bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotic use and other risk factors at hospital level for outbreaks with Clostridium difficile PCR ribotype 027
Authors: van der Kooi T. I. I. , Koningstein M. , Lindemans A. , Notermans D. W. , Kuijper E. , van den Berg R. , Boshuizen H. , Filius P. M. G. , van den Hof S.
Published: May 2008

The first Dutch outbreak due to Clostridium difficile ribotype 027 was observed in mid-2005; by the end of that year, eight hospitals were affected. To study the relationship between hospital-wide antibiotic use and the incidence of 027-linked C. difficile-associated disease (CDAD) three study groups were made: group A, all eight hospitals with an 027-associated epidemic; group B, five of a total of six hospitals with occasional 027 cases, without an increase in CDAD; and group C, ten randomly selected hospitals with no reported 027 epidemics or isolated 027 cases. Quarterly data on CDAD incidences, hygiene measures and the use of fluoroquinolones, second- and third-generation cephalosporins, extended-spectrum penicillins, penicillins with beta-lactamase inhibitors, carbapenems, lincomycins and macrolides were collected for 2004 and 2005, and divided into pre-epidemic and epidemic periods. Using a multilevel Poisson regression analysis, CDAD incidence was linked to antibiotic use in the previous quarter and to certain hygiene measures. In the pre-epidemic period, the total use of the studied antibiotics was comparable between affected and unaffected hospitals. Higher use of second-generation cephalosporins, macrolides and all of the studied antibiotics were independently associated with a small increase in CDAD incidence [relative risk (95 % confidence interval): 1.14 per increase of 100 defined daily doses per 10 000 bed days (1.06–1.23), 1.10 (1.01–1.19) and 1.02 (1.01–1.03), respectively]. However the effect was too small to predict which hospitals might be more prone to 027-associated outbreaks.
Processing of Clostridium difficile toxins
Authors: Giesemann Torsten , Egerer Martina , Jank Thomas , Aktories Klaus
Published: May 2008

The pathogenicity ofClostridium difficiledepends on the large clostridial glucosylating toxins A and B (TcdA and TcdB). The proteins accomplish their own uptake by a modular structure comprising a catalytic and a binding/translocation domain. Based on a proteolytic processing step solely the catalytic domain reaches the cytosol. Within the cells, the glucosyltransferases inactivate small GTPases by mono-O-glucosylation. Here, a short overview is given regarding latest insights into the intramolecular processing, which is mediated by an intrinsic protease activity.
Multicentre study of the prevalence of toxigenic Clostridium difficile in Korea: results of a retrospective study 2000–2005
Authors: Shin Bo-Moon , Kuak Eun Young , Yoo Hyeon Mi , Kim Eui Chong , Lee Kyungwon , Kang Jung-Oak , Whang Dong Hee , Shin Jeong-Hwan
Published: May 2008

The prevalence of toxigenic Clostridium difficile in Korea has been reported to be approximately 60–80 %. Although the prevalence of the tcdA−tcdB+ C. difficile strain was less then 5 % prior to the year 2000, it has become an emerging nosocomial pathogen in Korea. Therefore, we have attempted to determine the multicentre nationwide prevalence of tcdA+tcdB+
and tcdA−tcdB+ C. difficile for epidemiological purposes. C. difficile strains (n=724, 30 from 2000, 80 from 2001, 74 from 2002, 76 from 2003, 179 from 2004, 285 from 2005) were obtained retrospectively from January 2000 to December 2005 from in-patients at 6 hospitals, all of whom were suspected of having C. difficile-associated disease (CDAD), colitis or pseudomembranous colitis. The numbers of participating hospitals varied yearly (1 in 2000, 2 in 2001–2003, 3 in 2004, 5 in 2005). The hospitals were located in Seoul (n=4), Kyunggi Province (n=1) and Busan (n=1), Korea. PCR assays for tcdA and tcdB genes were conducted using 724 unduplicated C. difficile isolates. The mean prevalence of tcdA+tcdB+
and tcdA−tcdB+ C. difficile strains over the 6 years was 51.8 % (38.4–59.3 %) and 25.8 %(10–56.0 %), respectively. The mean prevalence of tcdA−tcdB+ C. difficile strains was less than 7 % until 2002, but began to increase in 2003 (13.2 %) and achieved a peak in 2004 (50.3 %). In 2005, the mean prevalence of tcdA+tcdB+
and tcdA−tcdB+ C. difficile strains was 47.7 % (30.9–60.3 %) and 27.0 % (17.6–54.8 %), respectively. This nationwide epidemiological study showed that tcdA−tcdB+ C. difficile strains have already spread extensively throughout Korea, and our results provide basic data regarding the controversies currently surrounding the toxigenicity of tcdA−tcdB+

C. difficile. The use of enzyme immunoassays capable of detecting both TcdA and TcdB is strongly recommended for the diagnosis of CDAD in microbiology laboratories, in order to control the spread of the tcdA−tcdB+
strains of C. difficile.
Clostridium difficile toxin synthesis is negatively regulated by TcdC
Authors: Dupuy B. , Govind R. , Antunes A. , Matamouros S.
Published: May 2008

Clostridium difficile toxin synthesis is growth phase-dependent and is regulated by various environmental signals. The toxin genes tcdA and tcdB are located in a pathogenicity locus, which also includes three accessory genes, tcdR, tcdC and tcdE. TcdR has been shown to act as an alternative σ factor that mediates positive regulation of both the toxin genes and its own gene. The tcdA, tcdB and tcdR genes are transcribed during the stationary growth phase. The tcdC gene, however, is expressed during exponential phase. This expression pattern suggested that TcdC may act as a negative regulator of toxin gene expression. TcdC is a small acidic protein without any conserved DNA-binding motif. It is able to form dimers and its N-terminal region includes a putative transmembrane domain. Genetic and biochemical evidence showed that TcdC negatively regulates C. difficile toxin synthesis by interfering with the ability of TcdR-containing RNA polymerase to recognize the tcdA and tcdB promoters. In addition, the C. difficile NAP1/027 epidemic strains that produce higher levels of toxins have mutations in tcdC. Interestingly, a frameshift mutation at position 117 of the tcdC coding sequence seems to be, at least in part, responsible for the hypertoxigenicity phenotype of these epidemic strains.
Increased copy number of the TERT and TERC telomerase subunit genes in cancer cells
Authors: Cao Ying , Bryan Tracy M. , Reddel Roger R.
Published: May 2008

Telomerase is a ribonucleoprotein enzyme complex that adds telomeric repeats to the ends of chromosomes. The core telomerase components are the telomerase reverse transcriptase (TERT) catalytic subunit, and the telomerase RNA (TR) template subunit. In most cancers, telomerase is expressed at levels that are substantially higher than in normal cells. A known consequence of telomerase up‐regulation which is considered to play a critical role in oncogenesis is maintenance of telomere length, and thus evasion by cancer cells of the normal limits on proliferation that are associated with the steady decrease in telomere length that accompanies proliferation of normal cells. It has also been suggested that telomerase up‐regulation confers other advantages on cancer cells independent of its enzymatic activity. The mechanisms responsible for up‐regulation of telomerase in cancer are incompletely understood. Here we review evidence suggesting that this frequently results from increased copy number of the genes encoding telomerase components. The TERT gene is located at human chromosome band 5p15.33, and the telomerase RNA component (TERC) gene that encodes TR is at 3q26.3. Chromosomal gains and gene amplifications involving chromosome arms 5p and 3q are among the most frequent in human tumors. Increased TERT and TERC gene dosage has been detected frequently in a variety of human cancers, and clonal evolution of cells with increased TERT or TERC copy number has been observed, suggesting a growth advantage in cells with increased TERT or TERC gene dosage. (Cancer Sci 2008; 99: 1092–1099)
Genes and cigarette smoking
Authors: Munafò Marcus R. , Johnstone Elaine C.
Published: May 2008

Aims  Attempts to further our understanding of the determinants of cigarette smoking, tobacco addiction and related behaviours have included the dissection of genetic influences on these phenotypes. This review summarizes the current state of evidence from both twin and adoption studies and molecular genetic studies. We also review future research horizons and the direction which studies of this kind are likely to take in the near future.

Findings  There is consistent evidence from twin and adoption studies that genetic factors play a role in the aetiology of cigarette smoking. Nevertheless, despite a large number of candidate gene studies, and a smaller number of linkage studies, few reported associations and chromosomal regions of interest have proved to replicate reliably. This is due most probably to the small effects of individual loci on complex behaviours such as smoking.

Conclusions  Future research is likely to include the study of gene × environment interactions (including gene × treatment interactions, which offer the prospect of genetically tailored smoking cessation treatment) and the use of more sophisticated smoking‐related phenotypes, such as longitudinal smoking trajectories, and intermediate phenotypes which use technologies such as neuroimaging and other laboratory and biobehavioural measures.
The association between cannabis abuse and dependence and childhood physical and sexual abuse: evidence from an offspring of twins design
Authors: Duncan Alexis E. , Sartor Carolyn E. , Scherrer Jeffrey F. , Grant Julia D. , Heath Andrew C. , Nelson Elliot C. , Jacob Theodore , Bucholz Kathleen Keenan
Published: May 2008

Aim This study examines the association between childhood physical abuse (CPA) and sexual abuse (CSA) and the development of cannabis abuse and dependence among adolescents and young adults while controlling for genetic and environmental risk factors.

Design To control for familial risk differences related to paternal drug dependence that might confound the relationship between CSA and CPA and cannabis abuse/dependence, we created four groups based on father's and uncle's substance use dependence (SUD) status reflecting different degrees of genetic and environmental risks to offspring: (i) high genetic, high environmental risk; (ii) high genetic, low environmental risk; (iii) medium genetic, low environmental risk; and (iv) low genetic, low environmental risk.

Participants Adolescent and young adult offspring of monozygotic and dizygotic US military veteran twin fathers (n = 819).

Measurements Data on CPA and CSA, DSM‐IV offspring cannabis abuse/dependence, other SUD and psychopathology and maternal and paternal SUD and psychopathology were collected via semi‐structured telephone interview.

Findings Twenty‐three per cent of the offspring sample met life‐time criteria for cannabis abuse/dependence and 8.55% and 12.82% reported CSA and CPA, respectively. Offspring exposed to CSA, but not CPA, were at significantly greater risk of developing cannabis abuse/dependence compared to those who had not experienced CSA (hazard ratio = 2.16; 95% confidence interval = 1.48–3.16) after controlling for genetic and familial environmental risk and offspring gender, alcohol abuse and dependence and conduct disorder.

Conclusions These results indicate that there are effects of CSA on development of cannabis abuse/dependence in addition to the genetic and familial environmental risk imparted by having a drug‐dependent father.
A qualitative analysis of compliance with smoke‐free legislation in community bars in Scotland: implications for public health
Authors: Eadie Douglas , Heim Derek , MacAskill Susan , Ross Alastair , Hastings Gerard , Davies John
Published: May 2008

Aim  To explore compliance with the smoke‐free legislation within a cross‐section of community bars in Scotland.

Design  Ethnographic case study combining unobtrusive observation and in‐depth interviews conducted pre‐ and post‐introduction.

Setting  Eight Scottish community bars in three contrasting study communities.

Participants  Ten bar proprietors, 16 bar workers and 44 customers.

Measurements  Observations and participant reports of compliance over the first 12 months of the smoking ban.

Findings  All eight study bars endeavoured to enforce the ban, but with varying enthusiasm. Compliance varied, with violations more prevalent in those bars serving deprived communities. Most violations occurred in peripheral areas and generally went unchallenged. Six bars reported some form of complicit behaviour with staff and customers smoking together, either in the entrance area or during ‘lock‐ins’ when access to the bar was restricted to regular customers. Three factors were particularly important to explaining variance between bars: smoking norms, management competency and management attitudes towards the ban. The first and last were related to social disadvantage.

Conclusions  Official data provide only a crude assessment of compliance in licensed premises. Data from this study offer a detailed picture of the nature and levels of compliance, and suggest a need for more sophisticated surveillance methods, greater enforcement and use of prosecutions where merited, and targeted support for bars serving deprived communities to help ensure that the major gains already achieved are retained and built upon. It is also suggested that acceptance of the smoke‐free legislation could be enhanced by complementary initiatives targeting support to smokers in deprived communities. Those planning to introduce smoke‐free legislation need to set in place these measures in advance in order to realize the benefits of full compliance.
Recombinant LH (lutropin alfa) for the treatment of hypogonadotrophic women with profound LH deficiency: a randomized, double‐blind, placebo‐controlled, proof‐of‐efficacy study
Authors: Shoham Z. , Smith H. , Yeko T. , O’Brien F. , Hemsey G. , O'Dea L.
Published: May 2008

Objective  To confirm the safety and efficacy of 75 IU lutropin alfa with concomitant follitropin alfa in inducing follicular development in women with profound gonadotrophin deficiency.

Design  Double‐blind, randomized, placebo‐controlled trial conducted in 25 medical centres in four countries.

Patients  Thirty‐nine patients with LH < 1·2 IU/l and FSH < 5·0 IU/l were treated with concomitant 75 IU lutropin alfa and 150 IU follitropin alfa or concomitant placebo and 150 IU follitropin alfa.

Measurements  Primary efficacy end‐point (intent‐to‐treat): follicular development defined by (i) at least one follicle ≥ 17 mm; (ii) serum E2 level ≥ 400 pmol/l on day of hCG administration (DhCG); and (iii) mid‐luteal phase progesterone level ≥ 25 nmol/l.

Results  In the analysis of evaluable patients, 66·7% (16 of 24) of patients given lutropin alfa achieved follicular development compared with 20·0% (2 of 10) of patients receiving placebo (P = 0·023). In the intent‐to‐treat analysis, follicular development was achieved in 65·4% (17 of 26) of patients receiving lutropin alfa and 15·4% (2 of 13) of patients receiving placebo (P = 0·006). The statistical difference between treatment groups was preserved when over‐response leading to cycle cancellation was analysed as a failed response (P = 0·034). Lutropin alfa was well tolerated.

Conclusion  Subcutaneous co‐administration of 75 IU lutropin alfa with follitropin alfa is safe and effective in inducing follicular development in women with profound gonadotrophin deficiency.
13C solid‐state NMR assessment of decomposition pattern during co‐composting of sewage sludge and green wastes
Authors: Albrecht R. , Ziarelli F. , Alarcón‐Gutiérrez E. , Le Petit J. , Terrom G. , Perissol C.
Published: May 2008

The fate of organic matter during composting is poorly understood. Therefore, we analysed composts of sewage sludges and green wastes (44 samples representative of 11 stages of biodegradation) by conventional chemical methods: pH, humic (HA) and fulvic acid (FA) content, C, N and organic matter (OM) content, and by 13C CPMAS NMR to assess the decomposition process of the organic matter. Chemical changes clearly occurred in two phases: first, decomposition of OM during the first 2 months was characterized by decreased C/N ratios, OM content and increased pH; and second, a humification process with increased HA/FA ratios. NMR spectrum changes confirmed this pattern, with an increase in aromaticity and a decrease in alkyl C. A decrease of syringyl to guaiacyl ratio (S/G), a sign of lignin transformation, also indicated humification during composting. NMR spectroscopic properties of composts were also studied by means of principal components analysis (PCA) and revealed changes according to the degree of compost maturation. The factorial map presents a chronological distribution of composts on the two first principal components. The influences of eight chemical factors on the PCA ordination of composts as monitored by their evolution by NMR were also studied by multivariate analyses. PCA clearly indicated two phases: the rapid decomposition of organic matter followed by the formation of humic‐like substances. The first phase, that is ‘new’ composts, was strongly correlated with OM contents, pH and C/N ratios whereas the second phase, corresponding to ‘old’ compost, was correlated with pH, HA content and HA/FA ratio. These results confirm that knowledge of the formation of humic substances is indispensable to suitable monitoring of the composting process.
Soil organic phosphorus in tropical forests: an assessment of the NaOH–EDTA extraction procedure for quantitative analysis by solution 31P NMR spectroscopy
Authors: Turner B. L.
Published: May 2008

The extraction of soil organic phosphorus by the NaOH–EDTA procedure was assessed in detail for a tropical forest soil (clay‐loam, pH 4.3, total carbon 2.7%). Optimum conditions for the quantification of soil organic phosphorus and characterization of its composition by solution 31P NMR spectroscopy were extraction in a solution containing 0.25 m NaOH and 50 mm Na2EDTA in a 1:20 solid to solution ratio for 4 hours at ambient laboratory temperature. Replicate analyses yielded a coefficient of variation of 3% for organic phosphorus as a proportion of the spectral area. There was no significant difference in total phosphorus extraction from fresh and air‐dried soil, although slightly more organic phosphorus and less paramagnetic ions were extracted from dried soil. The procedure was not improved by changing the concentration of NaOH or EDTA, extraction time, or solid to solution ratio. Pre‐extraction with HCl or Na2EDTA did not increase subsequent organic phosphorus extraction in NaOH–EDTA or improve spectral resolution in solution 31P NMR spectroscopy. Post‐extraction treatment with Chelex resin did not improve spectral resolution, but removed small concentrations of phosphorus from the extracts. Increasing the pH of NaOH–EDTA extracts (up to 1.0 m NaOH) increased the concentration of phosphate monoesters, but decreased DNA to an undetectable level, indicating its hydrolysis in strong alkali. The standardized NaOH–EDTA extraction procedure is therefore recommended for the analysis of organic phosphorus in tropical forest soils.
DHMEQ, a novel nuclear factor‐κB inhibitor, induces selective depletion of alloreactive or phytohaemagglutinin‐stimulated peripheral blood mononuclear cells, decreases production of T helper type 1 cytokines, and blocks maturation of dendritic cells
Authors: Nishioka Chie , Ikezoe Takayuki , Jing Yang , Umezawa Kazuo , Yokoyama Akihito
Published: May 2008

Dehydroxymethylepoxyquinomicin (DHMEQ), a novel nuclear factor κB (NF‐κB) inhibitor, has been shown to be active against variety types of solid tumours as well as haematological malignant cells. This study explored the anti‐inflammatory effects of DHMEQ in vitro. DHMEQ inhibited the proliferation of phytohaemagglutinin (PHA)‐stimulated or alloreactive peripheral blood mononuclear cells (PBMC) in mixed lymphocyte cultures as measured using a 3‐(4,5‐dimethylithiazol‐2‐yl)‐2,5‐diphenyl tetrazolium (MTT) assay. In contrast, DHMEQ did not affect the viability of resting PBMC. In addition, real‐time polymerase chain reaction showed that DHMEQ decreased PHA‐stimulated expression of T helper type 1 (Th1) cytokines, including interleukin‐2, interferon‐γ, and tumour necrosis factor α, in PBMC as well as Jurkat T‐lymphoblastic leukaemia cells, and also decreased levels of p65 isoforms of NF‐κB in the nucleus. Furthermore, we found that DHMEQ inhibited the endocytic capacity of dendritic cells (DCs) and down‐regulated the expression of cell surface antigen CD40, suggesting that DHMEQ blocked the maturation as well as the function of DCs. Taken together, the results suggest that DHMEQ may be useful for treatment of inflammatory diseases, including graft‐versus‐host disease after allogenic haematopoietic stem cell transplantation.
Functional characterization of the Arabidopsis ubiquitin‐specific protease gene family reveals specific role and redundancy of individual members in development
Authors: Liu Yanfen , Wang Feng , Zhang Huiyong , He Hang , Ma Ligeng , Deng Xing Wang
Published: May 2008

Ubiquitin‐specific proteases (UBPs) are a highly conserved family of proteins in eukaryotes, and play critical roles in protein de‐ubiquitination. Here we report a systematic genetic and expression profiling analysis of the UBP gene family in the Arabidopsis thaliana genome. Mutation analysis of 25 of the 27 member genes representing 13 of the 14 sub‐families of the UBP gene family revealed that single‐gene mutants of three genes in two sub‐families exhibit visible phenotypes. Two of these three genes belonging to the UBP15 sub‐family were selected for further characterization. The ubp15 mutants display narrower, serrated and flat rosette leaves, partially due to a defect in cell proliferation, as well as other phenotypes such as early flowering, weak apical dominance and reduced fertility, while the line over‐expressing UBP15 shows opposite phenotypes. We demonstrated that UPB15 has UBP activity in vitro, and that this biochemical activity is essential for its in vivo function. A genetic interaction analysis among members of this sub‐family revealed that UBP15 and UBP16, but not UBP17, have functional redundancy. Our data thus suggest that distinct UBPs, even within a closely related sub‐family, can function in different developmental pathways. Although there are clearly functional redundancies among related sub‐family members, those redundancies cannot be inferred simply based on the amino acid identity of the family members.
Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyond
Authors: Pertwee Roger G.
Published: May 2008

A major finding—that (–)‐trans‐Δ9‐tetrahydrocannabinol (Δ9‐THC) is largely responsible for the psychotropic effects of cannabis—prompted research in the 1970s and 1980s that led to the discovery that this plant cannabinoid acts through at least two types of cannabinoid receptor, CB1and CB2, and that Δ9‐THC and other compounds that target either or both of these receptors as agonists or antagonists have important therapeutic applications. It also led to the discovery that mammalian tissues can themselves synthesize and release agonists for cannabinoid receptors, the first of these to be discovered being arachidonoylethanolamide (anandamide) and 2‐arachidonoylglycerol. These ‘endocannabinoids’ are released onto their receptors in a manner that appears to maintain homeostasis within the central nervous system and sometimes either to oppose or to mediate or exacerbate the unwanted effects of certain disorders. This review provides an overview of the pharmacology of cannabinoid receptors and their ligands. It also describes actual and potential clinical uses both for cannabinoid receptor agonists and antagonists and for compounds that affect the activation of cannabinoid receptors less directly, for example by inhibiting the enzymatic hydrolysis of endocannabinoids following their release.
The role of CB1 receptors in psychostimulant addiction
Authors: Wiskerke Joost , Pattij Tommy , Schoffelmeer Anton N.M. , De Vries Taco J.
Published: May 2008

Recent studies have implicated the endocannabinoid (eCB) system in the neuronal mechanisms underlying substance dependence. Here, we review results of studies using cannabinoid receptor subtype 1 (CB1) knockout mice as well as CB1 antagonists to elucidate the role of this neurotransmitter system in psychostimulant addiction. The overall picture is that CB1 receptors appear not to be involved in psychostimulant reward, nor in the development of dependence to such substances. In contrast, the eCB system appears to play a role in the persistence of psychostimulant addiction. In particular, CB1 receptors have been found to play a cardinal role in mediating reinstatement of previously extinguished drug‐seeking behavior upon re‐exposure to the drug or drug‐associated cues. The anatomical loci as well as the neuronal mechanisms of the relapse‐preventing effects of CB1 antagonists are still poorly understood, although interactions of the eCB system with afferent glutamatergic and possibly dopaminergic projections to the nucleus accumbens are most likely involved. In addition, CB1 receptors seem to modulate drug‐related memories, in line with the hypothesized role of the eCB system in memory‐related plasticity. Together, these findings suggest that modulators of the eCB system represent a promising novel type of therapy to treat drug addiction.
Blocking cannabinoid CB1receptors for the treatment of nicotine dependence: insights from pre‐clinical and clinical studies
Authors: Foll Bernard Le , Forget Benoit , Aubin Henri‐Jean , Goldberg Steven R.
Published: May 2008

Tobacco use is one of the leading preventable causes of death in developed countries. Since existing medications are only partially effective in treating tobacco smokers, there is a great need for improved medications for smoking cessation. It has been recently proposed that cannabinoid CB1receptor antagonists represent a new class of therapeutic agents for drug dependence, and notably, nicotine dependence. Here, we will review current evidence supporting the use of this class of drugs for smoking cessation treatment. Pre‐clinical studies indicate that nicotine exposure produces changes in endocannabinoid content in the brain. In experimental animals, N‐piperidinyl‐5‐(4‐chlorophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methylpyrazole‐3‐carboxamide (rimonabant, SR141716) andN‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide (AM251), two cannabinoid CB1receptor antagonists, block nicotine self‐administration behavior, an effect that may be related to the blockade of the dopamine‐releasing effects of nicotine in the brain. Rimonabant also seems efficacious in decreasing the influence of nicotine‐associated stimuli over behavior, suggesting that it may act on two distinct neuronal pathways, those implicated in drug‐taking behavior and those involved in relapse phenomena. The utility of rimonabant has been evaluated in several clinical trials. It seems that rimonabant is an efficacious treatment for smoking cessation, although its efficacy does not exceed that of nicotine‐replacement therapy and its use may be limited by emotional side effects (nausea, anxiety and depression, mostly). Rimonabant also appears to decrease relapse rates in smokers. These findings indicate significant, but limited, utility of rimonabant for smoking cessation.
Temporal and Contextual Patterns of Killer Whale (Orcinus orca) Call Type Production
Authors: Foote Andrew D. , Osborne Richard W. , Rus Hoelzel A.
Published: May 2008

Fish‐eating killer whales Orcinus orca in the northeastern Pacific live in highly stable matrifocal social groups called pods. Each pod produces a repertoire of seven or more stereotyped call types. We compared the relative production of call types of free‐ranging killer whale pods over time and between social contexts. The relative production of call types by each pod during directional travel was distinct over a 27‐yr period; however, both temporal stability and pod distinctiveness were strongly influenced by a subset of dominant call types within the repertoire of each pod. Some call types within the repertoires contain biphonation (two overlapping independently modulated tones) and have a higher estimated active space than call types containing just one tone. In multi‐pod aggregations the relative production of the dominant call types of each pod decreased and the relative production of a subset of call types that are rarely recorded from single‐pod groupings increased. The majority of these contained biphonation. The data suggest a distinction between a subset of dominant call types that may function to identify the pod and a subset of less common call types including several call types containing biphonation that are more commonly produced during inter‐pod affiliations.
Multiplicative random regression model for heterogeneous variance adjustment in genetic evaluation for milk yield in Simmental
Authors: Lidauer M.H. , Emmerling R. , Mäntysaari E.A.
Published: May 2008

A multiplicative random regression (M‐RRM) test‐day (TD) model was used to analyse daily milk yields from all available parities of German and Austrian Simmental dairy cattle. The method to account for heterogeneous variance (HV) was based on the multiplicative mixed model approach of Meuwissen. The variance model for the heterogeneity parameters included a fixed region × year × month × parity effect and a random herd × test‐month effect with a within‐herd first‐order autocorrelation between test‐months. Acceleration of variance model solutions after each multiplicative model cycle enabled fast convergence of adjustment factors and reduced total computing time significantly. Maximum Likelihood estimation of within‐strata residual variances was enhanced by inclusion of approximated information on loss in degrees of freedom due to estimation of location parameters. This improved heterogeneity estimates for very small herds. The multiplicative model was compared with a model that assumed homogeneous variance. Re‐estimated genetic variances, based on Mendelian sampling deviations, were homogeneous for the M‐RRM TD model but heterogeneous for the homogeneous random regression TD model. Accounting for HV had large effect on cow ranking but moderate effect on bull ranking.
Genetic diversity in Egyptian and Italian goat breeds measured with microsatellite polymorphism
Authors: Agha S.H. , Pilla F. , Galal S. , Shaat I. , D’Andrea M. , Reale S. , Abdelsalam A.Z.A. , Li M.H.
Published: May 2008

Seven microsatellite markers were used to study genetic diversity of three Egyptian (Egyptian Baladi, Barki and Zaraibi) and two Italian (Maltese and Montefalcone) goat breeds. The microsatellites showed a high polymorphic information content (PIC) of more than 0.5 in most of the locus–breed combinations and indicated that the loci were useful in assessing within‐ and between‐breed variability of domestic goat (Capra hircus). The expected heterozygosity of the breeds varied from 0.670 to 0.792. In the geographically wider distributed Egyptian Baladi breed there were indications for deviations from random breeding. Analysis of genetic distances and population structure grouped the three Egyptian goat breeds together, and separated them from the two Italian breeds. The studied Mediterranean breeds sampled from African and European populations seem to have differentiated from each other with only little genetic exchange between the geographically isolated populations.
Trends in genetic variance components during 30 years of hybrid maize breeding at the University of Hohenheim
Authors: Fischer S. , Möhring J. , Schön C. C. , Piepho H.‐P. , Klein D. , Schipprack W. , Utz H. F. , Melchinger A. E. , Reif J. C.
Published: May 2008

The ratio of variance due to specific vs. general combining ability (GCA) (σ2SCA:σ2GCA) is of central importance for predicting hybrid performance from GCA effects. The objectives of our study were to (1) analyse the changes in estimates of σ2GCA, σ2SCA and their ratio during 30 years of hybrid maize breeding and (2) compare the observed trends in genetic variances with those expected under a simple genetic model. We analysed multilocation yield trials based on the North Carolina Design II conducted in the maize breeding programme of the University of Hohenheim from 1975 to 2004 for grain yield (GY) and dry matter content (DMC). GY showed a significant (P < 0.05) annual increase of 0.17 Mg/ha, but no linear trend was found for DMC. Since the beginning of hybrid breeding at the University of Hohenheim, the sum of estimates of σ2GCA of the flint and dent heterotic groups were higher than the estimates of their σ2SCA. This predominance did not change with ongoing inter‐population improvement. Consequently, superior hybrids can be identified and selected mainly based on their prediction from GCA effects.
A model calculation approach towards the optimization of a standard scheme of seed‐parent line development in hybrid rye breeding
Authors: Tomerius A.‐M. , Miedaner T. , Geiger H. H.
Published: May 2008

The importance of hybrid rye (Secale cereale L.) breeding has steadily increased over the last decades. This paper presents results of model calculations aiming to optimize the number of candidates, testers to assess combining ability and test locations at each selection stage of a standard scheme of seed‐parent line development. Two variants of the scheme differing in the number of stages and the cycle length are investigated. Optimization criterion is the expected selection gain per year under the restriction of a fixed budget. Prediction of selection gain rests on quantitative–genetic and economic parameters estimated from breeders’ data. Optimization covers different genetical and economical situations. Results show that the optimum number of testers to assess combining ability depends on the relative amount of dominance variance. The efficiency of a breeding scheme strongly increases with decreasing cycle length. A larger budget should mainly be used to increase the number of candidates at all selection stages. Recommendations for practical breeding schemes are given. We conclude that model calculations are a valuable tool for the optimization of breeding schemes.
Inheritance of very high linoleic acid content and its relationship with nuclear male sterility in safflower
Authors: Hamdan Y. A. S. , Pérez‐Vich B. , Fernández‐Martínez J. M. , Velasco L.
Published: May 2008

Safflower (Carthamus tinctorius L.) possesses the highest amount of linoleic acid among the 10 major vegetable oil crops of the world. Very high linoleic acid content is controlled by recessive alleles at a single locus Li. However, deviated segregations from the expected monogenic inheritance have been observed in crosses involving nuclear male‐sterile (NMS) lines. The present research was undertaken to study the inheritance of very high linoleic acid content in safflower and its relationship with nuclear male sterility. F1, F2, F3, BC1F1 and BC1F2 seed generations were evaluated in a cross between CR‐142 (a line with very high linoleic acid content, 88%) and CL1 (an NMS line with wild‐type linoleic acid content, 74%). The genetics of linoleic acid content in male‐sterile plants was determined by testcrossing with CR‐142. The results confirmed monogenic inheritance. The analysis of the F3 and BC1F2 to CL1 seed generations demonstrated a repulsion‐phase linkage between Li and Ms loci, the latter conferring the NMS trait. The recombination rate between Li and Ms was estimated to be 0.09.
Biphasic insulin aspart 30 in the treatment of elderly patients with type 2 diabetes: a subgroup analysis of the PRESENT Korea NovoMix®study
Authors: Jang H. C. , Lee S. R. , Vaz J. A.
Published: May 2008

Aims:  To evaluate the efficacy, safety and treatment satisfaction with biphasic insulin aspart 30 (BIAsp30) in elderly patients with type 2 diabetes.

Methods:  The Physicians’ Routine Evaluation of Safety and Efficacy of NovoMix®30 Therapy Korea study was a 6‐month, prospective, observational study. No study‐specific interventions were involved except the collection of data. All patients with type 2 diabetes not adequately controlled on their previous therapy, and who were prescribed BIAsp30 as monotherapy, or in combination with oral hypoglycaemic agents, were eligible for the study. This subgroup analysis was based on the outcomes in patients ≥65 years (n = 1720).

Results:  BIAsp30 treatment was associated with significant mean reductions in haemoglobin A1c, fasting plasma glucose and post‐prandial plasma glucose levels of 1.2 ± 1.6%, 2.3 ± 3.5 mmol/l and 4.8 ± 5.3 mmol/l at 6 months (p < 0.0001 for all), from baseline levels of 9.1 ± 1.7%, 10.7 ± 3.4 mmol/l and 16.7 ± 5.0 mmol/l, respectively. The rate of hypoglycaemia declined from 3.02 to 1.31 episodes per patient year, between baseline and study end. The proportion of patients reporting adverse drug reactions was low (0.3 and 0.1% at 3 and 6 months, respectively). Body weight gain was mild at <0.1 kg at 3 months, and 0.3 kg at 6 months. As compared to the previous treatment, >80% of patients were rated as being either ‘very satisfied’ or ‘satisfied’ with BIAsp30 treatment.

Conclusions:  In this subanalysis of Korean elderly patients with type 2 diabetes inadequately controlled on their previous therapies, treatment with BIAsp30 offered improvements in glycaemic control and was well tolerated. Body weight gain was minimal with BIAsp30, and treatment satisfaction among these patients appeared to be high.
Massive Modularity and the Flexibility of Human Cognition
Authors: MACHERY EDOUARD
Published: May 2008

Abstract:  In The Architecture of the Mind, Carruthers proposes a new and detailed explanation for how human cognition could be both flexible and massively modular. The combinatorial nature of our linguistic faculty and our capacity to engage in inner speech are the cornerstones of this new explanation. Despite the ingenuity of this proposal, I argue that Carruthers has failed to explain how a massively modular mind could display the flexibility that is characteristic of human thought.
On Fodor‐Fixation, Flexibility, and Human Uniqueness: A Reply to Cowie, Machery, and Wilson
Authors: CARRUTHERS PETER
Published: May 2008

Abstract:  This paper argues that two of my critics (Cowie and Wilson) have become fixated on Fodor’s notion of modularity, both to their own detriment and to the detriment of their understanding of Carruthers, 2006. The paper then focuses on the supposed inadequacies of the latter’s explanations of both content flexibility and human uniqueness, alleged by Machery and Cowie respectively.
Systematic review of the effects of aromatase inhibitors on pain associated with endometriosis
Authors: Patwardhan S , Nawathe A , Yates D , Harrison GR , Khan KS
Published: May 2008

Objective  To assess the effects of aromatase inhibitors in women symptomatic of pain with endometriosis.

Design  A systematic review of published literature.

Material and methods  We conducted a comprehensive literature search to identify all the published observational and randomised studies evaluating the efficacy of aromatase inhibitors on pain associated with endometriosis. A combination of keywords was used to identify the maximum number of relevant citations in MEDLINE, EMBASE, CINAHL and the Cochrane Database.

Outcome  Pain relief, lesion size and quality of life.

Results  There were eight studies (137 women) evaluating outcomes of aromatase inhibitors. In case series/reports (seven studies, 40 women), aromatase inhibitors combined with progestogens or oral contraceptive pill or gonadotrophin‐releasing hormone (GnRH) analogues reduced mean pain scores and lesion size and improved quality of life. An RCT (97 women) demonstrated that aromatase inhibitors in combination with GnRH analogues significantly improved pain (P < 0.0001) compared with GnRH analogues alone together with significant improvement in multidimensional patient scores (P < 0.0001). There was no significant reduction in spine or hip‐bone densities.

Conclusion  Aromatase inhibitors appear to have a promising effect on pain associated with endometriosis, but the strength of this inference is limited due to a dearth of the evidence available.
Efficacy and Tolerability of Almotriptan in Adolescents: A Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Linder Steven L. , Mathew Ninan T. , Cady Roger K. , Finlayson Gary , Ishkanian Gary , Lewis Donald W.
Published: May 2008

Objectives.— To assess the efficacy and safety of almotriptan 6.25 mg, 12.5 mg, and 25 mg vs placebo for acute migraine treatment in adolescents.

Patients and Methods.— In this double‐blind, placebo‐controlled, parallel‐group, multicenter trial, 866 patients aged 12 to 17 years with a >1 year history of migraine (per International Headache Society criteria) were randomized to treat one migraine headache with almotriptan 6.25 mg, 12.5 mg, 25 mg, or placebo. The primary efficacy endpoint was headache pain relief 2 hours after dosing, adjusted for baseline severity, with absence of nausea, photophobia, and phonophobia 2 hours after dosing as coprimary endpoints.

Results.— The 2‐hour pain‐relief rate was significantly higher with almotriptan 25 mg compared with placebo (66.7% vs 55.3%; P = .022). The incidence of nausea, photophobia, and phonophobia at 2 hours (adjusted for baseline pain intensity) for the almotriptan 25 mg and placebo groups was not significantly different. The 2‐hour pain‐relief rates (unadjusted) were significantly higher with almotriptan 6.25 mg (71.8%), 12.5 mg (72.9%), and 25 mg (66.7%) than with placebo (55.3%; P = .001, P < .001, and P = .028, respectively). Rates for sustained pain relief also were significantly greater with almotriptan 6.25 mg (67.2%), 12.5 mg (66.9%), and 25 mg (64.5%) than with placebo group (52.4%), P < .01 for the 6.25‐ and 12.5‐mg doses and P < .05 for the 25‐mg dose. Age group subanalysis demonstrated significantly greater 2‐hour pain‐relief rates with all 3 doses of almotriptan compared with placebo for patients aged 15 to 17 years, a significantly lower incidence of photophobia and phonophobia at 2 hours with almotriptan 12.5 mg compared with placebo for patients aged 15 to 17 years, and a significantly lower incidence of photophobia with almotriptan 12.5 mg compared with placebo for those aged 12 to 14 years. Almotriptan treatment was well tolerated, with the most common adverse events (>2%) of nausea, dizziness, and somnolence.

Conclusions.— Oral almotriptan was efficacious for relieving migraine headache pain in adolescents, with the 12.5‐mg dose associated with the most favorable efficacy profile with respect to relieving headache pain and associated symptoms of migraine (photophobia and phonophobia). Almotriptan treatment was well tolerated in this adolescent population.
Therapeutic Potential of Fluoxetine in Neurological Disorders
Authors: Mostert Jop P. , Koch Marcus W. , Heerings Marco , Heersema Dorothea J. , De Keyser Jacques
Published: May 2008

The selective serotonin reuptake inhibitor (SSRI) fluoxetine, which is registered for a variety of psychiatric disorders, has been found to stimulate the cAMP‐responsive element binding protein (CREB), increase the production of brain‐derived neurotrophic factor (BNDF) and the neurotrophic peptide S100β, enhance glycogenolysis in astrocytes, block voltage‐gated calcium and sodium channels, and decrease the conductance of mitochondrial voltage‐dependent anion channels (VDACs). These mechanisms of actions suggest that fluoxetine may also have potential for the treatment of a number of neurological disorders. We performed a Pubmed search to review what is known about possible therapeutic effects of fluoxetine in animal models and patients with neurological disorders. Beneficial effects of fluoxetine have been noted in animal models of stroke, multiple sclerosis, and epilepsy. Fluoxetine was reported to improve neurological manifestations in patients with Alzheimer's disease, stroke, Huntington's disease, multiple sclerosis, traumatic brain injury, and epilepsy. Clinical studies so far were small and often poorly designed. Results were inconclusive and contradictory. However, the available preclinical data justify further clinical trials to determine the therapeutic potential of fluoxetine in neurological disorders.
Gender Differences in Response to Emotional Stress: An Assessment Across Subjective, Behavioral, and Physiological Domains and Relations to Alcohol Craving
Authors: Chaplin Tara M. , Hong Kwangik , Bergquist Keri , Sinha Rajita
Published: May 2008

Background:  Women and men are at risk for different types of stress‐related disorders, with women at greater risk for depression and anxiety and men at greater risk for alcohol‐use disorders. The present study examines gender differences in emotional and alcohol craving responses to stress that may relate to this gender divergence in disorders.

Method:  Healthy adult social drinkers (27 men, 27 women) were exposed to individually developed and calibrated stressful, alcohol‐related, and neutral‐relaxing imagery, 1 imagery per session, on separate days and in random order. Subjective emotions, behavioral/bodily responses, cardiovascular arousal [heart rate (HR), blood pressure (BP)], and self‐reported alcohol craving were assessed.

Results:  Women reported and displayed greater sadness and anxiety following stress than men and men had greater diastolic BP response than women. No gender differences in alcohol craving, systolic BP or HR were observed. Subjective, behavioral, and cardiovascular measures were correlated in both genders. However, for men, but not women, alcohol craving was associated with greater subjective emotion and behavioral arousal following stress and alcohol cues.

Conclusions:  These data suggest that men and women respond to stress differently, with women experiencing greater sadness and anxiety, while men show a greater integration of reward motivation (craving) and emotional stress systems. These findings have implications for the gender‐related divergence in vulnerability for stress‐related disorders, with women at greater risk for anxiety and depression than men, and men at greater risk for alcohol‐use disorders than women.
Decisional Capacity for Research Participation in Individuals with Mild Cognitive Impairment
Authors: Jefferson Angela L. , Lambe Susan , Moser David J. , Byerly Laura K. , Ozonoff Al , Karlawish Jason H.
Published: May 2008

OBJECTIVES:To assess decisional capacity performance and the neuropsychological correlates of such performance to better understand higher‐level instrumental activities of daily living in individuals with mild cognitive impairment (MCI).

DESIGN:Cross‐sectional.

SETTING:Research center, medical center, or patient's home.

PARTICIPANTS:Forty participants with MCI and 40 cognitively normal older controls (NCs) aged 60 to 90 (mean age±standard deviation 73.3±6.6; 54% female).

MEASUREMENTS:Capacity to provide informed consent for a hypothetical, but ecologically valid, clinical trial was assessed using the MacArthur Competence Assessment Tool for Clinical Research. Neuropsychological functioning was assessed using a comprehensive protocol.

RESULTS:Adjusted between‐group comparisons yielded significant differences for most decisional capacity indices examined, including Understanding (P=.001; NC>MCI) and Reasoning (P=.002; NC>MCI). Post hoc analyses revealed that participants with MCI who were categorized as capable of providing informed consent according to expert raters had higher levels of education than those who were categorized as incapable.

CONCLUSION:The findings suggest that many individuals with MCI perform differently on a measure of decisional capacity than their NC peers and that participants with MCI who are incapable of providing informed consent on a hypothetical and complex clinical trial are less educated. These findings are consistent with prior studies documenting functional and financial skill difficulties in individuals with MCI.