T. , Newton Bishop J.A.
Published: July 2011

Background Skin ageing is said to be caused by multiple factors. The relationship with sun exposure is of particular interest because the detrimental cutaneous effects of the sun may be a strong motivator to sun protection. We report a study of skin ageing in participants of an epidemiological study of melanoma.

Objectives To determine the predictors of periorbital cutaneous ageing and whether it could be used as an objective marker of sun exposure.

Methods Photographs of the periorbital skin in 1341 participants were graded for wrinkles, degree of vascularity and blotchy pigmentation and the resultant data assessed in relation to reported sun exposure, sunscreen use, body mass index (BMI), smoking and the melanocortin 1 receptor (MC1R) gene status. Data were analysed using proportional odds regression.

Results Wrinkling was associated with age and heavy smoking. Use of higher sun-protection factor sunscreen was protective (P =0·01). Age, male sex, MC1R variants (‘r’, P =0·01; ‘R’, P =0·02), higher reported daily sun exposure (P =0·02), increased BMI (P =0·01) and smoking (P =0·02) were risk factors for hypervascularity. Blotchy pigmentation was associated with age, male sex, higher education and higher weekday sun exposure (P =0·03). More frequent sunscreen use (P =0·02) and MC1R variants (‘r’, P =0·03; ‘R’, P =0·001) were protective.

Conclusions Periorbital wrinkling is a poor biomarker of reported sun exposure. Vascularity is a better biomarker as is blotchy pigmentation, the latter in darker-skinned individuals. In summary, male sex, sun exposure, smoking, obesity and MC1R variants were associated with measures of cutaneous ageing. Sunscreen use showed some evidence of being protective.
BIOMED‐2 PCR assays for IGK gene rearrangements are essential for B‐cell clonality analysis in follicular lymphoma
Authors: Payne Karen , Wright Penny , Grant John W. , Huang Yuanxue , Hamoudi Rifat , Bacon Chris M. , Du Ming‐Qing , Liu Hongxiang
Published: July 2011

B‐cell clonality analysis is commonly performed by polymerase chain reaction (PCR) targeting the IGH genes although a high false‐negative rate is recognized for germinal centre/post‐germinal centre B‐cell malignancies, especially follicular lymphoma. We assessed the diagnostic value of BIOMED‐2 IGK assays and investigated the cause of IGH PCR failure in 77 patients with follicular lymphoma. Using the full set of BIOMED‐2 reactions, clonal immunoglobulin gene rearrangements were detected in 74 (96%) cases. The clonality detection rate was 86% by two IGK reactions but only 68% by five IGH reactions (P < 0·001). Sequencing of the clonal PCR products showed significantly fewer somatic mutations in the rearranged IGKV (9/27 cases, 33%, mean mutation rate 0·5%) than IGHV (17/17 cases, 100%, rate 11·0%) (P < 0·01). All IGHV‐IGHJ PCR failures occurred in cases with at least one mutation at the corresponding IGHV primer binding sites. t(14:18)(q32:q21)/IGH‐BCL2 was detected in 50 of 71 (70%) cases and the presence of the translocation was not associated with the poor performance of IGH assays. Our results showed that BIOMED‐2 IGK assays are significantly more sensitive than IGH assays in follicular lymphoma due to the fact that the rearranged IGKV is less frequently targeted by somatic hypermutation than IGHV, and therefore, are essential in routine clonality analysis of these lymphomas.
FADS gene variants modulate the effect of dietary fatty acid intake on allergic diseases in children
Authors: Standl M. , Sausenthaler S. , Lattka E. , Koletzko S. , Bauer C.‐P. , Wichmann H.‐E. , von Berg A. , Berdel D. , Krämer U. , Schaaf B. , Röder S. , Herbarth O. , Klopp N. , Koletzko B. , Heinrich J. ,   for the GINIplus and LISAplus Study Group
Published: July 2011

Background The association between dietary fatty acid intake and the development of atopic diseases has been inconsistent. This could be due to inter‐individual genetic differences in fatty acid metabolism.

Objective The aim of the current study was to assess the influence of FADS1 FADS2 gene cluster polymorphisms on the association between dietary fatty acid intake and atopic diseases and allergic sensitization in 10‐year‐old children.

Methods The analysis was based on data from two German prospective birth cohort studies. Data on margarine and fatty acid intake were collected using a food frequency questionnaire. Information on atopic diseases was collected using a questionnaire completed by the parents. Specific IgE against common food and inhalant allergens were measured. Six variants of the FADS1 FADS2 gene cluster (rs174545, rs174546, rs174556, rs174561, rs174575 and rs3834458) were tested. Logistic regression modelling, adjusted for gender, age, maternal education level and study centre, was used to analyse the association between fatty acid intake and atopic diseases stratified by genotype.

Results No significant association was found between the six FADS single nucleotide polymorphisms (SNPs) and allergic diseases or atopic sensitization. The total n‐3/total n‐6 ratio was positive associated with an increased risk of hayfever in homozygous major allele carriers ranging from an adjusted odds ratios of 1.25 (95%‐CI: 1.00–1.57) to 1.31 (95%‐CI: 1.01–1.69) across the six tested SNPs although this association was not significant anymore after correcting for multiple testing. Daily margarine intake was significantly associated with asthma [1.17 (1.03–1.34) to 1.22 (1.06–1.40)] in individuals carrying the homozygous major allele. This association was also significant after correcting for multiple testing.

Conclusions & Clinical Relevance The association between dietary intake of fatty acids and allergic diseases might be modulated by FADS gene variants in children.

Cite this as: M. Standl, S. Sausenthaler, E. Lattka, S. Koletzko, C.‐P. Bauer, H.‐E. Wichmann, A. von Berg, D. Berdel, U. Krämer, B. Schaaf, S. Röder, O. Herbarth, N. Klopp, B. Koletzko and J. Heinrich for the GINIplus and LISAplus Study Group, Clinical & Experimental Allergy, 2011 (41) 1757–1766.
Assessment of gonadotrophin suppression in girls treated with GnRH analogue for central precocious puberty; validity of single luteinizing hormone measurement after leuprolide acetate injection
Authors: Demirbilek Huseyin , Alikasifoglu Ayfer , Gonc Nazli E. , Ozon Alev , Kandemir Nurgun
Published: July 2011

Objective  Intravenous GnRH stimulation test has often been used as gold standard test for the evaluation of hypothalamic–pituitary–gonadal axis in the diagnosis of central precocious puberty (CPP) and in the assessment of pubertal suppression. However, this test is time‐consuming, costly and uncomfortable for the patients. We aimed to analyse the validity of single LH sample 90 min after GnRH analogue (GnRHa) administration in the evaluation of gonadotrophin suppression during CPP therapy and to determine a cut‐off level for LH indicating adequate suppression.

Design  Prospective study.

Patients and Methods  One hundred and forty‐two patients with CPP were included in this study. Peak LH level during iv GnRH stimulation test after the third dose of GnRHa was compared with LH level 90 min after injection of the 3rd dose of GnRHa.

Results  There was a positive correlation between LH level following a GnRHa injection and peak LH during standard iv GnRH stimulation test (r = 0·83; P < 0·0001). A LH value of 2·5 mIU/ml or less 90 min after GnRHa injection was considered to be the cut‐off for the determination of pubertal suppression (sensitivity and specificity was 100% and 88%, respectively). In 117 patients, gonadotrophin suppression was existed according to both GnRHa and iv GnRH tests. In 25 patients, gonadotrophin suppression was not found in the GnRHa test. However, 16 of them were suppressed according to the iv GnRH test.

Conclusion  Single LH determination 90 min after GnRHa administration using a cut‐off level of 2·5 mIU/ml reflects pubertal suppression with a high sensitivity and specificity. However, this test may fail to show pubertal suppression in some cases. Those patients who appear to be inadequately suppressed should be reassessed using standard iv GnRH stimulation test for optimal dose adjustment.
Human spermatogonial stem cells: a possible origin for spermatocytic seminoma
Authors: Waheeb R. , Hofmann M.‐C.
Published: July 2011

In mammals, spermatogenesis is maintained throughout life by a small subpopulation of type A spermatogonia called spermatogonial stem cells (SSCs). In rodents, SSCs, or Asinglespermatogonia, form the self‐renewing population. SSCs can also divide into Apaired(Apr) spermatogonia that are predestined to differentiate. Apairedspermatogonia produce chains of Aaligned(Aal) spermatogonia that divide to form A1 to A4, then type B spermatogonia. Type B spermatogonia will divide into primary spermatocytes that undergo meiosis. In human, there are only two different types of A spermatogonia, the Adarkand Apalespermatogonia. The Adarkspermatogonia are considered reserve stem cells, whereas the Apalespermatogonia are the self‐renewing stem cells. There is only one generation of type B spermatogonia before differentiation into spermatocytes, which makes human spermatogenesis less efficient than in rodents. Although the biology of human SSCs is not well known, a panel of phenotypic markers has recently emerged that is remarkably similar to the list of markers expressed in mice. One such marker, the orphan receptor GPR125, is a plasma membrane protein that can be used to isolate human SSCs. Human SSCs proliferate in culture in response to growth factors such as GDNF, which is essential for SSC self‐renewal in mice and triggers the same signalling pathways in both species. Therefore, despite differences in the spermatogonial differentiation scheme, both species use the same genes and proteins to maintain the pool of self‐renewing SSCs within their niche. Spermatocytic seminomas are mainly found in the testes of older men, and they rarely metastasize. It is believed that these tumours originate from a post‐natal germ cell. Because these lesions can express markers specific for meiotic prophase, they might originate from a primary spermatocyte. However, morphological appearance and overall immunohistochemical profile of these tumours indicate that the cell of origin could also be a spermatogonial stem cell.
Oestrogen Receptors and Signalling Pathways: Implications for Neuroprotective Effects of Sex Steroids in Parkinson’s Disease
Authors: Al Sweidi S. , Sánchez M. G. , Bourque M. , Morissette M. , Dluzen D. , Di Paolo T.
Published: July 2011

Parkinson’s disease (PD) is an age‐related neurodegenerative disorder with a higher incidence in the male population. In the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) mouse model of PD, 17β‐oestradiol but not androgens were shown to protect dopamine (DA) neurones. We report that oestrogen receptors (ER)α and β distinctly contribute to neuroprotection against MPTP toxicity, as revealed by examining the membrane DA transporter (DAT), the vesicular monoamine transporter 2 (VMAT2) and tyrosine hyroxylase in ER wild‐type (WT) and knockout (ERKO) C57Bl/6 male mice. Intact ERKOβ mice had lower levels of striatal DAT and VMAT2, whereas ERKOα mice were the most sensitive to MPTP toxicity compared to WT and ERKOβ mice and had the highest levels of plasma androgens. In both ERKO mice groups, treatment with 17β‐oestradiol did not provide neuroprotection against MPTP, despite elevated plasma 17β‐oestradiol levels. Next, the recently described membrane G protein‐coupled oestrogen receptor (GPER1) was examined in female Macaca fascicularis monkeys and mice. GPER1 levels were increased in the caudate nucleus and the putamen of MPTP‐monkeys and in the male mouse striatum lesioned with methamphetamine or MPTP. Moreover, neuroprotective mechanisms in response to oestrogens transmit via Akt/glycogen synthase kinase‐3 (GSK3) signalling. The intact and lesioned striata of 17β‐oestradiol treated monkeys, similar to that of mice, had increased levels of pAkt (Ser 473)/βIII‐tubulin, pGSK3 (Ser 9)/βIII‐tubulin and Akt/βIII‐tubulin. Hence, ERα, ERβ and GPER1 activation by oestrogens is imperative in the modulation of ER signalling and serves as a basis for evaluating nigrostriatal neuroprotection.
The mosquito Aedes (Aedimorphus) vexans arabiensis as a probable vector bridging the West Nile virus between birds and horses in Barkedji (Ferlo, Senegal)
Authors: FALL A. G. , DIAÏTÉ A. , ETTER E. , BOUYER J. , NDIAYE T. D. , KONATÉ L.
Published: July 2011

Active catches of adult females of Aedes vexans arabiensis Patton, (Diptera: Culicidae) Patton by nets or aspirator, were conducted in 2003 and 2004 in the vegetation at the edge of temporary ponds in Barkedji, Senegalese Ferlo area. Two hundred and forty‐one engorged females were captured, dissected and the gut content adsorbed on a Whatman filter paper and analysed using the enzyme‐linked immunosorbent assay (ELISA) technique to determinate the bloodmeal origin. Results indicated that Ae v. arabiensis fed primarily on mammals, including horses (35.7% of the bloodmeals), but also on birds (10%). Moreover, associations between horses and birds accounted for 42% of the mixed bloodmeals. These results show an opportunistic feeding behaviour and suggest that Ae v. arabiensis is a probable vector bridging the West Nile virus between horses and birds hosts in the Ferlo area.
Identification and characterization of sources of resistance in Avena sativa, A. byzantina and A. strigosa germplasm against a pathotype of Puccinia coronata f.sp. avenae with virulence against the Pc94 resistance gene
Authors: Sánchez‐Martín J. , Rubiales D. , Sillero J. C. , Prats E.
Published: July 2011

An isolate of Puccinia coronata f.sp. avenae with virulence against the oat crown rust resistance gene Pc94 was discovered in oat fields in Córdoba, Spain. In order to identify alternative sources of resistance to this virulent isolate, a collection of 159 Avena accessions, including 107 A. sativa and 29 A. byzantina landraces and 23 commercial A. sativa and A. strigosa cultivars, was screened. Eight resistant landraces and four cultivars were selected according to macroscopic assessment to further characterize the operative defence mechanisms. Histological studies showed a range of defence mechanisms, acting alone or in combination, which impeded fungal development at different stages. Some accessions allowed reduced fungal growth before mesophyll penetration. In others, the fungus was arrested at the penetration stage by mesophyll cell wall strengthening and/or papilla deposition. Mesophyll cells of several accessions were penetrated by the fungus, but then the hypersensitive response (HR) leading to cell death hampered fungal development. In some cases cell death was very fast and colonies aborted early, whereas in other cases necrosis was observed later and associated with numerous secondary hyphae, suggesting a slow HR. Characterization of defence mechanisms will be useful for breeding programmes and for further cellular and molecular studies to unravel the bases of resistance. Commonalities with the resistance of the same oat collection to powdery mildew are discussed.
Improved cognitive flexibility in serotonin transporter knockout rats is unchanged following chronic cocaine self‐administration
Authors: Nonkes Lourens J. P. , Maes Joseph H. R. , Homberg Judith R.
Published: July 2011

Cocaine dependence is associated with orbitofrontal cortex (OFC)‐dependent cognitive inflexibility in both humans and laboratory animals. A critical question is whether cocaine self‐administration affects pre‐existing individual differences in cognitive flexibility. Serotonin transporter knockout (5‐HTT−/−) mice show improved cognitive flexibility in a visual reversal learning task, whereas 5‐HTT−/− rats self‐administer increased amounts of cocaine. Here we assessed: (1) whether 5‐HTT−/− rats also show improved cognitive flexibility (next to mice); and (2) whether this is affected by cocaine self‐administration, which is increased in these animals. Results confirmed that naïve 5‐HTT−/− rats (n = 8) exhibit improved cognitive flexibility, as measured in a sucrose reinforced reversal learning task. A separate group of rats was subsequently trained to intravenously self‐administer cocaine (0.5 mg/kg/infusion), and we observed that the 5‐HTT−/− rats (n = 10) self‐administered twice as much cocaine [632.7 mg/kg (±26.3)] compared with 5‐HTT+/+ rats (n = 6) [352.3 mg/kg (±62.0)] over 50 1‐hour sessions. Five weeks into withdrawal the cocaine‐exposed animals were tested in the sucrose‐reinforced reversal learning paradigm. Interestingly, like the naïve 5‐HTT−/− rats, the cocaine exposed 5‐HTT−/− rats displayed improved cognitive flexibility. In conclusion, we show that improved reversal learning in 5‐HTT−/− rats reflects a pre‐existing trait that is preserved during cocaine‐withdrawal. As 5‐HTT−/− rodents model the low activity s‐allele of the human serotonin transporter‐linked polymorphic region, these findings may have heuristic value in the treatment of s‐allele cocaine addicts.
Awareness of Deficit After Traumatic Brain Injury: A Literature Review
Authors: Crisp Ross
Published: July 2011

Much of the research literature on long term psychosocial adjustment to traumatic brain injury (TBI) suggests that persons with TBI do not adequately perceive their deficits of higher cortical functioning and, as a consequence, they may adopt maladaptive responses to their social environment. This issue poses a major challenge for occupational therapists and other rehabilitation professionals involved in the social and vocational rehabilitation of persons with TBI. However, the literature is characterised by disagreement concerning the nature and extent of unawareness of deficits in this group. In addressing this issue, several factors are considered: severity of injury, time since injury, prevailing neuropsychological and psychosocial perspectives, and access to intensive rehabilitation programmes. Implications for occupational therapists as practitioners and researchers are discussed.
Isometric Joystick: A Study of Control by Adolescents and Young Adults with Cerebral Palsy
Authors: Stewart Hugh , Noble Glenda , Seeger Barry R.
Published: July 2011

This research was undertaken to determine the best wheelchair driving method for clients with cerebral palsy who were experiencing difficulties using displacement joysticks. The hypothesis was that adolescents with cerebral palsy would perform better in a tracking task using an isometric joystick (which has no moving parts) than a displacement joystick of the type used in commercial wheelchair controllers. A series of single subject case studies was performed in which the activating force of the isometric joystick was individualised for each subject. Comparative evaluation of the isometric joystick and a displacement joystick was then carried out. Results indicate that performance using the displacement joystick was superior to performance with the isometric joystick for the able‐bodied subject and four of the five subjects with cerebral palsy. One of the subjects showed significantly better performance on the displacement joystick using his hand, and no significant difference between joysticks using his foot. The remaining subject, who used his foot, showed no significant difference between joysticks. These findings suggest that subjects with cerebral palsy with prior experience using a displacement joystick do not appear to benefit by the use of an isometric joystick compared to a displacement joystick. No difference in the use of the two joysticks was found for subjects with cerebral palsy who had no prior experience using a joystick. This suggests that an isometric joystick is an option for people beginning to learn to drive an electric wheelchair.
Comparison of the organization of t‐tubules, sarcoplasmic reticulum and ryanodine receptors in rat and human ventricular myocardium
Authors: Jayasinghe ID , Crossman DJ , Soeller C , Cannell MB
Published: July 2011

1. It is apparent from the literature that there are significant differences in excitation–contraction coupling between species, particularly in the density of calcium transporting proteins in the t‐system and sarcoplasmic reticulum (SR) Ca2+ release channels. Unfortunately, there is a lack of information as to how the principal structures that link electrical excitation to the activation of calcium‐induced calcium release (CICR) are different between human and animal models (particularly rat).

2. Comparison of wheat germ agglutinin and caveolin‐3 labelling revealed a non‐uniform distribution of surface membrane glycosylation in the rat, rabbit and human, and that the rat t‐system appeared more complex in geometry than the latter species. Analysis of the t‐system skeleton showed that the t‐system was highly branched in the rat compared with that of the human (0.8 ± 0.08 and 0.2 ± 0.07 branch points per μm2, respectively; P < 0.001).

3. We also compared the distribution of contractile machinery, sodium–calcium exchange, SR and ryanodine receptors (RyR) in rat and human. F‐Actin and RyR labelling was used to estimate the area of contractile apparatus supplied by each RyR cluster. In the rat, each RyR cluster supplied an average cross‐sectional area of contractile machinery of 0.36 ± 0.03μm2 compared with 0.49 ± 0.04 μm2 in human (P = 0.048). Sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA2a) labelling showed that the SR formed a tight network of loops surrounding contractile fibrils that were denser than the t‐tubule network, but otherwise appeared similar in both species.

4. In general, the results show a higher density in structures involved in CICR in the rat compared with human.
Diagnosis in developmental–behavioural paediatrics: The art of diagnostic formulation
Authors: O'Keeffe Mick , Macaulay Caroline
Published: July 2011

This paper considers diagnostic frameworks in developmental–behavioural paediatrics. The purpose of a diagnostic assessment is reviewed, and the use of categorical diagnoses is explored. A multi‐level process of diagnostic formulation is outlined, highlighting the importance of a comprehensive focus on presenting symptoms, neuropsychological constructs, biological factors and environmental influences. The axis of time, developmental benchmarks and the enhancement of resilience are discussed as part of the diagnostic formulation framework. Limitations imposed on diagnostic practice by systemic and personal factors are reviewed. Implications for training and practice are discussed.
What makes patients perceive their health care worker as an epistemic authority?
Authors: Barnoy Sivia , Ofra Levy , Bar‐Tal Yoram
Published: July 2011

BARNOY S, OFRA L and BAR‐TAL Y. Nursing Inquiry 2012; 19: 128–133 [Epub ahead of print]

What makes patients perceive their health care worker as an epistemic authority?

Health care workers’ (HCW) perceived epistemic authority (EA) may have an effect on patient decision‐making and compliance. The present study investigated the hypotheses that higher EA is attributed to staff perceived to be experts; to physicians rather than nurses; to HCWs who recommend taking a test more than to the ones who make no recommendation. The study was based on a factorial 2 × 2 × 2 within‐between subjects design. The questionnaire presented four scenarios, each illustrating a HCW presenting information on a devastating genetic disease. The three variables manipulated were: HCW expertise, HCW role, and making a recommendation or not. After each scenario participants were asked questions about the EA they attributed to the HCW in the scenario. The results show main effects for perceived expertise and recommendation/no recommendation on the level of EA attributed. Expert nurses were judged to have the same high EA as expert physicians. But expert physicians who recommended taking a test were judged as having significantly higher EA than expert physicians who made no recommendation. Among nurses who made no recommendation, expert nurses were evaluated as having significantly higher EA than novices. Since expert nurses were perceived to have equal expertise as expert physicians, it follows that information given by both nurses and physicians can reduce patient uncertainty.
Investigating the adverse respiratory effects of beta‐blocker treatment: six years of prospective longitudinal data in a cohort with cardiac disease
Authors: Cochrane B. , Quinn S. , Walters H. , Young I.
Published: July 2011

Background:  Globally, cardiovascular disease (CVD) is the leading cause of death. Beta‐blocker medications have well‐established survival benefit for myocardial infarction and heart failure. However, CVD frequently coexists with chronic obstructive airways disease (COPD), a disease in which beta‐blockers are traditionally avoided.

Aim:  We sought to investigate the adverse respiratory effects associated with long‐term beta‐blocker treatment in patients with cardiac disease, and presumed high risk of COPD.

Methods:  In this prospective cohort study, patients admitted with acute cardiac disease were recruited from the cardiology unit of a tertiary referral hospital. The treating cardiologist determined beta‐blocker treatment, independent of the study. Repeated measures of spirometry and respiratory symptom scores were assessed over 12 months. Respiratory exacerbations, cardiac events and survival were recorded over 6 years. Outcomes were compared according to beta‐blocker exposure.

Results:  Sixty‐four subjects participated, 30 of whom received beta‐blockers. Beta‐blockers did not adversely affect spirometry, respiratory symptoms or survival. However, considering two categories of respiratory exacerbations (symptom‐based vs treated), subjects taking beta‐blockers accumulated increased annual risk (relative risk (RR) 1.30, 95% confidence interval (CI) 1.11–1.53, P= 0.001 and RR 1.37, 95% CI 1.09–1.72, P= 0.008) and concluded with overall increased risk (RR 3.67, 95% CI 1.65–8.18, P= 0.001 and RR 4.03, 95% CI 1.26–12.9, P= 0.019), when compared with the group not taking beta‐blockers.

Conclusion:  Long‐term beta‐blocker treatment did not adversely affect lung function, respiratory symptom scores or survival, but was associated with increased risk of respiratory exacerbations.
Effects of combined estrogen and progesterone replacement treatment on detrusor contractility and histology in oophorectomized rats
Authors: Etiz Sayharman Sema , Tosun Nihan , Aka Nurettin , Köse Gültekin , Tekin Ali , Gören Zafer
Published: July 2011

Aim:  The aim of this study was to investigate the effects of estrogen plus progesterone treatment administered after surgical menopause on morphological and muscarinic receptor sensitivity in detrusor muscle bands of rats.

Materials and Methods:  A total of 40 female Albino–Wistar rats were assigned into two groups to undergo surgical menopause with sham operation (n = 10) and bilateral oophorectomy (n = 30). Thirty oophorectomized rats were assigned into three groups for different treatments administered for 8 weeks beginning from the 7th postoperative day. At the end of the 8th postoperative week, laparotomy was performed in all of them and the urinary bladders were excised and investigated with light microscope. All statistical analysis and graphs were performed using GraphPad Prism version 4. P < 0.05 was considered to be statistically significant.

Results:  It was determined that average bodyweights were increased to some extent in oophorectomized and sham groups after treatment and while it was more marked in the group receiving estrogen therapy, bodyweights were decreased in the group receiving estrogen plus progesterone therapy. However, this was not statistically significant. No statistically significant difference was determined between the sham, placebo and 17‐β estradiol treatment groups regarding contractile response of urinary bladder tapes to carbachol (P > 0.05). Contractile responses of urinary bladder tapes of the estrogen plus progesterone treatment group were found to be statistically lower than the placebo group (P < 0.05).

Conclusion:  Our in vitro findings demonstrate that treatment with estrogen plus progesterone decreases muscarinic activity in oophorectomized rats, whereas estrogen‐only treatment does not. Our study establishes the basis for further studies to answer whether combination of estrogen and progesterone treatment can restore detrusor overactivity associated with sex hormone defects seen at menopause.
Small cell carcinoma of the endometrium: A report of two cases
Authors: Matsumoto Harunobu , Takai Noriyuki , Nasu Kaei , Narahara Hisashi
Published: July 2011

Primary small cell carcinoma of the endometrium is rare and has an extremely poor prognosis. This report describes two cases of small cell carcinoma of the endometrium diagnosed as stage III. Case 1 was diagnosed as stage IIIc. She underwent surgery and chemotherapy. For a locally recurrent tumor, she received radiotherapy. She has been well with no evidence of disease for 4 years. Case 2 was diagnosed as stage IIIa. She underwent surgery. The tumor recurred soon after the surgery, and she died 33 days after the surgery. In the literature, the median survival reported for patients with stage III and IV is only 5 months. Case 1 is the 4th case showing long‐term survival with advanced‐stage disease. The optimal treatment for this rare tumor has not been established. Considering its rarity and variability, it is difficult to establish an evidence‐based therapeutic regimen.
Acquisition of anti‐Diego b antibodies possibly resulting from feto‐maternal hemorrhage during pregnancy
Authors: Oishi Yuriko , Watanabe Noriyoshi , Ozawa Nobuaki , Sago Haruhiko
Published: July 2011

Anti‐Diego b (Dib) antibodies, rare antibodies against red blood cell antigens, can cause severe hemolysis. We report a patient who most likely acquired anti‐Dib antibodies during pregnancy. The patient was a 39‐year‐old Japanese woman who delivered by cesarean section at 38 weeks of gestation. She required a second operation to treat re‐bleeding of the surgical scar, but it was difficult to schedule this surgery because we could not obtain enough blood for transfusion due to the presence of anti‐Dib antibodies. These antibodies were likely acquired during pregnancy; she did not have irregular antibodies at 11 weeks of gestation. We speculate that she became sensitized to fetal blood due to feto‐maternal hemorrhage. The infant had no hemolytic conditions. Testing for the presence of irregular antibodies should be performed during late stages of pregnancy as well as early stages.
Diabetes in care homes: current care standards and residents’ experience
Authors: Yarnall A. J. , Hayes L , Hawthorne G. C. , Candlish C. A. , Aspray T. J.
Published: July 2011

Diabet. Med. 29, 132–135 (2012)

Aims  The Diabetes UK good clinical practice guidelines for care home residents were revised in 2010. In this study, we examined current care against these standards and sought the views of residents on their diabetes.

Methods  Mixed methods (qualitative and quantitative), including interviews with residents, carers and staff, participant record reviews and focus group discussions were used to gather data in care homes in Newcastle upon Tyne.

Results  Thirty‐one residents from seven care homes participated. Eighty‐seven per cent of residents had probable dementia (based on abbreviated mental test score or clock‐drawing test). Weight, body mass index and blood pressure were satisfactorily monitored. Glucose monitoring took place in all residents who received insulin, but was monitored unnecessarily in those with diet‐controlled diabetes (63%). The majority of residents (90%) had seen a chiropodist and had received eye screening (> 80%) recently. Only one of the care homes had staff that had diabetes training. Residents reported little knowledge of diabetes management. However, when asked what they knew about diabetes, comments included ‘It’s a common thing… like cancer’; ‘[I would have liked a] plain language explanation of diabetes’ and ‘They told me they could control it by diet, and then it was tablets, then insulin. They didn’t explain why.’

Conclusions  In Newcastle upon Tyne care homes there is good care provided but also evidence of inadequacies. Despite high levels of dementia, many patients have strong and valid opinions about their disease and the care they receive. Despite the challenges, we believe that residents must be included in discussions about service development.
The Flip Side of Organized Decentralization: Company‐Level Bargaining in Denmark
Authors: Ilsøe Anna
Published: July 2011

The Danish collective bargaining system is often considered a good example of organized decentralization. It has been characterized as a centralized decentralization suggesting a reproduction of sector‐level bargaining relations at company level. A recent survey on company‐level bargaining in the Danish industrial sector confirms this hypothesis with regard to the experiences of local managers and shop stewards. However, part of the survey also questions whether the reproduction will continue in the future. Small‐ and medium‐sized enterprises and their employees tend to miss out on the mutual benefits obtained through company‐level agreements. Furthermore, shop stewards often find it difficult to gain employee support during negotiations, which jeopardizes their bargaining relations with management.
Cantharidin–podophylotoxin–salicylic acid versus cryotherapy in the treatment of plantar warts: a randomized prospective study
Authors: Kaçar N. , Taşlı L. , Korkmaz S. , Ergin Ş. , Erdoğan B.Ş.
Published: July 2011

Background  Plantar warts are refractory to any form of treatment. High cure rates have been reported with a topical proprietary formulation consisting of 1% cantharidin, 5% podophyllotoxin and 30% salicylic acid (CPS). However, no data exists comparing the efficacy of this formulation with another treatment. Cryotherapy is a method that is also widely used in the treatment of plantar warts. Likewise, there is no evidence that it is more effective than any topical treatment.

Objective  We aim to compare the efficacy of topical CPS and cryotherapy in the treatment of plantar warts.

Methods  Patients with plantar warts were consecutively treated with either cryotherapy or topical CPS. Both treatments were performed every 2 weeks for up to five sessions. In patients without complete clearance, the therapy was switched to the other treatment option.

Results  Twenty‐six patients with a total of 134 warts were included. Fourteen patients were completely cleared of their warts with topical CPS, whereas only in five of 12 patients (41.7%) warts were completely cleared with cryotherapy (P = 0.001). In seven patients without complete clearance, the therapy was switched to CPS. Four of these patients missed the follow‐up. While the two of the remaining three patients were cleared of their warts, one patient’s warts still failed to clear.

Conclusion  Topical CPS is more effective than cryotherapy in the treatment of plantar warts.