bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Yearly Zoledronic Acid 5 mg on Bone Turnover Markers and Relation of PINP With Fracture Reduction in Postmenopausal Women With Osteoporosis
Authors: Delmas Pierre D , Munoz Francoise , Black Dennis M , Cosman Felicia , Boonen Steven , Watts Nelson B , Kendler David , Eriksen Erik F , Mesenbrink Peter G , Eastell Richard
Published: April 2009

In patients with osteoporosis treated with antiresorptive agents, reduction in bone turnover explains much of the observed fracture risk reduction. Lower levels of bone turnover markers (BTMs) appear to be associated with a lower risk of fracture in bisphosphonate-treated patients. BTMs were measured in a subset of subjects in the HORIZON Pivotal Fracture Trial. Annual infusions of zoledronic acid 5 mg significantly reduced BTMs: median decrease of 50% for β-C-terminal telopeptides of type 1 collagen (β-CTX), 30% for bone alkaline phosphatase (ALP), and 56% for procollagen type 1 amino-terminal propeptide (PINP). The mean level of BTMs decreased in treated patients but remained within the premenopausal range before the next injection. The percentage of zoledronic acid–treated patients with values below the premenopausal reference range at all time points was 1.7%, 17.8%, and 19% for bone ALP, CTX, and PINP, respectively. The third injection of zoledronic acid resulted in 60% reduction of β-CTX within 9–11 days, followed by a gradual increase, indicating the persistence of osteoclastic bone resorption. The association between changes in BTMs and fracture incidence was assessed in 1132 patients who had PINP measurements at baseline and 1 yr. There was no association between low PINP levels at 1 yr and increased fracture incidence. In summary, (1) annual injections of zoledronic acid reduced BTMs in the premenopausal range, with a significant response persisting after the third infusion; and (2) low levels of PINP were not associated with increased fracture risk.
Repeat Low-Trauma Fractures Occur Frequently Among Men and Women Who Have Osteopenic BMD
Authors: Langsetmo Lisa , Goltzman David , Kovacs Christopher S , Adachi Jonathan D , Hanley David A , Kreiger Nancy , Josse Robert , Papaioannou Alexandra , Olszynski Wojciech P , Jamal Sophie A
Published: April 2009

Fracture risk assessment based solely on BMD has limitations. Additional risk factors include the presence of a previous low-trauma fracture. We sought to quantify the fracture burden attributable to first versus repeat fracture. We studied 2179 men and 5269 women, 50–90 yr of age, participating in the Canadian Multicentre Osteoporosis Study (CaMos). We included all low-trauma fractures that occurred over 8 yr of follow-up and classified these as either first or repeat clinical low-trauma fracture based on lifetime fracture history. Analyses were further stratified by sex, age, BMD risk categories (normal, osteopenia, osteoporosis), and vertebral deformity status. There were 128 fractures in men and 577 fractures in women. About 25% of fractures in men and 40% in women were repeat fractures. Just over one half of first fractures occurred in those with osteopenic BMD (58% in men, 54% in women). Just under one half of repeat fractures also occurred in those with osteopenic BMD (42% in men, 47% in women). The incidence of repeat fracture was, in most cases, nearly double, but sometimes nearly quadruple, the incidence of first fracture within a given BMD risk category in both men and women. Repeat fractures contribute substantially to overall fracture burden, and the contribution is independent of BMD. Furthermore, those with a combination of prior low-trauma fracture and another risk factor were at especially high risk of future fracture.
Osteoblast Function Is Compromised at Sites of Focal Bone Erosion in Inflammatory Arthritis
Authors: Walsh Nicole C , Reinwald Susan , Manning Catherine A , Condon Keith W , Iwata Ken , Burr David B , Gravallese Ellen M
Published: April 2009

In rheumatoid arthritis (RA), synovial inflammation results in focal erosion of articular bone. Despite treatment attenuating inflammation, repair of erosions with adequate formation of new bone is uncommon in RA, suggesting that bone formation may be compromised at these sites. Dynamic bone histomorphometry was used in a murine model of RA to determine the impact of inflammation on osteoblast function within eroded arthritic bone. Bone formation rates at bone surfaces adjacent to inflammation were similar to those observed in nonarthritic bone; therefore, osteoblast activity is unlikely to compensate for the increased bone resorption at these sites. Within arthritic bone, the extent of actively mineralizing surface was reduced at bone surfaces adjacent to inflammation compared with bone surfaces adjacent to normal marrow. Consistent with the reduction in mineralized bone formation, there was a notable paucity of cells expressing the mid- to late stage osteoblast lineage marker alkaline phosphatase, despite a clear presence of cells expressing the early osteoblast lineage marker Runx2. In addition, several members of the Dickkopf and secreted Frizzled-related protein families of Wnt signaling antagonists were upregulated in arthritic synovial tissues, suggesting that inhibition of Wnt signaling could be one mechanism contributing to impaired osteoblast function within arthritic bone. Together, these data indicate that the presence of inflammation within arthritic bone impairs osteoblast capacity to form adequate mineralized bone, thus contributing to the net loss of bone and failure of bone repair at sites of focal bone erosion in RA.
Dopamine Signaling Differences in the Nucleus Accumbens and Dorsal Striatum Exploited by Nicotine
Authors: Zhang Tianxiang , Zhang Lifen , Liang Yong , Siapas Athanassios G. , Zhou Fu-Ming , Dani John A.
Published: April 2009

The dorsal striatum and the nucleus accumbens (NAc) shell of the ventral striatum have similar cellular components and are both richly innervated by dopamine neurons. Despite similarities that extend throughout the striatum, only the NAc shell has a conspicuous increase in basal dopamine upon the initial administration of psychostimulant drugs such as nicotine. As measured by microdialysis, the elevated dopamine in the NAc shell is considered an identifying functional characteristic of addictive drugs. To examine this general functional difference between nicotine's action on the dorsolateral striatum and NAc shell, we directly monitored dopamine release in rat striatal slices using fast-scan cyclic voltammetry. In addition, we separately monitored thein vivounit firing activity of putative midbrain dopamine neurons from freely moving rats using chronic multiple tetrodes. Nicotine administration increased the firing frequency of dopamine neurons and specifically increased the number and the length of phasic burst firing. The frequency dependence for dopamine release in the dorsolateral striatum and NAc shell is fundamentally different, enabling mainly the NAc shell to capitalize on the nicotine-induced phasic burst firing by dopamine neurons. Although nicotine decreased low-frequency (tonic) dopamine release in both areas, the increased ratio of phasic bursts relative to tonic firing caused by nicotine boosted the basal dopamine concentration predominantly in the NAc shell. By favoring release from bursts while depressing release from tonic signals, nicotine spreads the range of dopamine signaling and effectively increases the signal-to-noise relationship along dopamine afferents.
17β-Estradiol-Mediated Neuroprotection and ERK Activation Require a Pertussis Toxin-Sensitive Mechanism Involving GRK2 and β-Arrestin-1
Authors: Dominguez Reymundo , Hu Eric , Zhou Miou , Baudry Michel
Published: April 2009

17-β-Estradiol (E2) is a steroid hormone involved in numerous bodily functions, including several brain functions. In particular, E2 is neuroprotective against excitotoxicity and other forms of brain injuries, a property that requires the extracellular signal-regulated kinase (ERK) pathway and possibly that of other signaling molecules. The mechanism and identity of the receptor(s) involved remain unclear, although it has been suggested that E2 receptor α (ERα) and G proteins are involved. We, therefore, investigated whether E2-mediated neuroprotection and ERK activation were linked to pertussis toxin (PTX)-sensitive G-protein-coupled effector systems. Biochemical and image analysis of organotypic hippocampal slices and cortical neuronal cultures showed that E2-mediated neuroprotection as well as E2-induced ERK activation were sensitive to PTX. The sensitivity to PTX suggested a possible role of G-protein- and β-arrestin-mediated mechanisms. Western immunoblots from E2-treated cortical neuronal cultures revealed an increase in phosphorylation of both G-protein-coupled receptor-kinase 2 and β-arrestin-1, a G-protein-coupled receptor adaptor protein. Transfection of neurons with β-arrestin-1 small interfering RNA prevented E2-induced ERK activation. Coimmunoprecipitation experiments indicated that E2 increased the recruitment of β-arrestin-1 and c-Src to ERα. These findings suggested that ERα is regulated by a mechanism associated with receptor desensitization and downregulation. In support of this idea, we found that E2 treatment of cortical synaptoneurosomes resulted in internalization of ERα, whereas treatment of cortical neurons with the ER agonists E-6-BSA-FITC [β-estradiol-6-(O-carboxymethyl)oxime-bovine serum albumin conjugated with fluorescein isothiocyanate] and E-6-biotin [1,3,5(10)-estratrien-3,17β-diol-6-one-6-carboxymethloxime-NH-propyl-biotin] resulted in agonist internalization. These results demonstrate that E2-mediated neuroprotection and ERK activation involve ERα activation of G-protein- and β-arrestin-mediated mechanisms.
MeCP2-Mediated Transcription Repression in the Basolateral Amygdala May Underlie Heightened Anxiety in a Mouse Model of Rett Syndrome
Authors: Adachi Megumi , Autry Anita E. , Covington Herb E. , Monteggia Lisa M.
Published: April 2009

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that results from loss of function mutations in the methyl-CpG binding protein 2 (MECP2) gene. Using viral-mediated basolateral amygdala (BLA)-specific deletion ofMecp2in mice, we show that intactMecp2function is required for normal anxiety behavior as well as some types of learning and memory. To examine whether these behavioral deficits are the result of impaired transcriptional repression, becauseMecp2is believed to act as a transcriptional repressor in complex with histone deacetylases (HDACs), we infused a HDAC inhibitor chronically into the BLA of wild-type mice. We found that HDAC inhibition produces behavioral deficits similar to those observed after the deletion ofMecp2in the BLA. These results suggest a key role forMecp2as a transcriptional repressor in the BLA in mediating behavioral features of RTT.
Splice-Variant- and Stage-Specific RNA Editing of theDrosophilaGABA Receptor Modulates Agonist Potency
Authors: Jones Andrew K. , Buckingham Steven D. , Papadaki Magdalini , Yokota Maiko , Sattelle Benedict M. , Matsuda Kazuhiko , Sattelle David B.
Published: April 2009

The molecular diversity of many gene products functioning in the nervous system is enhanced by alternative splicing and adenosine-to-inosine editing of pre-mRNA. Using RDL, aDrosophila melanogasterGABA-gated ion channel, we examined the functional impact of RNA editing at several sites along with alternative splicing of more than one exon. We show that alternative splicing and RNA editing have a combined influence on the potency of the neurotransmitter GABA, and the editing isoforms detectedin vivospan the entire functional range of potencies seen for all possible edit variants expressed inXenopus laevisoocytes. The extent of RNA editing is developmentally regulated and can also be linked to the choice of alternative exons. These results provide insights into how the rich diversity of signaling necessary for complex brain function can be achieved by relatively few genes.
Synaptic Cross Talk between Perisomatic-Targeting Interneuron Classes Expressing Cholecystokinin and Parvalbumin in Hippocampus
Authors: Karson Miranda A. , Tang Ai-Hui , Milner Teresa A. , Alger Bradley E.
Published: April 2009

Cholescystokinin (CCK)- or parvalbumin (PV)-containing interneurons are the major perisomatic-targeting interneurons in the cerebral cortex, including hippocampus, and are thought to form mutually exclusive networks. We used several techniques to test the alternative hypothesis that CCK and PV cells are coupled by chemical synapses. Triple immunofluorescence confocal microscopy revealed numerous axosomatic, axodendritic, and axoaxonic contacts stained for CCK, PV, and the presynaptic marker synaptophysin. The existence of mutual CCK and PV synapses was supported by dual EM immunolabeling. Paired whole-cell recordings detected unitary GABAAergic synaptic transmission between identified CCK and PV cells, and single CCK cells could transiently inhibit action potential firing of synaptically coupled PV cells. We conclude that the major hippocampal perisomatic-targeting interneurons communicate synaptically. This communication should affect neuronal network activity, including neuronal oscillations, in which the CCK and PV cells have well established roles. The prevalence of CCK and PV networks in other brain regions suggests that internetwork interactions could be generally important.
Regulation of Cdh1–APC Function in Axon Growth by Cdh1 Phosphorylation
Authors: Huynh Mai Anh , Stegmüller Judith , Litterman Nadia , Bonni Azad
Published: April 2009

The ubiquitin ligase Cdh1–anaphase promoting complex (Cdh1–APC) plays a key role in the control of axonal morphogenesis in the mammalian brain, but the mechanisms that regulate neuronal Cdh1–APC function remain incompletely understood. Here, we have characterized the effect of phosphorylation of Cdh1 at cyclin-dependent kinase (Cdk) sites on Cdh1–APC function in neurons. We replaced nine conserved sites of Cdk-induced Cdh1 phosphorylation with alanine (9A) or aspartate (9D) to mimic hypo- or hyper-phosphorylation, respectively. We found that the 9A mutation triggered the proteasome-dependent degradation of Cdh1, and conversely the 9D mutation stabilized Cdh1 in neuronal cells. However, the phosphomimic 9D Cdh1 protein failed to associate with the APC core protein Cdc27. In addition, whereas wild-type and 9A Cdh1 predominantly localized to the nucleus, the 9D Cdh1 protein accumulated in the cytoplasm in neurons. Importantly, in contrast to wild-type and 9A Cdh1, the 9D Cdh1 mutant failed to inhibit axon growth in primary cerebellar granule neurons. Collectively, our results suggest that phosphorylation of neuronal Cdh1 at Cdk sites triggers the stabilization of an inactive form of Cdh1 that accumulates in the cytoplasm, leading to the inhibition of Cdh1–APC function in the control of axon growth. Thus, phosphorylation of Cdh1 may represent a critical mechanism regulating Cdh1–APC function in the nervous system.
Functional Specificity of Mossy Fiber Innervation of GABAergic Cells in the Hippocampus
Authors: Szabadics János , Soltesz Ivan
Published: April 2009

One million mossy fibers in the rat provide individually sparse but functionally important synaptic connections between the dentate gyrus and hippocampus. Although the majority of mossy fiber targets are GABAergic cells, the functional organization of the feedforward GABAergic machinery modulating the interactions of granule cells and CA3 pyramidal cells are not yet understood. We used mossy fiber bouton to GABA neuron paired recordings in the CA3 to demonstrate that mossy fibers provide cell type-specific innervation to distinct GABAergic neurons with specialized intra- and extrahippocampal outputs. Our results show that mossy fibers contact the perisomatically projecting fast-spiking and regular-spiking basket cells, in addition to the dendritically projecting ivy cells, and the septum-projecting spiny stratum lucidum cells. Monosynaptic mossy fiber inputs to fast-spiking basket cells and spiny stratum lucidum cells were found to be numerous, but they were small in amplitude and displayed low transmission probabilities. In contrast, regular-spiking basket cells and ivy cells were less likely to be innervated by mossy fibers, but the amplitudes of mossy fiber EPSCs were large and the transmission probabilities were high. The dependence of the numbers and strengths of the mossy fiber inputs to CA3 GABAergic cells on the postsynaptic cell type was correlated with the frequency of the background synaptic events, so that cells with weak but numerous mossy fiber inputs received high rates of spontaneous synaptic events. Together, these results reveal the diverse components and high degree of functional specificity of the GABAergic cellular machinery underlying the dentate gyrus–CA3 interface.
Neural Control of Unloaded Leg Posture and of Leg Swing in Stick Insect, Cockroach, and Mouse Differs from That in Larger Animals
Authors: Hooper Scott L. , Guschlbauer Christoph , Blümel Marcus , Rosenbaum Philipp , Gruhn Matthias , Akay Turgay , Büschges Ansgar
Published: April 2009

Stick insect (Carausius morosus) leg muscles contract and relax slowly. Control of stick insect leg posture and movement could therefore differ from that in animals with faster muscles. Consistent with this possibility, stick insect legs maintained constant posture without leg motor nerve activity when the animals were rotated in air. That unloaded leg posture was an intrinsic property of the legs was confirmed by showing that isolated legs had constant, gravity-independent postures. Muscle ablation experiments, experiments showing that leg muscle passive forces were large compared with gravitational forces, and experiments showing that, at the rest postures, agonist and antagonist muscles generated equal forces indicated that these postures depended in part on leg muscles. Leg muscle recordings showed that stick insect swing motor neurons fired throughout the entirety of swing. To test whether these results were specific to stick insect, we repeated some of these experiments in cockroach (Periplaneta americana) and mouse. Isolated cockroach legs also had gravity-independent rest positions and mouse swing motor neurons also fired throughout the entirety of swing. These data differ from those in human and horse but not cat. These size-dependent variations in whether legs have constant, gravity-independent postures, in whether swing motor neurons fire throughout the entirety of swing, and calculations of how quickly passive muscle force would slow limb movement as limb size varies suggest that these differences may be caused by scaling. Limb size may thus be as great a determinant as phylogenetic position of unloaded limb motor control strategy.
A role for kisspeptins in pregnancy: facts and speculations
Authors: Reynolds Rebecca M , Logie James J , Roseweir Antonia K , McKnight Angus J , Millar Robert P
Published: April 2009

Kisspeptin is a neuropeptide that was originally discovered in 1996 from a metastasis tumour suppressor gene,KISS1and was appropriately named metastin. More recently, the discovery of inactivating mutations in the receptor for kisspeptin, a G protein-coupled receptor, GPR54 (KISS1R), have been shown to result in a failure to progress through puberty in man. These findings have led to the kisspeptin/KISS1R system being described as an essential gatekeeper of reproductive function. Recent studies have suggested additional roles of kisspeptin, other than in the central control of the gonadotropic axis including placentation and pregnancy, energy homeostasis and cardiovascular function. Therefore, kisspeptin–KISS1R signalling potentially plays diverse roles in human physiology. Here, we review the literature regarding the role and physiological significance of kisspeptin in pregnancy and highlight some of the key questions that require addressing.
Estimating clay undrained shear strength using CPTu results
Authors: Kim C. , Kim S. , Lee J.
Published: April 2009

Estimation of the undrained shear strength su of clays using piezocone penetration test (CPTu) results has been based mainly on the cone factor Nk. In this study a new CPTu-based method for estimating su is proposed and evaluated. It is aimed at reducing uncertainties in the estimation of su and enhancing the application of CPTu results. To develop the method, a selected site on a marine clay deposit was subjected to an extensive experimental testing programme. The proposed method defines a direct correlation between su and the cone resistance qt, involving the initial in situ pore pressure but excluding the need for overburden pressure calculation and therefore the need for undisturbed soil sampling. To verify the proposed method, additional test sites and example sites from the literature that encompass a variety of soil conditions are selected and examined. Values of su obtained from the proposed method are in good agreement with measured values of su for all the selected verification cases.
Reports of Rape Reperpetration by Newly Enlisted Male Navy Personnel
Authors: McWhorter Stephanie K. , Stander Valerie A. , Merrill Lex L. , Thomsen Cynthia J. , Milner Joel S.
Published: April 2009

This study examined the frequency and characteristics of repeated attempted and completed rape (ACR) incidents reported by newly enlisted male navy personnel (N = 1,146) who participated in a longitudinal study during the transition from civilian to military life. Overall, 13% (n = 144) reported engaging in sexual behavior that approximates legal definitions of ACR since the age of 14. Among those men, most (71%) reperpetrated ACR incidents (M = 6.36, SD = 9.55). Demographic variables were unrelated to perpetration history. Regardless of time period, respondents reported perpetrating primarily completed rather than attempted rape, perpetrating multiple ACR incidents rather than a single incident, using substances to incapacitate victims more frequently than force, and knowing their victim rather than targeting a stranger in completed rape incidents.
Women’s Judgments of a Sexual Assault Scenario: The Role of Prejudicial Attitudes and Victim Weight
Authors: Clarke Allyson K. , Lawson Karen L.
Published: April 2009

One potential barrier facing sexual assault survivors is that prejudicial attitudes and perceptions of victim appearance can influence the amount of blame, sympathy, and help that they receive from others. Using Weiner’s (1980) attribution–affect–action theory as a guide, the present study investigated the relation between observer attitudinal characteristics (rape myth acceptance [RMA] and antifat attitudes [AFA]), victim weight, and specific judgments regarding a hypothetical sexual assault case. Female undergraduate participants (N = 173) were presented with a sexual assault scenario and asked to complete a series of self-report questionnaires. Consistent with past research, attributions of victim fault were positively associated with adherence to rape myths and were higher toward thin victims than overweight victims. Further, the relation between the rater attitudinal variables and sentencing recommendations was found to be dependent on victim weight. When the victim was presented as thin, neither RMA nor AFA emerged as a predictor of sentencing recommendations. In contrast, both RMA and AFA were positively related to sentencing recommendations when the victim was presented as overweight. Theoretical and practical implications of these findings are discussed.
CD4+CD25+ T-Cells Control Autoimmunity in the Absence of B-Cells
Authors: Mariño Eliana , Villanueva Jeanette , Walters Stacey , Liuwantara David , Mackay Fabienne , Grey Shane T.
Published: April 2009

OBJECTIVE

Tumor necrosis factor ligand family members B-cell–activating factor (BAFF) and a proliferation-inducing ligand (APRIL) can exert powerful effects on B-cell activation and development, type 1 T-helper cell (Th1) immune responses, and autoimmunity. We examined the effect of blocking BAFF and APRIL on the development of autoimmune diabetes.

RESEARCH DESIGN AND METHODS

Female NOD mice were administered B-cell maturation antigen (BCMA)-Fc from 9 to 15 weeks of age. Diabetes incidence, islet pathology, and T- and B-cell populations were examined.

RESULTS

BCMA-Fc treatment reduced the severity of insulitis and prevented diabetes development in NOD mice. BCMA-Fc–treated mice showed reduced follicular, marginal-zone, and T2MZ B-cells. B-cell reduction was accompanied by decreased frequencies of pathogenic CD4+CD40+ T-cells and reduced Th1 cytokines IL-7, IL-15, and IL-17. Thus, T-cell activation was blunted with reduced B-cells. However, BCMA-Fc–treated mice still harbored detectable diabetogenic T-cells, suggesting that regulatory mechanisms contributed to diabetes prevention. Indeed, BCMA-Fc–treated mice accumulated increased CD4+CD25+ regulatory T-cells (Tregs) with age. CD4+CD25+ cells were essential for maintaining euglycemia because their depletion abrogated BCMA-Fc–mediated protection. BCMA-Fc did not directly affect Treg homeostasis given that CD4+CD25+Foxp3+ T-cells did not express TACI or BR3 receptors and that CD4+CD25+Foxp3+ T-cell frequencies were equivalent in wild-type, BAFF−/−, TACI−/−, BCMA−/−, and BR3−/− mice. Rather, B-cell depletion resulted in CD4+CD25+ T-cell–mediated protection from diabetes because anti-CD25 monoclonal antibody treatment precipitated diabetes in both diabetes-resistant NOD.μMT−/− and BCMA-Fc–treated mice.

CONCLUSIONS

BAFF/APRIL blockade prevents diabetes. BCMA-Fc reduces B-cells, subsequently blunting autoimmune activity and allowing endogenous regulatory mechanisms to preserve a prehyperglycemic state.
Extremes of Clinical and Enzymatic Phenotypes in Children With Hyperinsulinism Caused by Glucokinase Activating Mutations
Authors: Sayed Samir , Langdon David R. , Odili Stella , Chen Pan , Buettger Carol , Schiffman Alisa B. , Suchi Mariko , Taub Rebecca , Grimsby Joseph , Matschinsky Franz M. , Stanley Charles A.
Published: April 2009

OBJECTIVE

Heterozygous activating mutations of glucokinase have been reported to cause hypoglycemia attributable to hyperinsulinism in a limited number of families. We report three children with de novo glucokinase hyperinsulinism mutations who displayed a spectrum of clinical phenotypes corresponding to marked differences in enzyme kinetics.

RESEARCH DESIGN AND METHODS

Mutations were directly sequenced, and mutants were expressed as glutathionyl S-transferase–glucokinase fusion proteins. Kinetic analysis of the enzymes included determinations of stability, activity index, the response to glucokinase activator drug, and the effect of glucokinase regulatory protein.

RESULTS

Child 1 had an ins454A mutation, child 2 a W99L mutation, and child 3 an M197I mutation. Diazoxide treatment was effective in child 3 but ineffective in child 1 and only partially effective in child 2. Expression of the mutant glucokinase ins454A, W99L, and M197I enzymes revealed a continuum of high relative activity indexes in the three children (26, 8.9, and 3.1, respectively; wild type = 1.0). Allosteric responses to inhibition by glucokinase regulatory protein and activation by the drug RO0281675 were impaired by the ins454A but unaffected by the M197I mutation. Estimated thresholds for glucose-stimulated insulin release were more severely reduced by the ins454A than the M197I mutation and intermediate in the W99L mutation (1.1, 3.5, and 2.2 mmol/l, respectively; wild type = 5.0 mmol/l).

CONCLUSIONS

These results confirm the potency of glucokinase as the pancreatic β-cell glucose sensor, and they demonstrate that responsiveness to diazoxide varies with genotype in glucokinase hyperinsulinism resulting in hypoglycemia, which can be more difficult to control than previously believed.
DURAbility of Basal Versus Lispro Mix 75/25 Insulin Efficacy (DURABLE) Trial 24-Week Results
Authors: Buse John B. , Wolffenbuttel Bruce H.R. , Herman William H. , Shemonsky Natalie K. , Jiang Honghua H. , Fahrbach Jessie L. , Scism-Bacon Jamie L. , Martin Sherry A.
Published: April 2009

OBJECTIVE

To compare the ability of two starter insulin regimens to achieve glycemic control in a large, ethnically diverse population with type 2 diabetes.

RESEARCH DESIGN AND METHODS

During the initiation phase of the DURABLE trial, patients were randomized to a twice-daily lispro mix 75/25 (LM75/25; 75% lispro protamine suspension, 25% lispro) (n = 1,045) or daily glargine (GL) (n = 1,046) with continuation of prestudy oral antihyperglycemic drugs.

RESULTS

Baseline A1C was similar (LM75/25: 9.1 ± 1.3%; GL: 9.0 ± 1.2%; P = 0.414). At 24 weeks, LM75/25 patients had lower A1C than GL patients (7.2 ± 1.1 vs. 7.3 ± 1.1%, P = 0.005), greater A1C reduction (–1.8 ± 1.3 vs. –1.7 ± 1.3%, P = 0.005), and higher percentage reaching A1C target <7.0% (47.5 vs. 40.3%, P < 0.001). LM75/25 was associated with higher insulin dose (0.47 ± 0.23 vs. 0.40 ± 0.23 units · kg−1· day−1, P < 0.001) and more weight gain (3.6 ± 4.0 vs. 2.5 ± 4.0 kg, P < 0.0001). LM75/25 patients had a higher overall hypoglycemia rate than GL patients (28.0 ± 41.6 vs. 23.1 ± 40.7 episodes · pt−1· year−1, P = 0.007) but lower nocturnal hypoglycemia rate (8.9 ± 19.3 vs. 11.4 ± 25.3 episodes · pt−1· year−1, P = 0.009). Severe hypoglycemia rates were low in both groups (LM75/25: 0.10 ± 1.6 vs. GL: 0.03 ± 0.3 episodes · pt−1· year−1, P = 0.167).

CONCLUSIONS

Compared with GL, LM75/25 resulted in slightly lower A1C at 24 weeks and a moderately higher percentage reaching A1C target <7.0%. Patients receiving LM75/25 experienced more weight gain and higher rates of overall hypoglycemia but lower rates of nocturnal hypoglycemia. Durability of regimens will be evaluated in the following 2-year maintenance phase.
Primary bacterial peritonitis in dogs and cats: 24 cases (1990–2006)
Authors: Culp William T. N. , Zeldis Tracy E. , Reese Michael S. , Drobatz Kenneth J.
Published: April 2009

Objective—To determine clinical characteristics of primary bacterial peritonitis (infection of the peritoneal cavity with no identifiable intraperitoneal source of infection) and compare characteristics of primary and secondary peritonitis in dogs and cats.

Design—Retrospective case series.

Animals—24 (primary peritonitis) and 60 (secondary peritonitis) client-owned dogs and cats.

Procedures—Data from medical records of dogs and cats with primary and secondary peritonitis were reviewed for descriptive information regarding primary peritonitis and for comparison between the 2 forms of peritonitis.

Results—15 dogs and 9 cats met inclusion criteria for primary peritonitis, and 49 dogs and 11 cats met inclusion criteria for secondary peritonitis. The most common historical findings in dogs and cats with primary and secondary peritonitis were lethargy, vomiting, and anorexia. Dogs with secondary peritonitis more often developed peritoneal exudates than those with primary peritonitis, and dogs with primary peritonitis were more often infected with gram-positive bacteria than those with secondary peritonitis. No difference in outcome was detected between all animals with primary versus secondary peritonitis; however, dogs with secondary peritonitis treated with surgery were more commonly discharged than those with primary peritonitis treated with surgery.

Conclusions and Clinical Relevance—Differences in primary and secondary peritonitis related to historical, physical examination, and clinical laboratory findings; bacteriologic findings; peritoneal effusion characteristics; and outcome were detected. However, larger case numbers are needed before alternative recommendations, such as avoidance of surgery, can be made.
Use of a chain écraseur for excision of a pharyngeal granuloma in a cow
Authors: Boileau Mélanie J. , Jann Henry W. , Confer Anthony W.
Published: April 2009

Case Description—A 10-year-old Longhorn cow pregnant with a valuable fetus was evaluated because of progressive inspiratory dyspnea of 6 weeks' duration.

Clinical Findings—Physical examination findings were consistent with upper respiratory tract obstruction. A large pedunculated soft tissue mass was evident in the mid-dorsal aspect of the pharynx during palpation and endoscopic examination. Results of microscopic examination of transendoscopic fine-needle aspirates and a biopsy specimen were suggestive of a bacterial granuloma.

Treatment and Outcome—Transtracheal intubation was performed, and the mass was excised with a chain écraseur. Results of histologic examination were consistent with a diagnosis of actinobacillosis. The owner reported that the cow was doing well without any recurrence of respiratory distress 8 months after surgery.

Clinical Relevance—Findings suggested that pharyngeal granuloma resulting from actinobacillosis should be included in the differential diagnoses when examining mature cattle with upper respiratory tract obstruction and that a chain écraseur may be useful for excising soft tissue pharyngeal masses in cattle.
Impact of cytogenetic abnormalities on the management of skull base chordomas
Authors: Almefty Kaith K. , Pravdenkova Svetlana , Sawyer Jeffrey R. , Al-Mefty Ossama
Published: April 2009

Object

Cytogenetic studies of chordomas are scarce and show multiple changes involving different chromosomes. These abnormalities are implicated in the pathogenesis of chordoma, but the clinical significance of these changes is yet to be determined. In this study, the authors discuss the cytogenetic changes in a large series of skull base chordomas with long-term follow-up and focus on the impact of these changes on the prognosis, progression, and management of the disease.

Methods

The karyotypes of chordomas in 64 patients (36 men and 28 women) were studied in relation to survival and recurrence or progression over a mean follow-up period of 48 ± 37.5 months. The standard G-banding technique was used for karyotype analysis. Statistical analysis was performed with the Fisher exact test and ORs, and Kaplan-Meier curves were generated for survival and recurrence/progression of disease.

Results

Seventy-four percent of de novo chordomas had normal karyotypes and a 3% recurrence rate; there was a 45% recurrence rate in de novo tumors with abnormal karyotypes (p < 0.01). Recurrent tumors were associated with a high incidence of abnormal karyotype (75%). The OR for recurrence in lesions with an abnormal versus a normal karyotype was 12. Aberrations in chromosomes 3, 4, 12, 13, and 14 were associated with frequent recurrence and decreased survival time. Ninety-five percent of cases with progression involved chromosome 3 and/or 13. The median survival time was 4 months when both of these chromosomes had aberrations (p = 0.02).

Conclusions

Chordomas with normal karyotypes were associated with a low rate of recurrence and a long patient survival, and recurrent chordomas were associated with an abnormal karyotype, disease progression, and poor survival. De novo chordomas with normal karyotypes may be amenable to radical resection and adjunctive proton beam therapy. Recurrent and de novo chordomas with abnormal karyotypes were associated with complex cytogenetic abnormalities and a poor prognosis, particularly in the presence of aberrations underlying tumor progression in chromosomes 3, 4, 12, 13, and 14.
Thermal Actuation Based 3-DoF Non-Resonant Microgyroscope Using MetalMUMPs
Authors: Shakoor Rana Iqtidar , Bazaz Shafaat Ahmed , Kraft Michael , Lai Yongjun , Ul Hassan Muhammad Masood
Published: April 2009

High force, large displacement and low voltage consumption are a primary concern for microgyroscopes. The chevron-shaped thermal actuators are unique in terms of high force generation combined with the large displacements at a low operating voltage in comparison with traditional electrostatic actuators. A Nickel based 3-DoF micromachined gyroscope comprising 2-DoF drive mode and 1-DoF sense mode oscillator utilizing the chevron-shaped thermal actuators is presented here. Analytical derivations and finite element simulations are carried out to predict the performance of the proposed device using the thermo-physical properties of electroplated nickel. The device sensitivity is improved by utilizing the dynamical amplification of the oscillation in 2-DoF drive mode using an active-passive mass configuration. A comprehensive theoretical description, dynamics and mechanical design considerations of the proposed gyroscopes model are discussed in detail. Parametric optimization of gyroscope, its prototype modeling and fabrication using MetalMUMPs has also been investigated. Dynamic transient simulation results predicted that the sense mass of the proposed device achieved a drive displacement of 4.1µm when a sinusoidal voltage of 0.5V is applied at 1.77 kHz exhibiting a mechanical sensitivity of 1.7μm /o/s in vacuum. The wide bandwidth frequency response of the 2-DoF drive mode oscillator consists of two resonant peaks and a flat region of 2.11 kHz between the peaks defining the operational frequency region. The sense mode resonant frequency can lie anywhere within this region and therefore the amplitude of the response is insensitive to structural parameter variations, enhancing device robustness against such variations. The proposed device has a size of 2.2 x 2.6 mm2, almost one third in comparison with existing M-DoF vibratory gyroscope with an estimated power consumption of 0.26 Watts. These predicted results illustrate that the chevron-shaped thermal actuator has a large voltage-stroke ratio shifting the paradigm in MEMS gyroscope design from the traditional interdigitated comb drive electrostatic actuator. These actuators have low damping compared to electrostatic comb drive actuators which may result in high quality factor microgyroscopes operating at atmospheric pressure.
DIVERSIFICATION BENEFITS IN THE FINNISH COMMERCIAL PROPERTY MARKET
Authors: Falkenbach Heidi
Published: April 2009

The Finnish commercial property market internationalised rapidly in the beginning of the 21st century. According to the portfolio theory and previous research on international property investments, the main motivation factor driving international real estate investments is the possibility to reach diversification benefits. The paper discusses the diversification benefits offered by the Finnish property market in its early years of internationalisation. As international real estate investors in the Finnish property market include investors with both real estate only, as well as mixed‐asset portfolios, the diversification benefits are studied both in terms of a Finnish mixed-asset portfolio, as well as international real estate portfolio. Santruka XXI a. pradžioje Suomijos komercinio nekilnojamojo turto rinkoje sparčiai vyko tarptautiniai procesai. Remiantis portfelio teorija ir ankstesniais tyrimais apie tarptautines investicijas i nekilnojamaji turta, pag rindinis veiksnys, kuris skatina tarptautines nekilnojamojo turto investicijas ‐ tai galimybe gauti diversifi kacijos teikiama nauda. Darbe aptariama, kokia nauda siūle Suomijos nekilnojamojo turto rinka ankstyvaisiais internacionalizacijos metais. Kadangi kai kurie Suomijos nekilnojamojo turto rinkoje veikiantys tarptautiniai nekilnojamojo turto investuotojai užsiima tik nekilnojamuoju turtu, o yra ir tokiu, kurie turi mišraus turto portfelius, diversifi kacijos nauda nagrinejama ir pagal Suomijos mišraus turto portfeli, ir pagal tarptautini nekilnojamojo turto portfeli.
Transfection of Cultured Primary Neurons via Nucleofection
Authors: Zeitelhofer Manuel , Vessey John P. , Thomas Sabine , Kiebler Michael , Dahm Ralf
Published: April 2009

Despite the development of various transfection methods, the transfection of post‐mitotic cells, including neurons, poses a challenging task. Nucleofection, a specialized form of electroporation described in this unit, achieves high transfection efficiencies in primary mammalian neurons, such as hippocampal neurons, while simultaneously maintaining high cell viability. Therefore, it allows for biochemical analyses that rely on large numbers of transfected cells. The recently developed 96‐well shuttle system described in this unit further permits the transfection of up to 96 different constructs in a single experiment. This opens up the possibility for large‐scale experiments in primary neurons, such as shRNA‐mediated knock‐down of a wide range of target genes.Curr. Protoc. Neurosci. 47:4.32.1‐4.32.21. © 2009 by John Wiley & Sons, Inc.
Members' perception of their participation in the governance of cooperatives: the key to trust and commitment in agricultural cooperatives
Authors: Österberg Peter , Nilsson Jerker
Published: April 2009

This study explores the extent to which members' assessment of their cooperatives' degree of success is related to various member attributes, notably the members' perception of their participation in the governance of the cooperatives. Three categories of member attributes are identified: satisfaction with the profitability of farm operations, age of the member, and experience from board work. The cooperatives' degree of success is measured as members' commitment towards cooperatives, and members' trust in the board of directors.

The data originate from a mail survey among 2,250 Swedish farmers. The results indicate differences in members' commitment and their trust towards directors to be due to farm profitability, the members' age and experience as directors. After adding members' perception of their participation in the governance as a covariate, most of the other differences are explained by this variable. Age is still partly associated with trust towards directors; older farmers have less trust. [EconLit Classifications: Q13, D23, D72]. © 2009 Wiley Periodicals, Inc.
Application of Non‐Destructive Testing to Analyse SOFC Cells and Stacks
Authors: Wyss P. , Hack E. , Holtappels P.
Published: April 2009

Assuring high level of manufacturing quality and understanding degradation and ageing phenomena is a key requirement for the SOFC technology. In order to analyse structural failures in SOFC cells and stacks, electron and optical microscopy as well as chemical analysis require the destruction of cells and stacks in order to access the relevant structural areas. Non‐destructive test methods like thermography and radiography can assist in identifying the so‐called ‘hidden defects' in cells for both, quality assurance during production and identifying relevant areas for further destructive post mortem analysis. The evaluation of these non‐destructive test methods showed that useful information can be obtained with standard equipment, and the resolution limits have been identified. Combination of both thermography and radiography was applied to identify pores and other irregularities in the range of 10–100 μ. Pores in the vicinity of the cathode/electrolyte interface were observed by X‐ray tomography.
Seasonal hydrochemistry of a high Arctic wetland complex
Authors: Thompson Dan K. , Woo Ming‐Ko
Published: April 2009

The seasonal evolution in the hydrochemistry of four types of wetland (pond, ice wedge trough, wet meadow and mesic site) was studied in a 0·5 km2 wetland complex in the Canadian High Arctic on the Fosheim Peninsula, Ellesmere Island. In the spring, a large influx of overland runoff from snowmelt quickly flushed away the solutes of the ice stored on the wetland surface over the winter, and homogenized the hydrochemistry across the entire wetland complex. As the surface flow receded, various wetland patches became hydrologically disconnected and their hydrochemical characteristics evolved differently. Although underlain by marine sediments and saline permafrost, solute concentrations in much of the wetland complex remained dilute compared with many Arctic wetlands. Through continued evaporation, melting of ground ice and localized thermokarst activities, the hydrochemistry of different wetland types acquired their distinctive characteristics as the summer progressed. This study demonstrates that large diversity in wetland hydrochemistry occurs even within a limited area, indicating the need to caution against generalizations based on limited spatial and temporal samples. Copyright © 2009 John Wiley & Sons, Ltd.
The mediating role of social support in the community environment—psychological distress link among low‐income African American women
Authors: Lin Jielu , Thompson Martie P. , Kaslow Nadine J.
Published: April 2009

Living in a disordered community is negatively associated with psychological well‐being. We investigated the role of social support in the link between community environment and psychological distress in a sample of 152 African American women from low socioeconomic backgrounds in a large metropolitan southeastern city. Structural equation modeling revealed that the association between low quality of community environment and increased psychological distress was accounted for by the mediating role of social support. Findings suggest the importance of social support in improving the mental health of African American women from low socioeconomic backgrounds. Because social support is affected by the environment in which women live, interventions should be community‐focused. © 2009 Wiley Periodicals, Inc.
The assessment of positivity and negativity in social networks: the reliability and validity of the social relationships index
Authors: Campo Rebecca A. , Uchino Bert N. , Holt‐Lunstad Julianne , Vaughn Allison , Reblin, Maija , Smith Timothy W.
Published: April 2009

The Social Relationships Index (SRI) was designed to examine positivity and negativity in social relationships. Unique features of this scale include its brevity and the ability to examine relationship positivity and negativity at the level of the specific individual and social network. The SRI's psychometric properties were examined in three studies. The SRI demonstrated good psychometric properties, including test–retest reliability for the assessment of positivity and negativity, and of relationship classifications across social networks. Additionally, discriminant and convergent validity was established with existing social relationship and personality scales. Finally, the SRI showed some generalizability across different contexts. These studies suggest that the SRI is a reliable and valid alternative measure for use in health studies that require a shorter assessment of relationships. © 2009 Wiley Periodicals, Inc.
Macromol. Chem. Phys. 7/2009
Authors: Ulbricht Christoph , Rehmann Nina , Holder Elisabeth , Hertel Dirk , Meerholz Klaus , Schubert Ulrich S.
Published: April 2009

Cover: The cover image presents the design of a phosphorescent Ir(III) complex equipped with an oxetane unit. Admixed to crosslinkable matrix moieties the emitter can be copolymerized by a photoinduced cationic ring opening polymerization forming an insoluble network. Applied as emissive layer, fully solution processed multi‐layer OLEDs can be obtained. Further details can be found in the article by C. Ulbricht, N. Rehmann, E. Holder, D. Hertel, K. Meerholz,* U. S. Schubert* on page 531.
Organische Chemie 2008
Authors: Bräse Stefan
Published: April 2009

Organische Chemie — a la carte: Lotus‐Effekte mit Nanonadeln, heterolytische Aktivierung von Diwasserstoff durch frustrierte Lewis‐Säure/Base‐Paare, Hydroxycarben durch Blitzvakuumpyrolyse, nachwachsende Rohstoffe als Bausteine für die organische Synthese, Totalsynthese von Neopeltolid.