bluuebunny/crossref_metadata_2025 huggingface dataset:
Social impairments in Rett syndrome: characteristics and relationship with clinical severity
Authors: Kaufmann W. E. , Tierney E. , Rohde C. A. , Suarez‐Pedraza M. C. , Clarke M. A. , Salorio C. F. , Bibat G. , Bukelis I. , Naram D. , Lanham D. C. , Naidu S.
Published: March 2011

Background  While behavioural abnormalities are fundamental features of Rett syndrome (RTT), few studies have examined the RTT behavioural phenotype. Most of these reports have focused on autistic features, linked to the early regressive phase of the disorder, and few studies have applied standardised behavioural measures. We used a battery of standardised measures of behaviour and functioning to test the following hypotheses: (1) autistic behaviour is prominent throughout childhood in RTT; (2) autistic features are more salient in individuals with milder presentation; (3) severity of autistic behaviour is associated with a wider range of behavioural problems; and (4) specific MECP2 mutations are linked to more severe autistic behaviour.

Methods  Eighty MECP2 mutation‐positive girls with RTT (aged 1.6–14.9 years) were administered: (1) the Screen for Social Interaction (SSI), a measure of autistic behaviour suited for individuals with severe communication and motor impairment; (2) the Rett Syndrome Behaviour Questionnaire (RSBQ), covering a wide range of abnormal behaviours in RTT; (3) the Vineland Adaptive Behavior Scales (VABS); and (4) a modified version of the Rett Syndrome Severity Scale (RSSS). Regression analyses examined the predictive value of age and RSSS on autistic behaviour and other behavioural abnormalities. T‐tests further characterised the behavioural phenotype of individual MECP2 mutations.

Results  While age had no significant effect on SSI or RSBQ total scores in RTT, VABS Socialization and Composite scores decreased over time. Clinical severity (i.e. RSSS) also increased with age. Surprisingly, SSI performance was not related to either RSSS or VABS Composite scores. Autistic behaviour was weakly linked with the RSBQ Hand behaviour factor scores, but not with the RSBQ Fear/Anxiety factor. Clinical (neurological) severity did not predict RSBQ scores, as evidenced by the analysis of individual MECP2 mutations (e.g. p.R106W, p.R270X and p.R294X).

Conclusions  Our data suggest that in RTT, autistic behaviour persists after the period of regression. It also demonstrated that neurological and behavioural impairments, including autistic features, are relatively independent of one another. Consistent with previous reports of the RTT phenotype, individual MECP2 mutations demonstrate complex associations with autistic features. Evidence of persistent autistic behaviour throughout childhood, and of a link between hand function and social skills, has important implications not only for research on the RTT behavioural phenotype, but also for the clinical management of the disorder.
In vivo activity of CRISPR‐mediated virus defence in a hyperthermophilic archaeon
Authors: Manica Andrea , Zebec Ziga , Teichmann Daniela , Schleper Christa
Published: March 2011

Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas systems are found widespread in bacterial and archaeal genomes and exhibit considerable diversity. However, closer insights into the action of most of the CRISPR modules have remained elusive in particular in Archaea as a result of the lack of suitable in vivo test systems. Here we demonstrate CRISPR/Cas‐based immune defence in the hyperthermophilic archaeon Sulfolobus solfataricus. Recombinant variants of the SSV1 virus containing a gene of the conjugative plasmid pNOB8 that represents a target for a corresponding CRISPR spacer in the chromosome were tested in transfection experiments. Almost 100% immunity against the recombinant virus was observed when the chromosomal CRISPR spacer matched perfectly to the protospacer. Different from bacterial systems immunity was still detected, albeit at decreased levels, when mutations distinguished target and spacer. CRISPR/Cas targeting was independent of the transcription of the target gene. Furthermore, a mini‐CRISPR locus introduced on the viral DNA with spacers targeting the (non‐essential) chromosomal beta‐galactosidase gene was unstable in host cells and triggered recombination with the indigenous CRISPR locus. Our experiments demonstrate in vivo activity of CRISPR/Cas in archaea for the first time and suggest that – unlike the recently demonstrated in vitro cleavage of RNA in Pyrococcus– DNA is targeted in this archaeon.
IgE cross‐reactivity between Ascaris lumbricoides and mite allergens: possible influences on allergic sensitization and asthma
Authors: ACEVEDO N. , CARABALLO L.
Published: March 2011

Nematode infections such as Ascariasis are important health problems in underdeveloped countries, most of them located in the tropics where environmental conditions also promote the perennial co‐exposure to high concentrations of domestic mite allergens. Allergic diseases are common, and most of patients with asthma exhibit a predominant and strong IgE sensitization to mites. It is unknown whether co‐exposure to Ascaris lumbricoides and the domestic mites Blomia tropicalis and Dermatophagoides pteronyssinus potentiates Th2 responses and IgE sensitization, thereby modifying the natural history of allergy. Recently, we obtained experimental evidence of a high cross‐reactivity between the allergenic extracts of these invertebrates, involving well‐known allergens such as tropomyosin and glutathione transferases. There is indirect evidence suggesting that the clinical impact of these findings may be important. In this review, we discuss the potential role of this cross‐reactivity on several aspects of allergy in the tropics that have been a focus of a number of investigations, some of them with controversial results.
Disentangling the contributions of ontogeny and water stress to photosynthetic limitations in almond trees
Authors: EGEA GREGORIO , GONZÁLEZ‐REAL MARÍA M. , BAILLE ALAIN , NORTES PEDRO A. , DIAZ‐ESPEJO ANTONIO
Published: March 2011

Very few studies have attempted to disentangle the respective role of ontogeny and water stress on leaf photosynthetic attributes. The relative significance of both effects on photosynthetic attributes has been investigated in leaves of field‐grown almond trees [Prunus dulcis (Mill.) D. A. Webb] during four growth cycles. Leaf ontogeny resulted in enhanced leaf dry weight per unit area (Wa), greater leaf dry‐to‐fresh weight ratio and lower N content per unit of leaf dry weight (Nw). Concomitantly, area‐based maximum carboxylation rate (Vcmax), maximum electron transport rate (Jmax), mesophyll conductance to CO2 diffusion (gm)′ and light‐saturated net photosynthesis (Amax) declined in both well‐watered and water‐stressed almond leaves. Although gm and stomatal conductance (gs) seemed to be co‐ordinated, a much stronger coordination in response to ontogeny and prolonged water stress was observed between gm and the leaf photosynthetic capacity. Under unrestricted water supply, the leaf age‐related decline of Amax was equally driven by diffusional and biochemical limitations. Under restricted soil water availability, Amax was mainly limited by gs and, to a lesser extent, by photosynthetic capacity and gm. When both ontogeny and water stress effects were combined, diffusional limitations was the main determinant of photosynthesis limitation, while stomatal and biochemical limitations contributed similarly.
Crosstalk between reactive oxygen species and hormonal signalling pathways regulates grain dormancy in barley
Authors: BAHIN EMILIE , BAILLY CHRISTOPHE , SOTTA BRUNO , KRANNER ILSE , CORBINEAU FRANÇOISE , LEYMARIE JULIETTE
Published: March 2011

Seed dormancy, defined as the inability to germinate under favourable conditions, is controlled by abscisic acid (ABA) and gibberellins (GAs). Phytohormone signalling interacts with reactive oxygen species (ROS) signalling regarding diverse aspects of plant physiology and is assumed to be important in dormancy alleviation. Using dormant barley grains that do not germinate at 30 °C in darkness, we analysed ROS content and ROS‐processing systems, ABA content and metabolism, GA‐responsive genes and genes involved in GA metabolism in response to hydrogen peroxide (H2O2) treatment. During after‐ripening, the ROS content in the embryo was not affected, while the antioxidant glutathione (GSH) was gradually converted to glutathione disulphide (GSSG). ABA treatment up‐regulated catalase activity through transcriptional activation of HvCAT2. Exogenous H2O2 partially alleviated dormancy although it was associated with a small increase in embryonic ABA content related to a slight induction of HvNCED transcripts. H2O2 treatment did not affect ABA sensitivity but up‐regulated the expression of HvExpA11 (GA‐induced gene), inhibited the expression of HvGA2ox3 involved in GA catabolism and enhanced the expression of HvGA20ox1 implicated in GA synthesis. In barley, H2O2 could be implicated in dormancy alleviation through activation of GA signalling and synthesis rather than repression of ABA signalling.
Regulatory control of high levels of carotenoid accumulation in potato tubers
Authors: ZHOU XIANGJUN , MCQUINN RYAN , FEI ZHANGJUN , WOLTERS ANNE‐MARIE A. , VAN ECK JOYCE , BROWN CHARLES , GIOVANNONI JAMES J. , LI LI
Published: March 2011

Potato (Solanum tuberosum L.) tubers contain a wide range of carotenoid contents. To decipher the key factors controlling carotenoid levels in tubers, four potato lines (Atlantic, Désirée, 91E22 and POR03) were examined by a combination of biochemical, molecular and genomics approaches. These lines contained incremental levels of carotenoids, which were found to be associated with enhanced capacity of carotenoid biosynthesis as evident from norflurazon treatment. Microarray analysis of high and low carotenoid lines (POR03 versus Atlantic) revealed 381 genes that showed significantly differential expression. The carotenoid metabolic pathway genes β‐carotene hydroxylase 2 (BCH2) and β‐carotene hydroxylase 1 (BCH1), along with zeaxanthin epoxidase (ZEP), and carotenoid cleavage dioxygenase 1A (CCD1A) were among the most highly differentially expressed genes. The transcript levels of BCH2 and BCH1 were lowest in Atlantic and highest in POR03, whereas those of ZEP and CCD1A were high in low carotenoid lines and low in high carotenoid lines. The high expression of BCH2 in POR03 line was associated with enhanced response to sugars. Our results indicate that high levels of carotenoid accumulation in potato tubers were due to an increased metabolic flux into carotenoid biosynthetic pathway, as well as the differential expression of carotenoid metabolic genes.
Isoprene synthesis in plants: lessons from a transgenic tobacco model
Authors: VICKERS CLAUDIA E. , POSSELL MALCOLM , LAOTHAWORNKITKUL JULLADA , RYAN ANNETTE C. , HEWITT C. NICHOLAS , MULLINEAUX PHILIP M.
Published: March 2011

Isoprene is a highly reactive gas, and is emitted in such large quantities from the biosphere that it substantially affects the oxidizing potential of the atmosphere. Relatively little is known about the control of isoprene emission at the molecular level. Using transgenic tobacco lines harbouring a poplar isoprene synthase gene, we examined control of isoprene emission. Isoprene synthase required chloroplastic localization for catalytic activity, and isoprene was produced via the methyl erythritol (MEP) pathway from recently assimilated carbon. Emission patterns in transgenic tobacco plants were remarkably similar to naturally emitting plants under a wide variety of conditions. Emissions correlated with photosynthetic rates in developing and mature leaves, and with the amount of isoprene synthase protein in mature leaves. Isoprene synthase protein levels did not change under short‐term increase in heat/light, despite an increase in emissions under these conditions. A robust circadian pattern could be observed in emissions from long‐day plants. The data support the idea that substrate supply and changes in enzyme kinetics (rather than changes in isoprene synthase levels or post‐translational regulation of activity) are the primary controls on isoprene emission in mature transgenic tobacco leaves.
Cadmium‐induced oxalate secretion from root apex is associated with cadmium exclusion and resistance in Lycopersicon esulentum
Authors: ZHU XIAO FANG , ZHENG CHENG , HU YI TING , JIANG TAO , LIU YU , DONG NING YU , YANG JIAN LI , ZHENG SHAO JIAN
Published: March 2011

The mechanisms of heavy metal resistance in plants can be classified into internal tolerance and exclusion mechanisms, but exclusion of heavy metals with the help of organic acids secretion has not been well documented. Here we demonstrated the contribution of oxalate secretion to cadmium (Cd) exclusion and resistance in tomato. Different Cd resistance between two tomato cultivars was evaluated by relative root elongation (RRE) and Cd accumulation. Cultivar ‘Micro‐Tom’ showed better growth and lower Cd content in roots than ‘Hezuo903’ at different Cd concentrations not only in short‐term hydroponic experiment but also in long‐term hydroponic and soil experiments, indicating that the genotypic difference in Cd resistance is related to the exclusion of Cd from roots. ‘Micro‐Tom’ had greater ability to secrete oxalate, suggesting that oxalate secretion might contribute to Cd resistance. Cd‐induced secretion of oxalate was localized to root apex at which the majority of Cd accumulated. Phenylglyoxal, an anion‐channel inhibitor, effectively blocked Cd‐induced oxalate secretion and aggravated Cd toxicity while exogenous oxalate supply ameliorated Cd toxicity efficiently. These results indicated that the oxalate secreted from the root apex helps to exclude Cd from entering tomato roots, thus contributes to Cd resistance in the Cd‐resistant tomato cultivar.
Perforin‐Mediated Cytotoxicity in non‐ST Elevation Myocardial Infarction
Authors: Laskarin G. , Persic V. , Ruzic A. , Miletic B. , Rakic M. , Samsa D. Travica , Raljevic D. , Pejcinovic V. Pehar , Miskulin R. , Rukavina D.
Published: March 2011

The aim of this investigation was to examine the role of perforin (P)‐mediated cytotoxicity in the dynamics of tissue damage in patients with non‐ST‐segment elevation myocardial infarction (NSTEMI) treated with anti‐ischaemic drugs. We enrolled 48 patients with NSTEMI in this study [age, 71.5 years; 61.5/76 (median, 25th/75th percentiles)]. The percentage of total peripheral blood P+ lymphocytes was elevated owing to the increased frequency of P+ cells within natural killer (NK) subsets, T and NKT cells in patients on day 1 after NSTEMI when compared with healthy controls. Positive correlations were found between cardiac troponin I plasma concentrations and the frequency of P+ cells, P+ T cells, P+ NK cells and their CD56+dim and CD56+bright subsets during the first week after the NSTEMI. The expression of P in NK cells was accompanied by P‐mediated cytotoxicity against K‐562 targets at all days examined, except day 21, when an anti‐perforin monoclonal antibody did not completely abolish the killing. The percentage of P+ T cells, P+ NKT cells and P+ NK subsets was the highest on the day 1 after NSTEMI and decreased in the post‐infarction period. CD56+ lymphocytes were found in damaged myocardium, suggesting their tissue recruitment. In conclusion, patients with NSTEMI have a strong and prolonged P‐mediated systemic inflammatory reaction, which may sustain autoaggressive reactions towards myocardial tissue during the development of myocardial infarction.
Gene Interaction Network Regulates Plasma Cell Differentiation
Authors: Alinikula J. , Lassila O.
Published: March 2011

Effective humoral immunity depends on B cells, plasma cells and follicular helper T cells (TFH) and secreted high‐affinity antibodies. The differentiation of mature B cell into plasma cells is ultimately hardwired in a regulatory network of transcription factors. This circuitry is responding to extracellular stimuli, which leads to production of higher‐affinity antibodies after germinal centre (GC) reaction. The understanding of the transcriptional regulation of GCs and the initiation of plasma cell differentiation is becoming increasingly clear. It is evident that transcriptional repressor Blimp‐1 can drive the plasma cell differentiation, but the initiation of plasma cell differentiation in GCs is likely coupled to the loss of B cell characteristics maintained by transcription factors Pax5 and Bcl6.
Molecular Mechanism of Immunoglobulin V‐Region Diversification Regulated by Transcription and RNA Metabolism in Antigen‐Driven B Cells
Authors: Sakaguchi N. , Maeda K. , Kuwahara K.
Published: March 2011

The immune system produces specific antibodies (Ab) against any antigens (Ag) of exogenous and endogenous origins with a diverse repertoire of V‐region specificities. The primary V‐region repertoire is created by the rearrangement of immunoglobulin (Ig) V‐region, D‐ and J‐segments with the insertion of N‐ and P‐sequences during early B cell differentiation. Recent studies revealed that secondary diversification of the IgV‐region generated in the peripheral lymphoid organs plays a critical role in the generation of effective Ab production for protection from various pathogens. Naïve B cells that react with Ags initiate proliferation and differentiation in the follicular region and create the germinal centres (GCs), where activation‐induced cytidine deaminase (AID)‐dependent IgV‐region somatic hypermutation (SHM) and class‐switch recombination generate high‐affinity and class‐switched mature Ag‐specific B cells. Our studies have discovered a 210‐kDa nuclear protein, named GC‐associated nuclear protein (GANP) that is up‐regulated in GC B cells during the T cell–dependent (TD) immune responses. By studying mice with mutant forms of the ganp gene, we demonstrated that GANP is essential for the generation of high‐affinity B cells against TD‐Ag by affecting SHM at the IgV‐regions. GANP is associated with AID in the cytoplasm and the GANP/AID complex is recruited to the nucleus, specifically, the chromatin, and targeted selectively to the IgV‐region gene in B cells. GANP augments the access of AID towards IgV‐regions in B cells. Here, we review the role of GANP in acquired immunity through the detailed analysis of the molecular mechanism generating SHM specifically at IgV‐regions in B cells.
‐174G/C interleukin‐6 gene polymorphism and the risk of transplanted kidney failure or graft loss during a 5‐year follow‐up period
Authors: Kocierz M. , Siekiera U. , Kolonko A. , Karkoszka H. , Chudek J. , Cierpka L. , Wiȩcek A.
Published: March 2011

The influence of cytokine gene polymorphisms on transplanted kidney outcome is not well understood. The aim of this one‐centre study was to analyse the association between tumour necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), IL‐10, interferon‐γ (IFN‐γ) and transforming growth factor‐β1 (TGF‐β1) genotypes and the incidence of delayed graft function (DGF), acute rejection (AR) and 5‐year kidney graft loss. Genotyping was performed in 199 subsequent kidney graft recipients from deceased donors without induction therapy based on polymerase chain reaction method using sequence‐specific primers for TNF‐α (‐308A/G), IL‐10 (‐1082A/G, ‐819T/C and ‐592A/C), IL‐6 (‐174G/C), IFN‐γ (+874T/A) and TGF‐β1 (in codons 10T/C and 25G/C). Genotypes were grouped according to the strength of cytokine expression. During a 5‐year follow‐up period, 14 patients died with functioning graft and 33 developed graft failure. The analysed polymorphisms were not associated with the incidence of DGF. The frequency of early episodes of AR was significantly associated only with TGF‐β1 genotype. There was an association between ‐174G/C IL‐6 gene polymorphism and the death‐censored kidney graft survival. The risk of graft loss during 5‐year follow‐up period was greater by 57% for GG or GC (higher IL‐6 production) than for CC carriers. None of the other analysed polymorphisms significantly influenced both patients and kidney graft survival, also in the analysis of the subgroup with human leucocyte antigen‐DR mismatch. ‐174G/C IL‐6 genotype of the kidney graft recipient could modulate the rate of graft excretory function deterioration and the risk of graft loss by influencing their constitutional expression.
Vascular endothelial growth factor A and cardiovascular disease in rheumatoid arthritis patients
Authors: Rodríguez‐Rodríguez L. , García‐Bermúdez M. , González‐Juanatey C. , Vazquez‐Rodriguez T. R. , Miranda‐Filloy J. A. , Fernández‐Gutierrez B. , Llorca J. , Martín J. , González‐Gay M. A.
Published: March 2011

To determine the contribution of the vascular endothelial growth factor A (VEGFA) rs2010963 (‐634 G>C) and rs1570360 (‐1154 G>A) polymorphisms to the risk of cardiovascular (CV) disease in a series of patients with rheumatoid arthritis (RA). Six hundred sixty‐one patients fulfilling the 1987 American College of Rheumatology classification criteria for RA, seen at the rheumatology outpatient clinics of the Hospital Xeral‐Calde, Lugo, and the Hospital San Carlos, Madrid, Spain, were studied. Patients were genotyped for the VEGFA rs2010963 (‐634 G>C) and rs1570360 (‐1154 G>A) polymorphisms using predesigned TaqMan single nucleotide polymorphism (SNP) genotyping assay (Applied Biosystems, Foster City, CA). Also, human leukocyte antigen (HLA) DRB1 genotyping was performed using molecular‐based methods. Clinical histories of the patients were reviewed for the presence of CV events that were considered to be present if the patient had ischemic heart disease, heart failure, cerebrovascular accident, or peripheral arteriopathy. Also, a subgroup of patients without the history of CV events was assessed for the presence of subclinical atherosclerosis manifested by the presence of endothelial dysfunction by brachial artery reactivity (n = 126) and increased carotid artery intima–media thickness (n = 105) using high resolution Doppler ultrasonography. No significant association between the VEGFA rs2010963 and the rs1570360 polymorphisms (neither isolated nor joined as allelic combinations) with clinically evident CV disease was found in this series of patients with RA. It was also the case when we examined the contribution of these polymorphisms to the development of subclinical atherosclerosis. VEGFA polymorphisms do not seem to exert a significant influence on the risk of CV disease in patients with RA.
Expression of activating and inhibitory leukocyte immunoglobulin‐like receptors in rheumatoid synovium: correlations to disease activity
Authors: Tedla N. , An H. , Borges L. , Vollmer‐Conna U. , Bryant K. , Geczy C. , Patrick McNeil H.
Published: March 2011

Rheumatoid arthritis (RA) is a heterogeneous chronic inflammatory joint disease characterized by excessive activation of inflammatory cells of which the underlying mechanisms are not fully elucidated. Perturbed expression and function of immune regulatory molecules called leukocyte immunoglobulin‐like receptors (LILRs) may contribute to uncontrolled inflammation. LILRs primarily expressed on the surface of leukocytes are emerging as critical regulators of the threshold and amplitude of leukocyte activation. Inhibitory LILRs (LILRBs) contain cytoplasmic tails with immunoreceptor tyrosine‐based inhibitory motifs that provide negative signals. Activating LILRs (LILRAs) have short cytoplasmic domains lacking signaling motifs but transmit activating signals by linking to immunoreceptor tyrosine‐based activation motifs of the FcR γ‐chain. Here we show that activating LILRA2, A5 and inhibitory LILRB2, B3 were abundantly expressed in synovial tissue of > 75% RA patients. Expression of LILRA2, A5, and B3 significantly correlated to disease activity. In contrast, LILRA1 and B4 were expressed in a subset of patients and no B1 or B5 expression was detected. LILRA2 and A5 were mainly expressed by synovial macrophages and endothelial cells but not lymphocytes, whereas B2 and B3 were expressed by macrophages and lymphocytes. Increase in the number of macrophages expressing activating LILRs and macrophages and lymphocytes expressing inhibitory LILRs suggest a crosstalk between these cells that may regulate the levels of cellular activation and disease severity, while differences in expression pattern may contribute to disease heterogeneity.
MICA*002:04: a new allele identified by sequence‐based typing in a Chinese individual
Authors: Tan Y. , Ye X. , Xu X. Z. , Xia W. , Fu Y. S. , Huang Y. F.
Published: March 2011

The novel MICA*002:04 allele differs from MICA*002:01 by a single mutation at position 486 (C>A) in codon 20 (GCC>GCA) in exon 3.
Twenty‐three novel major histocompatibility complex class I B alleles identified in cynomolgus macaques of Vietnamese origin
Authors: Wang H.‐B. , Ling F. , Zhuo M. , Wang J.‐F. , Wang X.‐N.
Published: March 2011

We report herein the identification of 23 novel Mafa‐B alleles in cynomolgus macaques of Vietnamese origin.
Early protective and risk factors for allergic rhinitis at age 4½ yr
Authors: Alm Bernt , Goksör Emma , Thengilsdottir Hrefna , Pettersson Rolf , Möllborg Per , Norvenius Gunnar , Erdes Laslo , Åberg Nils , Wennergren Göran
Published: March 2011

To cite this article: Alm B, Goksör E, Thengilsdottir H, Pettersson R, Möllborg P, Norvenius G, Erdes L, Åberg N, Wennergren G. Early protective and risk factors for allergic rhinitis at age 4½ years. Pediatr Allergy Immunol 2011; 22: 398–404.

Allergic heredity plays a major role in the development of allergic rhinitis. In addition the introduction of food may influence the risk of subsequent allergic disease. The aim of this study was to analyse early risk factors and protective factors for allergic rhinitis at preschool age. Data were obtained from a prospective, longitudinal study of a cohort of children born in the region of western Sweden in 2003 and 8,176 families (50% of the birth cohort) were randomly selected. The parents answered questionnaires at 6 and 12 months and at 4½ yr of age. The response rate at 4½ yr was 4,496, i.e. 83% of the 5,398 questionnaires distributed at 4½ yr. At 4½ yr of age, 5.5% reported symptoms of allergic rhinitis during the last year. In the multivariate analysis, independent risk factors for allergic rhinitis were: allergic sensitisation to food allergens at 4½ yr (OR 10.21; 95% confidence interval 4.22–24.73), recurrent wheeze at 4½ yr (3.33; 1.56–7.10), doctor‐diagnosed eczema at 4½ yr (2.72; 1.62–4.55), parental rhinitis (2.21; 1.39–3.53), eczema first year (1.97; 1.19–3.26) and male gender (1.82; 1.13–2.94). The risk was reduced with fish introduction before 9 months (0.49; 0.29–0.82). In conclusion, we found that previous and present allergic disease, heredity and male gender increased the risk of allergic rhinitis at 4½ yr of age. The introduction of fish before the age of 9 months reduced the risk.
Effects of Complement Component 3 Derivatives on Pig Oocyte Maturation, Fertilization and Early Embryo Development In Vitro
Authors: Georgiou AS , Gil MA , Almiñana C , Cuello C , Vazquez JM , Roca J , Martinez EA , Fazeli A
Published: March 2011

Content

Complement component 3 (C3) has well‐established roles within immune system, but its roles outside of immune system are less characterized. The extensive presence of C3 throughout the female reproductive tract, and its temporal, and gamete‐specific regulation of expression suggest a potential role for C3 in reproduction. In the present investigation, the effects of C3, C3b and iC3b on porcine oocyte maturation, fertilization and embryonic development were examined. We identified the ability of iC3b to positively influence oocyte maturation. No effects on fertilization efficiency, penetration rates, polyspermy and blastocyst formation were observed. However, C3, C3b and iC3b presence in embryo culture medium resulted in fewer total cells in test blastocysts compared to control blastocysts. The results of this study indicate a potential function for iC3b in oocyte maturation. Furthermore, it was demonstrated that the presence of either C3, C3b or iC3b has a negative influence on early embryonic development in the porcine species.
Data presentation and the use of statistical tests in biomedical journals: can we reach a consensus?
Authors: Evans Roger G , Su Ding‐Feng
Published: March 2011

[See editorial on page 287]
Allitridi inhibits transient outward potassium currents in human atrial myocytes
Authors: Deng Chun‐Yu , Rao Fang , Kuang Su‐Juan , Wu Shu‐Lin , Shan Zhi‐Xin , Li Xiao‐Hong , Zhou Zhi‐Ling , Lin Qiu‐Xiong , Liu Xiao‐Ying , Yang Min , Lin Shu‐Guang , Yu Xi‐Yong
Published: March 2011

1. It has been reported that allitridi, an active compound extracted from garlic, has many cardiovascular effects. However, it remains unknown whether allitridi affects major repolarization currents, such as the transient outward K+ current (Ito), ultrarapid delayed rectifier K+ current (IKur) and the L‐type Ca2+current (ICa), in human atrial myocytes.

2. In the present study, we investigated the effects of allitridi on Ito, IKur, ICa and the action potential in human isolated atrial myocytes using the whole‐cell patch recording technique.

3. Allitridi reversibly inhibited Ito, but not IKur and ICa, in human atrial myocytes. These effects of allitridi on Ito were concentration dependent (IC50 = 44.9 μmol/L). Inactivation of Ito was accelerated and the voltage‐dependent inactivation potential was shifted towards the negative direction. Allitridi (30 μmol/L) significantly prolonged action potential duration in human atrial myocytes.

4. The results of the present study indicate that allitridi inhibits Ito, but not IKur and ICa, and prolongs the action potential duration in human atrial myocytes.
Osteopontin, intrinsic tissue regulator of intractable inflammatory diseases
Authors: Uede Toshimitsu
Published: March 2011

Within classical extracellular matrix (ECM) proteins, there are a unique group of proteins that should be regarded as a distinct functional group of molecules. Matricellular proteins including osteopontin (OPN) and tenascin‐c (TN‐C) are highly expressed at the pathological foci of various inflammatory diseases. Unlike classical ECM proteins, these are soluble proteins and induce cell motility and persistent inflammation rather than providing a scaffold for stable cell adhesion. Osteopontin is a pleiotropic cytokine expressed by various cells. Two forms of OPN are present. A secreted form of OPN (sOPN) is involved in generation of T helper type 1 (Th1) and Th17 cells that are pathogenic T cells for various autoimmune diseases. An intracellular form of OPN (iOPN) is a critical regulator for Toll like receptor‐9 (TLR‐9) and/or TLR‐7‐dependent interferon‐α (IFN‐α) expression by plasmacytoid dendritic cells (DCs) and Th17 development. Indeed, both OPN and TN‐C deficient mice are resistant to various Th1‐ and/or Th17‐related autoimmune diseases. Interestingly, thrombin‐cleaved forms of sOPN and TN‐C share a common integrin receptor, α9β1, and α9β1 integrin‐mediated signaling is involved in the pathogenesis of various autoimmune diseases. Thus, OPN, TN‐C and its common receptor, α9β1 integrin may serve as potential therapeutic targets for various intractable inflammatory diseases.
Mixed squamous cell and glandular papilloma of the lung: A case study and literature review
Authors: Inamura Kentaro , Kumasaka Toshio , Furuta Reiko , Shimada Kei , Hiyama Noriko , Furuhata Yoshiaki , Tanaka Isao , Takemura Tamiko
Published: March 2011

Mixed squamous cell and glandular papilloma (mixed papilloma) of the lung is an extremely rare neoplasm, with only 10 cases reported so far in the English literature. We present a case study of endobronchial mixed papilloma with immunohistochemical and etiological investigations. A 49‐year‐old male with a smoking history complained of hemoptysis, presented with a lung mass closely adjacent to large vessels in the computed tomography findings, and underwent lobectomy. The 3.0‐cm sized polypoid tumor was histologically diagnosed as endobronchial mixed papilloma. Immunohistochemically, intracellular mucin was positive for MUC5AC, which is expressed in tracheobronchial goblet cells. CAM5.2 and CK19 were diffusely positive, indicating that the tumor originated from the columnar epithelium by squamous metaplasia. CEA and CA19‐9 were focally positive. A human papillomavirus (HPV) investigation with in situ hybridization using a wide spectrum probe and a newly‐developed PCR system did not detect any HPV infection. Including this case with a detailed HPV investigation, all of the reported cases of mixed papilloma were HPV‐negative, and a literature review including newly‐reported cases indicated a high frequency of smoking in such cases. Endobronchial mixed papillomas might have a smoking‐related etiology.
Use of Chinese medicine among prostate cancer patients in Taiwan: A retrospective longitudinal cohort study
Authors: Lin Yi‐Hsien , Chen Kuang‐Kuo , Chiu Jen‐Hwey
Published: March 2011

The National Health Insurance (NHI) covers Western medicine and Chinese medicine (CM) in Taiwan. The present study aimed to investigate the trends and characteristics of CM use among prostate cancer patients before and after diagnosis. A retrospective longitudinal cohort study was carried out using the NHI research database. The present study cohort consisted of 4720 prostate cancer patients diagnosed in 2004. Claims of CM services of these patients between 2003 and 2008 were analyzed. The prevalence of CM use of this cohort was 25.8%, 26.8%, 23.6%, 22.4%, 22.0% and 21.1% in 2003–2008, respectively. Overall, 52.6% of this cohort had ever used CM. In the first year of diagnosis, there was the greatest increase of new CM users (12.1%). The total number of CM users and visits reached the peak in 2004 and decreased in the subsequent years (2005–2008). The average number of CM visits per user was 6.7, 6.7, 7.0, 7.1, 7.3 and 7.2 in 2003–2008, respectively. The most frequently recorded principal diagnosis of CM visits was musculoskeletal diseases (21.4%), symptoms/signs (17.6%) and neoplasms (11.7%). Chinese herbal medicine (75.1%) was the most commonly used, followed by acupuncture/traumatological manipulative therapies (29.7%). Patients using CM before diagnosis tended to be CM users after diagnosis. The increase of CM use over the first year of prostate cancer diagnosis can be primarily attributed to an increase of new CM users, rather than of CM visits per users.
Transverse testicular ectopia with splenogonadal fusion: A case report
Authors: Hasegawa Yuichi , Kanemitsu Izumi , Ueoka Katsuhiko
Published: March 2011

Both transverse testicular ectopia (TTE) and splenogonadal fusion (SGF) are rare congenital abnormalities. We report a case with both TTE and SGF, simultaneously. As far as we know, this is the first reported case. In order to identify a case of TTE or SGF, it is necessary to consider that the testes and ectopic spleens have similar patterns on ultrasonograph and magnetic resonance imaging.
Mental health nursing education in preregistration nursing curricula: A national report
Authors: Moxham Lorna , McCann Terence , Usher Kim , Farrell Gerry , Crookes Patrick
Published: March 2011

The Australian Mental Health Nurse Education Taskforce conducted a national examination of mental health content of preregistration nursing curricula in order to develop a framework for including mental health in future curricula. This paper presents the qualitative findings from national consultations about the framework. Content analysis of data was undertaken, and the findings show four key themes. First, the mental health content of curricula should be increased; second, overall mental health nursing leadership should be strengthened; third, mental health consumer participation should be increased in all aspects of curricula; and finally, a repository should be established for mental health teaching resources.
Continuous moderate‐intensity exercise with or without intermittent high‐intensity work: effects on acute and late glycaemia in athletes with Type 1 diabetes mellitus
Authors: Iscoe K. E. , Riddell M. C.
Published: March 2011

Diabet. Med. 28, 824–832 (2011)

Aims  Individuals with Type 1 diabetes mellitus are susceptible to hypoglycaemia during and after continuous moderate‐intensity exercise, but hyperglycaemia during intermittent high‐intensity exercise. The combination of both forms of exercise may have a moderating effect on glycaemia in recovery. The aims of this study were to compare the physiological responses and associated glycaemic changes to continuous moderate‐intensity exercise vs. continuous moderate‐intensity exercise + intermittent high‐intensity exercise in athletes with Type 1 diabetes.

Methods  Interstitial glucose levels were measured in a blinded fashion in 11 trained athletes with Type 1 diabetes during two sedentary days and during 2 days in which 45 min of afternoon continuous moderate‐intensity exercise occurred either with or without intermittent high‐intensity exercise. The total amount of work performed and the duration of exercise was identical between sessions.

Results  During exercise, heart rate, respiratory exchange ratio, oxygen utilization, ventilation and blood lactate levels were higher during continuous moderate‐intensity + intermittent high‐intensity exercise vs. continuous moderate‐intensity exercise (all P < 0.05). Despite these marked cardiorespiratory differences between trials, there was no difference in the reduction of interstitial glucose or plasma glucose levels between the exercise trials. Nocturnal glucose levels were higher in continuous moderate‐intensity + intermittent high‐intensity exercise and in sedentary vs. continuous moderate‐intensity exercise (P < 0.05). Compared with continuous moderate‐intensity exercise alone, continuous moderate‐intensity + intermittent high‐intensity exercise was associated with less post‐exercise hypoglycaemia (5.2 vs. 1.5% of the time spent with glucose < 4.0 mmol/l) and more post‐exercise hyperglycaemia (33.8 vs. 20.4% of time > 11.0 mmol/l).

Conclusions  Although the decreases in glucose level during continuous moderate‐intensity exercise and continuous moderate‐intensity + intermittent high‐intensity exercise are similar, the latter form of exercise protects against nocturnal hypoglycaemia in athletes with Type 1 diabetes.
Cardiovascular autonomic dysfunction is associated with central obesity in persons with impaired glucose tolerance
Authors: Laitinen T. , Lindström J. , Eriksson J. , Ilanne‐Parikka P. , Aunola S. , Keinänen‐Kiukaanniemi S. , Tuomilehto J. , Uusitupa M.
Published: March 2011

Diabet. Med. 28, 699–704 (2011)

Aims  The aim of this study was to investigate the prevalence of cardiovascular autonomic neuropathy in persons with previously diagnosed impaired glucose tolerance and to characterize associations between components of metabolic syndrome and cardiovascular autonomic neuropathy in the Finnish Diabetes Prevention Study cohort.

Methods  Two hundred and sixty‐eight individuals with impaired glucose tolerance at baseline in the Finnish Diabetes Prevention Study, but not diagnosed with diabetes during follow‐up, were studied for cardiovascular autonomic neuropathy. At the second annual follow‐up visit after the end of lifestyle intervention, we performed deep‐breathing and active orthostatic tests to detect possible parasympathetic and sympathetic dysfunction. To describe metabolic characteristics, anthropometric measurements, an oral glucose tolerance test and assessments for HbA1c, serum lipids and blood pressure were carried out.

Results  Prevalence of parasympathetic dysfunction was 25% and prevalence of sympathetic dysfunction was 6%, with no difference between the former intervention and control group participants or between men and women. Subjects with parasympathetic dysfunction were older, more obese (weight, waist circumference, body mass index) and had higher triglyceride concentration compared with those with normal parasympathetic function (P < 0.01 for all). Parasympathetic dysfunction was not significantly associated with other characteristics of metabolic syndrome; for example, high cholesterol, glucose and insulin levels or HbA1c. Correlations between the Expiration/Inspiration (E/I) ratio (the longest heart beat duration in expiration divided by the shortest heart beat duration in inspiration) and measures reflecting obesity were statistically significant in the pooled population and in men but not in women.

Conclusions  Cardiovascular autonomic neuropathy is common in persons with impaired glucose tolerance. Obesity, especially among men, seems to play an important role in the early pathogenesis of cardiovascular autonomic neuropathy.
When Cooperation is the Norm of Appropriateness: How Does CEO Cooperative Behaviour Affect Organizational Performance?
Authors: Espedal Bjarne , Kvitastein Olav , Grønhaug Kjell
Published: March 2011

The current study has tested the prediction that CEO cooperative behaviour has an impact upon organizational performance. This is a fundamental organizational issue that is in clear need of illumination through studies of practice. We pursued the issue through a study of leadership in organizations located in the Norwegian socio‐cultural context in which cooperation has been, and still is, a norm of appropriateness. The study provided empirical evidence of a positive relationship between CEO cooperative behaviour and organizational performance. This relationship appeared to be stronger in organizational contexts in which CEOs are perceived to have legitimacy and managerial discretion, and it appeared to be weaker in organizations in which individual performance pay is the rule. Since some organizational characteristics have the potential to enhance the impact of CEO cooperative behaviour while other characteristics might inhibit this impact, leaders have to consider carefully how to develop and maintain individual and organizational capabilities that are needed to act appropriately.
Consumption and Hedging in Oil‐Importing Developing Countries
Authors: Aldunate Felipe , Casassus Jaime
Published: March 2011

We study the consumption and hedging strategy of an oil‐importing developing country that faces multiple crude oil shocks. In our model, developing countries have two particular characteristics: their economies are mainly driven by natural resources and their technologies are less efficient in energy usage. The natural resource exports can be correlated with the crude oil shocks. The country can hedge against the crude oil uncertainty by taking long/short positions in existing crude oil futures contracts. We find that both inefficiencies in energy usage and shocks to the crude oil price lower the productivity of capital. This generates a negative income effect and a positive substitution effect, because today’s consumption is relatively cheaper than tomorrow’s consumption. Optimal consumption of the country depends on the magnitudes of these effects and on its risk‐aversion degree. Shocks to other crude oil factors, such as the convenience yield, are also studied. We find that the persistence of the shocks magnifies the income and substitution effects on consumption, thus also affecting the hedging strategy of the country. The demand for futures contracts is decomposed in a myopic demand, a pure hedging term and productive hedging demands. These hedging demands arise to hedge against changes in the productivity of capital due to changes in crude oil spot prices. We calibrate the model for Chile and study to what extent the country’s copper exports can be used to hedge the crude oil risk.
Evidence‐based recommendations on conventional systemic treatments in psoriasis: systematic review and expert opinion of a panel of dermatologists
Authors: Paul C , Gallini A , Maza A , Montaudié H , Sbidian E , Aractingi S , Aubin F , Bachelez H , Cribier B , Joly P , Jullien D , Le Maître M , Misery L , Richard M‐A , Ortonne J‐P
Published: March 2011

Background  There is a high level of heterogeneity regarding the practical use of conventional systemic treatment in psoriasis.

Objectives  The aim of this study was to develop evidence‐based recommendations for the use of traditional systemic treatments in psoriasis in daily clinical practice: methotrexate (MTX), cyclosporin and retinoids.

Methods  A scientific committee selected clinically relevant questions concerning the use of MTX, cyclosporin and retinoids in psoriasis. This selection was made using the Delphi method. A systematic literature search was performed in Medline, Embase and the Cochrane Library. The articles selected for analysis were reviewed and the level of evidence was appraised according to the Oxford Levels of Evidence. An Expert consensus meeting took place in June 2010, including 66 dermatologists. Recommendations for daily use of psoriasis systemic treatments were made during interactive workshops where the evidence was reviewed. Agreement among participants and the impact of the recommendations on clinical practice were systematically assessed using voting procedure in a plenary session.

Results  A total of 2800 references were identified, among which 122 articles were included in the systematic reviews. Three key recommendations on the use of MTX in psoriasis were formulated, including optimal dosage and route, use of folic acid, risk factors for liver fibrosis and monitoring of hepatotoxicity. The recommendations for cyclosporin in psoriasis focused on the modalities of cyclosporin prescription: dosage, scheme of treatment, optimal duration of treatment, renal toxicity monitoring and evidence for use of cyclosporin in non‐plaque psoriasis (erythrodermic, pustular and ungueal). Recommendations were also made concerning the efficacy and safety of retinoids (mainly acitretin) in plaque and non‐plaque psoriasis.

Conclusions  These recommendations for the use of traditional systemic therapies in psoriasis are evidence based and supported by a panel of dermatologists. The next step will be to disseminate these recommendations and assess the agreement of physicians who were not involved in generating the recommendations.