bluuebunny/crossref_metadata_2025 huggingface dataset:
Pattern recognition receptor expression is not impaired in patients with chronic mucocutanous candidiasis with or without autoimmune polyendocrinopathy candidiasis ectodermal dystrophy
Authors: Hong M , Ryan K R , Arkwright P D , Gennery A R , Costigan C , Dominguez M , Denning D W , McConnell V , Cant A J , Abinun M , Spickett G P , Swan D C , Gillespie C S , Young D A , Lilic D
Published: January 2009

Patients with chronic mucocutaneous candidiasis (CMC) have an unknown primary immune defect and are unable to clear infections with the yeast Candida. CMC includes patients with AIRE gene mutations who have autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), and patients without known mutations. CMC patients have dysregulated cytokine production, suggesting that defective expression of pattern recognition receptors (PRRs) may underlie disease pathogenesis. In 29 patients with CMC (13 with APECED) and controls, we assessed dendritic cell (DC) subsets and monocyte Toll-like receptor (TLR) expression in blood. We generated and stimulated monocyte-derived (mo)DCs with Candida albicans, TLR-2/6 ligand and lipopolysaccharide and assessed PRR mRNA expression by polymerase chain reaction [TLR-1–10, Dectin-1 and -2, spleen tyrosine kinase (Syk) and caspase recruitment domain (CARD) 9] in immature and mature moDCs. We demonstrate for the first time that CMC patients, with or without APECED, have normal blood levels of plasmocytoid and myeloid DCs and monocyte TLR-2/TLR-6 expression. We showed that in immature moDCs, expression levels of all PRRs involved in anti-Candida responses (TLR-1, -2, -4, -6, Dectin-1, Syk, CARD9) were comparable to controls, implying that defects in PRR expression are not responsible for the increased susceptibility to Candida infections seen in CMC patients. However, as opposed to healthy controls, both groups of CMC patients failed to down-regulate PRR mRNA expression in response to Candida, consistent with defective DC maturation, as we reported recently. Thus, impaired DC maturation and consequent altered regulation of PRR signalling pathways rather than defects in PRR expression may be responsible for inadequate Candida handling in CMC patients.
Immune regulation by non-lymphoid cells in transplantation
Authors: Dugast A-S , Vanhove B
Published: January 2009

Regulatory cells play a crucial role in the induction and maintenance of tolerance by controlling T cell as well as B and natural killer (NK) cell-mediated immunity. In transplantation, CD4+CD25+forkhead box P3+ T regulatory cells are instrumental in the maintenance of immunological tolerance, as are several other T cell subsets such as NK T cells, double negative CD3+ T cells, γδ T cells, interleukin-10-producing regulatory type 1 cells, transforming growth factor-β-producing T helper type 3 cells and CD8+CD28- cells. However, not only T cells have immunosuppressive properties, as it is becoming increasingly clear that both T and non-T regulatory cells co-operate and form a network of cellular interactions controlling immune responses. Non-T regulatory cells include tolerogenic dendritic cells, plasmacytoid dendritic cells, mesenchymal stem cells, different types of stem cells, various types of alternatively activated macrophages and myeloid-derived suppressor cells. Here, we review the mechanism of action of these non-lymphoid regulatory cells as they relate to the induction or maintenance of tolerance in organ transplantation.
BclI polymorphism of the glucocorticoid receptor gene is associated with decreased bone mineral density in patients with endogenous hypercortisolism
Authors: Szappanos Ágnes , Patócs Attila , Tõke Judit , Boyle Belema , Sereg Márta , Majnik Judit , Borgulya Gábor , Varga Ibolya , Likó István , Rácz Károly , Tóth Miklós
Published: January 2009

Objective  The hypothalamic–pituitary–adrenal axis setpoint and the glucocorticoid sensitivity of various tissues are at least partially genetically determined. We investigated the impact of glucocorticoid receptor (GR) gene polymorphisms, including the BclI, N363S, ER22/23EK and A3669G variants on bone turnover and/or mineral density (BMD) in patients with endogenous glucocorticoid excess.

Design  Sixty patients including 35 patients with ACTH producing pituitary adenoma (CD) and 25 patients with adrenal Cushing's syndrome (ACS) as well as 129 healthy subjects were genotyped. Analysis of the GR gene polymorphisms were determined using allele specific PCR, PCR‐RFLP and Taqman allelic discrimination assays. Hormonal evaluation, BMD and bone marker measurements were carried out.

Results  No significant differences were found in allelic frequencies of the four polymorphisms between patients with ACS, CD and healthy controls. Patients with endogenous hypercortisolism carrying the BclI polymorphism in a homozygous form had reduced BMD at femoral subregions compared to patients with the wild‐type variant; femoral neck Z‐score (–1·44 ± 0·73 vs. –0·39 ± 0·91; P < 0·05), trochanteric Z‐score (–1·89 ± 0·47 vs.–0·54 ± 0·98; P < 0·05). Patients with homozygous BclI polymorphism had significantly higher β‐CrossLaps Z‐scores compared to those with the heterozygous and wild‐type variants (+4·42 ± 2·37 vs. +0·79 ± 1·67 and +0·11 ± 1·47; P < 0·01).

Conclusions  The BclI, N363S, ER22/23EK and A3669G polymorphisms of the GR gene probably do not modify the risk for the development of CD or ACS. Contrary to healthy subjects, however, the BclI polymorphism may modify the skeletal sensitivity to glucocorticoids in patients with endogenous glucocorticoid excess.
Serum concentrations of 17β‐E2 and 25‐hydroxycholecalciferol (25OHD) in relation to all‐cause mortality in older men – the MINOS study
Authors: Szulc Pawel , Claustrat Bruno , Delmas Pierre D.
Published: January 2009

Objective  To examine the association of serum hormone levels with all‐cause mortality in older community‐dwelling men.

Design  Single centre cohort study.

Subjects  Men aged 50 and older, insured by Société de Secours Minière de Bourgogne (Montceau les Mines, France). Among 3400 men invited to participate, 782 volunteers had serum hormone measurements and were followed up for 10 years. No exclusion criteria were used.

Results  Nonsurvivors (n = 182) were older, had more comorbidities and lower physical performance. The lowest quartile of 25‐hydroxycholecalciferol (25OHD) level predicted mortality [HR = 1·44, 95% confidence interval (CI): 1·03–2·03, P < 0·05] regardless of age, BMI, smoking, physical activity, vitamin D supplementation, and health status; mainly for the first 3 years. The 17β‐E2 level predicted mortality independent of confounders after the third year (HR = 1·21 per 1 SD increase, 95% CI: 1·09–1·35, P < 0·001). In the fully adjusted models, risk of death increased per quartiles of 17β‐E2 (trend –P < 0·001) and was higher in the third and the fourth quartiles compared with the lowest quartile (HR = 1·80, 95% CI: 1·09–2·98, P < 0·05 and HR = 2·83, 95% CI: 1·71–4·67, P < 0·001). Concentrations of testosterone and PTH did not predict mortality independent of the model.

Conclusions  In older men, increased 17β‐E2 level predicted mortality after 3 years of follow‐up. Thus, high 17β‐E2 level may reflect presence of risk factors precipitating development of diseases. Low 25OHD level predicted mortality more weakly, mainly for the first 3 years of the follow‐up, and was strongly influenced by the confounding variables. Thus, low 25OHD level may reflect poor current health status and unhealthy lifestyle.
Intra‐plant heterogeneity influences the preference and performance of juveniles and adults of a gall midge
Authors: MORRISON ANDREW , QUIRING DAN
Published: January 2009

Abstract 1. Field studies were conducted to evaluate the preference and performance of a gall‐inducing midge (Harmandia tremulae) within the crown of trembling aspen (Populus tremuloides). Females did not select oviposition sites preferentially within leaves, but did lay preferentially on young leaves.

2. Larvae were the only life stage involved in gall site selection within leaves and in gall initiation and development. Gall size, which was positively related to survival, was highest for galls on mid veins that were located close to the petiole. However, one‐third of galls were located on lateral veins and most galls were not adjacent to the petiole, indicating that many larvae choose sub‐optimal gall initiation sites.

3. Gall density was positively associated with leaf length, and leaf length, was positively associated with gall size. However, gall density per leaf was not related to larval survival in galls. This latter result may be a result of an observed inverse relationship between gall size and gall density for similar‐sized leaves.

4. The results partially support the plant vigour and optimal plant module size hypotheses, which predict that galler fitness in successfully induced galls should be highest on large, fast‐growing plant modules. The lack of a strong preference‐performance link supports the confusion hypothesis, which predicts that oviposition and gall site selection may often be suboptimal in systems where galler lifespan is short. This study suggests that small‐scale variations in plant quality within leaves, can render gall site selection by juveniles as important as that previously reported for adult females.
Response of Mediterranean coralline algae to ocean acidification and elevated temperature
Authors: MARTIN SOPHIE , GATTUSO JEAN‐PIERRE
Published: January 2009

The effects of elevated partial pressure of CO2(pCO2) and temperature, alone and in combination, on survival, calcification and dissolution were investigated in the crustose coralline algaLithophyllum cabiochae. Algae were maintained in aquaria during 1 year at near‐ambient conditions of irradiance, at ambient or elevated temperature (+3 °C) and at ambient [ca. 400 parts per million (ppm)] or elevatedpCO2(ca. 700 ppm). Algal necroses appeared at the end of summer under elevated temperature first at 700 ppm (60% of the thallus surface) and then at 400 ppm (30%). The death of algae was observed only under elevated temperature and was two‐ to threefold higher under elevatedpCO2. During the first month of the experiment, net calcification was significantly reduced under elevatedpCO2. At the end of the summer period, net calcification decreased by 50% when both temperature andpCO2were elevated while no effect was found under elevated temperature and elevatedpCO2alone. In autumn and winter, net calcification in healthy algae increased with increasing temperature, independently of thepCO2level, while necroses and death in the algal population caused a net dissolution at elevated temperature andpCO2. The dissolution of dead algal thalli was affected by elevatedpCO2, being two‐ to fourfold higher than under ambientpCO2. These results suggest that net dissolution is likely to exceed net calcification inL. cabiochaeby the end of this century. This could have major consequences in terms of biodiversity and biogeochemistry in coralligenous communities dominated by these algae.
‘It's pretty hard with our ones, they can't talk, the more able bodied can participate’: staff attitudes about the applicability of disability policies to people with severe and profound intellectual disabilities
Authors: Bigby C. , Clement T. , Mansell J. , Beadle‐Brown J.
Published: January 2009

Background  The level of resident's adaptive behaviour and staff facilitative practices are key sources of variation in outcomes for residents in community‐based residential services. The higher the resident support needs the poorer their outcome. Although substantial investment has been made in values‐based training for staff, their attitudes and the impact of these on practice is largely unexplored.

Method and findings  The first study used ethnographic and action research methods to examine the daily lives of 25 residents with severe and profound intellectual disabilities (ID), who lived in five small group homes, and the attitudes of the staff supporting them. Thematic analysis of the data led to a proposition that although staff accept principles of inclusion, choice and participation for people with ID in general, they do not consider it feasible to apply these to the people with severe and profound ID to whom they provide support. The findings from a second study that used a group comparison design and administered a short questionnaire about staff attitudes to 144 direct‐care staff and first‐line managers working in disability services confirmed this hypothesis.

Conclusions  The study suggests more focused attention is needed to staff understanding the values embedded in current policies and their application to people with more severe disabilities.
Neurobiological Mechanisms Underlying Oestradiol Negative and Positive Feedback Regulation of Gonadotrophin‐Releasing Hormone Neurones
Authors: Moenter S. M. , Chu Z. , Christian C. A.
Published: January 2009

The feedback actions of ovarian oestradiol during the female reproductive cycle are among the most unique in physiology. During most of the cycle, oestradiol exerts homeostatic, negative feedback upon the release of gonadotrophin‐releasing hormone (GnRH). Upon exposure to sustained elevated oestradiol levels, however, there is a switch in the feedback effects of this hormone to positive, resulting in induction of a surge in the release of GnRH that serves as a neuroendocrine signal to initiate the ovulatory cascade. We review recent developments stemming from studies in an animal model exhibiting daily switches between positive and negative feedback that have probed the neurobiological mechanisms, including changes in neural networks and intrinsic properties of GnRH neurones, underlying this switch in oestradiol action.
Prenatal Programming of Sexual Partner Preference: The Ram Model
Authors: Roselli C. E. , Stormshak F.
Published: January 2009

In our laboratory, the domestic ram is used as an experimental model to study the early programming of neural mechanisms underlying same‐sex partner preference. This interest developed from the observation that approximately 8% of domestic rams are sexually attracted to other rams (male‐oriented) in contrast to the majority of rams that are attracted to oestrous ewes (female‐oriented). One prominent feature of sexual differentiation in many species is the presence of a sexually dimorphic nucleus (SDN) in the preoptic/anterior hypothalamus that is larger in males than in females. Lesion studies in rats and ferrets implicate the SDN in the expression of sexual preferences. We discovered an ovine SDN (oSDN) in the preoptic/anterior hypothalamus that is smaller in male‐ than in female‐oriented rams and similar in size to the oSDN of ewes. Neurones of the oSDN show abundant aromatase expression that is also reduced in male‐oriented compared to female‐oriented rams. This observation suggests that sexual partner preferences are neurologically hard‐wired and could be influenced by hormones. Aromatase‐containing neurones constitute a nascent oSDN as early as day 60 of gestation, which becomes sexually dimorphic by day 135 of gestation when it is two‐fold larger in males than in females. Exposure of fetal female lambs to exogenous testosterone from days 30–90 of gestation resulted in a masculinised oSDN. These data demonstrate that the oSDN develops prenatally and may influence adult sexual preferences. Surprisingly, inhibition of aromatase activity in the brain of ram foetuses during the critical period did not interfere with defeminisation of adult sexual partner preference or oSDN volume. These results fail to support an essential role for neural aromatase in the sexual differentiation of sheep brain and behaviour. Thus, we propose that oSDN morphology and male‐typical partner preferences may instead be programmed through an androgen receptor mechanism not involving aromatisation.
Brain Sex Differences and Hormone Influences: A Moving Experience?
Authors: Tobet S. , Knoll J. G. , Hartshorn C. , Aurand E. , Stratton M. , Kumar P. , Searcy B. , McClellan K.
Published: January 2009

Sex differences in the nervous system come in many forms. Although a majority of sexually dimorphic characteristics in the brain have been described in older animals, mechanisms that determine sexually differentiated brain characteristics often operate during critical perinatal periods. Both genetic and hormonal factors likely contribute to physiological mechanisms in development to generate the ontogeny of sexual dimorphisms in brain. Relevant mechanisms may include neurogenesis, cell migration, cell differentiation, cell death, axon guidance and synaptogenesis. On a molecular level, there are several ways to categorise factors that drive brain development. These range from the actions of transcription factors in cell nuclei that regulate the expression of genes that control cell development and differentiation, to effector molecules that directly contribute to signalling from one cell to another. In addition, several peptides or proteins in these and other categories might be referred to as ‘biomarkers’ of sexual differentiation with undetermined functions in development or adulthood. Although a majority of sex differences are revealed as a direct consequence of hormone actions, some may only be revealed after genetic or environmental disruption. Sex differences in cell positions in the developing hypothalamus, and steroid hormone influences on cell movements in vitro, suggest that cell migration may be one target for early molecular actions that impact brain development and sexual differentiation.
A Role for the Androgen Metabolite, 5α‐Androstane‐3β,17β‐Diol, in Modulating Oestrogen Receptor β‐Mediated Regulation of Hormonal Stress Reactivity
Authors: Handa R. J. , Weiser M. J. , Zuloaga D. G.
Published: January 2009

Activation of the hypothalamic‐pituitary‐adrenal (HPA) axis is a basic response of animals to environmental perturbations that threaten homeostasis. These responses are regulated by neurones in the paraventricular nucleus of the hypothalamus (PVN) that synthesise and secrete corticotrophin‐releasing hormone (CRH). Other PVN neuropeptides, such as arginine vasopressin and oxytocin, can also modulate activity of CRH neurones in the PVN and enhance CRH secretagogue activity of the anterior pituitary gland. In rodents, sex differences in HPA reactivity are well established; females exhibit a more robust activation of the HPA axis after stress than do males. These sex differences primarily result from opposing actions of sex steroids, testosterone and oestrogen, on HPA function. Ostreogen enhances stress activated adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) secretion, whereas testosterone decreases the gain of the HPA axis and inhibits ACTH and CORT responses to stress. Data show that androgens can act directly on PVN neurones in the male rat through a novel pathway involving oestrogen receptor (ER)β, whereas oestrogen acts predominantly through ERα. Thus, we examined the hypothesis that, in males, testosterone suppresses HPA function via an androgen metabolite that binds ERβ. Clues to the neurobiological mechanisms underlying such a novel action can be gleaned from studies showing extensive colocalisation of ERβ in oxytocin‐containing cells of the PVN. Hence, in this review, we address the possibility that testosterone inhibits HPA reactivity by metabolising to 5α‐androstane‐3β,17β‐diol, a compound that binds ERβ and regulates oxytocin containing neurones of the PVN. These findings suggest a re‐evaluation of studies examining pathways for androgen receptor signalling.
DNA binding of citrus dehydrin promoted by zinc ion
Authors: HARA MASAKAZU , SHINODA YURI , TANAKA YASUTAKA , KUBOI TORU
Published: January 2009

Dehydrins are hydrophilic proteins that accumulate during embryogenesis and osmotic stress responses in plants. Here, we report an interaction between citrus dehydrin Citrus unshiu cold‐regulated 15 kDa protein (CuCOR15) and DNA. Binding of CuCOR15 to DNA was detected by an electrophoretic mobility shift assay, a filter‐binding assay and Southwestern blotting. The binding was stimulated by physiological concentrations of Zn2+, but little stimulation occurred when other divalent cations, such as Mg2+, Ca2+, Mn2+, Ni2+ and Cu2+, were substituted for Zn2+. Ethylenediaminetetraacetic acid cancelled the Zn2+‐stimulated binding. A binding curve and competitor experiments suggested that the DNA binding of CuCOR15 exhibited low affinity and non‐specificity. Moreover, tRNA competed with the DNA binding. Histidine‐rich domains and a polylysine segment‐containing domain participated in the DNA binding. These results suggest that CuCOR15 can interact with DNA, and also RNA, in the presence of Zn2+. Dehydrin may protect nucleic acids in plant cells during seed maturation and stress responses.
Elevated Expression of Transmembrane IL‐15 in Immune Cells Correlates with the Development of Murine Lupus: a Potential Target for Immunotherapy Against SLE
Authors: Bo H. , Wei X.‐Q. , Dong H. , Zhang Y. , Lv P. , Liu W. , Koutoulaki A. , Gao X.‐M.
Published: January 2009

Presentation in trans by the Interleukin‐15 receptor α chain (IL‐15Rα) has been suggested as the main mechanism for IL‐15 anchoring to the cell surface, but it is also evident that IL‐15 can exist as a transmembrane protein. We herein demonstrate that replacement of the first 41 residues of human IL‐15 (hIL‐15) with Igκ chain leader sequence resulted in secretion of most of the recombinant hIL‐15 expressed in transfectant cells, thus identifying the transmembrane region of IL‐15. A fusion protein (hIL‐15Rα‐Fc) between the extracellular domain of hIL‐15Rα and the Fc fragment of IgG1 was prepared and shown to be able to bind with transmembrane IL‐15 (tmIL‐15). The level of tmIL‐15 expression in macrophages, activated T cells and B cells from 6‐month‐old BXSB male mice, an animal model for systemic lupus erythematosus (SLE), was significantly increased compared with that from BXSB females or young males. In addition, hIL‐15Rα‐Fc was able to block the T cell stimulating and anti‐apoptotic effect of the tmIL‐15‐positive BXSB macrophages in vitro. Intravenous administration of hIL‐15Rα‐Fc reduced the titre of autoantibodies against dsDNA and also proteinuria in aged BXSB males, implying that neutralization of IL‐15 activity in vivo may be an effective way of treating SLE.
A Novel Anti‐inflammatory Compound, Artonkin‐4′‐O‐glucoside, from the Leaves of Artocarpus tonkinensis Suppresses Experimentally Induced Arthritis*
Authors: Dang D. T. N. , Eriste E. , Liepinsh E. , Trinh T. T. , Erlandsson‐Harris H. , Sillard R. , Larsson P.
Published: January 2009

Artocarpus tonkinenesis (Moraceae) has been used in Vietnamese traditional medicine for the treatment of backache and joint diseases since many 100 years. We have previously shown that a crude extract of A. tonkinensis elicited anti‐inflammatory effects in rat collagen‐induced arthritis (CIA), with significant improvement of disease symptoms. However, the pharmacological basis of the bioactivity of A. tonkinensis extract is not known. In the present study, we have isolated four individual active components from A. tonkinensis extract by reverse phase high‐pressure liquid chromatography. The structures of the compounds were determined by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry and their biological effects investigated. A novel biologically active flavonoid glucoside (5‐hydroxy‐8‐hydroxymethyl‐8‐methyl‐2‐[4‐(3,4,5‐trihydroxy‐6‐hydroxymethyl‐tetrahydro‐pyran‐2‐yloxy)‐phenyl]‐8H‐pyrano[3,2‐g]chromen‐4‐one) with an average molecular mass of 514.49 Da was isolated. We have named the compound artonkin‐4′‐O‐glucoside. The name ‘artonkin’ for the novel flavonoid part of the compound was coined from the Latin name of its source Artocarpus tonkinensis. The three other active flavonoid glucosides isolated and characterized were alphitonin‐4‐O‐β‐d‐glucoside, maesopsin‐4‐O‐β‐d‐glucoside and kaempherol‐3‐O‐β‐d‐glucoside. All four compounds were found to cause anti‐inflammatory effect with different potencies. The anti‐inflammatory effects demonstrated in the rat model of arthritis correlate well with the inhibition of mitogen‐induced T‐cell proliferation. Furthermore, the compounds inhibit production of cytokines, such as tumour necrosis factor‐α and interferon‐γ, in mitogen‐stimulated T cells in a concentration‐dependent manner. We postulate that the isolated flavonoids suppress T‐cell proliferation as well as cytokine expression and thereby contribute to an amelioration of arthritis severity in CIA.
Contribution of Intestinal Epithelial Cells to Innate Immunity of the Human Gut – Studies on Polarized Monolayers of Colon Carcinoma Cells
Authors: Ou G. , Baranov V. , Lundmark E. , Hammarström S. , Hammarström M.‐L.
Published: January 2009

The aim was to establish an in vitro model for studies of innate defence mechanisms of human intestinal epithelium. Ultrastructural characterization and determination of mRNA expression levels for apical glycocalyx and mucous components showed that polarized, tight monolayers of the colon carcinoma cell lines T84 and Caco2 acquire the features of mature‐ and immature columnar epithelial cells, respectively. Polarized monolayers were challenged with non‐pathogenic Gram+ and Gram− bacteria from the apical side and the proinflammatory cytokines interferon‐γ (IFN‐γ), tumour necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) from the basolateral side. Immune responses were estimated as changes in mRNA expression levels for the mucous component mucin‐2 (MUC2), the glycocalyx components carcinoembryonic antigen (CEA), CEA‐related cell adhesion molecule‐1 (CEACAM1), CEACAM6, CEACAM7 and MUC3, the antimicrobial factors human β‐defensin‐1 (hBD1), hBD2, hBD3 and lysozyme, the chemokine IL‐8 and the cytokines IL‐6 and TNF‐α. Tight monolayer cells were generally unresponsive to bacterial challenge, but increased their hBD2 levels when challenged with Bacillus megaterium. T84 cells also increased their TNF‐α levels upon bacterial challenge. Tight monolayer cells responded to cytokine challenge suggesting awareness of basolateral attack. TNF‐α induced significantly increased levels of IL‐8 and TNF‐α itself in both cell lines suggesting recruitment and activation of immune cells in the underlying mucosa in vivo. Cytokine challenge also increased levels of CEACAM1, which includes two functionally different forms, CEACAM1‐L and CEACAM1‐S. In T84 cells, IFN‐γ was selective for CEACAM1‐L while TNF‐α upregulated both forms. Increased CEACAM1 expression may influence epithelial function and communication between epithelial cells and intraepithelial lymphocytes.
Private local pharmacies in low‐ and middle‐income countries: a review of interventions to enhance their role in public health
Authors: Smith Felicity
Published: January 2009

Objectives  To review the evidence regarding the potential of pharmacy services to play an enhanced role in contributing to health care and policy initiatives in low‐ and middle‐income countries.

Methods  Literature search, using computer and hand searching, to identify original research reporting the results of interventions to improve services from private local pharmacies in low‐ and middle‐income countries.

Results  Eighteen studies were identified which spanned all regions: 12 evaluations of training initiatives, three studies evaluating the impact of policy of regulatory interventions, one regarding a collaboration of pharmacy services with a national TB programme, and two evaluating a pharmaceutical care initiative for patients with hypertension. A total of 14 studies used advice and recommendations to simulated clients as the primary outcome measures. Whilst most studies reported some improvements to practice, these were often small, limited to specific outcomes and believed to be short‐lived.

Conclusion  The studies in this review demonstrate international interest in enhancing the place of pharmacy services in the provision and delivery of health care. But the small number of studies provides inadequate evidence on how to assure the quality of local pharmacy services can be assured, or how to develop them within a wider reform framework.
A pig–human comparative RH map comprising 20 genes on pig chromosome 13q41 that harbours the ETEC F4ac receptor locus
Authors: Ren J. , Tang H. , Yan X. , Huang X. , Zhang B. , Ji H. , Yang B. , Milan D. , Huang L.
Published: January 2009

The enterotoxigenic Escherichia coli (ETEC) F4ac is a major cause of diarrhoea in newborn and young pigs. The locus for the intestinal ETEC F4ac receptor (F4acR) has been mapped to pig chromosome (SSC) 13q41 with known homology to human chromosome (HSA) 3q21 and q29. However, the causative gene and mutation(s) remain unknown. The aim of this study was to characterize gene‐derived markers on SSC13q41 for fine mapping of the F4acR locus, and construct a high‐resolution pig–human comparative map to select positional candidate genes for F4acR. Pig‐specific sequence‐tagged site markers were developed for 20 genes that are located in a 6.8‐Mb region on HSA3q21 and q29, and a total of 34 single‐nucleotide polymorphisms (SNPs) were identified in 14 of 20 markers developed. Eighteen markers were mapped to SSC13q41, while the other two markers (PLXNA1 and KLF15) were assigned to SSC13q32 and SSC7q13, respectively, by radiation hybrid mapping. This result showed that there was a small conserved segment on SSC7 corresponding to HSA3q21. A framework map comprising 18 markers on SSC13q41 was established, refining the synteny breakpoint on SSC13q41 to a region of 12.3 centiRay. The comparative radiation hybrid (RH) map revealed three interesting candidate genes for F4acR from the human genome, viz. MUC4, MUC13 and MUC20. Linkage analysis with six marker polymorphisms revealed that MUC4 had the most significant linkage with the F4acR locus.
Estimation of (co)variance components and genetic parameters of greasy fleece weights in Muzaffarnagari sheep
Authors: Mandal A. , Neser F.W. C. , Roy R. , Rout P.K. , Notter D.R.
Published: January 2009

Variance components and genetic parameters for greasy fleece weights of Muzaffarnagari sheep maintained at the Central Institute for Research on Goats, Makhdoom, Mathura, India, over a period of 29 years (1976 to 2004) were estimated by restricted maximum likelihood (REML), fitting six animal models including various combinations of maternal effects. Data on body weights at 6 (W6) and 12 months (W12) of age were also included in the study. Records of 2807 lambs descended from 160 rams and 1202 ewes were used for the study. Direct heritability estimates for fleece weight at 6 (FW6) and 12 months of age (FW12), and total fleece weights up to 1 year of age (TFW) were 0.14, 0.16 and 0.25, respectively. Maternal genetic and permanent environmental effects did not significantly influence any of the traits under study. Genetic correlations among fleece weights and body weights were obtained from multivariate analyses. Direct genetic correlations of FW6 with W6 and W12 were relatively large, ranging from 0.61 to 0.67, but only moderate genetic correlations existed between FW12 and W6 (0.39) and between FW12 and W12 (0.49). The genetic correlation between FW6 and FW12 was very high (0.95), but the corresponding phenotypic correlation was much lower (0.28). Heritability estimates for all traits were at least 0.15, indicating that there is potential for their improvement by selection. The moderate to high positive genetic correlations between fleece weights and body weights at 6 and 12 months of age suggest that some of the genetic factors that influence animal growth also influence wool growth. Thus selection to improve the body weights or fleece weights at 6 months of age will also result in genetic improvement of fleece weights at subsequent stages of growth.
Riverine status and genetic structure of Chilika buffalo of eastern India as inferred from cytogenetic and molecular marker‐based analysis
Authors: Mishra B.P. , Kataria R.S. , Bulandi S.S. , Prakash B. , Kathiravan P. , Mukesh M. , Sadana D.K.
Published: January 2009

The present study aimed at assessing the status of the Chilika buffalo population of eastern India employing cytogenetic and molecular markers. The Chilika buffaloes investigated cytogenetically possess a somatic chromosome count of 50, identical to that of typical riverine buffaloes. Various diversity estimates, viz. observed number of alleles (4.68), effective number of alleles (2.79), and observed (0.487) and expected (0.602) heterozygosity across 25 heterologous microsatellite markers indicated the presence of a moderate level of genetic diversity in Chilika buffaloes, comparable with three other prominent Indian riverine buffalo breeds (Murrah, Nagpuri and Toda) included in this study. Across the four buffalo populations, mean estimates of F‐statistics from Jackknifing over loci were significantly different from zero (p < 0.05), with FIT (total inbreeding estimate) = 0.315 ± 0.038, FIS (within‐population inbreeding estimate) = 0.178 ± 0.038, and FST (population differentiation) = 0.166 ± 0.025. Inter‐breed analysis reflected Chilika buffaloes to be genetically close to Nagpuri followed by Murrah and Toda buffaloes. Factorial correspondence analysis (FCA) revealed low breed‐specific clustering of Chilika and Nagpuri buffaloes. Additionally, the neighbour‐joining tree structure of mitochondrial DNA D‐loop haplotypes indicated clear grouping of the Chilika haplotypes with the riverine buffalo. Thus the cytogenetic, microsatellite and mitochondrial data analysed in the present study classify Chilika buffalo of eastern India to be of the riverine type and not swamp‐type buffalo.
Defensins and inflammation: The role of defensins in inflammatory bowel disease
Authors: Ramasundara Malith , Leach Steven T , Lemberg Daniel A , Day Andrew S
Published: January 2009

Defensins are antimicrobial peptides produced at a variety of epithelial surfaces. In the intestinal tract, they contribute to host immunity and assist in maintaining the balance between protection from pathogens and tolerance to normal flora. However, attenuated expression of defensins compromises host immunity and hence may alter the balance toward inflammation. Altered defensin production is suggested to be an integral element in the pathogenesis of inflammatory bowel disease (IBD). Evidence for this is shown in Crohn's disease where reduced α‐defensin levels are seen in patients with ileal disease and reduced β‐defensin levels in those with colonic involvement. Further evidence is provided by research linking nucleotide oligomerization domain 2 (NOD2) mutations and deficient defensin expression. However, alternate studies suggest that NOD2 status and defensin expression are independent, and that defensin deficiency is due to mucosal surface destruction as a result of inflammatory changes, indicating that reduced defensin expression is a symptom of the disease and not the cause. Although it is clear that defensin expression is altered in IBD, it is less clear whether defensin deficiency is implicated in the pathogenesis of IBD or is a consequence of the disease process. The aim of this article is to review the current knowledge of defensins in IBD and discuss their potential role in IBD pathogenesis.
Intestinal metaplasia: A premalignant lesion involved in gastric carcinogenesis
Authors: Busuttil Rita A , Boussioutas Alex
Published: January 2009

Despite a plateau in incidence, gastric cancer remains a significant problem globally. The majority of gastric cancer is associated with histologically recognizable premalignant stages as first described by Pelayo Correa in the mid‐1970s. The mortality from gastric cancer remains high especially in Western countries where, arguably, the index of suspicion of gastric cancer in patients presenting with upper abdominal symptoms is lower than in high prevalence countries. What is the evidence that intestinal metaplasia (IM) is a premalignant condition? What should the clinician know about IM and the relative risks of progression to gastric cancer? Finally, what are the current and future strategies that may help stratify patients into high risk and low risk for the development of gastric cancer? This review focuses on gastric IM and outlines some of the literature that discusses it as a premalignant condition. It also reviews the issue of surveillance of patients with IM in order to attempt to reduce the significant mortality of gastric cancer by detection of earlier stages of disease which are eminently treatable.
Stuve Wiedemann syndrome and related syndromes: case report and possible anesthetic complications
Authors: BONTHUIS DOMINIQUE , MORAVA EVA , BOOIJ LEO H.D.J. , DRIESSEN JACQUES J.
Published: January 2009

Stuve Wiedemann syndrome (SWS) is an autosomal recessively inherited syndrome which is characterized by bowing of the long bones, camptodactyly, facial dysmorphism, hypotonia, feeding and swallowing difficulties, and respiratory distress. In most cases episodes of unexplained hyperthermia are present. Patients with SWS can develop hyperthermia in conjunction with anesthesia and surgery, and a relationship has been suggested between the syndrome and malignant hyperthermia. We describe a 3‐year‐old child diagnosed with SWS to whom we administered general anesthesia during the removal of a corneal ulcer and dilatation of the lacrimal duct. Our patient had received, uncomplicated, inhalational anesthesia five times previously for different operations. There were no anesthesia‐related complications in the present or previous perioperative periods. On one occasion the patient developed mild postoperative hyperthermia. We believe that this hyperthermia is different from the specific disorder of malignant hyperthermia and that sevoflurane can be safely used in patients with SWS. We also describe symptomatically related syndromes and their theoretical risks for anesthesia.
Are peripheral and neuraxial blocks with ultrasound guidance more effective and safe in children?
Authors: RUBIN KASIA , SULLIVAN DENISE , SADHASIVAM SENTHILKUMAR
Published: January 2009

Background and aims:  The efficacy and safety of ultrasound guided (USG) pediatric peripheral nerve and neuraxial blocks in children have not been evaluated. In this review, we have looked at the success rate, efficacy and complications with USG peripheral nerve blocks and compared with nerve stimulation or anatomical landmark based techniques in children.

Methods:  All suitable studies in MEDLINE, EMBASE Drugs and Cochrane Evidence Based Medicine Reviews: Cochrane Database of Systemic Reviews databases were identified. In addition, citation review and hand search of recent pediatric anesthesia and surgical journals were done. All three authors read all selected articles independently and a consensus was achieved. All randomized controlled trials (RCTs) comparing USG peripheral and neuraxial blocks with other techniques in children were included.

Results:  Ultrasound guidance has been demonstrated to improve block characteristics in children including shorter block performance time, higher success rates, shorter onset time, longer block duration, less volume of local anesthetic agents and visibility of neuraxial structures.

Conclusion:  Clinical studies in children suggest that US guidance has some advantages over more traditional nerve stimulation–based techniques for regional block. However, the advantage of US guidance on safety over traditional has not been adequately demonstrated in children except ilio‐inguinal blocks.
KARL POLANYI ET LA PÉDAGOGIE DE L'INCOHÉRENCE
Authors: Gazier Bernard , Mendell Marguerite
Published: January 2009

RESUME**:  Cet article vise à examiner de manière critique et constructive l'actualité de la pensée de Karl Polanyi pour comprendre le développement de l'économie plurielle au XXIe siècle et pour agir sur celui‐ci. Il montre la très grande actualité de cette pensée, ainsi que la nécessité de s'intéresser à l'œuvre entière de Karl Polanyi, et pas seulement à«La grande transformation». Partant des usages multiples du concept d'encastrement et de désencastrement, il relie les propositions inspirées par Karl Polanyi sur «le processus institué de démocratisation économique»à des développements récents tant pratiques que théoriques: les «>marchés transitionnels du travail» et la «nouvelle finance publique».
ASSESSING THE PERFORMANCE OF THE PUBLIC SECTOR
Authors: Pestieau Pierre
Published: January 2009

ABSTRACT**:  One is used to hearing harsh statements about inefficient public services. It is not surprising to see public sector performance questioned. What is surprising is that what is meant by performance, and how it is measured, does not seem to matter much to either the critics or the advocates of the public sector.

The purpose of this paper is to suggest a definition, and a way to measure the performance of the public sector or rather of its main components. Our approach is explicitly rooted in the principles of welfare and production economics. We will proceed in four stages. First of all we present what we call the ‘performance approach’ to the public sector. This concept rests on the principal‐agent relation that links a principal, i.e., the State, and an agent, i.e., the person in charge of the public sector unit, and on the definition of performance as the extent to which the agent fulfils the objectives assigned by the principal. The performance is then measured by using the notion of productive efficiency and the ‘best practice’ frontier technique.

In the second stage we move to the issue of measuring the performance of some canonical components of the public sector (education, health care and railways transport), assuming that there is no constraint as to data availability. The idea is to disentangle the usual confusion between conceptual and data problems. In the third stage, we move to real world data problems. The question is then given the available data, whether it makes sense to assess and measure the performance of such public sector activities. The final stage is devoted to explaining performance or rather lack thereof. This exercise has clear implications for public policy.

Finally we argue that when the scope is not components but the entirety of the public sector, one should restrict the performance analysis to outcomes and not relate them to inputs.
Natural Relations: Horses, Knowledge, Technology
Authors: Latimer Joanna , Birke Lynda
Published: January 2009

Maintaining the tensions and divisions between the human and non-human, nature and culture has been a mainstay of Euro-American thought. Drawing upon two studies of people's associations with horses, we examine how these divisions are being reworked in the social sciences as well in everyday life. We focus on how different ideas about ‘horses’, ‘horsemanship’ and how knowledge is acquired, accomplishes different social worlds. Specifically, what emerges in these differential discourses is that a paradox is put into play to make a distinction between traditional and contemporary ways of being in relation to nature and the animal; it is the paradox of what we want to refer to as ‘natural technologies’. We suggest that the paradox of ‘natural technologies’ is a proliferating feature of Euro-American cultural life that troubles old divisions between nature and culture and propose that it indicates less about a politics of nature than a politics of culture. Specifically, we show that the preoccupation with bringing nature, and the non-human, more into alignment with the human promotes ethics and equality as matters of lifestyle choice to the exclusion of very specific ideas about tradition, hierarchy, evolution and socialization.
Patterns of Income Allocation among Poor Gecekondu Households in Turkey: Overt Mechanisms and Women's Secret Kitties
Authors: Eroğlu Şebnem
Published: January 2009

This article examines the extent to which patterns of income allocation within the household influence poverty. The study proposes a new conceptual distinction between overt and covert mechanisms. It makes use of established concepts of financial management and control to explain the overt mechanisms, but questions the significance of existing management typologies in understanding poverty. The data draws on interviews conducted separately with both spouses in low-income households carefully selected from a gecekondu settlement in Ankara. Contrary to the dominant view, the research demonstrates a general tendency for both spouses to care for the ‘collective good’ in their income allocation decisions; thereby minimising further deprivation of the overall household and its individual members. It is also demonstrated that how total income is distributed in practice may be of greater relevance in understanding overall household deprivation than systems of financial management and control. Finally, secret kitties are shown to operate as a covert mechanism whereby women claim enhanced financial agency and indirectly challenge men's authority without causing increased deprivation for the overall household or the children.
Waste Management in Ireland: Discourses of Domination in an (un)Reflexive Society
Authors: Murray Michael
Published: January 2009

In recent times, Ireland has experienced dramatic changes in its economic fortunes, primarily as a result of global/transnational processes. One result of this dynamic modernity has been a greater public and political focus on its environmental consequences, evident for instance in the issue of waste management. Ulrich Beck's highly influential writings on Reflexive Modernity promise a seismic social transformation, where risks such as waste can be negotiated through processes of self-confrontation and democratisation. Yet, this has clearly not happened in the Irish case, where waste policy concentrates on disposal rather than prevention options, governance processes are characterised by power centralisation and marginalisation, and where certain communities are engaged in campaigns of opposition to government plans. This article argues that part of the problem in adapting Beck's framework to Irish waste is that it fails to account for an asymmetry of power relations, at both a macro and micro level, and as a result, underestimates the tenacity of certain societal elites to maintain the current trajectory of economic and technological development. It is proposed here that the application of a Foucauldian framework of a multi-dimensional framework of power can address some of these shortcomings by offering a focus on issues of consent, coercion, self-regulation (individualisation) and subjugation. In doing so, it is hoped that a novel contribution can be made to the relatively under-developed field of sociology of waste and offer a more general critique of Beck's Reflexive Modernisation thesis.
Dilemmas of Settler Belonging: Roots, Routes and Redemption in New Zealand National Identity Claims
Authors: Bell Avril
Published: January 2009

This paper explores the identity markers and rules used in the process of national identity construction by young adult New Zealanders, drawing on empirical data from qualitative interviews with members of the majority culture of ‘Pakeha’ or ‘European’ New Zealanders. While these young New Zealanders draw on the markers of ‘birth’, ‘blood’ and ‘belonging’ identified in other studies, their claims to identity and belonging are troubled by the settler origins of their ancestors. The dilemmas these origins create for these young New Zealanders are identified along with the strategies they deploy as they seek to resolve them. The existence of these dilemmas suggests that a distinct identity rule is at work for this group that has not previously been identified in earlier studies. Thus, this analysis provides further evidence for the deployment of a common set of markers and rules as well as highlighting some of the ways in which these differ in different national contexts.