bluuebunny/crossref_metadata_2025 huggingface dataset:
Daylight metrics and energy savings
Authors: Mardaljevic J , Heschong L , Lee E
Published: September 2009

The drive towards sustainable, low-energy buildings has increased the need for simple, yet accurate methods to evaluate whether a ‘daylit’ building meets minimum standards for energy and human comfort performance. Current metrics do not account for the temporal and spatial aspects of daylight, nor of occupants comfort or interventions. This paper reviews the historical basis of current compliance methods for achieving daylit buildings, proposes a technical basis for development of better metrics, and provides two case study examples to stimulate dialogue on how metrics can be applied in a practical, real-world context.
Three Dimensionality
Authors: Wojcieszak Magdalena E.
Published: September 2009

Visual critics interested in news primarily analyze still photographs in print media. Thus, the questions of how images in television news are contextualized, complemented, displaced, explained, or contradicted by the auditory channel and linguistic messages on the screen have not been studied extensively. Based on an exploratory content analysis of CNN, MSNBC, and FOX News coverage of the 9/11 terrorist attacks and Hurricane Katrina, the author categorizes the interplay between the three modes of information transmission in the broadcast news: moving footage (iconic messages), on-screen textual elements (linguistic messages), and voiceover (audio messages). The analysis identifies six organizing categories: (1) polysemy reduction, (2) meaning attainment through audio, (3) reinforcement, (4) contextualization and acquiring meaning, (5) contradiction, and (6) slogano-symbolism. These categories provide an interpretative framework for visual analyses of television news and offer new directions for research.
“Making It Our Own”
Authors: Matthews Julian
Published: September 2009

This article, based on an observational study of the BBC children’s news program Newsround (UK), discusses how news professionals’ particularized news culture shapes the production of the specialized news agenda. Studying the agenda-building process with this concern reveals how an understanding of their target audience plays an important role within the news-making process. This informs professionals’ collective understanding of an “ideal” Newsround story that is used within production to select and shape a simplified and personalized news agenda for children. The impact of this process on children’s “cultural rights” as would-be citizens as well as the importance of the news form and its inscribed audience for an understanding of agenda building is then addressed within the article’s conclusion.
Management of Spasticity After Spinal Cord Injury: Current Techniques and Future Directions
Authors: Elbasiouny Sherif M. , Moroz Daniel , Bakr Mohamed M. , Mushahwar Vivian K.
Published: September 2009

Spasticity, resulting in involuntary and sustained contractions of muscles, may evolve in patients with stroke, cerebral palsy, multiple sclerosis, brain injury, and spinal cord injury (SCI). The authors critically review the neural mechanisms that may contribute to spasticity after SCI and assess their likely degree of involvement and relative significance to its pathophysiology. Experimental data from patients and animal models of spasticity as well as computer simulations are evaluated. The current clinical methods used for the management of spasticity and the pharmacological actions of drugs are discussed in relation to their effects on spinal mechanisms. Critical assessment of experimental findings indicates that increased excitability of both motoneurons and interneurons plays a crucial role in pathophysiology of spasticity. New interventions, including forms of spinal electrical stimulation to suppress increased neuronal excitability, may reduce the severity of spasticity and its complications.
Acute Management of Stoma-Related Colocutaneous Fistula by Temporary Placement of a Self-Expanding Plastic Stent
Authors: Nikfarjam Mehrdad , Champagne Brad , Reynolds Harry L. , Poulose Benjamin K. , Ponsky Jeffrey L. , Marks Jeffrey M.
Published: September 2009

Colocutaneous fistulas are frequently the result of complications related to previous operative procedures and are a major cause of morbidity. Most are initially treated conservatively, with a large percentage eventually requiring further surgery for definitive treatment. The use of a temporary colonic stent for the management of colostomy-related colocutaneous fistula has not been previously described. Two patients with colocutaneous fistula related to end colostomies and opening into midline laparotomy wounds were treated by temporary plastic stenting. A removable Polyflex silicone stent was inserted into the stoma. Stent redeployment was needed on several occasions following partial stent expulsion. Midline wound healing was achieved in both cases by 6 weeks post—stent insertion, and complete fistula closure occurred in 1 case. Temporary stent placement in certain cases may aid in the management of a colocutaneous fistula associated with a colostomy to allow fecal diversion from wounds and aid fistula closure.
Lactoferrin decreases LPS-induced mitochondrial dysfunction in cultured cells and in animal endotoxemia model
Authors: Kruzel Marian L. , Actor Jeffrey K. , Radak Zsolt , Bacsi Attila , Saavedra-Molina Alfredo , Boldogh Istvan
Published: September 2009

Lactoferrin is a non-heme iron-binding glycoprotein, produced by mucosal epithelial cells and granulocytes in most mammalian species. It is involved in regulation of immune responses, possesses anti-oxidant, anti-carcinogenic, anti-inflammatory properties, and provides protection against various microbial infections. In addition, lactoferrin has been implicated in protection against the development of insult-induced systemic inflammatory response syndrome (SIRS) and its progression into septic conditions in vivo. Here we show a potential mechanism by which lactoferrin lessens oxidative insult at the cellular and tissue levels after lipopolysaccharide (LPS) exposure. Lactoferrin pretreatment of cells decreased LPS-mediated oxidative insults in a dose-dependent manner. Lipopolysaccharide-induced oxidative burst was found to be of mitochondrial origin, and release of reactive oxygen species (ROS) was localized to the respiratory complex III. Importantly, lactoferrin nearly abolished LPS-induced increases in mitochondrial ROS generation and the accumulation of oxidative damage in the DNA. In vivo, pretreatment of experimental animals with lactoferrin significantly (P<0.05) lowered LPS-induced mitochondrial dysfunction as shown by both decreased release of H2O2 and DNA damage in the mitochondria. In contrast, deferoxamine, an iron chelating compound, provided only partial protection in LPS-treated animals. Together, these data suggest that lactoferrin protects against oxidative insult at the mitochondrial level, and indicate a potential utility of lactoferrin in prevention and treatment of SIRS.
Histologically proven isoniazid hepatoxicity in complicated tuberculous salpingitis
Authors: Semfke Almut , Wackernagel Cornelia , Vier Hannelore , Schütz Alexander , Wiechmann Volker , Gillissen Adrian
Published: September 2009

Isoniazid (INH) hepatic injury is histologically indistinguishable from viral hepatitis and is related to individual susceptibility of patients who hydrolyze the drug to isonicotinic acid at different rates. We here present a case initially involving a complaint of lower abdominal pain, which was diagnosed after a long diagnostic work-up as tuberculous salpingitis and which is rare in women in developed countries. A lack of pulmonary effects further delayed correct diagnosis of the underlying tuberculosis infection. Based on the clinical follow up and liver histology, INH-induced severe hepatoxicity, which further contributed to the abdominal symptoms, could be confirmed. After adaptation of the standard therapeutic regimen no further complications occurred.
Special Segment: Soft Tissue Matrices—Soft-Tissue Augmentation of the Foot and Ankle Using an Acellular Regenerative Tissue Scaffold
Authors: Brigido Stephen A.
Published: September 2009

Surgical treatment of damaged soft-tissue structures in the young and physically active patient requires keen understanding of biomechanical forces that are placed on the repair during rehabilitation. Over the years, several materials have been evaluated to mechanically augment suture repair. Autograft tissues such as the gastrocnemius fascia, flexor hallicus longus, peroneus brevis, fascia lata, and plantaris have been implemented successfully. Concerns over donor site morbidity have limited the use of these autologous tissues. Allografts such as fascia lata and tendon have been used successfully but are plagued with practical issues such as inflammatory reaction and suture retention weakness. Acellular regenerative tissue scaffolds have gained in popularity in recent years because of the limited host inflammatory response, ease of use, and high tensile strength.
MAL/SRF complex is involved in platelet formation and megakaryocyte migration by regulating MYL9 (MLC2) and MMP9
Authors: Gilles Laure , Bluteau Dominique , Boukour Siham , Chang Yunhua , Zhang Yanyan , Robert Thomas , Dessen Philippe , Debili Najet , Bernard Olivier A. , Vainchenker William , Raslova Hana
Published: September 2009

Megakaryoblastic leukemia 1 (MAL) is a transcriptional coactivator of serum response factor (SRF). In acute megakaryoblastic leukemia, the MAL gene is translocated and fused with the gene encoding one twenty-two (OTT). Herein, we show that MAL expression increases during the late differentiation steps of neonate and adult human megakaryopoiesis and localized into the nucleus after Rho GTPase activation by adhesion on collagen I or convulxin. MAL knockdown in megakaryocyte progenitors reduced the percentage of cells forming filopodia, lamellipodia, and stress fibers after adhesion on the same substrates, and reduced proplatelet formation. MAL repression led to dysmorphic megakaryocytes with disorganized demarcation membranes and α granules heterogeneously scattered in the cytoplasm. Gene expression profiling revealed a marked decrease in metalloproteinase 9 (MMP-9) and MYL9 expression after MAL inhibition. Luciferase assays in HEK293T cells and chromatin immunoprecipitation in primary megakaryocytes showed that the MAL/SRF complex directly regulates MYL9 and MMP9 in vitro. Megakaryocyte migration in response to stromal cell–derived factor 1, through Matrigel was considerably decreased after MAL knockdown, implicating MMP9 in migration. Finally, the use of a shRNA to decrease MYL9 expression showed that MYL9 was involved in proplatelet formation. MAL/SRF complex is thus involved in platelet formation and megakaryocyte migration by regulating MYL9 and MMP9.
On the adaptation of endosteal stem cell niche function in response to stress
Authors: Jiang Yi , Bonig Halvard , Ulyanova Tatiana , Chang KaiHsin , Papayannopoulou Thalia
Published: September 2009

Although the influence of microenvironmental “niche” on the function of a variety of stem cells is undisputed, the details of hematopoietic stem cell/niche interactions at the cellular and molecular level have sparked a continuous debate. We studied the microanatomic partitioning of transplanted normal and α4 integrin-deficient Lin−kit+ cells in trabecular and compact bone before and after irradiation and present robust quantitative data on both. We found that (1) the microanatomic distribution of normal highly enriched progenitor cells is random in nonirradiated recipients based on area distribution analyses, (2) in contrast, in irradiated hosts normal cells distribute preferentially near the endosteum, (3) the overall cell seeding efficiency was higher in trabecular versus compact bone both before and after irradiation, and (4) α4 integrin-deficient cells not only lodge with reduced overall efficiency confirming previous data, but fail to preferentially partition themselves into endosteal regions in irradiated hosts, as normal cells do. A similar phenotype was observed with cells rendered Gi-protein signaling incompetent by pertussis toxin treatment, supporting an active stromal-derived factor 1 (SDF-1) gradient near endosteum after irradiation.
Deferasirox pharmacokinetics in patients with adequate versus inadequate response
Authors: Chirnomas Deborah , Smith Amber Lynn , Braunstein Jennifer , Finkelstein Yaron , Pereira Luis , Bergmann Anke K. , Grant Frederick D. , Paley Carole , Shannon Michael , Neufeld Ellis J.
Published: September 2009

Tens of thousands of transfusion-dependent (eg, thalassemia) patients worldwide suffer from chronic iron overload and its potentially fatal complications. The oral iron chelator deferasirox has become commercially available in many countries since 2006. Although this alternative to parenteral deferoxamine has been a major advance for patients with transfusional hemosiderosis, a proportion of patients have suboptimal response to the maximum approved doses (30 mg/kg per day), and do not achieve negative iron balance. We performed a prospective study of oral deferasirox pharmacokinetics (PK), comparing 10 transfused patients with inadequate deferasirox response (rising ferritin trend or rising liver iron on deferasirox doses > 30 mg/kg per day) with control transfusion-dependent patients (n = 5) with adequate response. Subjects were admitted for 4 assessments: deferoxamine infusion and urinary iron measurement to assess readily chelatable iron; quantitative hepatobiliary scintigraphy to assess hepatic uptake and excretion of chelate; a 24-hour deferasirox PK study following a single 35-mg/kg dose of oral deferasirox; and pharmacogenomic analysis. Patients with inadequate response to deferasirox had significantly lower systemic drug exposure compared with control patients (P < .00001). Cmax, volume of distribution/bioavailability (Vd/F), and elimination half-life (t1/2) were not different between the groups, suggesting bioavailability as the likely discriminant. Effective dosing regimens for inadequately responding patients to deferasirox must be determined. This trial has been registered at http://www.clinicaltrials.gov under identifier NCT00749515.
Pancreatic iron loading predicts cardiac iron loading in thalassemia major
Authors: Noetzli Leila J. , Papudesi Jhansi , Coates Thomas D. , Wood John C.
Published: September 2009

Diabetes mellitus and cardiomyopathy are common in chronically transfused thalassemia major patients, occurring in the second and third decades of life. We postulated that pancreatic iron deposition would precede cardiac iron loading, representing an environment favorable for extrahepatic iron deposition. To test this hypothesis, we examined pancreatic and cardiac iron in 131 thalassemia major patients over a 4-year period. Cardiac iron (R2* > 50 Hz) was detected in 37.7% of patients and pancreatic iron (R2* > 28 Hz) in 80.4% of patients. Pancreatic and cardiac R2* were correlated (r2 = 0.52), with significant pancreatic iron occurring nearly a decade earlier than cardiac iron. A pancreatic R2* less than 100 Hz was a powerful negative predictor of cardiac iron, and pancreatic R2* more than 100 Hz had a positive predictive value of more than 60%. In serial analysis, changes in cardiac iron were correlated with changes in pancreatic iron (r2 = 0.33, P < .001), but not liver iron (r2 = 0.025, P = .25). As a result, pancreatic R2* measurements offer important early recognition of physiologic conditions suitable for future cardiac iron deposition and complementary information to liver and cardiac iron during chelation therapy. Staging abdominal and cardiac magnetic resonance imaging examinations could significantly reduce costs, magnet time, and need for sedation in young patients.
The small heat shock protein (sHSP) genes in the silkworm, Bombyx mori, and comparative analysis with other insect sHSP genes
Authors: Li Zi-Wen , Li Xue , Yu Quan-You , Xiang Zhong-Huai , Kishino Hirohisa , Zhang Ze
Published: September 2009

Background

Small heat shock proteins (sHSPs) are products of heat shock response and of other stress responses, and ubiquitous in all three domains of life, archaea, bacteria, and eukarya. They mainly function as molecular chaperones to protect proteins from being denatured in extreme conditions. Study on insect sHSPs could provide some insights into evolution of insects that have adapted to diverse niches in the world.

Results

Taking advantage of the newly assembled genome sequence, we performed a genome-wide analysis of the candidate sHSP genes in the silkworm, Bombyx mori. Based on known silkworm sHSP sequences, we identified 16 silkworm sHSP genes. Most of them are distributed on two silkworm chromosomes 5 and 27, respectively. 15 of 16 silkworm sHSPs have expression evidence. The comparative analysis of insect sHSPs from B. mori, Drosophila melanogaster, Apis mellifera, Tribolium castaneum, and Anopheles gambiae revealed that there is only one orthologous cluster whereas remaining clusters are species-specific on the phylogenetic tree. This suggested that most of sHSPs might have diverged in function across insects investigated. In addition, the data presented in this study also revealed that sHSPs in the insect orthologous cluster are highly conserved in both sequence and expression pattern. In sum, insect sHSPs show a completely different evolutionary pattern from that found in vertebrate sHSPs.

Conclusion

B. mori has the largest number of insect sHSP genes characterized to date, including 16 genes. The inference that most species-specific sHSPs might have diverged in function across insects investigated will help us understand the adaptability of these insects to diverse environments.
Procalcitonin as a biomarker for severe Plasmodium falciparum disease: a critical appraisal of a semi-quantitative point-of-care test in a cohort of travellers with imported malaria
Authors: Hesselink Dennis A , Burgerhart Jan-Steven , Bosmans-Timmerarends Hanna , Petit Pieter , van Genderen Perry JJ
Published: September 2009

Background

Imported malaria occurs as a relatively rare event in developed countries. As a consequence, most clinicians have little experience in making clinical assessments of disease severity and decisions regarding the need for parenteral therapy or high-level monitoring. In this study, the diagnostic accuracy of procalcitonin (PCT) for severe Plasmodium falciparum disease was assessed in a cohort of 100 consecutive travellers with various species of imported malaria.

Methods and results

In all patients, PCT was measured on admission with a semi-quantitative 'point-of-care' test. Patients with severe P. falciparum malaria had significantly higher median PCT levels on admission as compared with patients with uncomplicated P. falciparum disease. In addition, PCT levels in patients with non-falciparum malaria were also higher compared with patients with non-severe falciparum malaria but lower compared with severe P. falciparum malaria. At a cut-off point of 10 ng/mL, PCT had a sensitivity of 0,67 and a specificity of 0,94 for severe falciparum disease. However, at lower cut-off points the specificity and positive predictive value were rather poor although the sensitivity and negative predictive value remained high.

Discussion

Potential drawbacks in the interpretation of elevated PCT levels on admission may be caused by infections with non-falciparum species and by concomitant bacterial infections.

Conclusion

Semi-quantitative determination of PCT on admission is of limited use in the initial clinical assessment of disease severity in travellers with imported malaria, especially in settings with limited experience with the treatment of malaria.
The neurological assessment in young children treated with artesunate monotherapy or artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria
Authors: Ambler Michael T , Dubowitz Lilly M , Arunjerdja Ratree , Hla Eh Paw , Thwai Kyaw Lay , Viladpainguen Jacher , Singhasivanon Pratap , Luxemburger Christine , Nosten François , McGready Rose
Published: September 2009

Background

Mefloquine and artesunate combination therapy is the recommended first-line treatment for uncomplicated malaria throughout much of south-east Asia. Concerns have been raised about the potential central nervous system (CNS) effects of both drug components and there are no detailed reports in very young children.

Methods

Children, aged between three months and five years, with acute uncomplicatedPlasmodium falciparummalaria were randomized to either 7 days of artesunate monotherapy or the same schedule of artesunate plus mefloquine on day 7 and 8. Neurological testing targeting coordination and behaviour was carried out at day 0, 7, 9, 10, 14 and 28. Non-febrile healthy control children from the same population were tested on days 0, 7, 14 and 28.

Results

From December 1994 to July 1997, 91 children with uncomplicatedP. falciparum, 45 treated with artesunate monotherapy, 46 treated with mefloquine and artesunate combination therapy and 36 non-febrile controls, underwent neurological testing. Malaria and fever had a significant negative impact on testing performance. By contrast, the anti-malarial treatments were not associated with worsening performances in the various components of the test. Artesunate and mefloquine do not appear to have a significant influence on coordination and behaviour. Children treated with mefloquine were significantly less likely to suffer recurrent malaria infection during follow-up compared to those treated with artesunate alone (P = 0.033).

Conclusion

In keeping with the results of randomized controlled trials in adults, mefloquine was not associated with a decrease in specific items of neurological performance. Likewise, children treated with artesunate did not perform significantly differently to control children. This study does not exclude subtle or rare treatment CNS effects of artesunate or mefloquine. Treatment of acute uncomplicated malaria results in a significant improvement on items of neurological performance.
Surgical management of giant Brunner's gland hamartoma: case report and literature review
Authors: Stewart Zoe A , Hruban Ralph H , Fishman Elliot F , Wolfgang Christopher L
Published: September 2009

Brunner's gland hamartomas (BGH) are uncommon benign tumors of the duodenum forming mature Brunner's glands. We report here an unusual case of a giant BGH that was not amenable to endoscopic or surgical local resection thus requiring a pancreaticoduodenectomy for extirpation. The relevant literature is discussed.
Phylogeographic analysis reveals association of tick-borne pathogen, Anaplasma marginale, MSP1a sequences with ecological traits affecting tick vector performance
Authors: Estrada-Peña Agustín , Naranjo Victoria , Acevedo-Whitehouse Karina , Mangold Atilio J , Kocan Katherine M , de la Fuente José
Published: September 2009

Background

The tick-borne pathogen Anaplasma marginale, which is endemic worldwide, is the type species of the genus Anaplasma (Rickettsiales: Anaplasmataceae). Rhipicephalus (Boophilus) microplus is the most important tick vector of A. marginale in tropical and subtropical regions of the world. Despite extensive characterization of the genetic diversity in A. marginale geographic strains using major surface protein sequences, little is known about the biogeography and evolution of A. marginale and other Anaplasma species. For A. marginale, MSP1a was shown to be involved in vector-pathogen and host-pathogen interactions and to have evolved under positive selection pressure. The MSP1a of A. marginale strains differs in molecular weight because of a variable number of tandem 23-31 amino acid repeats and has proven to be a stable marker of strain identity. While phylogenetic studies of MSP1a repeat sequences have shown evidence of A. marginale-tick co-evolution, these studies have not provided phylogeographic information on a global scale because of the high level of MSP1a genetic diversity among geographic strains.

Results

In this study we showed that the phylogeography of A. marginale MSP1a sequences is associated with world ecological regions (ecoregions) resulting in different evolutionary pressures and thence MSP1a sequences. The results demonstrated that the MSP1a first (R1) and last (RL) repeats and microsatellite sequences were associated with world ecoregion clusters with specific and different environmental envelopes. The evolution of R1 repeat sequences was found to be under positive selection. It is hypothesized that the driving environmental factors regulating tick populations could act on the selection of different A. marginale MSP1a sequence lineages, associated to each ecoregion.

Conclusion

The results reported herein provided the first evidence that the evolution of A. marginale was linked to ecological traits affecting tick vector performance. These results suggested that some A. marginale strains have evolved under conditions that support pathogen biological transmission by R. microplus, under different ecological traits which affect performance of R. microplus populations. The evolution of other A. marginale strains may be linked to transmission by other tick species or to mechanical transmission in regions where R. microplus is currently eradicated. The information derived from this study is fundamental toward understanding the evolution of other vector-borne pathogens.
Signal Transduction Mechanisms Underlying Group I Mglur-Mediated Increase in Frequency and Amplitude of Spontaneous EPSCs in the Spinal Trigeminal Subnucleus Oralis of the Rat
Authors: Song Ji-Hyeon , Park Eun-Sung , Han Sang-Mi , Han Seung-Ro , Ahn Dong-Kuk , Youn Dong-Ho
Published: September 2009

Group I mGluRs (mGluR1 and 5) pre- and/or postsynaptically regulate synaptic transmission at glutamatergic synapses. By recording spontaneous EPSCs (sEPSCs) in the spinal trigeminal subnucleus oralis (Vo), we here investigated the regulation of glutamatergic transmission through the activation of group I mGluRs. Bath-applied DHPG (10 μM/5 min), activating the group I mGluRs, increased sEPSCs both in frequency and amplitude; particularly, the increased amplitude was long-lasting. The DHPG-induced increases of sEPSC frequency and amplitude were not NMDA receptor-dependent. The DHPG-induced increase in the frequency of sEPSCs, the presynaptic effect being further confirmed by the DHPG effect on paired-pulse ratio of trigeminal tract-evoked EPSCs, an index of presynaptic modulation, was significantly but partially reduced by blockades of voltage-dependent sodium channel, mGluR1 or mGluR5. Interestingly, PKC inhibition markedly enhanced the DHPG-induced increase of sEPSC frequency, which was mainly accomplished through mGluR1, indicating an inhibitory role of PKC. In contrast, the DHPG-induced increase of sEPSC amplitude was not affected by mGluR1 or mGluR5 antagonists although the long-lasting property of the increase was disappeared; however, the increase was completely inhibited by blocking both mGluR1 and mGluR5. Further study of signal transduction mechanisms revealed that PLC and CaMKII mediated the increases of sEPSC in both frequency and amplitude by DHPG, while IP3receptor, NO and ERK only that of amplitude during DHPG application. Altogether, these results indicate that the activation of group I mGluRs and their signal transduction pathways differentially regulate glutamate release and synaptic responses in Vo, thereby contributing to the processing of somatosensory signals from orofacial region.
Influence of Duration of Diabetes, Glycemic Control, and Traditional Cardiovascular Risk Factors on Early Atherosclerotic Vascular Changes in Adolescents and Young Adults with Type 2 Diabetes Mellitus
Authors: Shah Amy S. , Dolan Lawrence M. , Kimball Thomas R. , Gao Zhiqian , Khoury Philip R. , Daniels Stephen R. , Urbina Elaine M.
Published: September 2009

Background: Carotid intima-media thickness (IMT) provides a mechanism for detecting early atherosclerosis. Little information is available concerning carotid IMT and the progression of atherosclerosis in adolescents and young adults with type 2 diabetes mellitus.

Objective: We sought to determine the factors that contribute to early changes in carotid IMT in youth with type 2 diabetes mellitus and to identify any predictors of increased carotid IMT.

Methods: Demographic, anthropometric, laboratory data and carotid imaging were obtained in 129 youth of mixed ethnicity, ages 10–23 yr. Associations of carotid IMT outcomes and risk variables were analyzed by regression analysis. Logistic regression was performed to elucidate independent determinants that predict a worse carotid IMT.

Results: Carotid IMT increased with higher glycosylated hemoglobin (HbA1c) levels and longer duration of diabetes. Regression modeling showed that HbA1c and duration of diabetes in the presence of traditional cardiovascular risk factors (male sex, LDL cholesterol, and blood pressure) were independent determinants of carotid IMT. Logistic regression analysis demonstrated that each 1% increase in HbA1c or each year increase in duration of type 2 diabetes mellitus is associated with approximately 30% increased odds of a thicker carotid IMT.

Conclusions: Poorer glycemic control and longer disease duration have independent adverse effects on carotid IMT in youth with type 2 diabetes mellitus. These adverse effects appear to be more prominent in males. Developing effective strategies to improve blood glucose control in youth with type 2 diabetes mellitus is essential to prevent or limit the development and progression of atherosclerotic cardiovascular disease.

Poor glucose control, longer duration of diabetes, and traditional cardiovascular risk factors are associated with increased carotid intimal wall thickness in adolescents with type 2 diabetes mellitus.
Dual Inhibition of Mitogen-Activated Protein Kinase Kinase and Mammalian Target of Rapamycin in Differentiated and Anaplastic Thyroid Cancer
Authors: Jin Ning , Jiang Tianyun , Rosen D. Marc , Nelkin Barry D. , Ball Douglas W.
Published: September 2009

Context: Differentiated thyroid cancer and anaplastic thyroid cancer tumors frequently have activation of the ras/raf /MAPK kinase (MEK)/ERK and phosphatidylinositol 3-kinase (PI-3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathways.

Objective: The objective of the study was to investigate the efficacy of MEK and mTOR inhibitors in preclinical thyroid cancer treatment models with defined mutation status.

Experimental Design: The MEK inhibitor AZD6244 (ARRY-142886) and mTOR inhibitor rapamycin were tested separately and in combination in 10 differentiated thyroid cancer and anaplastic thyroid cancer cell lines and in a xenograft model for evidence of pathway inhibition, growth inhibition, apoptosis, and long-range adaptation and resistance.

Results: Seven of 10 tested lines had evidence of significant basal activity of the PI-3K/AKT/mTOR pathway, with elevated phosphorylated AKT and phosphorylated p70 S6 kinase. Activation of ras/RAF/MEK/ERK was equally common in this panel. All 10 lines exhibited better than 60% growth inhibition with combined MEK and mTOR inhibition, including lines with BRAF, Ret-PTC, ras, and PTEN mutations. Rapamycin or AZD6244 alone achieved this threshold in six and two lines, respectively. Dual-pathway inhibition in the Ret-PTC mutant cell line TPC1 caused an intense G1 arrest in cell culture and reversible cytostatic inhibition in a xenograft model. We did not observe significant feedback up-regulation of AKT activation in either acute or prolonged exposures.

Conclusion: These preclinical results support the inclusion of thyroid cancer patients in early-phase clinical trials combining ras/RAF/MEK/ERK and PI-3K/AKT/mTOR pathway inhibition.

Combined treatment with a MEK inhibitor (AZD6244/ARRY-142886) plus an mTOR inhibitor (Rapamycin) inhibited growth of thyroid cancer cells in vitro, and in a xenograft model, more potently than either agent alone.
A Missense GATA3 Mutation, Thr272Ile, Causes the Hypoparathyroidism, Deafness, and Renal Dysplasia Syndrome
Authors: Gaynor Katherine U. , Grigorieva Irina V. , Nesbit M. Andrew , Cranston Treena , Gomes Thushari , Gortner Ludwig , Thakker Rajesh V.
Published: September 2009

Context: The hypoparathyroidism, deafness, renal dysplasia (HDR) syndrome is caused by mutations in the gene encoding GATA3, which belongs to a family of dual zinc-finger transcription factors that have a role in vertebrate embryonic development.

Objective: The aim of the study was to identify the GATA3 mutation in a HDR patient and determine its functional consequences.

Patient and Design: A patient with HDR was studied after approval from the local ethical committee. Leukocyte DNA was used with GATA3-specific primers for PCR amplification, and the DNA sequences of the PCR products were determined. Wild-type and mutant GATA3 constructs were transfected into COS-7 cell, and their functions were assessed by Western blot analysis, immunocytochemistry, EMSAs, luciferase reporter assays, and three-dimensional modeling.

Results: A novel missense mutation, Thr272Ile, in zinc finger 1 (ZnF1) of GATA3 was identified. Western blot analysis and immunofluorescence revealed that the mutation did not affect nuclear localization of GATA3. However, EMSAs showed it to reduce DNA binding affinity, but not stability, and yeast two-hybrid assays demonstrated that the mutant GATA3 resulted in a loss of interaction with ZnF1 and ZnF6 of the cofactor FOG2. The mutant GATA3 significantly reduced luciferase reporter activity by more than 65% (P < 0.001), and three-dimensional modeling indicated that the functional abnormalities may be due to a loss of Thr272 polar side chain interaction with Leu268.

Conclusions: A novel missense HDR-associated GATA3 mutation, Thr272Ile, has been identified and shown to result in reduced DNA binding, a partial loss of FOG2 interaction, and a decrease in gene transcription.

Hypoparathyroidism, Deafness, and Renal Dysplasia syndrome can result from the missense mutation Thr272Il3 in the transcription factor GATA3, which results in reduced DNA binding, partial loss of interaction with the protein cofactor FOG2, and a decrease in transcriptional activity.
Gendered Borders: The Historical Formation of Women's Nationality under Law in Taiwan
Authors: Chen Chao-ju
Published: September 2009

What does the nation mean to women? How does the law draw national borders, and in what way is it gendered? This paper examines the ways in which women are related to the nation in Taiwan by discussing the legal regulation of nationality. Historically and contemporarily, the decisive and determinative power of the law in choosing members of the nation and in drawing national boundaries shapes women's overall relationship with the nation as an unequal one, as an inequality that is informed by women's subordinate status in the nation. My investigation into the subject of women and nationality in Taiwan reveals, through historical lenses, the ways in which law constructs national membership along gendered lines that subordinate women. Specifically, I examine how a woman's membership to the nation was dependent on her marital status, how citizen-mothers were deprived of the entitlement to define the nation through passing down her nationality, and how the law has been changed to reshape gendered borders. I begin with a discussion on various forms of gender inequality in nationality laws that existed during the Japanese colonial period, which reveals the gendered process of “becoming Japanese nationals,” and the gender politics of Japanese nationality in the context of imperial conquest as exemplified by the intermarriage between Japanese and Taiwanese. Gender inequality under nationality law survived the end of World War II, and new forms of discrimination in the legal regulation of women and national community membership emerged under the Guomindang (GMD) regime. The law confirmed male supremacy in the constitution of the national community by embracing married women's outsiderness and upholding the system of patrilineality. In the new millennium, legal reforms pursued by social movements have effectively reconceptualized national membership in an egalitarian, albeit incomplete, fashion. The new laws empower women's entitlement to national membership, but the extent of this empowerment remains limited. Male dominance in the drawing and redrawing of national borders is preserved through transformation. Discrimination against women functions not according to the old-fashioned mandatory commands but rather by the creation of a regulatory or disciplinary regime that compels a woman to adopt a husband's nationality and children to adopt their father's nationality. The historical retrospect of women's nationality under law hence suggests the necessity of developing new approaches to pursue and promote gender equality in the construction of national community membership.
How Are Taiwanese Shanghaied?
Authors: Wang Horng-luen
Published: September 2009

Using the English verb shanghai as a pun, this essay analyzes the ways in which Taiwanese were induced into an undesirable situation during the course of Taiwan's recent interactions with China. As Shanghai (re)emerges as a global city, we have witnessed a “Shanghai fever” in Taiwan since 2000 that is rather different than the so-called mainland fever of the previous period. Men and women of various backgrounds—entrepreneurs and professionals, students, preschool children and their moms, shopkeepers, outlaws and flaneurs—swarmed to Shanghai, some voluntarily and some not, only to find themselves in an awkward situation in which their presence was both ubiquitous and invisible. Moreover, globalization and nationalization jointly brought about a predicament in which the state, corporations, individuals, and Taiwanese society collectively were all shanghaied in one way or another. These shanghai(ed) experiences added up to a bizarre and paradoxical mixture of romanticized business ventures, pursuits of better personal lives, ambiguous citizenships, and conflicting nation-building projects, all imbued with a somewhat nostalgic projection of, along with deep anxieties about, Taiwan's future as well as self-identity.
Genealogies of NGO-ness: The Cultural Politics of a Global Buddhist Movement in Contemporary Taiwan
Authors: Huang C. Julia
Published: September 2009

Is the concept of the NGO, or nongovernmental organization, a global catchall? This article tries to respond to the globalization of the concept of NGO by tracing the historical and local development of a Taiwanese grassroots Buddhist organization, the Buddhist Tzu Chi (Ciji) Foundation, in the public sphere of Taiwan since the late 1960s, and particularly the controversies surrounding the group's rapid growth during Taiwan's democratization since the late 1980s. The development of the Buddhist group from an unknown grassroots to a global United Nations NGO, as the article will show, attests to the plural genealogies of NGO-ness. In addition, the article argues that the genealogy of Ciji illustrates the nuanced relationship between society and the Taiwan “state,” and that Ciji embodies the shifting cultural “state” of civil society in Taiwan. The concept of the “regime of civil morality” will be introduced for the understanding of the cultural politics of NGO-ness.
Sea squirts and immune tolerance
Authors: De Tomaso Anthony W.
Published: September 2009

Transplantation specificity and protective immunity occur in both adaptive and innate branches of the vertebrate immune system. Understanding the mechanisms that underlie specificity and self-tolerance of immune function has major significance, from preventing a rejection reaction after transplantation to dissecting the causes of autoimmune disease. The core of vertebrate immunity is the ability to discriminate between highly polymorphic ligands, and this process is also found in allorecognition systems throughout the metazoa. Botryllus schlosseri is a tunicate, the modern-day descendents of the phylum that made the transition between invertebrates and vertebrates. In addition, B. schlosseri undergoes a natural transplantation reaction, which is controlled by a single, highly polymorphic locus called fuhc, reminiscent of major histocompatibility complex (MHC)-based allorecognition. The life-history characteristics of Botryllus make it an excellent model to dissect the functional and developmental mechanisms underlying allorecognition, and have the potential to reveal novel insights into issues from innate recognition strategies to the evolution of genetic polymorphism. In addition, we hypothesize that allorecognition in Botryllus must be based on conserved processes that are fundamental to all immune function: education and tolerance, or the ontogeny and maintenance of specificity.
The small chromatin-binding protein p8 coordinates the association of anti-proliferative and pro-myogenic proteins at the myogenin promoter
Authors: Sambasivan Ramkumar , Cheedipudi Sirisha , Pasupuleti NagaRekha , Saleh Amena , Pavlath Grace K. , Dhawan Jyotsna
Published: September 2009

Quiescent muscle progenitors called satellite cells persist in adult skeletal muscle and, upon injury to muscle, re-enter the cell cycle and either undergo self-renewal or differentiate to regenerate lost myofibers. Using synchronized cultures of C2C12 myoblasts to model these divergent programs, we show that p8 (also known as Nupr1), a G1-induced gene, negatively regulates the cell cycle and promotes myogenic differentiation. p8 is a small chromatin protein related to the high mobility group (HMG) family of architectural factors and binds to histone acetyltransferase p300 (p300, also known as CBP). We confirm this interaction and show that p300-dependent events (Myc expression, global histone acetylation and post-translational acetylation of the myogenic regulator MyoD) are all affected in p8-knockdown myoblasts, correlating with repression of MyoD target-gene expression and severely defective differentiation. We report two new partners for p8 that support a role in muscle-specific gene regulation: p68 (Ddx5), an RNA helicase reported to bind both p300 and MyoD, and MyoD itself. We show that, similar to MyoD and p300, p8 and p68 are located at the myogenin promoter, and that knockdown of p8 compromises chromatin association of all four proteins. Thus, p8 represents a new node in a chromatin regulatory network that coordinates myogenic differentiation with cell-cycle exit.
An approach to standardize, quantify and record progress of routine upper limb therapy for stroke subjects: The Action Medical Research Upper Limb Therapy protocol
Authors: Rosewilliam Sheeba B , BüCher Catherine , Roffe Christine , Pandyan Anand D
Published: September 2009

Introduction.

Explicitly describing therapy for research purposes, in terms of content and quantity, improves the validity of research and facilitates evidence-based clinical practice. However, such descriptions are not common in therapy research. The aim was to develop an upper limb therapy protocol which reflected local clinical practice in the stroke unit, and a recording form to document the content, quantity and progression of therapy.

Methods.

This was a multi-method study. A list of interventions commonly used for the rehabilitation of the stroke upper limb was compiled following a systematic literature search. This was then refined into the Action Medical Research Upper Limb Therapy (AMRULT) protocol in a two-stage process involving a survey and a group discussion. Six physical therapists and three occupational therapists supported its development. The AMRULT protocol was then piloted in a two-arm randomized controlled trial with 90 stroke patients for therapy and recording purposes.

Results.

The protocol classified therapies based on therapy input as passive, active assisted, active/strengthening and functional. Using this form it was possible to not only summarize the content of therapy but also objectively document progression (e.g. 14% of the participants progressed to functional exercises between the 5th and 8th weeks after stroke onset).

Discussion.

The AMRULT protocol and associated recording form were useful in both standardizing the delivery and quantification (content and progression) of therapy. While the AMRULT protocol was devised for a specific purpose, the method used can be adapted to develop protocols to support other research studies.
Echinocandins: The Newest Class of Antifungals
Authors: Sucher Allana J , Chahine Elias B , Balcer Holly E
Published: September 2009

Objective:

To review the mechanism of action, antifungal spectrum of activity, pharmacodynamics, pharmacokinetics, clinical efficacy, and safety of the echinocandins.

Data Sources:

A MEDLINE search (1982–May 2009) was conducted for articles published in the English language using the key words caspofungin, micafungin, anidulafungin, and echinocandins.

Study Selection and Data Extraction:

Medicinal chemistry, in vitro, and animal studies, as well as human trials were reviewed for information on the pharmacodynamics, pharmacokinetics, efficacy, and safety of each echinocandin. Clinical trials were reviewed and included to compare and contrast the available echinocandins.

Data Synthesis:

Three echinocandin antifungal agents are currently approved for use in the US: caspofungin, micafungin, and anidulafungin. The echinocandins have a unique mechanism of action, inhibiting β-(1,3)-d-glucan synthase, an enzyme that is necessary for the synthesis of an essential component of the cell wall of several fungi. The echinocandins display fungistatic activity against Aspergillus spp. and fungicidal activity against most Candida spp., including strains that are fluconazole-resistant. The echinocandins have been shown to be efficacious for the treatment of esophageal candidiasis, candidemia, and invasive candidiasis. In addition, caspofungin has demonstrated efficacy as empiric treatment of febrile neutropenia and salvage therapy for the treatment of invasive aspergillosis, and it is the only echinocandin approved for use in pediatric patients. Micafungin is the only echinocandin approved for use as prophylaxis against Candida infections in patients undergoing hematopoietic stem cell transplantation. Overall, resistance to echinocandins is still rare, and all agents are well tolerated, with similar adverse effect profiles and few drug–drug interactions.

Conclusions:

Echinocandins, the newest addition to the arsenal of antifungals, offer potential advantages over other classes of agents. Clinicians should assess their distinguishing characteristics, including route of metabolism, drug interaction profile, and approved indications for use, when determining which agent to include on a formulary.
Challenges in thermodynamics: Irreversible processes, nonextensive entropies, and systems without equilibrium states
Authors: Hołyst Robert
Published: September 2009

Recent works on evaporation and condensation demonstrate that even these simplest irreversible processes, studied for over 100 years, are not well understood. In the case of a liquid evaporating into its vapor, the liquid temperature is constant during evaporation and the evaporation flux is governed by the heat transfer from the hotter vapor into the colder liquid. Whether liquid evaporates into its own vapor or into the vacuum, the irreversible pathway in the process goes through a number of steps which quickly lead to the steady-state conditions with mechanical equilibrium in most parts of the system—the fact overlooked in all previous studies. Even less is known about general rules which govern systems far from equilibrium. Recently, it has been demonstrated that a work done in an irreversible process can be related to the free energy difference between equilibrium states joined by the process. Finally, a real challenge in thermodynamics is a description of living systems since they do not have equilibrium states, are nonextensive, (i.e., they cannot be divided into subsystems), and cannot be isolated. Thus, their proper description requires new paradigms in thermodynamics.