bluuebunny/crossref_metadata_2025 huggingface dataset:
Normothermic treatment in acute clinical encephalitis: a case report
Authors: Terashima Mari , Kataoka Hiroshi , Hirai Katsuji , Ueno Satoshi
Published: July 2008

Introduction

Encephalitis is a common infection of the brain, associated with a high risk of mortality and morbidity despite intensive supportive therapy. This report describes a patient with acute clinical meningoencephalitis who responded dramatically when her body temperature was decreased to normothermia (36 to 37°C) in combination with barbiturate therapy.

Case presentation

A 15-year-old, previously healthy girl presented with a 2-day history of headache and meningeal stiffness and pyrexia. Cranial magnetic resonance imaging showed high-intensity signals in the splenium of the corpus callosum on T2-weighted and diffusion-weighted images. On day 4 of admission, the level of consciousness decreased and ataxic respiration and apnea appeared. After that, fever (body temperature >40°C) developed with remarkable tachycardia. The body temperature was decreased with the use of a forced-air-cooling blanket and head cooling. The core temperature, measured in the bladder, was maintained at between 36 and 37°C for 5 days. During the period of normothermia, thiopental sodium was given continuously for 3 days. After normothermia, the level of consciousness increased without the development of fever, and ventilatory support was withdrawn.

Conclusion

Our experience suggests that normothermic treatment in combination with barbiturate therapy may be an effective option for the management of brain swelling associated with acute meningoencephalitis, particularly when accompanied by a persistent high fever.
A spatially explicit whole-system model of the lignocellulosic bioethanol supply chain: an assessment of decentralised processing potential
Authors: Dunnett Alex J , Adjiman Claire S , Shah Nilay
Published: July 2008

Background

Lignocellulosic bioethanol technologies exhibit significant capacity for performance improvement across the supply chain through the development of high-yielding energy crops, integrated pretreatment, hydrolysis and fermentation technologies and the application of dedicated ethanol pipelines. The impact of such developments on cost-optimal plant location, scale and process composition within multiple plant infrastructures is poorly understood. A combined production and logistics model has been developed to investigate cost-optimal system configurations for a range of technological, system scale, biomass supply and ethanol demand distribution scenarios specific to European agricultural land and population densities.

Results

Ethanol production costs for current technologies decrease significantly from $0.71 to $0.58 per litre with increasing economies of scale, up to a maximum single-plant capacity of 550 × 106 l year-1. The development of high-yielding energy crops and consolidated bio-processing realises significant cost reductions, with production costs ranging from $0.33 to $0.36 per litre. Increased feedstock yields result in systems of eight fully integrated plants operating within a 500 × 500 km2 region, each producing between 1.24 and 2.38 × 109 l year-1 of pure ethanol. A limited potential for distributed processing and centralised purification systems is identified, requiring developments in modular, ambient pretreatment and fermentation technologies and the pipeline transport of pure ethanol.

Conclusion

The conceptual and mathematical modelling framework developed provides a valuable tool for the assessment and optimisation of the lignocellulosic bioethanol supply chain. In particular, it can provide insight into the optimal configuration of multiple plant systems. This information is invaluable in ensuring (near-)cost-optimal strategic development within the sector at the regional and national scale. The framework is flexible and can thus accommodate a range of processing tasks, logistical modes, by-product markets and impacting policy constraints. Significant scope for application to real-world case studies through dynamic extensions of the formulation has been identified.
Diffusion-negative MRI in acute ischemic stroke: a case report
Authors: Rathakrishnan Rahul , Sharma Vijay K , Chan Bernard PL
Published: July 2008

Background

Diffusion-weighted magnetic resonance imaging is a very sensitive tool for the early diagnosis of acute ischemic stroke. This is employed in some stroke centers as the primary screening tool to select patients eligible for thrombolysis.

Methods

We present the case of a 49-years old Chinese man whose diffusion-weighted magnetic resonance imaging performed 12 hours of symptom onset was negative.

Results

Although the initial diffusion-weighted magnetic resonance imaging was negative, the imaging repeated after 4 days despite static neurological symptoms and signs, could demonstrate an acute medullary infarction.

Conclusion

Diffusion-weighted imaging may not be100% sensitive in very early stages, especially in posterior circulation strokes. Our case serves as a reminder that clinical assessment still retains priority until a diagnostic modality offering 100% sensitivity and specificity is discovered.
Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect
Authors: Koga Hideyuki , Shimaya Masayuki , Muneta Takeshi , Nimura Akimoto , Morito Toshiyuki , Hayashi Masaya , Suzuki Shiro , Ju Young-Jin , Mochizuki Tomoyuki , Sekiya Ichiro
Published: July 2008

Introduction

Current cell therapy for cartilage regeneration requires invasive procedures, periosteal coverage and scaffold use. We have developed a novel transplantation method with synovial mesenchymal stem cells (MSCs) to adhere to the cartilage defect.

Methods

For ex vivo analysis in rabbits, the cartilage defect was faced upward, filled with synovial MSC suspension, and held stationary for 2.5 to 15 minutes. The number of attached cells was examined. For in vivo analysis in rabbits, an autologous synovial MSC suspension was placed on the cartilage defect, and the position was maintained for 10 minutes to adhere the cells to the defect. For the control, either the same cell suspension was injected intra-articularly or the defects were left empty. The three groups were compared macroscopically and histologically. For ex vivo analysis in humans, in addition to the similar experiment in rabbits, the expression and effects of neutralizing antibodies for adhesion molecules were examined.

Results

Ex vivo analysis in rabbits demonstrated that the number of attached cells increased in a time-dependent manner, and more than 60% of cells attached within 10 minutes. The in vivo study showed that a large number of transplanted synovial MSCs attached to the defect at 1 day, and the cartilage defect improved at 24 weeks. The histological score was consistently better than the scores of the two control groups (same cell suspension injected intra-articularly or defects left empty) at 4, 12, and 24 weeks. Ex vivo analysis in humans provided similar results to those in rabbits. Intercellular adhesion molecule 1-positive cells increased between 1 minute and 10 minutes, and neutralizing antibodies for intercellular adhesion molecule 1, vascular cell adhesion molecule 1 and activated leukocyte-cell adhesion molecule inhibited the attachment.

Conclusion

Placing MSC suspension on the cartilage defect for 10 minutes resulted in adherence of >60% of synovial MSCs to the defect, and promoted cartilage regeneration. This adherent method makes it possible to adhere MSCs with low invasion, without periosteal coverage, and without a scaffold.
A crosstalk between intracellular CXCR7 and CXCR4 involved in rapid CXCL12-triggered integrin activation but not in chemokine-triggered motility of human T lymphocytes and CD34+ cells
Authors: Hartmann Tanja Nicole , Grabovsky Valentin , Pasvolsky Ronit , Shulman Ziv , Buss Eike C , Spiegel Asaf , Nagler Arnon , Lapidot Tsvee , Thelen Marcus , Alon Ronen
Published: July 2008

The chemokine CXCL12 promotes migration of human leukocytes, hematopoietic progenitors, and tumor cells. The binding of CXCL12 to its receptor CXCR4 triggers Gi protein signals for motility and integrin activation in many cell types. CXCR7 is a second, recently identified receptor for CXCL12, but its role as an intrinsic G-protein-coupled receptor (GPCR) has been debated. We report that CXCR7 fails to support on its own any CXCL12-triggered integrin activation or motility in human T lymphocytes or CD34+ progenitors. CXCR7 is also scarcely expressed on the surface of both cell types and concentrates right underneath the plasma membrane with partial colocalization in early endosomes. Nevertheless, various specific CXCR7 blockers get access to this pool and attenuate the ability of CXCR4 to properly rearrange by surface-bound CXCL12, a critical step in the ability of the GPCR to trigger optimal CXCL12-mediated stimulation of integrin activation in T lymphocytes as well as in CD34+ cells. In contrast, CXCL12-triggered CXCR4 signaling to early targets, such as Akt as well as CXCR4-mediated chemotaxis, is insensitive to identical CXCR7 blocking. Our findings suggest that although CXCR7 is not an intrinsic signaling receptor for CXCL12 on lymphocytes or CD34+ cells, its blocking can be useful for therapeutic interference with CXCR4-mediated activation of integrins.
Novel Insights in Chronic Lymphocytic Leukemia: Are We Getting Closer to Understanding the Pathogenesis of the Disease?
Authors: Caligaris-Cappio Federico , Ghia Paolo
Published: July 2008

Chronic lymphocytic leukemia (CLL) has unique epidemiologic, biologic, and clinical features. The progressively emerging picture leads us to consider that the critical genes for malignant CLL cells are those regulated by a number of microRNAs revealed by refined cytogenetic and molecular studies, and that the key molecule is the B-cell receptor (BCR). The hypothesis that CLL cells might be selected by some sort of antigenic pressure is strengthened by numerous findings indicating that a BCR-mediated stimulation plays a relevant role in the natural history of the disease and that autoantigens, as well as molecular structures instrumental in eliminating and scavenging apoptotic cells and pathogenic bacteria, may be relevant in triggering and/or facilitating the evolution of CLL. An important question is whether the tiny monoclonal B-cell populations phenotypically similar to CLL (that occur in the peripheral blood of about 3.5% of healthy individuals and are termed monoclonal B lymphocytosis) might be a critical step in the development of CLL. All relevant events of CLL occur in tissues in which a number of cellular and molecular interactions shape a microenvironment conducive to the accumulation of malignant cells and favor the organization of proliferating cells in focal aggregates of variable size that form the pseudofollicular proliferation centers. Given the impact that understanding the pathogenesis of CLL might have on the development of new treatments, the purposes of this review are to discuss whether the novel insights in CLL are leading us closer to understanding the tenet of the disease; to define the emerging new, stimulating questions; and to unfold the major challenges that still need to be addressed.
Renin Inhibition Attenuates Insulin Resistance, Oxidative Stress, and Pancreatic Remodeling in the Transgenic Ren2 Rat
Authors: Habibi Javad , Whaley-Connell Adam , Hayden Melvin R. , DeMarco Vincent G. , Schneider Rebecca , Sowers Susan D. , Karuparthi Poorna , Ferrario Carlos M. , Sowers James R.
Published: July 2008

Emerging evidence indicates that pancreatic tissue expresses all components of the renin-angiotensin system. However, the functional role is not well understood. This investigation examined renin inhibition on pancreas structure/function in the transgenic Ren2 rat harboring the mouse renin gene, a model of tissue renin overexpression. Renin is the rate-limiting step in the generation of angiotensin II (Ang II), which stimulates the generation of reactive oxygen species in a variety of tissues. Overexpression of renin in Ren2 rats results in hypertension, insulin resistance, and cardiovascular and renal damage. Young (6–7 wk old) insulin-resistant male Ren2 and age-matched insulin sensitive Sprague Dawley rats were treated with the renin inhibitor, aliskiren (50 mg/kg·d by ip injection), or placebo for 21 d. At 21 d, the Ren2 demonstrated insulin resistance with increased islet insulin, Ang II, and reduced total insulin receptor substrate (IRS)-1, IRS-2, and Akt immunostaining. There was increased islet nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and subunits (p47phox and Rac1) as well as increased nitrotyrosine immunostaining (each P < 0.05). These functional abnormalities were associated with a disordered islet architecture; increased islet-exocrine interface, pericapillary fibrosis, and structurally abnormal mitochondria and content in endocrine and exocrine pancreas. In vivo treatment with aliskiren normalized systemic insulin resistance and islet insulin, Ang II, NADPH oxidase activity/subunits, and nitrotyrosine and improved total IRS-1 and Akt phosphorylation (each P < 0.05) as well as islet/exocrine structural abnormalities. Collectively, these data suggest that pancreatic functional/structural changes are driven, in part, by tissue renin-angiotensin system-mediated increases in NADPH oxidase and reactive oxygen species generation, abnormalities attenuated with direct renin inhibition.
Cardiac Muscle Protein Catabolism in Diabetes Mellitus: Activation of the Ubiquitin-Proteasome System by Insulin Deficiency
Authors: Hu Junping , Klein Janet D. , Du Jie , Wang Xiaonan H.
Published: July 2008

Protein degradation is increased by both insulin deficiency and insulin resistance in humans and animal models. In skeletal muscle this insulin-dependent increase in protein degradation involves activation of both caspase-3 and the ubiquitin-proteasome system. The influence of abnormal insulin signaling on protein metabolism in cardiac muscle is not well understood; therefore, we measured protein degradation in cardiac muscle of mice with streptozotocin-induced diabetes. Insulin deficiency increased both total muscle proteolysis (measured as tyrosine release in muscle slices or extracts) and the degradation of the myofibrillar protein actin (measured as the appearance of a 14-kDa actin fragment). Expression of ubiquitin mRNA and chymotrypsin-like activity in the proteasome were increased, indicating activation of the ubiquitin-proteasome system in diabetic mouse heart. We also evaluated possible signaling pathways that might regulate cardiac muscle proteolysis. Insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, and Akt phosphorylation were decreased. Insulin replacement prevented the decrease in IRS-1/Akt phosphorylation, the increase in proteolysis, and attenuated the increase in ubiquitin mRNA. We conclude that insulinopenia accelerates proteolysis in cardiac muscle by reducing IRS-1/Akt signaling, which leads to activation of the ubiquitin-proteasome proteolytic pathway.
Transforming Growth Factor-β Blockade Down-Regulates the Renin-Angiotensin System and Modifies Cardiac Remodeling after Myocardial Infarction
Authors: Ellmers Leigh J. , Scott Nicola J. A. , Medicherla Satyanarayana , Pilbrow Anna P. , Bridgman Paul G. , Yandle Timothy G. , Richards A. Mark , Protter Andrew A. , Cameron Vicky A.
Published: July 2008

After myocardial infarction (MI), the heart may undergo progressive ventricular remodeling, resulting in a deterioration of cardiac function. TGF-β is a key cytokine that both initiates and terminates tissue repair, and its sustained production underlies the development of tissue fibrosis, particularly after MI. We investigated the effects of a novel orally active specific inhibitor of the TGF-β receptor 1 (SD-208) in an experimental model of MI. Mice underwent ligation of the left coronary artery to induce MI and were subsequently treated for 30 d after infarction with either SD-208 or a vehicle control. Blockade of TGF-β signaling reduced mean arterial pressure in all groups. SD-208 treatment after MI resulted in a trend for reduced ventricular and renal gene expression of TGF-β-activated kinase-1 (a downstream modulator of TGF-β signaling) and a significant decrease in collagen 1, in association with a marked decrease in cardiac mass. Post-MI SD-208 treatment significantly reduced circulating levels of plasma renin activity as well as down-regulating the components of the cardiac and renal renin-angiotensin system (angiotensinogen, angiotensin converting enzyme, and angiotensin II type I receptor). Our findings indicate that blockade of the TGF-β signaling pathway results in significant amelioration of deleterious cardiac remodeling after infarction.
Developmental Exposure to Bisphenol A Impairs the Uterine Response to Ovarian Steroids in the Adult
Authors: Varayoud Jorgelina , Ramos Jorge G. , Bosquiazzo Verónica L. , Muñoz-de-Toro Mónica , Luque Enrique H.
Published: July 2008

Morphoregulator genes like members of the Hox gene family regulate uterine development and are associated with endocrine-related processes such as endometrial proliferation and differentiation in the adult uterus. Exposure to neonatal endocrine disruptors could affect signaling events governed by Hox genes, altering the developmental trajectory of the uterus with lasting consequences. We investigated whether neonatal exposure to bisphenol A (BPA) alters Hoxa10 and Hoxa11 mRNA uterine expression shortly after treatment as well as in the adult. Moreover, we studied whether xenoestrogen exposure may affect the adult uterine response to hormonal stimuli. Newborn females received vehicle, 0.05 mg/kg·d BPA, 20 mg/kg•d BPA, or diethylstilbestrol (0.2 μg/kg•d) on postnatal d 1, 3, 5, and 7). At postnatal d 8, real time RT-PCR assays showed a decrease in Hoxa10 and Hoxa11 expression in all xenoestrogen-treated groups. To evaluate the long-term effects, we used adult ovariectomized rats with hormonal replacement. The subepithelial stroma in BPA- and diethylstilbestrol-treated animals showed an impaired proliferative response to steroid treatment associated with a silencing of Hoxa10 but not associated with changes in the methylation pattern of the Hoxa10 promoter. BPA animals showed that the Hoxa10 reduction was accompanied by an increased stromal expression of the silencing mediator for retinoic acid and thyroid hormone receptor. The spatial coexpression of steroid receptors Hoxa10 and silencing mediator for retinoic acid and thyroid hormone receptor was established using immunofluorescence. Our data indicate that postnatal BPA exposure affects the steroid hormone-responsiveness of uterine stroma in adulthood. Whether this impaired hormonal response is associated with effects on uterine receptivity and decidualization is currently under investigation.
The Historical Event
Authors: White Hayden
Published: July 2008

hayden white is University Professor, Emeritus, at the University of California and Professor of Comparative Literature at Stanford University.
World History according to Katrina
Authors: Dimock Wai Chee
Published: July 2008

wai chee dimock is the William Lampson Professor of English and American Studies at Yale University. She is the author, most recently, of Through Other Continents: American Literature across Deep Time (Princeton University Press, 2006) and coeditor, with Lawrence Buell, of Shades of the Planet: American Literature as World Literature (Princeton University Press, 2007).
Self-modulation of Notch signaling during ommatidial development via the Roughened eye transcriptional repressor
Authors: del Alamo David , Mlodzik Marek
Published: July 2008

The Notch (N) signaling pathway is involved in a vast number of patterning processes in all metazoans. The regulation of the core N pathway is largely understood, but little is known about fine-tuning modulatory effects. Here, we address the role of Drosophila Krüppel-family Zn-finger transcription factor roughened eye (roe) in the context of N signaling. We demonstrate that during eye patterning, N signaling regulates the expression of roe. In turn, Roe negatively modulates the expression of target genes of N-signaling activation. In the absence of roe function, expression of N target genes is elevated and the resulting phenotypes during patterning of the retina are similar to those of N gain-of-function scenarios. Importantly, our data show that Roe binds regulatory DNA sequences of N target genes of the E(spl)-complex both in vitro and in vivo, independently of Su(H)-DNA interaction. Thus, our data suggest that Roe acts as a transcriptional repressor in a negative-feedback loop of the N pathway.
The N-terminus and Phe52 residue of LC3 recruit p62/SQSTM1 into autophagosomes
Authors: Shvets Elena , Fass Ephraim , Scherz-Shouval Ruthie , Elazar Zvulun
Published: July 2008

LC3 belongs to a novel ubiquitin-like protein family that is involved in different intracellular trafficking processes, including autophagy. All members of this family share a unique three-dimensional structure composed of a C-terminal ubiquitin core and two N-terminal α-helices. Here, we focus on the specific contribution of these regions to autophagy induced by amino acid deprivation. We show that the ubiquitin core by itself is sufficient for LC3 processing through the conjugation machinery and for its consequent targeting to the autophagosomal membrane. The N-terminal region was found to be important for interaction between LC3 and p62/SQSTM1 (hereafter termed p62). This interaction is dependent on the first 10 amino acids of LC3 and on specific residues located within the ubiquitin core. Knockdown of LC3 isoforms and overexpression of LC3 mutants that fail to interact with p62 blocked the incorporation of p62 into autophagosomes. The accumulation of p62 was accompanied by elevated levels of polyubiquitylated detergent-insoluble structures. p62, however, is not required for LC3 lipidation, autophagosome formation and targeting to lysosomes. Our results support the proposal that LC3 is responsible for recruiting p62 into autophagosomes, a process mediated by phenylalanine 52, located within the ubiquitin core, and the N-terminal region of the protein.
Klf5 is involved in self-renewal of mouse embryonic stem cells
Authors: Parisi Silvia , Passaro Fabiana , Aloia Luigi , Manabe Ichiro , Nagai Ryozo , Pastore Lucio , Russo Tommaso
Published: July 2008

Self-renewal of embryonic stem cells (ESCs) is maintained by a complex regulatory mechanism involving transcription factors Oct3/4 (Pou5f1), Nanog and Sox2. Here, we report that Klf5, a Zn-finger transcription factor of the Kruppel-like family, is involved in ESC self-renewal. Klf5 is expressed in mouse ESCs, blastocysts and primordial germ cells, and its knockdown by RNA interference alters the molecular phenotype of ESCs, thereby preventing their correct differentiation. The ability of Klf5 to maintain ESCs in the undifferentiated state is supported by the finding that differentiation of ESCs is prevented when Klf5 is constitutively expressed. Maintenance of the undifferentiated state by Klf5 is, at least in part, due to the control of Nanog and Oct3/4 transcription, because Klf5 directly binds to the promoters of these genes and regulates their transcription.
Mechanistic characterization of the HDV genomic ribozyme: The cleavage site base pair plays a structural role in facilitating catalysis
Authors: Cerrone-Szakal Andrea L. , Chadalavada Durga M. , Golden Barbara L. , Bevilacqua Philip C.
Published: July 2008

The hepatitis delta virus (HDV) ribozyme occurs in the genomic and antigenomic strands of the HDV RNA and within mammalian transcriptomes. Previous kinetic studies suggested that a wobble pair (G•U or A+•C) is preferred at the cleavage site; however, the reasons for this are unclear. We conducted sequence comparisons, which indicated that while G•U is the most prevalent combination at the cleavage site, G-C occurs to a significant extent in genomic HDV isolates, and G•U, G-C, and A-U pairs are present in mammalian ribozymes. We analyzed the folding of genomic HDV ribozymes by free energy minimization and found that variants with purine–pyrimidine combinations at the cleavage site are predicted to form native structures while pyrimidine–purine combinations misfold, consistent with earlier kinetic data and sequence comparisons. To test whether the cleavage site base pair contributes to catalysis, we characterized the pH and Mg2+-dependence of reaction kinetics of fast-folding genomic HDV ribozymes with cleavage site base pair purine–pyrimidine combinations: G•U, A-U, G-C, and A+•C. Rates for these native-folding ribozymes displayed highly similar pH and Mg2+ concentration dependencies, with the exception of the A+•C ribozyme, which deviated at high pH. None of the four ribozymes underwent miscleavage. These observations support the A+•C ribozyme as being more active with a wobble pair at the cleavage site than with no base pair at all. Overall, the data support a model in which the cleavage site base pair provides a structural role in catalysis and does not need to be a wobble pair.
A glimpse into the active site of a group II intron and maybe the spliceosome, too
Authors: Dayie Kwaku T. , Padgett Richard A.
Published: July 2008

The X-ray crystal structure of an excised group II self-splicing intron was recently solved by the Pyle group. Here we review some of the notable features of this structure and what they may tell us about the catalytic active site of the group II ribozyme and potentially the spliceosome. The new structure validates the central role of domain V in both the structure and catalytic function of the ribozyme and resolves several outstanding puzzles raised by previous biochemical, genetic and structural studies. While lacking both exons as well as the cleavage sites and nucleophiles, the structure reveals how a network of tertiary interactions can position two divalent metal ions in a configuration that is ideal for catalysis.
Potent RNAi by short RNA triggers
Authors: Chu Chia-ying , Rana Tariq M.
Published: July 2008

RNA interference (RNAi) is a gene-silencing mechanism by which a ribonucleoprotein complex, the RNA-induced silencing complex (RISC) and a double-stranded (ds) short-interfering RNA (siRNA), targets a complementary mRNA for site-specific cleavage and subsequent degradation. While longer dsRNA are endogenously processed into 21- to 24-nucleotide (nt) siRNAs or miRNAs to induce gene silencing, RNAi studies in human cells typically use synthetic 19- to 20-nt siRNA duplexes with 2-nt overhangs at the 3′-end of both strands. Here, we report that systematic synthesis and analysis of siRNAs with deletions at the passenger and/or guide strand revealed a short RNAi trigger, 16-nt siRNA, which induces potent RNAi in human cells. Our results indicate that the minimal requirement for dsRNA to trigger RNAi is an ∼42 Å A-form helix with ∼1.5 helical turns. The 16-nt siRNA more effectively knocked down mRNA and protein levels than 19-nt siRNA when targeting the endogenous CDK9 gene, suggesting that 16-nt siRNA is a more potent RNAi trigger. In vitro kinetic analysis of RNA-induced silencing complex (RISC) programmed in HeLa cells indicates that 16-nt siRNA has a higher RISC-loading capacity than 19-nt siRNA. These results suggest that RISC assembly and activation during RNAi does not necessarily require a 19-nt duplex siRNA and that 16-nt duplexes can be designed as more potent triggers to induce RNAi.
Job mobility as predictor of health and burnout
Authors: Liljegren Mats , Ekberg Kerstin
Published: July 2008

A few earlier studies have shown that employee's turnover intentions and job mobility simultaneously could affect health and burnout. The present study investigated the cross‐sectional, 2‐year longitudinal and possible interactional or additive effects of turnover intentions and job mobility (internal and external mobility) on health (SF‐36) and burnout (CBI). The study used questionnaire data from 662 Swedish civil servants, 73% remained at the same workplace, 13% were internally mobile, and 14% left the organization (externally mobile) during the 2‐year follow‐up period. The results showed that high turnover intentions were cross‐sectionally associated with worse mental health (MH) and higher degree of burnout. The externally mobile group had, after the change of workplace, less degree of personal and work‐related burnout compared to the non‐mobile group. The effect of internal mobility on burnout and health was negligible compared to the effects of external mobility. The results also indicated that the relationship between turnover intentions and actual job mobility are additive rather than interactive. One practical implication of the present findings is that external mobility, if it is in concordance with the individual intentions, could be a powerful health promoting factor.
Cardiotrophin-1 Is an Osteoclast-Derived Stimulus of Bone Formation Required for Normal Bone Remodeling
Authors: Walker Emma C , McGregor Narelle E , Poulton Ingrid J , Pompolo Sueli , Allan Elizabeth H , Quinn Julian MW , Gillespie Matthew T , Martin T John , Sims Natalie A
Published: July 2008

Cardiotrophin (CT-1) signals through gp130 and the LIF receptor (LIFR) and plays a major role in cardiac, neurological, and liver biology. We report here that CT-1 is also expressed within bone in osteoclasts and that CT-1 is capable of increasing osteoblast activity and mineralization both in vitro and in vivo. Furthermore, CT-1 stimulated CAAT/enhancer-binding protein-δ (C/EBPδ) expression and runt-related transcription factor 2 (runx2) activation. In neonate CT-1−/− mice, we detected low bone mass associated with reduced osteoblasts and many large osteoclasts, but increased cartilage remnants within the bone, suggesting impaired resorption. Cultured bone marrow (BM) from CT-1−/− mice generated many oversized osteoclasts and mineralized poorly compared with wildtype BM. As the CT-1−/− mice aged, the reduced osteoblast surface (ObS/BS) was no longer detected, but impaired bone resorption continued resulting in an osteopetrotic phenotype in adult bone. CT-1 may now be classed as an essential osteoclast-derived stimulus of both bone formation and resorption.
Proteins, Dietary Acid Load, and Calcium and Risk of Postmenopausal Fractures in the E3N French Women Prospective Study
Authors: Dargent-Molina Patricia , Sabia Sèverine , Touvier Mathilde , Kesse Emmanuelle , Bréart Gérard , Clavel-Chapelon Françoise , Boutron-Ruault Marie-Christine
Published: July 2008

Excess dietary proteins and “acid ash” diets have been suspected to increase the risk of osteoporosis, but experimental and epidemiological evidence is mixed. We aimed to determine whether the association between protein intake and the overall acid-base equilibrium of the diet (as renal net acid excretion [RNAE] estimate) and fracture risk vary according to calcium intake. During an average of 8.37 ± 1.73 yr of follow-up, 2408 women reported a fracture (excluding high-impact trauma) among 36,217 postmenopausal women from the E3N prospective study. We used Cox regression models to study the interaction between calcium and, respectively, proteins and RNAE, from the 1993 dietary questionnaire for fracture risk determination, adjusting for potential confounders. There was no overall association between fracture risk and total protein or RNAE. However, in the lowest quartile of calcium (<400 mg/1000 kcal), high protein intake was associated with a significant increased fracture risk (RR = 1.51 for highest versus lowest quartile; 95% CI, 1.17–1.94). An increasing fracture risk with increasing animal protein intake was also observed (trend, p < 0.0001). A similar pattern of interaction for fracture risk was observed between RNAE and calcium. In this Western population of postmenopausal women with normal to high protein intake and fairly high calcium intake, there was no overall association between total protein or RNAE and fracture risk. However, there was some evidence that high protein–high acid ash diets were associated with an increased risk of fracture when calcium intake was low (<400 mg/1000 kcal).
IGF-1 and IGF-Binding Proteins and Bone Mass, Geometry, and Strength: Relation to Metabolic Control in Adolescent Girls With Type 1 Diabetes
Authors: Moyer-Mileur Laurie J , Slater Hillarie , Jordan Kristine C , Murray Mary A
Published: July 2008

Children and adolescents with poorly controlled type 1 diabetes mellitus (T1DM) are at risk for decreased bone mass. Growth hormone (GH) and its mediator, IGF-1, promote skeletal growth. Recent observations have suggested that children and adolescents with T1DM are at risk for decreased bone mineral acquisition. We examined the relationships between metabolic control, IGF-1 and its binding proteins (IGFBP-1, -3, -5), and bone mass in T1DM in adolescent girls 12–15 yr of age with T1DM (n = 11) and matched controls (n = 10). Subjects were admitted overnight and given a standardized diet. Periodic blood samples were obtained, and bone measurements were performed. Serum GH, IGFBP-1 and -5, glycosylated hemoglobin (HbA1c), glucose, and urine magnesium levels were higher and IGF-1 values were lower in T1DM compared with controls (p < 0.05). Whole body BMC/bone area (BA), femoral neck areal BMD (aBMD) and bone mineral apparent density (BMAD), and tibia cortical BMC were lower in T1DM (p < 0.05). Poor diabetes control predicted lower IGF-1 (r2 = 0.21) and greater IGFBP-1 (r2 = 0.39), IGFBP-5 (r2 = 0.38), and bone-specific alkaline phosphatase (BALP; r2 = 0.41, p < 0.05). Higher urine magnesium excretion predicted an overall shorter, lighter skeleton, and lower tibia cortical bone size, mineral, and density (r2 = 0.44–0.75, p < 0.05). In the T1DM cohort, earlier age at diagnosis was predictive of lower IGF-1, higher urine magnesium excretion, and lighter, thinner cortical bone (r2 ⩽ 0.45, p < 0.01). We conclude that poor metabolic control alters the GH/IGF-1 axis, whereas greater urine magnesium excretion may reflect subtle changes in renal function and/or glucosuria leading to altered bone size and density in adolescent girls with T1DM.
Application of Cognitive Behaviour Therapy to Patients Who Have Advanced Cancer
Authors: Edelman Sarah , Kidman Antony D.
Published: July 2008

Patients who are diagnosed with advanced cancer frequently experience high levels of anxiety and depression. Few of the studies that evaluated psychological interventions with this cohort have demonstrated improvements in psychological measures in the period following therapy. However, a recent study that evaluated the efficacy of a group cognitive behaviour therapy (CBT) intervention with patients who had advanced breast cancer found improved outcomes on measures of mood and self-esteem following the intervention. This paper describes some of the CBT techniques used in the intervention, which might also be useful in the treatment of patients with other types of terminal illness.
The Effects of Behavioural Contracting and Preferred Reinforcement on Appointment Keeping
Authors: Hayes Robert A. , Efron Lisa A. , Richman Gina S. , Harrison Kelley A. , Aguilera Elizabeth L.
Published: July 2008

The current study demonstrates the efficacy of using a behavioural contingency contract in conjunction with family-selected reinforcers to increase appointment keeping among low income families in a child and family therapy clinic. Three families with similar presenting problems participated. A multiple baseline across-subjects design with the addition of a reversal component was utilised. Upon treatment implementation, contracts were signed by family members stating that they would receive coupons valuing $30.00 after attending four consecutive clinic appointments. These coupons were selected by the family from a diverse menu. Results indicated increases in appointment keeping following implementation of the behavioural contract. The cost effectiveness of using a behavioural contract in conjunction with economic incentives with low-income families is discussed, and suggestions for future research on appointment keeping are made.
Test-anxious Children and Adolescents: Psychopathology, Cognition, and Psychophysiological Reactivity
Authors: King Neville J. , Ollendick Thomas H. , Prins Pier J.M.
Published: July 2008

Test anxiety in children has long been recognised to be a significant and challenging educational problem. Recent advances in diagnostic interviewing, cognitive assessment, and physiological recording have facilitated a considerable amount of research on test-anxious youth. This research has yielded important clinical insights about test-anxious children and adolescents of interest to teachers and psychologists. We describe and evaluate the findings of these investigations. Finally, we discuss the implications of the research findings for intervention in school settings. Cognitive-behavioural strategies are tentatively recommended for the treatment of test-anxious children and adolescents.
A Model of Leisure and Mental Health in Australian Adolescents
Authors: Passmore Anne , French Davina
Published: July 2008

Development and maintenance of mental health is a major requirement for successful adolescent transition. During this critical process of change, when many mental health concerns first manifest, it has been suggested that positive leisure experiences provide opportunities that support and promote adolescent development and mental health. This investigation examined the relationship between leisure and mental health in an adolescent population. Based on an extensive literature review and analysis of focus-group interviews with 130 adolescents, it was hypothesised that self-efficacy, competence, and self-worth act as mediators between leisure and mental health. Measures of leisure, mental health, and the three intervening factors were collected from a total sample of 850 adolescents aged from 12 to 18 years. Structural equation modelling was used to investigate the interrelationships of the variables and for testing the goodness-of-fit of the hypothesised model. Results suggest that some forms of positive leisure involvement, namely achievement-oriented leisure (which provides challenges and a range of demands), and social leisure, do significantly influence mental health through the identified intervening factors. The construct of competence, in particular, formed a crucial link in the model. However, the third type of leisure, time-out leisure (which typically involves solitary activities such as lying on one's bed and reflecting, or watching television), demonstrated a significant but negative association with mental health. These outcomes provide some guidelines for facilitating and promoting mental health through leisure in adolescence.
Pre- and Post-session Assessments: Problems and Recommendations
Authors: Guerin Bernard , Palmer Daniel , Brace Rachel
Published: July 2008

We discuss two common ways that assessment tests or probes have been given in relation to training during applied behavioural interventions when continuous assessment is not possible. With pre-session assessment, target behaviours are tested immediately before training sessions; with post-session assessment, target behaviours are tested immediately after training sessions. Although they are not optimal methods for testing performance, such assessments are not rare, and archival data on the incidence of these two methods for JABA publications in the period 1993 to 1996 show that about 25% of research articles use one or both of these methods. The distinction between pre- and post-session assessment is important because the two methods influence the interpretation of data, and the decision to move to the next phase of an intervention. This influence is illustrated with a comparison between two studies of correspondence training. We then discuss the different positive and negative aspects of each assessment type, and two new methodologies are developed that retain the positive aspects of each assessment type. The final recommendation when such designs are necessary is a new method in which a criterion of three correct post-session assessments is reached first, followed by three correct pre-session assessments, before moving into the next phase of intervention.
Cognitive Behaviour Therapy for the Management of Obsessive-Compulsive Disorder
Authors: Sofronoff Kate
Published: July 2008

Current research reflects conflict regarding best practice in the treatment of obsessive-compulsive disorder (OCD). The present study reports on the psychological treatment of a 54-year-old woman diagnosed with OCD, and follows the implementation of pharmacological treatment. The study utilises both exposure and response prevention (ERP) and cognitive therapy (CT), although there was no attempt to compare these approaches in an experimental design. Measures of avoiding and neutralising behaviours were taken on three occasions across treatment. Measures were also taken of intrusive thoughts, appraisal of responsibility, and effective challenging, both across treatment and at follow-up. The results indicate that gains were made in addition to those reported following the implementation of medication. The results also suggest that the addition of CT to exposure and response prevention facilitates the extinction of neutralising behaviours.
Controlled Comparison of Single-session Treatments for Spider Phobia: Live Graded Exposure Alone versus Computer-aided Vicarious Exposure
Authors: Heading Katharine , Kirkby Kenneth C. , Martin Frances , Daniels Brett A. , Gilroy Lisa J. , Menzies Ross G.
Published: July 2008

The efficacy of prolonged single sessions of live graded exposure (LGE) and computer-aided vicarious exposure (CAVE) for spider phobia was examined in a single-blind, controlled trial. Forty participants diagnosed with specific phobia (spiders) received a prolonged single-session treatment of either therapist-aided LGE comprising exposure only or CAVE, or were assigned to a waiting list. Phobic symptomatology was measured at pre- and post-treatment, and at 1-month follow-up on a range of behavioural and subjective assessments. The results showed that the single-session therapist-aided LGE was superior to both CAVE and the waiting-list control. In contrast with previous findings of comparability between LGE and CAVE, and superiority of CAVE over placebo, the present study found no significant differences between the CAVE and waiting-list groups, with the exception of subjective units of distress, providing little support for single-session CAVE treatment.
Evaluation of an Anxiety-prevention and Positive-coping Program (FRIENDS) for Children and Adolescents of Non-English-speaking Background
Authors: Barrett Paula M. , Sonderegger Robi , Sonderegger Noleen L.
Published: July 2008

This study aimed to (a) appraise the efficacy of a well validated Anglo-Australian anxiety-prevention and stress-resiliency program (FRIENDS) for use with culturally diverse migrant groups residing in Australia, (b) examine the social validity of FRIENDS, and (c) obtain information from both participants and facilitators regarding how the program can best be modified for specific use with non-English-speaking background (NESB) clients. To test the efficacy of the intervention, pre- and post-intervention evaluation of internalising symptoms and coping ability were compared with waiting-list control groups (matched according to ethnic group, gender, and school level). One hundred and six primary and ninety-eight high school students differentiated by cultural origin (former-Yugoslavian, Chinese, and mixed-ethnic) and school level (primary and high school), completed standardised measures of internalising symptoms and were allocated to either an intervention (n = 121) or a waiting-list (n = 83) condition. Both groups were readministered the assessment package for comparison following a 10-week treatment or waiting period. Consistent with a recent pilot study, pre/post-assessment indicated that participants in the intervention condition exhibited lower anxiety and a more positive future outlook than waiting-list participants. Participating students reported to be highly satisfied with the intervention. Despite the overall success of FRIENDS, the program may be enhanced by culturally sensitive supplements so that the program is more applicable for use with NESB participants. Suggestions for treatment program modifications of FRIENDS are discussed.
Motivational Enhancement and MEMS Review to Improve Medication Adherence
Authors: Rosen Marc I. , Ryan Caitlin , Rigsby Michael
Published: July 2008

Electronic caps (most often Microelectronic Monitoring Systems; MEMS) that record date and time of bottle opening have been widely used to describe medication adherence. This paper expands upon descriptions of adherence-focused therapy built around review of MEMS data with the patient, adding the application of Motivational Enhancement Therapy (MET) principles. MEMS Feedback Therapy involves (a) motivational interviewing to complement the skill-building aspects of MEMS review; (b) detailed MEMS review with discussion of patterns of missed doses, and thoughts, feelings and habits accompanying missed doses; and (c) medication-taking routines to suggest after MET and MEMS review have prepared the patient to follow advice.
A Feasibility Study of Enhanced Group Triple P — Positive Parenting Program for Parents of Children with Attention-deficit/Hyperactivity Disorder
Authors: Hoath Fiona E. , Sanders Matthew R.
Published: July 2008

The aim of this randomised controlled trial was to examine the efficacy of an Attention-deficit/ hyperactivity Disorder (ADHD)-specific, Enhanced (Level 5) Group Triple P intervention. Twenty families with a child with clinically diagnosed ADHD aged between 5 and 9 years participated. Families were randomly assigned to either an enhanced intervention group (Enhanced Group Triple P; EGTP) or a wait list (WL) condition. Using parent reports of child behaviour, parenting practices and family functioning in addition to teacher reports of child behaviour in the school environment, parents in the EGTP condition reported significant reductions in intensity of disruptive child behaviour problems, aversive parenting practices and increases in parental self-efficacy when compared to the WL condition. Parents' reports at 3-month follow-up indicated the gains in child behaviour and parenting practices achieved at post-intervention were maintained.
Sensory Differences and Stereotyped Movements in Children with Autism
Authors: Gal Eynat , Dyck Murray , Passmore Anne
Published: July 2008

This study was designed to test whether there is a functional relationship between sensory stimulation and stereotyped movements (SM). Four children with autism and intellectual disability (according to DSM-IV criteria) who showed stereotyped movements were studied. The Short Sensory Profile was used to define whether a child perceived stimulation within each sensory modality as aversive, attractive, or neutral. The Stereotyped and Self-Injurious Movements Interview was used to identify each child's repetitive movements. Children were then exposed to sensory stimuli that were neutral, aversive or attractive. Results indicate that children: (a) initiate or increase stereotyped movements immediately following the onset of an aversive stimulus, (b) terminate or decrease stereotyped movements following the onset of an attractive stimulus and (c) initiate or increase stereotyped movements during periods of neutral stimulation. We conclude that stereotyped movements are functionally related to sensory stimulation; individuals who frequently engage in stereotyped movements may do so in order to cope with under-stimulation and aversive over-stimulation.