bluuebunny/crossref_metadata_2025 huggingface dataset:
Resveratrol differentially modulates inflammatory responses of microglia and astrocytes
Authors: Lu Xiaofeng , Ma Lili , Ruan Lingfei , Kong Yan , Mou Haiwei , Zhang Zhijie , Wang Zhijun , Wang Ji Ming , Le Yingying
Published: August 2010

Background

Inflammatory responses in the CNS mediated by activated glial cells play an important role in host-defense but are also involved in the development of neurodegenerative diseases. Resveratrol is a natural polyphenolic compound that has cardioprotective, anticancer and anti-inflammatory properties. We investigated the capacity of resveratrol to protect microglia and astrocyte from inflammatory insults and explored mechanisms underlying different inhibitory effects of resveratrol on microglia and astrocytes.

Methods

A murine microglia cell line (N9), primary microglia, or astrocytes were stimulated by LPS with or without different concentrations of resveratrol. The expression and release of proinflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1) and iNOS/NO by the cells were measured by PCR/real-time PCR and ELISA, respectively. The phosphorylation of the MAP kinase superfamily was analyzed by western blotting, and activation of NF-κB and AP-1 was measured by luciferase reporter assay and/or electrophoretic mobility shift assay.

Results

We found that LPS stimulated the expression of TNF-α, IL-1β, IL-6, MCP-1 and iNOS in murine microglia and astrocytes in which MAP kinases, NF-κB and AP-1 were differentially involved. Resveratrol inhibited LPS-induced expression and release of TNF-α, IL-6, MCP-1, and iNOS/NO in both cell types with more potency in microglia, and inhibited LPS-induced expression of IL-1β in microglia but not astrocytes. Resveratrol had no effect on LPS-stimulated phosphorylation of ERK1/2 and p38 in microglia and astrocytes, but slightly inhibited LPS-stimulated phosphorylation of JNK in astrocytes. Resveratrol inhibited LPS-induced NF-κB activation in both cell types, but inhibited AP-1 activation only in microglia.

Conclusion

These results suggest that murine microglia and astrocytes produce proinflammatory cytokines and NO in response to LPS in a similar pattern with some differences in signaling molecules involved, and further suggest that resveratrol exerts anti-inflammatory effects in microglia and astrocytes by inhibiting different proinflammatory cytokines and key signaling molecules.
Utilisation of priority traditional medicinal plants and local people's knowledge on their conservation status in arid lands of Kenya (Mwingi District)
Authors: Njoroge Grace N , Kaibui Isaac M , Njenga Peter K , Odhiambo Peter O
Published: August 2010

Mwingi District lies within the Kenyan Arid and Semiarid lands (ASALs) in Eastern Province. Although some ethnobotanical surveys have been undertaken in some arid and semiarid areas of Kenya, limited studies have documented priority medicinal plants as well as local people's awareness of conservation needs of these plants. This study sought to establish the priority traditional medicinal plants used for human, livestock healthcare, and those used for protecting stored grains against pest infestation in Mwingi district. Further, the status of knowledge among the local people on the threat and conservation status of important medicinal species was documented. This study identified 18 species which were regarded as priority traditional medicinal plants for human health. In terms of priority, 8 were classified as moderate, 6 high, while 4 were ranked highest priority species. These four species are Albizia amara (Roxb.) Boiv. (Mimosacaeae), Aloe secundiflora (Engl. (Aloaceae), Acalypha fruticosa Forssk. (Euphorbiaceae) and Salvadora persica L. (Salvadoraceae).

In regard to medicinal plants used for ethnoveterinary purposes, eleven species were identified while seven species were reported as being important for obtaining natural products or concoctions used for stored grain preservation especially against weevils. The data obtained revealed that there were new records of priority medicinal plants which had not been documented as priority species in the past. Results on conservation status of these plants showed that more than 80% of the respondents were unaware that wild medicinal plants were declining, and, consequently, few of them have any domesticated species. Some of the species that have been conserved on farm or deliberately allowed to persist when wild habitats are converted into agricultural lands include: Croton megalocarpus Hutch., Aloe secundiflora, Azadirachta indica A. Juss., Warburgia ugandensis Sprague, Ricinus communis L. and Terminalia brownie Fresen. A small proportion of the respondents however, were aware of the threats facing medicnal plants. Some of the plants reported as declining include, Solanum renschii Vatke (Solanaceae), Populus ilicifolia (Engl.) Rouleau (Salicaceae), Strychnos henningsii Gilg (Loganiaceae) and Rumex usambarensis (Dammer) Dammer (Polygonaceae). Considering the low level of understanding of conservation concerns for these species, there is need therefore, to build capacity among the local communities in this area particularly in regard to sustainable use of natural resources, conservation methods as well as domestication processes.
Validation of bidimensional measurement in nasopharyngeal carcinoma
Authors: Chang Ting-Shou , Chu Sau-Tung , Hou Yu-Yi , Chang Kuo-Ping , Chi Chao-Chuan , Lee Ching-Chih
Published: August 2010

Background

Our previous study showed a close relationship between computed tomography (CT)-derived bidimensional measurement of primary tumor and retropharyngeal nodes (BDMprn) and gross tumor volume of primary tumor and retropharyngeal nodes (GTVprn) in nasopharyngeal carcinoma (NPC) and better prognosis for NPC patients with smaller BDMprn. In this study, we report the results on of a study to validate the use of BDM in a separate cohort of NPC patients.

Methods

We retrospectively reviewed 103 newly diagnosed NPC cases who were treated with radiotherapy/concurrent chemoradiotherapy (CCRT) or CCRT with adjuvant chemotherapy from 2002 to 2009. We used magnetic resonance imaging (MRI) to measure BDMprn. We calculated overall survival, recurrence-free and distant metastasis-free survival curves and set a BDMprn cut off point to categorize patients into a high- or low-risk group. We then used Cox proportional hazard model to evaluate the prognostic influence of BDMprn after correcting age, gender and chemotherapy status.

Results

After adjusting for age, gender, and chemotherapy status, BDMprn remained an independent prognostic factor for distant metastasis [Hazard ratio (HR) = 1.046; P = 0.042] and overall survival (HR = 1.012; P = 0.012). Patients with BDMprn < 15 cm2 had a greater 3-year overall survival rate than those with BDMprn ≧ 15 cm2 (92.3% vs. 73.7%; P = 0.009). They also had a greater 3-year distant metastasis-free survival (94% vs.75%; P = 0.034).

Conclusion

The predictive ability of BDMprn was validated in a separate NPC cohort. A BDMprn of 15 cm2 can be used to separate NPC patients into high- and low-risk groups and predict survival rates and metastasis potential. It can, therefore, be used as a reference to design clinical trials, predict prognosis, and make treatment decisions.
An interactive surgical planning tool for acetabular fractures: initial results
Authors: Fornaro Jürgen , Keel Marius , Harders Matthias , Marincek Borut , Székely Gábor , Frauenfelder Thomas
Published: August 2010

Background

Acetabular fractures still are among the most challenging fractures to treat because of complex anatomy, involved surgical access to fracture sites and the relatively low incidence of these lesions. Proper evaluation and surgical planning is necessary to achieve anatomic reduction of the articular surface and stable fixation of the pelvic ring. The goal of this study was to test the feasibility of preoperative surgical planning in acetabular fractures using a new prototype planning tool based on an interactive virtual reality-style environment.

Methods

7 patients (5 male and 2 female; median age 53 y (25 to 92 y)) with an acetabular fracture were prospectively included. Exclusion criterions were simple wall fractures, cases with anticipated surgical dislocation of the femoral head for joint debridement and accurate fracture reduction. According to the Letournel classification 4 cases had two column fractures, 2 cases had anterior column fractures and 1 case had a T-shaped fracture including a posterior wall fracture.

The workflow included following steps: (1) Formation of a patient-specific bone model from preoperative computed tomography scans, (2) interactive virtual fracture reduction with visuo-haptic feedback, (3) virtual fracture fixation using common osteosynthesis implants and (4) measurement of implant position relative to landmarks. The surgeon manually contoured osteosynthesis plates preoperatively according to the virtually defined deformation. Screenshots including all measurements for the OR were available.

The tool was validated comparing the preoperative planning and postoperative results by 3D-superimposition.

Results

Preoperative planning was feasible in all cases. In 6 of 7 cases superimposition of preoperative planning and postoperative follow-up CT showed a good to excellent correlation. In one case part of the procedure had to be changed due to impossibility of fracture reduction from an ilioinguinal approach. In 3 cases with osteopenic bone patient-specific prebent fixation plates were helpful in guiding fracture reduction. Additionally, anatomical landmark based measurements were helpful for intraoperative navigation.

Conclusion

The presented prototype planning tool for pelvic surgery was successfully integrated in a clinical workflow to improve patient-specific preoperative planning, giving visual and haptic information about the injury and allowing a patient-specific adaptation of osteosynthesis implants to the virtually reduced pelvis.
An in vivo evaluation of bone response to three implant surfaces using a rabbit intramedullary rod model
Authors: Hermida Juan C , Bergula Arnie , Dimaano Fred , Hawkins Monica , Colwell Clifford W , D'Lima Darryl D
Published: August 2010

Our study was designed to evaluate osseointegration among implants with three surface treatments: plasma-sprayed titanium (P), plasma-sprayed titanium with hydroxyapatite (PHA), and chemical-textured titanium with hydroxyapatite (CHA). Average surface roughness (Ra) was 27 microns for the P group, 17 microns for the PHA group, and 26 microns for the CHA group. Bilateral distal intramedullary implants were placed in the femora of thirty rabbits. Histomorphometry of scanning electron microscopy images was used to analyze the amount of bone around the implants at 6 and 12 weeks after implantation. Greater amounts of osseointegration were observed in the hydroxyapatite-coated groups than in the noncoated group. For all implant surfaces, osseointegration was greater at the diaphyseal level compared to the metaphyseal level. No significant differences were seen in osseointegration between the 6 and 12 week time points. Although the average surface roughness of the P and the CHA groups was similar, osseointegration of the CHA implants was significantly greater. The results of this in vivo lapine study suggest that the presence of an hydroxyapatite coating enhances osseointegration despite similarities in average surface roughness.
Practical screening of purified cellobiohydrolases and endoglucanases with α-cellulose and specification of hydrodynamics
Authors: Jäger Gernot , Wu Zhuojun , Garschhammer Kerstin , Engel Philip , Klement Tobias , Rinaldi Roberto , Spiess Antje C , Büchs Jochen
Published: August 2010

Background

It is important to generate biofuels and society must be weaned from its dependency on fossil fuels. In order to produce biofuels, lignocellulose is pretreated and the resulting cellulose is hydrolyzed by cellulases such as cellobiohydrolases (CBH) and endoglucanases (EG). Until now, the biofuel industry has usually applied impractical celluloses to screen for cellulases capable of degrading naturally occurring, insoluble cellulose. This study investigates how these cellulases adsorb and hydrolyze insoluble α-cellulose − considered to be a more practical substrate which mimics the alkaline-pretreated biomass used in biorefineries. Moreover, this study investigates how hydrodynamics affects cellulase adsorption and activity onto α-cellulose.

Results

First, the cellulases CBH I, CBH II, EG I and EG II were purified from Trichoderma reesei and CBH I and EG I were utilized in order to study and model the adsorption isotherms (Langmuir) and kinetics (pseudo-first-order). Second, the adsorption kinetics and cellulase activities were studied under different hydrodynamic conditions, including liquid mixing and particle suspension. Third, in order to compare α-cellulose with three typically used celluloses, the exact cellulase activities towards all four substrates were measured.

It was found that, using α-cellulose, the adsorption models fitted to the experimental data and yielded parameters comparable to those for filter paper. Moreover, it was determined that higher shaking frequencies clearly improved the adsorption of cellulases onto α-cellulose and thus bolstered their activity. Complete suspension of α-cellulose particles was the optimal operating condition in order to ensure efficient cellulase adsorption and activity. Finally, all four purified cellulases displayed comparable activities only on insoluble α-cellulose.

Conclusions

α-Cellulose is an excellent substrate to screen for CBHs and EGs. This current investigation shows in detail, for the first time, the adsorption of purified cellulases onto α-cellulose, the effect of hydrodynamics on cellulase adsorption and the correlation between the adsorption and the activity of cellulases at different hydrodynamic conditions. Complete suspension of the substrate has to be ensured in order to optimize the cellulase attack. In the future, screenings should be conducted with α-cellulose so that proper cellulases are selected to best hydrolyze the real alkaline-pretreated biomass used in biorefineries.
Patients' Experiences With Care for Lung Cancer and Colorectal Cancer: Findings From the Cancer Care Outcomes Research and Surveillance Consortium
Authors: Ayanian John Z. , Zaslavsky Alan M. , Arora Neeraj K. , Kahn Katherine L. , Malin Jennifer L. , Ganz Patricia A. , van Ryn Michelle , Hornbrook Mark C. , Kiefe Catarina I. , He Yulei , Urmie Julie M. , Weeks Jane C. , Harrington David P.
Published: August 2010

Purpose

To assess patients' experiences with cancer care, ratings of their quality of care, and correlates of these assessments.

Patients and Methods

For 4,093 patients with lung cancer and 3,685 patients with colorectal cancer in multiple US regions and health care delivery systems, we conducted telephone surveys of patients or their surrogates in English, Spanish, or Chinese at 4 to 7 months after diagnosis. The surveys assessed ratings of the overall quality of cancer care and experiences with three domains of interpersonal care (physician communication, nursing care, and coordination and responsiveness of care).

Results

English-speaking Asian/Pacific Islander patients and Chinese-speaking patients and those in worse health reported significantly worse adjusted experiences with all three domains of interpersonal care, whereas white, black, and Hispanic patients reported generally similar experiences with interpersonal care. The overall quality of cancer care was rated as excellent by 44.4% of patients with lung cancer and 53.0% of patients with colorectal cancer, and these ratings were most strongly correlated with positive experiences with coordination and responsiveness of care (Spearman rank coefficients of 0.49 and 0.42 for lung and colorectal cancer, respectively). After multivariate adjustment, excellent ratings were less common for each cancer among black patients, English-speaking Asian/Pacific Islander patients, Chinese-speaking patients, and patients reporting worse health status (all P ≤ .05).

Conclusion

Patients' reports and ratings of care differed significantly by race, language, and health status. Efforts to improve patients' experiences with cancer care should focus on problems affecting Asian and Pacific Islander patients and those in worse health.
Phase I Trial of Lapatinib in Children With Refractory CNS Malignancies: A Pediatric Brain Tumor Consortium Study
Authors: Fouladi Maryam , Stewart Clinton. F. , Blaney Susan M. , Onar-Thomas Arzu , Schaiquevich Paula , Packer Roger J. , Gajjar Amar , Kun Larry E. , Boyett James M. , Gilbertson Richard J.
Published: August 2010

Purpose

To estimate the maximum-tolerated dose, dose-limiting toxicities (DLTs), and pharmacokinetic properties of lapatinib, a selective epidermal growth factor receptor (EGFR) and ERBB2 inhibitor, in children with refractory or recurrent CNS malignancies.

Patients and Methods

Lapatinib was administered orally twice daily at escalating doses starting at 300 mg/m2 to patients who were not (stratum I) or were (stratum II) receiving steroids. Pharmacokinetic studies were performed during the first two courses. Expression of the four ERBB receptors and downstream signaling elements in tumor tissue was evaluated by immunohistochemistry.

Results

Fifty-nine patients were enrolled (stratum I, n = 32; stratum II, n = 27). Of 29 patients evaluable for toxicity in stratum I, one experienced a DLT (diarrhea) at 520 mg/m2 twice daily, and all three receiving 1,150 mg/m2 twice daily experienced DLTs (one each of rash, diarrhea, and fatigue). Two of 21 patients evaluable for toxicity in stratum II experienced DLTs of rash at 900 mg/m2 twice daily. Lapatinib dosage was related linearly to area under the [concentration-time] curve from start time to 12 hours later (AUC0-12) and dose-normalized maximum serum concentration and AUC values for patients in stratum II were both significantly higher (P = .001) than those for patients in stratum I. Frequent, high-level expression of activated (phosphorylated) EGFR and ERBB2 receptors and downstream signal intermediates were observed in tumors, particularly in ependymomas that displayed prolonged stable disease on lapatinib therapy.

Conclusion

Lapatinib is well tolerated in children with recurrent CNS malignancies, with rash, diarrhea, and fatigue identified as DLTs. The recommended phase II dose, regardless of steroid use, is 900 mg/m2 twice daily.
A Report on the Animal Turn
Authors: Weil Kari
Published: August 2010

Theory has gone to the birds . . . and to apes, dogs, and horses. The recent explosion of writing and teaching on animals has recharged those questions of identity and difference, of power and its effects that have embroiled academic theory over the past quarter century. Even trauma studies has turned its focus to nonhuman animals, both because of the violence they suffer at human hands and because of the difficulties humans have in assessing the extent of that violence. This article examines the animal turn by tracing three theoretical moments or trends for which the ``the animal'' (that word which, Jacques Derrida says, humans have given themselves the right to give to others) has become a test or limit case: the linguistic turn, the post- or counter-linguistic turn, and the ethical turn. It is also a report that builds on the words of Kafka's ape, Red Peter, who, in his ``Report to an Academy'' (1919) addressed and fell victim to the aporias in our knowledge about what it means to be an animal and, consequently, a human.
Other Fecundities: Proust and Irigaray on Sexual Difference
Authors: Guenther Lisa
Published: August 2010

Irigaray's early work seeks to multiply possibilities for women's self-expression by recovering a sexual difference in which male and female are neither the same nor opposites, but irreducibly different modes of embodiment. In her more recent work, however, Irigaray has emphasized the duality of the sexes at the expense of multiplicity, enshrining the heterosexual couple as the model of sexual ethics. Alison Stone's recent revision of Irigaray supplements her account of sexual duality with a theory of bodily multiplicity derived from Butler, Nietzsche, and certain German Romantics; but to the extent that Stone maintains the primacy of sexual duality, her revision fails to address the claims of multiplicity on their own terms. In this paper, I interpret a passage from Marcel Proust's novel, Sodom and Gomorrah, in order to develop an alternative theory of sexual difference in which sexual duality is affirmed in relation to a third, unsexed but sexual force which multiplies the possibilities for sexual pleasure beyond heterosexual coupling. Proust's emphasis on sexed ``parts'' rather than sexed morphologies is generative of maximally diverse combinations, all of which are equally natural and equally enhanced through artifice.
Transgender Subjectivity and the Logic of Sexual Difference
Authors: Carlson Shanna T.
Published: August 2010

In response to concerns voiced by Judith Butler and Joan Copjec regarding the possible incompatibility of the discourses of Lacanian psychoanalysis and gender studies, this paper argues that gender studies and Lacanian psychoanalysis can hope for a meeting ground precisely around the topic of ``sexual difference.'' Questions about transgender subjectivities afford a point of entry for thinking through the impasses and political purchase of a necessarily contestatory integration of these two domains; however, imagining this integration requires in part an analysis of each discourse's limitations. This paper suggests that one of the limitations of Lacanian psychoanalysis resides in the too easy capitulation of the terms ``feminine'' and ``masculine'' to ``gendered'' readings. Arguing that Jacques Lacan's formulas of sexuation write against the facile collapse of sexual difference into gender identity, the paper considers what it would look like to conceptualize transgender subjectivity as an expression of the logic of sexual difference, ultimately suggesting there may be a way of reading transgenderism as a ``feminine'' phenomenon. The paper responds to two texts also invested in the integration of Lacanian psychoanalytic and queer/feminist concerns: Judith Butler's Antigone's Claim and Tim Dean's Beyond Sexuality. Dean's project to ``de-gender'' desire offers a reply to Butler's concerns about the compulsory heterosexuality of the Oedipal scene; however, both texts, in their preoccupation with scenes Oedipal and object based, occlude to some extent a ``feminine'' perspective and by extension significant ``feminine''/transgender insights concerning sexual difference.
The Native Performant: Linguistic Authority in the Text of Romantic Orientalism
Authors: Sitter Zak
Published: August 2010

This article builds on postcolonial critiques of colonialism's reliance on the figure of the ``native informant.'' In early-nineteenth-century Britain, the emergent discipline of orientalism required the native informant to ratify its claims to knowledge; at the same time, orientalism was a key component of Romantic reimaginings of language as a productive force. While the native informant guarantees the referential truth of colonial discourse, this essay details the simultaneous emergence of a figure termed the ``native performant,'' who dramatizes the performative power of Western language. Examining scenes from Robert Southey's The Curse of Kehama, Lord Byron's Lara, and Thomas De Quincey's Confessions of an English Opium-Eater, the author argues that European power is staged by subjecting a figure of the East to a kind of language that functions as a conduit of pure force rather than a tool of communication. These scenes of linguistic triumphalism, the essay contends, highlight the double performativity of orientalist discourse: orientalism both performs and by performing enacts the West's power of command over the East.
Combined zebrafish-yeast chemical-genetic screens reveal gene–copper-nutrition interactions that modulate melanocyte pigmentation
Authors: Ishizaki Hironori , Spitzer Michaela , Wildenhain Jan , Anastasaki Corina , Zeng Zhiqiang , Dolma Sonam , Shaw Michael , Madsen Erik , Gitlin Jonathan , Marais Richard , Tyers Mike , Patton E. Elizabeth
Published: August 2010

Hypopigmentation is a feature of copper deficiency in humans, as caused by mutation of the copper (Cu2+) transporter ATP7A in Menkes disease, or an inability to absorb copper after gastric surgery. However, many causes of copper deficiency are unknown, and genetic polymorphisms might underlie sensitivity to suboptimal environmental copper conditions. Here, we combined phenotypic screens in zebrafish for compounds that affect copper metabolism with yeast chemical-genetic profiles to identify pathways that are sensitive to copper depletion. Yeast chemical-genetic interactions revealed that defects in intracellular trafficking pathways cause sensitivity to low-copper conditions; partial knockdown of the analogous Ap3s1 and Ap1s1 trafficking components in zebrafish sensitized developing melanocytes to hypopigmentation in low-copper environmental conditions. Because trafficking pathways are essential for copper loading into cuproproteins, our results suggest that hypomorphic alleles of trafficking components might underlie sensitivity to reduced-copper nutrient conditions. In addition, we used zebrafish-yeast screening to identify a novel target pathway in copper metabolism for the small-molecule MEK kinase inhibitor U0126. The zebrafish-yeast screening method combines the power of zebrafish as a disease model with facile genome-scale identification of chemical-genetic interactions in yeast to enable the discovery and dissection of complex multigenic interactions in disease-gene networks.
Cytoskeletal dysfunction dominates in DAP12-deficient osteoclasts
Authors: Zou Wei , Zhu Tingting , Craft Clarissa S. , Broekelmann Thomas J. , Mecham Robert P. , Teitelbaum Steven L.
Published: August 2010

Despite evidence that DAP12 regulates osteoclasts, mice lacking the ITAM-bearing protein exhibit only mild osteopetrosis. Alternatively, Dap12−/− mice, also lacking FcRγ, are severely osteopetrotic, suggesting that FcRγ compensates for DAP12 deficiency in the bone-resorbing polykaryons. Controversy exists, however, as to whether these co-stimulatory molecules regulate differentiation of osteoclasts or the capacity of the mature cell to degrade bone. We find that Dap12−/− osteoclasts differentiate normally when generated on osteoblasts but have a dysfunctional cytoskeleton, impairing their ability to transmigrate through the osteoblast layer and resorb bone. To determine whether the FcRγ co-receptor, OSCAR mediates osteoclast function in the absence of DAP12, we overexpressed OSCAR fused to FLAG (OSCAR-FLAG), in Dap12−/− osteoclasts. OSCAR-FLAG partially rescues the abnormal cytoskeleton of Dap12−/− osteoclasts grown on bone, but not those grown on osteoblasts. Thus, cytoskeletal dysfunction, and not arrested differentiation, is the dominant consequence of DAP12 deficiency in osteoclasts. The failure of osteoblasts to normalize Dap12−/− osteoclasts indicates that functionally relevant quantities of OSCAR ligand do not reside in bone-forming cells.
Strengthening Laboratory Systems in Resource-Limited Settings
Authors: Olmsted Stuart S. , Moore Melinda , Meili Robin C. , Duber Herbert C. , Wasserman Jeffrey , Sama Preethi , Mundell Ben , Hilborne Lee H.
Published: August 2010

Considerable resources have been invested in recent years to improve laboratory systems in resource-limited settings. We reviewed published reports, interviewed major donor organizations, and conducted case studies of laboratory systems in 3 countries to assess how countries and donors have worked together to improve laboratory services. While infrastructure and the provision of services have seen improvement, important opportunities remain for further advancement. Implementation of national laboratory plans is inconsistent, human resources are limited, and quality laboratory services rarely extend to lower tier laboratories (eg, health clinics, district hospitals). Coordination within, between, and among governments and donor organizations is also frequently problematic. Laboratory standardization and quality control are improving but remain challenging, making accreditation a difficult goal. Host country governments and their external funding partners should coordinate their efforts effectively around a host country’s own national laboratory plan to advance sustainable capacity development throughout a country’s laboratory system.
The Importance of Continuous Quality Assessment: A Lesson from Antiemetic Guidelines for Preventing Chemotherapy-Induced Nausea and Vomiting
Authors: Li Edward C. , Trovato James A.
Published: August 2010

At the University of Maryland Marlene and Stewart Greenebaum Cancer Center, we noticed that patients did not routinely receive a guideline recommended antiemetic regimen for the prevention of chemotherapy induced emesis. To achieve better compliance, treatment guidelines were incorporated into chemotherapy preprinted orders. The purpose of this study is to evaluate outcomes in the delayed period following highly emetogenic chemotherapy in patients receiving a guideline recommended antiemetic regimen. Outcomes were compared to a historical cohort of patients who did not receive a guideline recommended regimen.

This prospective, observational, quality-assessment study enrolled patients receiving highly emetogenic chemotherapy who received a standard delayed antiemetic regimen of dexamethasone for 5 days plus dolasetron for 3 days. Patients documented the number of emesis episodes, breakthrough nausea with medication use, and adverse effects. Quality of life was measured using the Modified Functional Living Index – Emesis. Originally, 40 to 60 patients were planned to be studied. This study was stopped early, because national consensus guidelines for preventing chemotherapy induced nausea and vomiting were recently updated and no longer recommended this regimen.

Overall, the incidence of vomiting was statistically similar ( P= 0.4) in the prospective study cohort (77.8%) vs the historical cohort (65.2%). Also, breakthrough antiemetic use was similar in both groups. Complete response was similar between the two groups (27.8% current, 30.4% historic).

Outcomes were similar in the current study vs the historical cohort. The institution's guidelines were modified and further studies will assess the efficacy of newer antiemetic regimens using these data as historical control.
Recent Publications on Medications and Pharmacy
Authors: Generali Joyce
Published: August 2010

Hospital Pharmacy presents this new feature to keep pharmacists abreast of new publications in the medical/pharmacy literature. Articles of interest will be abstracted monthly regarding a broad scope of topics. Suggestions or comments may be addressed to Joyce Generali, Director of Drug Information at Kansas University Medical Center, 3901 Rainbow Blvd, Kansas City KS 66160 or E-mail: jgeneral@kumc.edu .
Fentanyl Iontophoretic Transdermal System
Authors: Cada Dennis J. , Levien Terri , Baker Danial E.
Published: August 2010

Each month, subscribers to The Formulary Monograph Service receive five to six well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to your Pharmacy and Therapeutics Committee. Subscribers also receive monthly one-page summary monographs on the agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation (DUE) is also provided each month. With a subscription, the monographs are sent to you in print and CD-ROM forms and are available online. Monographs can be customized to meet the needs of your facility. Subscribers to the The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X.

Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. If you would like information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The October 2006 monograph topics are levetiracetam injection, idursulfase, certolizumab pegol, telbivudine, and etonogestrel implant. The DUE is levetiracetam injection.
New Drugs Approved by the FDA New Dosage Forms and Indications Agents Pending FDA Approval Significant Labeling Changes
Authors: Baker Danial E.
Published: August 2010

This monthly feature will help readers keep current on new drugs, indications, dosage forms, and safety-related changes in labeling or use. Efforts have been made to ensure the accuracy of the information; however, if there are any questions, let us know at hospitalpharmacy@drugfacts.com .
Medication Reconciliation Physician Order Form
Authors: Lacy Joann L. , Wilkinson Samaneh T.
Published: August 2010

Patient safety is a complex issue that is constantly evolving. Communication via standardized drug ordering is recognized as one of the key elements to providing a safer hospital stay, as well as a stronger patient outcome. This feature will publish bimonthly and will provide examples of standardized drug prescribing and a forum for discussion.

If you have a template that you believe other hospital pharmacies can benefit from, please submit it along with answers to the questions (seen below in the text) to Joyce Generali, Director of Drug Information at Kansas University Medical Center, 3901 Rainbow Center, Kansas City, KS 66160 or E-mail at jgeneral@kumc.edu .
Phosphorylation of Fascin Decreases the Risk of Poor Survival in Patients With Esophageal Squamous Cell Carcinoma
Authors: Zhao Qing , Shen Jin-Hui , Shen Zhong-Ying , Wu Zhi-Yong , Xu Xiu-E , Xie Jian-Jun , Wu Jian-Yi , Huang Qiao , Lu Xiao-Feng , Li En-Min , Xu Li-Yan
Published: August 2010

Phosphorylation of fascin at serine 39 (phospho-S39-fascin) could inhibit its actin-binding and actin-bundling activities and decrease filopodia formation. However, the relationship between phospho-S39-fascin expression and clinicopathological parameters in tumors is still unknown. Here, Western blot analysis and IHC applied to tissue microarray technology were performed to examine the expression status of non-phosphorylated fascin (fascin) and phospho-S39-fascin and their impacts on the prognosis of patients with esophageal squamous cell carcinoma (ESCC). Fascin and phospho-S39-fascin expressions were tested by cytoplasmic staining. Among the 254 patients, 90 cases showed high expression of fascin and 87 cases showed high expression of phospho-S39-fascin. Survival analysis showed that high expression of fascin was significantly associated with a poor prognosis of the patients with ESCC ( p = 0.004). In contrast, high expression of phospho-S39-fascin correlated significantly with an improved outcome of patients ( p = 0.020). Multivariate analysis showed that both fascin and phospho-S39-fascin were independent prognostic factors. In a combined analysis, the patients with high expression of fascin and low expression of phospho-S39-fascin tumors had a shorter overall survival than those with high expression of both fascin and phospho-S39-fascin tumors (5-year overall survival rate: 28.7% vs 48.3%, p = 0.068). Our results suggest that high expression of fascin correlates with poor outcome and that high expression of phospho-S39-fascin decreases the risk of poor prognosis in ESCC. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.
Hydraulic Properties of Asphalt Concrete
Authors: Pease R. Eric , Stormont John C. , Hines J. , O’Dowd Dan
Published: August 2010

This paper presents the laboratory results and methods used to measure the hydraulic parameters of asphalt concrete core samples. The same testing methods used to measure the saturated hydraulic conductivity and moisture retention in soils were applied to the asphalt concrete cores. Moisture retention was analyzed according to the van Genuchten (1980) mathematical model to produce the drying portion of the moisture retention curves. In addition to standard desorption tests, wetting curves were developed for two asphalt concrete cores. Saturated hydraulic conductivity was measured using a flexible wall permeameter. The asphalt concrete differs from these soils by maintaining a much lower porosity, and the dry asphalt concrete exhibited a water repellant behavior.
Dynamic Recrystallization in Zirconium Alloys
Authors: Chakravartty J. K. , Kapoor R. , Sarkar A. , Banerjee S.
Published: August 2010

In this investigation, the characteristics of dynamic recrystallization (DRX) in five Zr-alloys, namely, commercial pure zirconium (CP-Zr), Zircaloy-2 (Zr–Sn), Zr-2.5Nb (Zr–Nb), Zr-2.5Nb-0.5Cu (Zr–Nb-Cu), and Zr-1Nb-1Sn-0.1Fe (Zr–Nb–Sn–Fe), have been examined. For this purpose, processing maps were constructed using strain rate sensitivity (m) data as a function of temperature and strain rate. This has been done using compression tests carried out at constant true strain rate. The processing maps revealed the bounds of DRX domain as iso-contour of m in strain rate–temperature plane. Optical microscopy and transmission electron microscopy (TEM) were used to analyze the evolution of the microstructure and to ascertain the nature of dislocation mechanisms in deformed and quenched samples from the DRX domain. For all the alloys studied, TEM revealed complete modification of β-transformed microstructure to an equiaxed morphology containing dislocation substructure within. The variation of grain size with strain rate and temperature, high ductility, and a linear variation of log(grain size) with log(Z) (where Z is the Zener–Hollomon parameter) are some important characteristic features associated with DRX domains of Zr-alloys. While Nb exhibited strong influence on lowering the strain rate for the occurrence of DRX of CP-Zr, Sn addition (Zr–Sn) did not alter DRX characteristics. TEM observations neither revealed the nature of nucleation event nor identified the dislocation mechanism involved in the DRX process. In order to ascertain the rate controlling dislocation mechanism, the flow stress data were analyzed using a model of thermally activated flow. On the basis of the magnitudes of activation energy and apparent activation area, the cross-slip of screw dislocation has been identified as the rate controlling mechanism involved in the DRX process. The activation energy has been found to increase by alloying elements, which is expected to lower stacking fault energy (SFE) and increase separation between the partials. Further analysis of the data using Friedel’s model revealed that the activation energy for the cross-slip process can be decomposed into two parts—one related to the process of forming a constriction in the dissociated dislocations and the other needed for recombining the dissociated dislocations. While the former component (related to SFE) is dominant in Nb containing Zr-alloys, both the components are involved in controlling the deformation behavior of CP-Zr and Zr–Sn alloys. The effects of alloying elements on DRX characteristics and on the evolution of dislocation structure have been rationalized on the basis of cross-slip as the rate controlling dislocation mechanism in a qualitative manner. The importance of dynamic recovery in DRX process has been emphasized in view of this.
Ectopic Reelin Induces Neuronal Aggregation with a Normal Birthdate-Dependent “Inside-Out” Alignment in the Developing Neocortex
Authors: Kubo Ken-ichiro , Honda Takao , Tomita Kenji , Sekine Katsutoshi , Ishii Kazuhiro , Uto Asuka , Kobayashi Kazuma , Tabata Hidenori , Nakajima Kazunori
Published: August 2010

Neurons in the developing mammalian neocortex form the cortical plate (CP) in an “inside-out” manner; that is, earlier-born neurons form the deeper layers, whereas later-born neurons migrate past the existing layers and form the more superficial layers. Reelin, a glycoprotein secreted by Cajal–Retzius neurons in the marginal zone (MZ), is crucial for this “inside-out” layering, because the layers are inverted in the Reelin-deficient mouse,reeler(Relnrl). Even though more than a decade has passed since the discovery ofreelin, the biological effect of Reelin on individual migrating neurons remains unclear. In addition, although the MZ is missing in thereelercortex, it is unknown whether Reelin directly regulates the development of the cell-body-sparse MZ. To address these issues, we expressed Reelin ectopically in the developing mouse cortex, and the results showed that Reelin caused the leading processes of migrating neurons to assemble in the Reelin-rich region, which in turn induced their cell bodies to form cellular aggregates around Reelin. Interestingly, the ectopic Reelin-rich region became cell-body-sparse and dendrite-rich, resembling the MZ, and the late-born neurons migrated past their predecessors toward the central Reelin-rich region within the aggregates, resulting in a birthdate-dependent “inside-out” alignment even ectopically. Reelin receptors and intracellular adaptor protein Dab1 were found to be necessary for formation of the aggregates. The above findings indicate that Reelin signaling is capable of inducing the formation of the dendrite-rich, cell-body-sparse MZ and a birthdate-dependent “inside-out” alignment of neurons independently of other factors/structures near the MZ.
Direction-Selective Ganglion Cells Show Symmetric Participation in Retinal Waves During Development
Authors: Elstrott Justin , Feller Marla B.
Published: August 2010

Direction-selective ganglion cells (DSGCs) fire robustly for stimuli moving along one direction of motion and are strongly inhibited by stimuli moving in the opposite, or null, direction. In contrast to direction-selective neurons in primary visual cortex, a role for neural activity in the development of direction-selective retinal circuits has not been established. Direction-selective responses are detected at eye opening, before which spontaneous correlated activity known as retinal waves provide directional input to ganglion cells. Indeed, we observed a significant bias in wave propagation along the nasal over temporal direction. Using simultaneous calcium imaging and cell-attached recordings from three genetically labeled DSGC types in mice, we observed that all three DSGC types fire action potentials during retinal waves. However, we found that the direction of wave propagation did not influence DSGC spiking. These results indicate that the mechanisms guiding the formation of the asymmetric inhibition underlying direction selectivity in the retina are not dependent upon the directional properties of retinal waves.
The Scaffold Protein NHERF2 Determines the Coupling of P2Y1 Nucleotide and mGluR5 Glutamate Receptor to Different Ion Channels in Neurons
Authors: Filippov Alexander K. , Simon Joseph , Barnard Eric A. , Brown David A.
Published: August 2010

Expressed metabotropic group 1 glutamate mGluR5 receptors and nucleotide P2Y1 receptors (P2Y1Rs) show promiscuous ion channel coupling in sympathetic neurons: their stimulation inhibits M-type [Kv7, K(M)] potassium currents and N-type (CaV2.2) calcium currents (Kammermeier and Ikeda, 1999; Brown et al., 2000). These effects are mediated by Gqand Gi/oG-proteins, respectively. Via their C-terminal tetrapeptide, these receptors also bind to the PDZ domain of the scaffold protein NHERF2, which enhances their coupling to Gq-mediated Ca2+signaling (Fam et al., 2005; Paquet et al., 2006b). We investigated whether NHERF2 could modulate coupling to neuronal ion channels. We find that coexpression of NHERF2 in sympathetic neurons (by intranuclear cDNA injections) does not affect the extent of M-type potassium current inhibition produced by either receptor but strongly reduced CaV2.2 inhibition by both P2Y1R and mGluR5 activation. NHERF2 expression had no significant effect on CaV2.2 inhibition by norepinephrine (via α2-adrenoceptors, which do not bind NHERF2), nor on CaV2.2 inhibition produced by an expressed P2Y1R lacking the NHERF2-binding DTSL motif. Thus, NHERF2 selectively restricts downstream coupling of mGluR5 and P2Y1Rs in neurons to Gq-mediated responses such as M-current inhibition. Differential distribution of NHERF2 in neurons may therefore determine coupling of mGluR5 receptors and P2Y1 receptors to calcium channels.
Estimating Indirect Genetic Effects: Precision of Estimates and Optimum Designs
Authors: Bijma Piter
Published: August 2010

Social interactions among individuals are abundant both in natural and domestic populations. Such social interactions cause phenotypes of individuals to depend on genes carried by other individuals, a phenomenon known as indirect genetic effects (IGE). Because IGEs have drastic effects on the rate and direction of response to selection, knowledge of their magnitude and relationship to direct genetic effects (DGE) is indispensable for understanding response to selection. Very little is known, however, of statistical power and optimum experimental designs for estimating IGEs. This work, therefore, presents expressions for the standard errors of the estimated (co)variances of DGEs and IGEs and identifies optimum experimental designs for their estimation. It also provides an expression for optimum family size and a numerical investigation of optimum group size. Designs with groups composed of two families were optimal and substantially better than designs with groups composed at random with respect to family. Results suggest that IGEs can be detected with ∼1000–2000 individuals and/or ∼250–500 groups when using optimum designs. Those values appear feasible for agriculture and aquaculture and for the smaller laboratory species. In summary, this work provides the tools to optimize and quantify the required size of experiments aiming to identify IGEs. An R-package SE.IGE is available, which predicts SEs and identifies optimum family and group sizes.
Disparities in Peaks, Plateaus, and Declines in Prevalence of High BMI Among Adolescents
Authors: Madsen Kristine A. , Weedn Ashley E. , Crawford Patricia B.
Published: August 2010

OBJECTIVES:

The objective of this study was to investigate trends in prevalence of high BMI from 2001 to 2008 and examine racial/ethnic disparities.

METHODS:

Records for a total of 8 283 718 fifth-, seventh-, and ninth-grade students who underwent California's school-based BMI screening between 2001 and 2008 were included. Logistic regression identified trends in prevalence of high BMI (≥85th, ≥95th, ≥97th, and ≥99th percentiles).

RESULTS:

For 3 of 4 BMI cut points, prevalence continued to increase for black and American Indian girls through 2008, Hispanic girls plateaued after 2005, non-Hispanic white girls declined to 2001 prevalence levels after peaking in 2005, and Asian girls showed no increases. Non-Hispanic white boys peaked in 2005, then declined to 2001 prevalence levels for all BMI cut points; Hispanic and Asian boys declined after 2005 (for 3 lowest BMI cut points only) but remained above 2001 levels; and American Indian boys peaked later (2007) and declined only for BMI ≥95th. No girls and few boys showed a decline after peaking in prevalence of BMI ≥99th percentile. In 2008, disparities in prevalence were greatest for BMI ≥99th percentile, with prevalence of 4.9% for American Indian girls and 4.6% for black girls versus 1.3% for non-Hispanic white girls.

CONCLUSIONS:

On the basis of statewide California data, prevalence of high BMI is declining for some groups but has not declined for American Indian and black girls. These trends portend greater disparities over time, particularly in severe obesity. Interventions and policies that are tailored to the highest risk groups should be pursued.