bluuebunny/crossref_metadata_2025 huggingface dataset:
Performing politics
Authors: Juris Jeffrey S.
Published: March 2008

This article brings together the anthropological, sociological, and related literature on media, emotion, and performance to explore the role of counter-summit protests within anti-corporate globalization movements. Counter-summit actions produce both external and internal effects, allowing activists to communicate political messages, while generating deeply felt emotions and political identities. However, activists eventually tire while public interest may wane as protests become routine. Moreover, the most unpredictable, free form actions which produce high levels of affective solidarity among core activists often elicit media frames that stigmatize or trivialize protesters. Through comparative ethnographic accounts of mass mobilizations in Prague and Barcelona and subsequent media analysis, I argue that counter-summit protests are important networking tools, but they are difficult to reproduce over time, while the emotional and media impacts of counter-summit actions are often contradictory. I further suggest that grasping the affective dimensions of protest requires an engaged and embodied ethnographic praxis.
Hottentot b-b-blues
Authors: Weinreb Alexander
Published: March 2008

In this short article I describe the experience of being a stuttering academic, drawing on what I jokingly describe as my longue-durée, multi-sited ethnography of stuttering — that is, my personal identity and experiences as an exotic stutterer moving through space and time. The article plays with the nominal equivalence between Hottentots as the group that long serviced Europeans and their imagined Africa and Hottentots as stutterers ( hotteren-totteren in German). Throughout, I discuss the nature of Hottentot community, reflect on Hottentot paranoia and the lure of the Hottentot (suggesting a Hottentot twist to Simmel's foundational stranger), and engage with some other themes arising from the lived experience of these particular speech deviants.
Teachers, policies and practices: A historical review of literacy teaching in Australia
Authors: Whitehead Kay , Wilkinson Lyn
Published: March 2008

This article uses a historical lens to illuminate literacy teaching as it is constructed in two recent reports, Teaching Reading and In Teachers' Hands. In surveying these texts alongside 19th-century sources, we show that an autonomous view of literacy has always held sway, along with a primary focus on reading. Parents' influence over literacy instruction has been eroded since the mid-19th century and the state has increasingly been implicated in constructing literacy teaching and defining the role of the teacher. What stands out, however, are the ways in which contemporary reports decontextualize literacy teaching, downplaying students' social locations and failing to recognize the infrastructure of mass compulsory schooling. In contrast to the 19th century when students' social class and irregular attendance were seen to mediate literacy achievement, `teacher quality' is all that counts in recent reports. Our historical perspective, therefore, not only highlights present concerns but also exposes some of the silences in these reports.
Wellness for all: the possibilities of cultural safety and cultural competence in New Zealand
Authors: DeSouza Ruth
Published: March 2008

Abstract

Responses to cultural diversity in nursing need to consider the theory and practice developments of the profession, whilst also responding to broader social and historical process that prevent marginalised groups from utilising universal health services. A combination of approaches is suggested in this paper to meet these two imperatives. Cultural safety is one indigenous New Zealand nursing approach derived in response to inequalities for Maori, whereas cultural competence is an imported paradigm derived from a multicultural context. Furthermore, research and dialogue are required to examine points of complementarity and tension. This paper offers a beginning for this process.
Appraisal of immunoglobulin free light chain as a marker of response
Authors: Dispenzieri Angela , Zhang Lijun , Katzmann Jerry A. , Snyder Melissa , Blood Emily , DeGoey Roberta , Henderson Kimberly , Kyle Robert A. , Oken Martin M. , Bradwell Arthur R. , Greipp Philip R.
Published: March 2008

The immunoglobulin free light chain (FLC) assay is an invaluable tool for following patients with oligosecretory plasma cell dyscrasia. Baseline values have also been shown to be prognostic in all plasma cell disorders tested. A looming question, however, is the role it should play in following myeloma patients with disease that is measurable using serum and urine electrophoresis. We used the data and stored samples from a mature Eastern Cooperative Oncology Group clinical trial (E9486) to assess serum levels of FLC at baseline and after 2 months of alkylator-based therapy. For serial determinations, the absolute level of involved serum FLC or the difference of the involved and uninvolved FLC is preferred over the ratio of involved to uninvolved FLC. FLC response after 2 months of therapy was superior to early M-protein measurement to predict overall response. The ideal cut-point for FLC change appears to be between 40% and 50% reduction. The correlation between serial measurements of serum FLC and urine M-protein is inadequate to abolish the serial 24-hour urine protein. Although baseline values of FLC are prognostic in newly diagnosed myeloma patients, serial measurements do not appear to have added value in patients who have M-proteins measurable by electrophoresis.
Addition of the microchromosome GGA25 to the chicken genome sequence assembly through radiation hybrid and genetic mapping
Authors: Douaud Marine , Fève Katia , Gerus Marie , Fillon Valérie , Bardes Suzanne , Gourichon David , Dawson Deborah A , Hanotte Olivier , Burke Terry , Vignoles Florence , Morisson Mireille , Tixier-Boichard Michèle , Vignal Alain , Pitel Frédérique
Published: March 2008

Background

The publication of the first draft chicken sequence assembly became available in 2004 and was updated in 2006. However, this does not constitute a definitive and complete sequence of the chicken genome, since the microchromosomes are notably under-represented. In an effort to develop maps for the microchromosomes absent from the chicken genome assembly, we developed radiation hybrid (RH) and genetic maps with markers isolated from sequence currently assigned to "chromosome Unknown" (chrUn). The chrUn is composed of sequence contigs not assigned to named chromosomes. To identify and map sequence belonging to the microchromosomes we used a comparative mapping strategy, and we focused on the small linkage group E26C13.

Results

In total, 139 markers were analysed with the chickRH6 panel, of which 120 were effectively assigned to the E26C13 linkage group, the remainder mapping elsewhere in the genome. The final RH map is composed of 22 framework markers extending over a 245.6 cR distance. A corresponding genetic map was developed, whose length is 103 cM in the East Lansing reference population. The E26C13 group was assigned to GGA25 (Gallus gallus chromosome 25) by FISH (fluorescence in situ hybridisation) mapping.

Conclusion

The high-resolution RH framework map obtained here covers the entire chicken chromosome 25 and reveals the existence of a high number of intrachromosomal rearrangements when compared to the human genome. The strategy used here for the characterization of GGA25 could be used to improve knowledge on the other uncharacterized small, yet gene-rich microchromosomes.
Microsatellite data suggest significant population structure and differentiation within the malaria vector Anopheles darlingi in Central and South America
Authors: Mirabello Lisa , Vineis Joseph H , Yanoviak Stephen P , Scarpassa Vera M , Póvoa Marinete M , Padilla Norma , Achee Nicole L , Conn Jan E
Published: March 2008

Background

Anopheles darlingi is the most important malaria vector in the Neotropics. An understanding of A. darlingi's population structure and contemporary gene flow patterns is necessary if vector populations are to be successfully controlled. We assessed population genetic structure and levels of differentiation based on 1,376 samples from 31 localities throughout the Peruvian and Brazilian Amazon and Central America using 5–8 microsatellite loci.

Results

We found high levels of polymorphism for all of the Amazonian populations (mean R
S = 7.62, mean H
O = 0.742), and low levels for the Belize and Guatemalan populations (mean R
S = 4.3, mean H
O = 0.457). The Bayesian clustering analysis revealed five population clusters: northeastern Amazonian Brazil, southeastern and central Amazonian Brazil, western and central Amazonian Brazil, Peruvian Amazon, and the Central American populations. Within Central America there was low non-significant differentiation, except for between the populations separated by the Maya Mountains. Within Amazonia there was a moderate level of significant differentiation attributed to isolation by distance. Within Peru there was no significant population structure and low differentiation, and some evidence of a population expansion. The pairwise estimates of genetic differentiation between Central America and Amazonian populations were all very high and highly significant (F
ST = 0.1859 – 0.3901, P < 0.05). Both the D
A and F
ST distance-based trees illustrated the main division to be between Central America and Amazonia.

Conclusion

We detected a large amount of population structure in Amazonia, with three population clusters within Brazil and one including the Peru populations. The considerable differences in N
e among the populations may have contributed to the observed genetic differentiation. All of the data suggest that the primary division within A. darlingi corresponds to two white gene genotypes between Amazonia (genotype 1) and Central America, parts of Colombia and Venezuela (genotype 2), and are in agreement with previously published mitochondrial COI gene sequences interpreted as incipient species. Overall, it appears that two main factors have contributed to the genetic differentiation between the population clusters: physical distance between the populations and the differences in effective population sizes among the subpopulations.
Transduction of E2F-1 TAT fusion proteins represses expression of hTERT in primary ductal breast carcinoma cell lines
Authors: Elliott Kimberly A , Rickords Lee F , Labrum J Marcelete
Published: March 2008

Background

Telomerase expression is detectable in 81–95% of breast carcinomas and may serve as a therapeutic target. The objective of this study was to investigate repression of telomerase activity in primary ductal breast cancer cells through transcriptional regulation of the catalytic subunit hTERT. We hypothesized that inhibition of telomerase expression could be achieved via Tat mediated protein transduction of the repressor protein E2F-1.

Methods

Protein purification techniques were refined to yield biologically active Tat fusion proteins (TFPs) capable of transducing the breast cancer cell lines HCC1937 and HCC1599. Cell lines were treated with wildtype E2F-1 (E2F-1/TatHA), mutant E2F-1 (E132/TatHA) and a control Tat peptide (TatHA) for 24 hours. Total RNA was isolated from treated cells, reverse transcribed and fold changes in gene expression for hTERT determined via real-time RT-qPCR.

Results

Significant repression of the catalytic subunit of telomerase (hTERT) was present in both HCC1937 and HCC1599 cells following treatment with E2F-1/TatHA. In HCC1937 cells, hTERT was repressed 3.5-fold by E2F-1/TatHA in comparison to E132/TatHA (p < 0.0012) and the TatHA peptide controls (p < 0.0024). In HCC1599 cells, hTERT was also repressed with E2F-1/TatHA treatment by 4.0-fold when compared to the E132/TatHA control (p < 0.0001). A slightly lower hTERT repression of 3.3-fold was observed with E2F-1/TatHA in the HCC1599 cells when compared to the TatHA control (p < 0.0001).

Conclusion

These results suggest that transduction of E2F-1/TatHA fusion proteins in vitro is an effective repressor of hTERT expression in the primary ductal breast cancer cell lines HCC1937 and HCC1599.
The Quality Improvement Demonstration Study: An example of evidence-based policy-making in practice
Authors: Shimkhada Riti , Peabody John W , Quimbo Stella A , Solon Orville
Published: March 2008

Background

Randomized trials have long been the gold-standard for evaluating clinical practice. There is growing recognition that rigorous studies are similarly needed to assess the effects of policy. However, these studies are rarely conducted. We report on the Quality Improvement Demonstration Study (QIDS), an example of a large randomized policy experiment, introduced and conducted in a scientific manner to evaluate the impact of large-scale governmental policy interventions.

Methods

In 1999 the Philippine government proposed sweeping reforms in the National Health Sector Reform Agenda. We recognized the unique opportunity to conduct a social experiment. Our ongoing goal has been to generate results that inform health policy. Early on we concentrated on developing a multi-institutional collaborative effort. The QIDS team then developed hypotheses that specifically evaluated the impact of two policy reforms on both the delivery of care and long-term health status in children. We formed an experimental design by randomizing matched blocks of three communities into one of the two policy interventions plus a control group. Based on the reform agenda, one arm of the experiment provided expanded insurance coverage for children; the other introduced performance-based payments to hospitals and physicians. Data were collected in household, hospital-based patient exit, and facility surveys, as well as clinical vignettes, which were used to assess physician practice. Delivery of services and health status were evaluated at baseline and after the interventions were put in place using difference-in-difference estimation.

Results

We found and addressed numerous challenges conducting this study, namely: formalizing the experimental design using the existing health infrastructure; securing funding to do research coincident with the policy reforms; recognizing biases and designing the study to account for these; putting in place a broad data collection effort to account for unanticipated findings; introducing sustainable policy interventions based on the reform agenda; and providing results in real-time to policy makers through a combination of venues.

Conclusion

QIDS demonstrates that a large, prospective, randomized controlled policy experiment can be successfully implemented at a national level as part of sectoral reform. While we believe policy experiments should be used to generate evidence-based health policy, to do this requires opportunity and trust, strong collaborative relationships, and timing. This study nurtures the growing attitude that translation of scientific findings from the bedside to the community can be done successfully and that we should raise the bar on project evaluation and the policy-making process.
A transient benign lymph node-based proliferation of T-cells simulating non-Hodgkin lymphoma in a patient with psoriasis treated with tumor necrosis factor alpha and CD11a antagonists
Authors: Hurley M Yadira , George Mary Noel , Leonardi Craig L , Frater John L
Published: March 2008

Background

Therapeutic biologic agents are uncommonly associated with lymphoma.

Case presentation

We report a patient with psoriasis treated with the biologic agents efalizumab (Raptiva®) and etanercept (Enbrel®), who developed painless lymphadenopathy with peripheral lymphocytosis during treatment, simulating a non-Hodgkin lymphoma clinically and pathologically. Lymphocytosis and lymphadenopathy spontaneously remitted following cessation of etanercept therapy and have not recurred.

Conclusion

Distinction between clinically benign lymphoid proliferations related to antipsoriasis therapy and malignant lymphoma avoids the unnecessary use of anti-lymphoma chemotherapy.
Long term survival after coronary endarterectomy in patients undergoing combined coronary and valvular surgery – a fifteen year experience
Authors: Kumar Sanjay , Agarwala Sandeep , Talbot Charlie , Nair R. Unnikrishnan
Published: March 2008

Background

Coronary Endarterectomy (CE) in patients undergoing coronary artery bypass graft (CABG) surgery has been shown to be beneficial in those with diffuse coronary artery disease. There are no published data on its role and benefit in patients undergoing more complex operations. We present our experience with CE in patients undergoing valve surgery with concomitant CABG.

Materials and methods

Between 1989 and 2003, 237 patients underwent CABG with valve surgery under a single surgeon at our institution. Of these, 41 patients needed CE. Data was retrospectively obtained from hospital records and database. Further follow-up was obtained by telephone interview. All variables were analyzed by univariate analysis for significant factors relating to hospital mortality. Morbidity and long term survival was also studied. There were 29 males and 12 females with a mean age of 67.4 ± 8.1 and body mass index of 26.3 ± 3.3. Their mean euroscore was 7.6 ± 3.2 and the log euro score was 12.2 ± 16.1.

Results

Thirty-two patients were discharged from the intensive therapy unit within 48 hours after surgery. Average hospital stay was 12.7 ± 10.43 days. Thirty day mortality was 9.8%. Six late deaths occurred during the 14 year follow up. Ten year survival was 57.2% (95% CL 37.8%–86.6%). Three of the survivors had Class II symptoms, with one requiring nitrates. None required further percutaneous or surgical intervention. We compared the result with the available mortality figure from the SCTS database.

Conclusion

Compared to the SCTS database for these patients, we have observed that CE does not increase the mortality in combined procedures. By accomplishing revascularization in areas deemed ungraftable, we have shown an added survival benefit in this group of patients.
Maturation of dendritic cells for enhanced activation of anti-HIV-1 CD8+ T cell immunity
Authors: Huang Xiao-Li , Fan Zheng , Borowski LuAnn , Rinaldo Charles R
Published: March 2008

Maturation of dendritic cells (DC) to enhance their capacity to activate T cell immunity to HIV-1 is a key step in immunotherapy of HIV-1 infection with DC. We compared maturation of DC derived from HIV-1-uninfected subjects and infected subjects on antiretroviral therapy (ART) or ART naïve by CD40 ligand (CD40L) and combinations of TLR3 ligand polyinosinic:polycytidylic acid [poly(I:C)] and inflammatory cytokines IFN-γ, IFN-α, IL-1β, and TNF-α. The greatest levels of virus-specific IFN-γ production by CD8+ T cells were stimulated by DC treated with CD40L, followed by DC treated with the poly(I:C)-cytokine combination. The highest levels of IL-12p70 were produced by DC treated with CD40L + IFN-γ, followed by CD40L and the poly(I:C)-cytokine combination. Neutralization of IL-12p70 indicated that it was only partially involved in direct enhancement of antiviral CD8+ T cell activity. DC stimulation of antiviral CD8+ T cell reactivity was enhanced by activated CD4+ T cells at low concentrations but was suppressed at higher CD4+ T cell concentrations. Maturation of DC with CD40L obviated the need for CD4+ T cell help and overcame this suppressive activity. Finally, we showed that DC from HIV-1-infected subjects on ART, which were treated with the poly(I:C)-cytokine combination, retained the capacity to produce IL-12p70 and activate anti-HIV-1 CD8+ T cell responses after restimulation with CD40L, with or without IFN-γ. Thus, DC from HIV-1-infected subjects can be engineered with CD40L or a poly(I:C)-cytokine combination for enhancing CD8+ T cell responses to HIV-1, which has potential applications in HIV-1 immunotherapy.
Free Triiodothyronine Has a Distinct Circadian Rhythm That Is Delayed but Parallels Thyrotropin Levels
Authors: Russell W. , Harrison R. F. , Smith N. , Darzy K. , Shalet S. , Weetman A. P. , Ross R. J.
Published: March 2008

Context: TSH is known to have a circadian rhythm, but the relationship between this and any rhythm in T4 and T3 has not been clearly demonstrated.

Objective: With a view to optimizing thyroid hormone replacement therapy, we have used modern assays for free T4 (FT4) and free T3 (FT3) to investigate circadian rhythmicity.

Setting: The study was performed at a university hospital.

Design and Subjects: This was a cross-sectional study in 33 healthy individuals with 24-h blood sampling (TSH in 33 and FT4 and FT3 in 29 individuals) and cosinor analysis.

Results: Of the individuals, 100% showed a sinusoidal signal in TSH, for FT4 76%, and for FT3 86% (P < 0.05). For FT4 and FT3, the amplitude was low. For TSH the acrophase occurred at a clock time of 0240 h, and for FT3 approximately 90 minutes later at 0404 h. The group cosinor model predicts that TSH hormone levels remain above the mesor between 2020 and 0820 h, and for FT3 from 2200–1000 h. Cross correlation of FT3 with TSH showed that the peak correlation occurred with a delay of 0.5–2.5 h. When time-adjusted profiles of TSH and FT3 were compared, there was a strong correlation between FT3 and TSH levels (ρ = 0.80; P < 0.0001). In contrast, cross correlation revealed no temporal relationship between FT4 and TSH.

Conclusions: FT3 shows a circadian rhythm with a periodicity that lags behind TSH, suggesting that the periodic rhythm of FT3 is due to the proportion of T3 derived from the thyroid. Optimizing thyroid hormone replacement may need to take these rhythms into account.
Medullary Thyroid Cancer Responsiveness to Pentagastrin Stimulation: An Early Surrogate Parameter of Tumor Dissemination?
Authors: Machens Andreas , Hauptmann Steffen , Dralle Henning
Published: March 2008

Context: Because of its outstanding sensitivity, stimulation of calcitonin secretion with iv injection of pentagastrin is widely used for biochemical diagnosis of medullary thyroid cancer.

Objective: The objective of this study was to explore the relationship between the results of the pentagastrin stimulation test and extent of disease in patients with previously untreated medullary thyroid cancer.

Design: This was a retrospective study.

Setting: The investigation took place at a tertiary referral center.

Patients: Included were 89 patients with increased basal calcitonin levels who had a pentagastrin test at this institution before initial neck surgery for medullary thyroid cancer.

Main Outcome Measure: Measurements included basal and stimulated calcitonin levels, carcinoembryonic antigen levels, primary tumor diameter, extrathyroidal extension, lymph node metastases, and distant metastases.

Results: There was a strong dose-dependent relationship between a less than 10-fold increase in preoperative calcitonin levels after iv stimulation with pentagastrin and both the frequency (41–54 vs. 4–27%; P = 0.001) and number (means of 3.0–10.8 vs. 0–1.1 positive nodes, P < 0.001) of lymph node metastases. Weaker associations were identified with the respective frequency of extrathyroidal extension (14–27 vs. 0–7%; P = 0.027), distant metastasis (9–23 vs. 0%; P = 0.017), and postoperative normalization of calcitonin (40–55 vs. 53–82%; P = 0.029). On multivariate analysis, only lymph node metastases were associated with a less than 10-fold increase in preoperative calcitonin levels.

Conclusions: Based on these clinical data and preclinical literature, reduced responsiveness to stimulation with pentagastrin may reflect early dedifferentiation. Evidence of this condition may enable early risk stratification in patients with medullary thyroid cancer.
The use of a modified sliding-mode controller with time-delay control for unknown systems with uncertain disturbances
Authors: Chen Y-D , Tung P-C , Fuh C-C , Liao C-H
Published: March 2008

A modified sliding-mode controller (SMC) with time-delay control for non-linear systems with disturbance is presented. Unlike a conventional SMC, the proposed approach does not require the identification of system parameters or the estimation of the bounds of disturbances. A novel sliding surface is designed in the modified SMC. The proposed approach provides an easy design method to maintain the convergence of errors by design requirement and uses the lower switching gain to maintain robustness which is in contrast to using a conventional SMC. Simulation results demonstrate that the proposed method is better than a conventional SMC in controlling a non-linear system with disturbances.
Effects of fretting wear on rolling contact fatigue life of M50 bearing steel
Authors: Warhadpande A , Leonard B , Sadeghi F
Published: March 2008

The current study presents the results and effects of fretting wear on rolling contact fatigue (RCF) life of M50 bearing steel. A fretting wear test rig was designed and developed to induce fretting scars on the surface of standard M50 rods commonly used in a three ball and rod RCF testing machine. The fretting machine was used to induce fretting scars at a Hertzian contact pressure of 1.1 GPa, in the presence of MIL-L-23699 lubricant at a frequency of 10 Hz, slip amplitude of 21 µm for different number of cycles. The fretted rods were then evaluated at a contact pressure of 1.7 and 3.4 GPa in the three ball and rod RCF tester to determine the effect of fretted scar on fatigue life. The results indicate that a fretting scar can reduce the fatigue life at 3.4 GPa by an average of 30 per cent and fretted rods operating at 1.7 GPa behave very similar to an unfretted rod operating at 3.4 GPa.
Variable ordering schemes to apply to the binary decision diagram methodology for event tree sequences assessment
Authors: Ibáñez-Llano C , Meléndez E , F Nieto
Published: March 2008

Binary decision diagram (BDD) methodology is the most recent approach to improve Boolean reliability models assessment. The final size of the BDD, and therefore the ultimate benefits of this technique, are very sensitive to the initial variable ordering that has to be fixed prior to conversion. Several variable ordering strategies have been proposed in the literature, all of them focused on the treatment of single fault tree models. This paper proposes some extensions of existing variable ordering schemes for the case of combinations of non-disjoint fault trees, as is the case in quantifying sequences of event trees. These extensions work by combining ordering schemes applied to each fault tree, and exploring the cases where variables within the domains intersection are kept together or not. They have been specifically designed to be applied together with an incremental procedure to compute the BDD of the sequence accumulatively and to be used to quantify sequences of dynamic event trees. Preliminary results show the potential of this approach.
A Maximal-Space Algorithm for the Container Loading Problem
Authors: Parreño F. , Alvarez-Valdes R. , Tamarit J. M. , Oliveira J. F.
Published: March 2008

In this paper, a greedy randomized adaptive search procedure (GRASP) for the container loading problem is presented. This approach is based on a constructive block heuristic that builds upon the concept of maximal space, a nondisjoint representation of the free space in a container.

This new algorithm is extensively tested over the complete set of Bischoff and Ratcliff problems [Bischoff, E. E., M. S. W. Ratcliff. 1995. Issues in the development of approaches to container loading. Omega 23 377–390], ranging from weakly heterogeneous to strongly heterogeneous cargo, and outperforms all the known nonparallel approaches that, partially or completely, have used this set of test problems. When comparing against parallel algorithms, it is better on average but not for every class of problem. In terms of efficiency, this approach runs in much less computing time than that required by parallel methods. Thorough computational experiments concerning the evaluation of the impact of algorithm design choices and internal parameters on the overall efficiency of this new approach are also presented.
Efficacy of Add-On Topiramate Therapy in Psychiatric Patients with Weight Gain
Authors: Cates Marshall E , Feldman Jacqueline M , Boggs Angela A , Woolley Thomas W , Whaley Nanci P
Published: March 2008

BACKGROUND:

Weight gain is a common adverse effect of many psychotropic medications including antipsychotics, antidepressants, and mood stabilizers. There is a growing body of evidence that topiramate may be useful as an add-on therapy to induce weight loss in patients who have experienced psychotropic-induced weight gain.

OBJECTIVE:

To determine the efficacy and tolerability of topiramate for treatment of weight gain in a naturalistic mental health clinic setting.

METHODS:

A retrospective chart review was conducted at a community mental health clinic. Subjects were non-elderly adults who received topiramate therapy beginning in 2002–2005 for documented weight gain during treatment with psychotropic drugs. Primary outcome measures included response rate (based on weight loss of any magnitude) and mean changes in weight and body mass index (BMI).

RESULTS:

Forty-one patients were included in the study. There was a 58.5% (n = 24) response rate. Mean reductions in weight and BMI were approximately 2.2 kg and 0.5 points, respectively. Responders lost an average of 7.2 kg, whereas nonresponders gained an average of 5.0 kg. Patients with a baseline weight of at least 91 kg and those receiving a greater number of psychotropic medications were more likely to experience success with topiramate therapy. Of the 24 patients who responded to therapy, 22 experienced onset of weight reduction by the next clinic visit (1–4 mo) following either initiation of therapy or titration to the eventual therapeutic dose, and the usual rate of weight loss was 0.45–1.4 kg per month. Therapy was typically initiated at 50 mg/day. The mean maximum dose was 93.9 mg/day and the median maximum dose was 100 mg/day. Seven (17.1%) patients had documented adverse effects to topiramate therapy.

CONCLUSIONS:

Topiramate therapy resulted in overall modest (ie, <2%) decreases in weight and BMI, but many patients experienced more impressive weight loss. Therapy was generally well tolerated.
Phosphatidylinositol-3-Kinase–Atypical Protein Kinase C Signaling Is Required for Wnt Attraction and Anterior–Posterior Axon Guidance
Authors: Wolf Alex M. , Lyuksyutova Anna I. , Fenstermaker Ali G. , Shafer Beth , Lo Charles G. , Zou Yimin
Published: March 2008

Wnt proteins are conserved axon guidance cues that control growth cone navigation. However, the intracellular signaling mechanisms that mediate growth cone turning in response to Wnts are unknown. We previously showed that Wnt–Frizzled signaling directs spinal cord commissural axons to turn anteriorly after midline crossing through an attractive mechanism. Here we show that atypical protein kinase C (aPKC), is required for Wnt-mediated attraction of commissural axons and proper anterior–posterior (A–P) pathfinding. A PKCζ pseudosubstrate, a specific blocker of aPKC activity, and expression of a kinase-defective PKCζ mutant in commissural neurons resulted in A–P randomization in “open-book” explants. Upstream of PKCζ, heterotrimeric G-proteins and phosphatidylinositol-3-kinases (PI3Ks), are also required for A–P guidance, because pertussis toxin, wortmannin, and expression of a p110γ kinase-defective construct all resulted in A–P randomization. Overexpression of p110γ, the catalytic subunit of PI3Kγ, caused precocious anterior turning of commissural axons before midline crossing in open-book explants and caused dissociated precrossing commissural axons, which are normally insensitive to Wnt attraction, to turn toward Wnt4-expressing cells. Therefore, we propose that atypical PKC signaling is required for Wnt-mediated A–P axon guidance and that PI3K can act as a switch to activate Wnt responsiveness during midline crossing.
A Molecular Platform in Neurons Regulates Inflammation after Spinal Cord Injury
Authors: de Rivero Vaccari Juan Pablo , Lotocki George , Marcillo Alex E. , Dietrich W. Dalton , Keane Robert W.
Published: March 2008

Vigorous immune responses are induced in the immune privileged CNS by injury and disease, but the molecular mechanisms regulating innate immunity in the CNS are poorly defined. The inflammatory response initiated by spinal cord injury (SCI) involves activation of interleukin-1β (IL-1β) that contributes to secondary cell death. In the peripheral immune response, the inflammasome activates caspase-1 to process proinflammatory cytokines, but the regulation of trauma-induced inflammation in the CNS is not clearly understood. Here we show that a molecular platform [NALP1 (NAcht leucine-rich-repeat protein 1) inflammasome] consisting of caspase-1, caspase-11, ASC (apoptosis-associated speck-like protein containing a caspase-activating recruitment domain), and NALP1 is expressed in neurons of the normal rat spinal cord and forms a protein assembly with the X-linked inhibitor of apoptosis protein (XIAP). Moderate cervical contusive SCI induced processing of IL-1β, IL-18, activation of caspase-1, cleavage of XIAP, and promoted assembly of the multiprotein complex. Anti-ASC neutralizing antibodies administered to injured rats entered spinal cord neurons via a mechanism that was sensitive to carbenoxolone. Therapeutic neutralization of ASC reduced caspase-1 activation, XIAP cleavage, and interleukin processing, resulting in significant tissue sparing and functional improvement. Thus, rat spinal cord neurons contain a caspase-1, pro-ILβ, and pro-IL-18 activating complex different from the human NALP1 inflammasome that constitutes an important arm of the innate CNS inflammatory response after SCI.
Adaptation across the Cortical Hierarchy: Low-Level Curve Adaptation Affects High-Level Facial-Expression Judgments
Authors: Xu Hong , Dayan Peter , Lipkin Richard M. , Qian Ning
Published: March 2008

Adaptation is ubiquitous in sensory processing. Although sensory processing is hierarchical, with neurons at higher levels exhibiting greater degrees of tuning complexity and invariance than those at lower levels, few experimental or theoretical studies address how adaptation at one hierarchical level affects processing at others. Nevertheless, this issue is critical for understanding cortical coding and computation. Therefore, we examined whether perception of high-level facial expressions can be affected by adaptation to low-level curves (i.e., the shape of a mouth). After adapting to a concave curve, subjects more frequently perceived faces as happy, and after adapting to a convex curve, subjects more frequently perceived faces as sad. We observed this multilevel aftereffect with both cartoon and real test faces when the adapting curve and the mouths of the test faces had the same location. However, when we placed the adapting curve 0.2° below the test faces, the effect disappeared. Surprisingly, this positional specificity held even when real faces, instead of curves, were the adapting stimuli, suggesting that it is a general property for facial-expression aftereffects. We also studied the converse question of whether face adaptation affects curvature judgments, and found such effects after adapting to a cartoon face, but not a real face. Our results suggest that there is a local component in facial-expression representation, in addition to holistic representations emphasized in previous studies. By showing that adaptation can propagate up the cortical hierarchy, our findings also challenge existing functional accounts of adaptation.
Transducin γ-Subunit Sets Expression Levels of α- and β-Subunits and Is Crucial for Rod Viability
Authors: Lobanova Ekaterina S. , Finkelstein Stella , Herrmann Rolf , Chen Yen-Ming , Kessler Christopher , Michaud Norman A. , Trieu Lynn H. , Strissel Katherine J. , Burns Marie E. , Arshavsky Vadim Y.
Published: March 2008

Transducin is a prototypic heterotrimeric G-protein mediating visual signaling in vertebrate photoreceptor cells. Despite its central role in phototransduction, little is known about the mechanisms that regulate its expression and maintain approximately stoichiometric levels of the α- and βγ-subunits. Here we demonstrate that the knock-out of transducin γ-subunit leads to a major downregulation of both α- and β-subunit proteins, despite nearly normal levels of the corresponding transcripts, and fairly rapid photoreceptor degeneration. Significant fractions of the remaining α- and β-subunits were mislocalized from the light-sensitive outer segment compartment of the rod. Yet, the tiny amount of the α-subunit present in the outer segments of knock-out rods was sufficient to support light signaling, although with a markedly reduced sensitivity. These data indicate that the γ-subunit controls the expression level of the entire transducin heterotrimer and that heterotrimer formation is essential for normal transducin localization. They further suggest that the production of transducin β-subunit without its constitutive γ-subunit partner sufficiently stresses the cellular biosynthetic and/or chaperone machinery to induce cell death.
Low Endogenous G-Protein-Coupled Receptor Kinase 2 Sensitizes the Immature Brain to Hypoxia–Ischemia-Induced Gray and White Matter Damage
Authors: Nijboer Cora H. A. , Kavelaars Annemieke , Vroon Anne , Groenendaal Floris , van Bel Frank , Heijnen Cobi J.
Published: March 2008

Hypoxic–ischemic brain injury is regulated in part by neurotransmitter and chemokine signaling via G-protein-coupled receptors (GPCRs). GPCR-kinase 2 (GRK2) protects these receptors against overstimulation by inducing desensitization. Neonatal hypoxic–ischemic brain damage is preceded by a reduction in cerebral GRK2 expression. We determined the functional importance of GRK2 in hypoxic–ischemic brain damage.

Nine-day-old wild-type and GRK2+/−mice with a ∼50% reduction in GRK2 protein were exposed to unilateral carotid artery occlusion and hypoxia. In GRK2+/−animals, gray and white matter damage was aggravated at 3 weeks after hypoxia–ischemia. In addition, cerebral neutrophil infiltration was increased in GRK2+/−animals. Neutrophil depletion reduced brain damage, but neuronal loss was still more pronounced in GRK2+/−animals. Onset of neuronal loss was advanced in GRK2+/−animals regardless of neutrophil depletion. White matter injury was advanced in GRK2+/−animals and was not affected by neutrophil depletion. Activation/infiltration of microglia/macrophages was stronger in GRK2+/−brains but only occurred 24 h after hypoxia–ischemia and is therefore not the primary cause of increased damage. During hypoxia, cerebral blood flow was reduced to the same extent in both genotypes.In vitro, GRK2+/−hippocampal slices and cerebellar granular neurons were more sensitive to glutamate-induced death.

We propose the novel concept that the kinase GRK2 regulates onset and magnitude of hypoxic–ischemic brain damage. Increased gray and white matter damage in GRK2+/−animals was not dependent on infiltrating neutrophils and occurred before microglia/macrophage activation was detected. Collectively, our data suggest that cerebral GRK2 has an important endogenous neuroprotective role in ischemic cerebral damage.
The Crucial Role of Chromogranins in Storage and Exocytosis Revealed Using Chromaffin Cells from Chromogranin A Null Mouse
Authors: Montesinos Monica S. , Machado J. David , Camacho Marcial , Diaz Jesica , Morales Yezer G. , Alvarez de la Rosa Diego , Carmona Emilia , Castañeyra Agustin , Viveros O. Humberto , O'Connor Daniel T. , Mahata Sushil K. , Borges Ricardo
Published: March 2008

Chromogranins (Cgs) are the major soluble proteins of dense-core secretory vesicles. Chromaffin cells fromChganull mice [chromogranin A knock-out (CgA-KO)] exhibited ∼30% reduction in the content and in the release of catecholamines compared with wild type. This was because of a lower secretion per single exocytotic event, rather than to a lower frequency of exocytotic events. Cell incubation withl-DOPA produced an increase in the vesicular amine content of wild-type, but not CgA-KO vesicles. In contrast, intracellular electrochemistry showed thatl-DOPA produced a significantly larger increase in cytosolic amines in CgA-KO cells than in the wild type. These data indicate that the mechanisms for vesicular accumulation in CgA-KO cells were fully saturated. Patch-amperometry recordings showed a delayed initiation of the amperometric signal after vesicle fusion, whereas no changes were observed in vesicle size or fusion pore kinetics despite the smaller amine content. We conclude that intravesicular proteins are highly efficient systems directly implicated in transmitter accumulation and in the control of neurosecretion.
Connexin 43 Delimits Functional Domains of Neurogenic Precursors in the Spinal Cord
Authors: Russo Raúl E. , Reali Cecilia , Radmilovich Milka , Fernández Anabel , Trujillo-Cenóz Omar
Published: March 2008

The cells lining the central canal (CC) of the spinal cord derive from the ventral part of the neural tube and, in some vertebrates, are responsible for the functional recovery after spinal cord injury. The region that surrounds the CC in the turtle contains proliferating cells that seem to generate both glia and neurons. Understanding the biology of spinal progenitors with the potential to generate new neurons “in situ” is important for cell replacement therapies. Here, we aimed to identify and characterize precursor cells in the spinal cord ofTrachemys dorbignyi. To evaluate the population of proliferating cells, 5-bromo-2′-deoxyuridine (BrdU) was injected every 4 h (50 μg/g, i.p.) during 24 h. We found BrdU+nuclei around the CC with a higher density in the lateral quadrants, in which whole-cell patch-clamp recordings showed extensive dye coupling of cells. Carbenoxolone (100 μm) increased the input resistance, suggesting strong gap junction coupling among precursors. The expression of brain lipid binding protein (a marker of a subtype of radial glia) and Pax6 matched the location of clusters, suggesting these cells belonged to a domain of neurogenic precursors. These domains were delimited by a high density of connexin 43 (Cx43) located on the endfeet of CC contacting cells. Our findings indicate that spinal precursors share basic properties with those in the embryo and neurogenic niches of the adult brain, and support a key role of functional clustering via Cx43 in spinal cord neurogenesis.
Relación entre médicos y pacientes con VIH: influencia en apego terapéutico y calidad de vida
Authors: Herrera Cristina , Campero Lourdes , Caballero Marta , Kendall Tamil
Published: March 2008

OBJETIVO: Analizar factores de la relación con los médicos que afectan la adherencia terapéutica y la calidad de vida de las personas con VIH/Sida. MÉTODOS: Estudio cualitativo realizado en México en 2003 con informantes reclutados en grupos de autoayuda y organizaciones no gubernamentales de VIH/Sida y servicios de infectología de hospitales públicos. Fueron entrevistadas 40 personas viviendo con VIH/Sida y cinco líderes de grupos de autoapoyo. Para la recolección de datos los informantes respondieron un cuestionario sociodemográfico y entrevistas en profundidad sobre la experiencia de vivir con VIH/sida, incluyendo los tratamientos, la percepción de la enfermedad, la calidad de vida, la salud física y emocional y la relación con los médicos. Las respuestas fueron grabadas, transcritas y organizadas por temas en base a códigos, usando un análisis inductivo. RESULTADOS: La edad de la mayoría de los entrevistados varió entre 26 y 45 años. Los principales problemas durante la búsqueda de atención se relacionaron con la falta de conciencia de riesgo y de información entre las personas viviendo con VIH/Sida y los médicos. Los médicos mostraron falta de capacitación en VIH/Sida. En la etapa de continuidad de la atención, los problemas se relacionaron con una adherencia terapéutica deficiente, producto principalmente de la falta de comunicación con los médicos y de la discriminación en los servicios públicos. CONCLUSIONES: De manera general se observaron problemas de información; falta de capacitación y paternalismo por parte de los médicos, y estigma social de las personas viviendo con VIH/Sida asociado a la epidemia.
Effects of Pharmacist Outpatient Interventions on Adults with Diabetes Mellitus: A Systematic Review
Authors: Wubben Deborah P. , Vivian Eva M.
Published: March 2008

As an integral part of the United States health care delivery system, pharmacists are ideally positioned to provide diabetes mellitus management. In this systematic review, we assessed the effectiveness of diabetes quality improvement strategies delivered by pharmacists in outpatient settings. Five electronic databases were searched for articles published through August 2007. Only randomized controlled trials, controlled clinical trials, or cohort studies with a control group were eligible for inclusion. All interventions targeted adults with type 1 or 2 diabetes and measured diabetes‐related complications and/or surrogate outcomes of hemoglobin A1c (A1C), blood pressure, or lipid profiles. Study data were abstracted by one author and checked by a second author following a standardized template. Results were synthesized narratively, and study‐specific effect measures were calculated for the outcomes of interest. Twenty‐one articles met the inclusion criteria: nine randomized controlled trials, one controlled clinical trial, and 11 cohort studies. All interventions involved additional visits by pharmacists with expanded roles to care for adult patients with diabetes. The A1C was the primary outcome of interest for all but two studies. Results of this review revealed overall improvement in A1C for patients in a diverse group of settings and across multiple study designs. Studies with smaller numbers of participants and those performed in the United States generally showed greater improvements in intervention group measures of A1C. A greater effect was also noted when pharmacists were afforded prescriptive authority. Only a few studies examined health care resource use; their results suggested that pharmacist interventions can reduce long‐term costs by improving glycemic control and thus diminishing future diabetes complications. Findings from this review are limited by flaws in the study designs, including the high potential for selection bias in the study populations. However, due to the clinical significance of reported improvements in A1C, further trials with pharmacist case managers are warranted. Prospective assessments of the comparable efficacy of pharmacists to improve diabetes outcomes through self‐management education and pharmacologic management are recommended.