bluuebunny/crossref_metadata_2025 huggingface dataset:
Flow cytometry analysis of glucocorticoid receptor expression and binding in steroid-sensitive and steroid-resistant patients with systemic lupus erythematosus
Authors: Du Juan , Li Min , Zhang Denghai , Zhu Xiaoyan , Zhang Weiwei , Gu Wei , Feng Yinglu , Zhai Xiaofeng , Ling Changquan
Published: July 2009

Introduction

Glucocorticoid (GC) therapy is the main treatment for systemic lupus erythematosus (SLE). However, some patients are resistant to these agents. Abnormalities of glucocorticoid receptor (GR) seem to be related to steroid resistance. This study evaluated GRs in T lymphocytes and monocytes of SLE patients by flow cytometry (FCM) using a monoclonal antibody (mAb) and FITC-Dex probes.

Methods

Thirty-five patients with SLE before treatment and 27 age- and sex-matched normal controls were studied. Disease activity scores were determined before and after treatment and used to divide the patients into steroid-resistant (SR) and steroid-sensitive (SS) groups. GRs in T lymphocytes (CD3+) and monocytes (CD14+) were examined by FCM with GR-mAb and FITC-Dex probes before treatment. Peripheral blood mononuclear cells (PBMCs) were isolated for in vitro GCs sensitivity assays. The validity of FCM analysis of intracellular staining for GR with GR-mAb and FITC-Dex probes was evaluated through comparison with western blot and radioligand binding assay (RLBA) in U937 and K562 cells in vitro. One-way ANOVA, student's t test, linear regression and spearman correlation were performed.

Results

A significant decrease in GR binding and the expression in K562 and U937 cells with 10-6 M dexamethasone (Dex) was found compared with those without Dex. In addition, a positive correlation was found between FCM and RLBA as well as FCM and Western blot. The expression and binding of both CD3/GR and CD14/GR in SR patients with SLE, detected by FCM, were all lower than those in SS patients with SLE, whereas there was no significant difference in SS patients and controls. In vitro corticosteroid sensitivity assay indicated that PHA-stimulated tumour necrosis factor-α (TNF-α), IL-12 and interferon-γ (IFN-γ) secretion was significantly inhibited by 10-6 M Dexamethasone in all controls and SS patients, compared with that in SR group, which confirms patient classification as SR and SS by disease activity index (SLEDAI) score.

Conclusions

Abnormalities of expression and binding of the GR may be involved in tissue resistance to steroids in SLE patients. Determination of GR expression and binding by FCM may be useful in predicting the response to steroid treatment of SLE patients.

Trial registration

Clinical trial registration number NCT00600652.
Randomized Double-Blind 2 × 2 Trial of Low-Dose Tamoxifen and Fenretinide for Breast Cancer Prevention in High-Risk Premenopausal Women
Authors: Decensi Andrea , Robertson Chris , Guerrieri-Gonzaga Aliana , Serrano Davide , Cazzaniga Massimiliano , Mora Serena , Gulisano Marcella , Johansson Harriet , Galimberti Viviana , Cassano Enrico , Moroni Simona M. , Formelli Franca , Lien Ernst A. , Pelosi Giuseppe , Johnson Karen A. , Bonanni Bernardo
Published: July 2009

Purpose

Tamoxifen and fenretinide are active in reducing premenopausal breast cancer risk and work synergistically in preclinical models. The authors assessed their combination in a two-by-two biomarker trial.

Patients and Methods

A total of 235 premenopausal women with pT1mic/pT1a breast cancer (n = 21), or intraepithelial neoplasia (IEN, n = 160), or 5-year Gail risk ≥ 1.3% (n = 54) were randomly allocated to either tamoxifen 5 mg/d, fenretinide 200 mg/d, their combination, or placebo. We report data for plasma insulin-like growth factor I (IGF-I), mammographic density, uterine effects, and breast neoplastic events after 5.5 years.

Results

During the 2-year intervention, tamoxifen significantly lowered IGF-I and mammographic density by 12% and 20%, respectively, fenretinide by 4% and 10% (not significantly), their combination by 20% and 22%, with no evidence for a synergistic interaction. Tamoxifen increased endometrial thickness principally in women becoming postmenopausal, whereas fenretinide decreased endometrial thickness significantly. The annual rate of breast neoplasms (n = 48) was 3.5% ± 1.0%, 2.1% ± 0.8%, 4.7% ± 1.3%, and 5.2% ± 1.3% in the tamoxifen, fenretinide, combination, and placebo arms, respectively, with hazard ratios (HRs) of 0.70 (95% CI, 0.32 to 1.52), 0.38 (95% CI, 0.15 to 0.90), and 0.96 (95% CI, 0.46 to 1.99) relative to placebo (tamoxifen × fenretinide adverse interaction P = .03). There was no clear association with tumor receptor type. Baseline IGF-I and mammographic density did not predict breast neoplastic events, nor did change in mammographic density.

Conclusion

Despite favorable effects on plasma IGF-I levels and mammographic density, the combination of low-dose tamoxifen plus fenretinide did not reduce breast neoplastic events compared to placebo, whereas both single agents, particularly fenretinide, showed numerical reduction in annual odds of breast neoplasms. Further follow-up is indicated.
Index to Predict Invasive Mold Infection in High-Risk Neutropenic Patients Based on the Area Over the Neutrophil Curve
Authors: Portugal Rodrigo D. , Garnica Marcia , Nucci Marcio
Published: July 2009

Purpose

Patients with prolonged and profound neutropenia are at high risk to develop invasive mold infections (IMIs). We developed an index (D-index) that combines duration and severity of neutropenia. The aim of this study was to test the D-index as a predictor of IMI.

Patients and Methods

The D-index was based on a graph plotting the absolute neutrophil counts during neutropenia and was the area over the neutrophil curve. We tested the D-index in 11 patients with acute myeloid leukemia (AML) who developed IMI during neutropenia and 33 AML patients without IMI (controls). We also calculated a cumulative D-index (c-D-index), defined as the cumulative D-index from the start of neutropenia until the date of the first clinical manifestation of IMI in patient cases. We compared the D-index and c-D-index with duration of neutropenia and defined a cutoff for IMI using the receiver operating characteristic (ROC) curve.

Results

The median duration of neutropenia and profound neutropenia of patient cases were significantly higher compared with controls (P = .002 and P = .001, respectively), as were the D-index (P < .001) and c-D-index (P = .02). The D-index and c-D-index performed better than duration of neutropenia in ROC curve analysis. For a cutoff point of 5,800 of the c-D-index, the sensitivity and specificity were 91% and 58%, respectively, and for a prevalence of IMI of 5%, 10%, and 15%, the negative predictive values were 99%, 98%, and 97%, respectively.

Conclusion

The high negative predictive value of the c-D-index may be of help in defining different risks for IMI in febrile neutropenic patients.
Clinical Trial Designs for Predictive Biomarker Validation: Theoretical Considerations and Practical Challenges
Authors: Mandrekar Sumithra J. , Sargent Daniel J.
Published: July 2009

Purpose

Biomarkers can add substantial value to current medical practice by providing an integrated approach to prediction using the genetic makeup of the tumor and the genotype of the patient to guide patient-specific treatment selection. We discuss and evaluate various clinical trial designs for the validation of biomarker-guided therapy.

Methods

Designs for predictive marker validation are broadly classified as retrospective (ie, using data from previously well-conducted randomized controlled trials [RCTs]) versus prospective (enrichment, unselected, hybrid, or adaptive analysis). We discuss the salient features of each design in the context of real trials.

Results

Well-designed retrospective analysis from well-conducted prospective RCTs can bring forward effective treatments to marker-defined subgroups of patients in a timely manner (eg, KRAS and colorectal cancer). Enrichment designs are appropriate when preliminary evidence suggest that patients with or without that marker profile do not benefit from the treatments in question; however, this may sometimes leave questions unanswered (eg, trastuzumab and breast cancer). An unselected design is optimal where preliminary evidence regarding treatment benefit and assay reproducibility is uncertain (eg, epidermal growth factor receptor and lung cancer). Hybrid designs are appropriate when preliminary evidence demonstrate the efficacy of certain treatments for a marker-defined subgroup, making it unethical to randomly assign patients with that marker status to other treatments (eg, multigene assay and breast cancer). Adaptive analysis designs allow for prespecified marker-defined subgroup analyses of data from an RCT.

Conclusion

The implementation of these design strategies will lead to a more rapid clinical validation of biomarker-guided therapy.
Merkel Cell Carcinoma: Recent Progress and Current Priorities on Etiology, Pathogenesis, and Clinical Management
Authors:   The Rockville Merkel Cell Carcinoma Group
Published: July 2009

Purpose

To expedite improved understanding, diagnosis, treatment, and prevention of Merkel cell carcinoma (MCC), a rare malignancy of cutaneous neuroendocrine cells that has a 28% 2-year mortality rate.

Methods

This article summarizes a workshop that discussed the state-of-the-art research and priorities for research on MCC and on a new human polyomavirus (ie, MCPyV) recently discovered in 80% of MCC tumors.

Results

Normal Merkel cells are widely distributed in the epidermis near the end of nerve axons and may function as mechanoreceptors or chemoreceptors. Malignant MCC cells typically stain for cytokeratin 20 as well as for other epithelial and neuroendocrine markers. MCC subtypes, which are based on histology, on cell line growth properties, and on gene expression profiles, have been reported but have not been linked to prognosis. Clinical management has been empiric. MCPyV is clonally integrated at various sites in the human genome of MCC tumors, with truncating mutations in the viral, large T antigen gene that interrupt viral replication. MCPyV seroprevalence may be high, as with previously known human polyomaviruses. MCC risk is increased 11-fold with AIDS and with other cell-mediated immune deficiencies, B-cell neoplasms, and ultraviolet radiation exposure.

Conclusion

Development and validation of a range quantitative polymerase chain reaction and serologic assays for detection of MCPyV, as well as an infectious clone of the virus, would clarify the fundamental biology, natural history, and epidemiology of the virus, of MCC, and of other diseases. Contingent on standardized histologic diagnosis and staging of MCC, consortia are needed to clarify the risks and benefits of sentinel lymph node biopsy, adjuvant radiation therapy, and salvage therapies; consortia are needed also for epidemiologic studies of MCC etiology.
Electronic Surveillance of Testicular Cancer: Understanding Patient Perspectives on Access to Electronic Medical Records
Authors: Groll Ryan J. , Leonard Kevin J. , Eakin Joan , Warde Padraig , Bender Jackie , Jewett Michael A.S.
Published: July 2009

This study explores the basis for providing effective access to electronic medical record data as a reference source for patients with early-stage testicular cancer undergoing surveillance follow-up programs.
Survey of Provider Perspectives on Patient Assistance Programs
Authors: Buell Roberta , Gesme Dean
Published: July 2009

This survey attempts to quantify the costs of applying for patient assistance programs, which oncologists say too often involves weeks of paperwork, repeated telephone calls, and bureaucratic delays.
Nesprin-2 interacts with meckelin and mediates ciliogenesis via remodelling of the actin cytoskeleton
Authors: Dawe Helen R. , Adams Matthew , Wheway Gabrielle , Szymanska Katarzyna , Logan Clare V. , Noegel Angelika A. , Gull Keith , Johnson Colin A.
Published: July 2009

Meckel-Gruber syndrome (MKS) is a severe autosomal recessively inherited disorder caused by mutations in genes that encode components of the primary cilium and basal body. Here we show that two MKS proteins, MKS1 and meckelin, that are required for centrosome migration and ciliogenesis interact with actin-binding isoforms of nesprin-2 (nuclear envelope spectrin repeat protein 2, also known as Syne-2 and NUANCE). Nesprins are important scaffold proteins for maintenance of the actin cytoskeleton, nuclear positioning and nuclear-envelope architecture. However, in ciliated-cell models, meckelin and nesprin-2 isoforms colocalized at filopodia prior to the establishment of cell polarity and ciliogenesis. Loss of nesprin-2 and nesprin-1 shows that both mediate centrosome migration and are then essential for ciliogenesis, but do not otherwise affect apical-basal polarity. Loss of meckelin (by siRNA and in a patient cell-line) caused a dramatic remodelling of the actin cytoskeleton, aberrant localization of nesprin-2 isoforms to actin stress-fibres and activation of RhoA signalling. These findings further highlight the important roles of the nesprins during cellular and developmental processes, particularly in general organelle positioning, and suggest that a mechanistic link between centrosome positioning, cell polarity and the actin cytoskeleton is required for centrosomal migration and is essential for early ciliogenesis.
FAM29A, a target of Plk1 regulation, controls the partitioning of NEDD1 between the mitotic spindle and the centrosomes
Authors: Zhu Hui , Fang Kayleen , Fang Guowei
Published: July 2009

We previously showed that FAM29A, a spindle-associated protein, promotes microtubule-dependent microtubule amplification through its interaction with and recruitment of NEDD1, the targeting subunit of the γ-tubulin ring complex. We report here that FAM29A is regulated by Plk1, a kinase essential for spindle assembly and its bipolarity. Plk1, FAM29A and NEDD1 form three separate complexes in vivo, not one single complex. Plk1 recruits FAM29A to spindle microtubules, which, in turn, targets NEDD1 to the spindle. Plk1 also recruits NEDD1 to the centrosomes, probably through a Plk1-NEDD1 interaction, but this interaction does not contribute to targeting NEDD1 to the spindle. Altering intracellular levels of FAM29A changes the distribution of NEDD1 between the centrosomes and the spindle, indicating that FAM29A controls the partition of NEDD1 between these two mitotic structures. Thus, Plk1 promotes microtubule nucleation from the centrosomes through a FAM29A-independent pathway and from the spindle through a FAM29A-dependent pathway. FAM29A controls the relative contributions of these two pathways to microtubule polymerization during mitosis.
Nicotiana tabacumTTG1 contributes to ParA1-induced signalling and cell death in leaf trichomes
Authors: Wang Yunpeng , Liu Ruoxue , Chen Lei , Wang Yuancong , Liang Yuancun , Wu Xiaojing , Li Baoyan , Wu Jiandong , Liang Yuan , Wang Xiaomeng , Zhang Chunling , Wang Qiuxia , Hong Xiaoyue , Dong Hansong
Published: July 2009

Leaf trichomes serve as a physical barrier and can also secrete antimicrobial compounds to protect plants from attacks by insects and pathogens. Besides the use of the physical and chemical mechanisms, leaf trichomes might also support plant responses by communicating the extrinsic cues to plant intrinsic signalling pathways. Here we report a role of leaf trichomes in tobacco (Nicotiana tabacum) hypersensitive cell death (HCD) induced by ParA1, an elicitin protein from a plant-pathogenic oomycete. After localized treatment with ParA1, reactive oxygen species were produced first in the leaf trichomes and then in mesophylls. Reactive oxygen species are a group of intracellular signals that are crucial for HCD to develop and for cells to undergo cell death subsequent to chromatin condensation, a hallmark of HCD. These events were impaired when the production of hydrogen peroxide (H2O2) was inhibited by catalase or a NADPH-oxidase inhibitor applied to trichomes, suggesting the importance of H2O2 in the pathway of HCD signal transduction from the trichomes to mesophylls. This pathway was no longer activated when leaf trichomes were treated with C51S, a ParA1 mutant protein defective in its interaction with N. tabacum TTG1 (NtTTG1), which is a trichome protein that binds ParA1, rather than C51S, in vitro and in trichome cells. The ParA1-NtTTG1 interaction and the HCD pathway were also abrogated when NtTTG1 was silenced in the trichomes. These observations suggest that NtTTG1 plays an essential role in HCD signal transduction from leaf trichomes to mesophylls.
Effects of eccentric compression by a crossed-tape technique after endovenous laser ablation of the great saphenous vein: a randomized study
Authors: Lugli M , Cogo A , Guerzoni S , Petti A , Maleti O
Published: July 2009

Objectives

To evaluate the effect of eccentric compression applied by a new crossed-tape technique on procedure-related pain occurrence after endovenous laser ablation (ELA) of the great saphenous vein (GSV).

Methods

From April 2005 to June 2006, 200 consecutive ELA procedures were randomized to receive (group A: 100) or not (group B: 100) an eccentric compression applied in the medial aspect of the thigh. Patients were scheduled for a seven-day examination to assess the level of pain experienced. Pain intensity was measured using a visual analogue scale giving a numerical grade from 0 (no pain) to 10 (worst pain ever).

Results

The intensity of postoperative pain was significantly reduced ( P < 0.001) in the eccentric compression group as compared with the non-compression one.

Conclusions

This technique of eccentric compression greatly reduces the intensity of postoperative pain after ELA of the GSV.
Sclerotherapy of varicose veins in patients with documented thrombophilia: a prospective controlled randomized study of 105 cases
Authors: Hamel-Desnos C M , Gillet J-L , Desnos P R , Allaert F A
Published: July 2009

Objectives

The aim of this study was to assess thrombotic complications following sclerotherapy in thrombophilic patients in combination with thromboprophylaxis, in two randomized arms using low molecular weight heparin (LMWH) or warfarin.

Patients and methods

This study received approval from the Ethics Committee. A total of 105 patients (81 females, 24 males) ranging in age from 20 to 82 years (mean 50) were selected: 75 with Factor V Leiden mutation, 18 with prothrombin 20210A mutation, 7 with high level of Factor VIII, 5 combinations of these. After randomization, 51 and 54 patients received warfarin and LMWH, respectively. A total of 199 sclerotherapy sessions were performed. Foam was used in 160 treatments.

Results

No episodes of symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) occurred; no instances of DVT were revealed by ultrasound-monitoring.

Conclusions

This study suggests that in the three most common forms of thrombophilia, sclerotherapy, in combination with thromboprophylaxis, can be performed safely. Prophylaxis with LMWH is easier to use than warfarin.
Candidate gene analysis of femoral neck trabecular and cortical volumetric bone mineral density in older men
Authors: Yerges Laura M , Klei Lambertus , Cauley Jane A , Roeder Kathryn , Kammerer Candace M , Ensrud Kristine E , Nestlerode Cara S , Lewis Cora , Lang Thomas F , Barrett-Connor Elizabeth , Moffett Susan P , Hoffman Andrew R , Ferrell Robert E , Orwoll Eric S , Zmuda Joseph M
Published: July 2009

In contrast to conventional dual-energy X-ray absorptiometry, quantitative computed tomography separately measures trabecular and cortical volumetric bone mineral density (vBMD). Little is known about the genetic variants associated with trabecular and cortical vBMD in humans, although both may be important for determining bone strength and osteoporotic risk. In the current analysis, we tested the hypothesis that there are genetic variants associated with trabecular and cortical vBMD at the femoral neck by genotyping 4608 tagging and potentially functional single-nucleotide polymorphisms (SNPs) in 383 bone metabolism candidate genes in 822 Caucasian men aged 65 years or older from the Osteoporotic Fractures in Men Study (MrOS). Promising SNP associations then were tested for replication in an additional 1155 men from the same study. We identified SNPs in five genes (IFNAR2, NFATC1, SMAD1, HOXA, and KLF10) that were robustly associated with cortical vBMD and SNPs in nine genes (APC, ATF2, BMP3, BMP7, FGF18, FLT1, TGFB3, THRB, and RUNX1) that were robustly associated with trabecular vBMD. There was no overlap between genes associated with cortical vBMD and trabecular vBMD. These findings identify novel genetic variants for cortical and trabecular vBMD and raise the possibility that some genetic loci may be unique for each bone compartment. © 2010 American Society for Bone and Mineral Research
Peano differentiable extensions in o-minimal structures
Authors: Fischer Andreas
Published: July 2009

Peano differentiability generalizes ordinary differentiability to higher order. There are two ways to define Peano differentiability for functions defined on non-open sets. For both concepts, we investigate the question under which conditions a function defined on a closed set can be extended to a Peano differentiable function on the ambient space if the sets and functions are definable in an o-minimal structure expanding a real closed field.
Anti-Terrorismus-Politik. Ein deutsch-italienischer Vergleich 1969–1982
Authors: Hürter Johannes
Published: July 2009

Vorspann

Zwei Staaten, ein Problem. Nirgendwo im Europa der 1970er Jahre verübten linksextreme Terroristen so viele Anschläge und Morde wie in Italien und der Bundesrepublik. Beide Demokratien waren gezwungen, auf diese Herausforderung zu reagieren. Die Interaktion von Terrorismus, Staat und Gesellschaft prägte ein ganzes Jahrzehnt. Dabei fiel dem politisch-administrativen Handeln eine Schlüsselrolle zu. Für welche Gegenmaßnahmen entschieden sich Regierung und Parlament? Erwies sich der demokratische Rechtsstaat als stark und gefestigt und zugleich als flexibel und integrativ genug, um die terroristische Gefahr zu bewältigen, ohne selbst Schaden zu nehmen? Ein Ländervergleich verspricht neue Erkenntnisse für beide nationalen Beispiele.
Epistatic Effects of the Protease/Chaperone HflB on Some Damaged Forms of the Escherichia coli Ammonium Channel AmtB
Authors: Inwood William B , Hall Jason A , Kim Kwang-Seo , Demirkhanyan Lusine , Wemmer David , Zgurskaya Helen , Kustu Sydney
Published: July 2009

The Escherichia coli ammonium channel AmtB is a trimer in which each monomer carries a pore for substrate conduction and a cytoplasmic C-terminal extension of ∼25 residues. Deletion of the entire extension leaves the protein with intermediate activity, but some smaller lesions in this region completely inactivate AmtB, as do some lesions in its cytoplasmic loops. We here provide genetic evidence that inactivation depends on the essential protease HflB, which appears to cause inactivation not as a protease but as a chaperone. Selection for restored function of AmtB is a positive selection for loss of the ATPase/chaperone activity of HflB and reveals that the conditional lethal phenotype for hflB is cold sensitivity. Deletion of only a few residues from the C terminus of damaged AmtB proteins seems to prevent HflB from acting on them. Either yields the intermediate activity of a complete C-terminal deletion. HflB apparently “tacks” damaged AmtB tails to the adjacent monomers. Knowing that HflB has intervened is prerequisite to determining the functional basis for AmtB inactivation.
Conservation of Domain Structure in a Fast-Evolving Heterochromatic SUUR Protein in Drosophilids
Authors: Yurlova Anna A , Makunin Igor V , Kolesnikova Tatyana D , Posukh Olga V , Belyaeva Elena S , Zhimulev Igor F
Published: July 2009

Different genomic regions replicate at a distinct time during S-phase. The SuUR mutation alters replication timing and the polytenization level of intercalary and pericentric heterochromatin in Drosophila melanogaster salivary gland polytene chromosomes. We analyzed SuUR in different insects, identified conserved regions in the protein, substituted conserved amino acid residues, and studied effects of the mutations on SUUR function. SuUR orthologs were identified in all sequenced drosophilids, and a highly divergent ortholog was found in the mosquito genome. We demonstrated that SUUR evolves at very high rate comparable with that of Transformer. Remarkably, upstream ORF within 5′ UTR of the gene is more conserved than SUUR in drosophilids, but it is absent in the mosquito. The domain structure and charge of SUUR are maintained in drosophilids despite the high divergence of the proteins. The N-terminal part of SUUR with similarity to the SNF2/SWI2 proteins displays the highest level of conservation. Mutation of two conserved amino acid residues in this region impairs binding of SUUR to polytene chromosomes and reduces the ability of the protein to cause DNA underreplication. The least conserved middle part of SUUR interacting with HP1 retains positively and negatively charged clusters and nuclear localization signals. The C terminus contains interlacing conserved and variable motifs. Our results suggest that SUUR domains evolve with different rates and patterns but maintain their features.
Transcription Independent Insulation at TFIIIC-Dependent Insulators
Authors: Valenzuela Lourdes , Dhillon Namrita , Kamakaka Rohinton T
Published: July 2009

Chromatin insulators separate active from repressed chromatin domains. In yeast the RNA pol III transcription machinery bound to tRNA genes function with histone acetylases and chromatin remodelers to restrict the spread of heterochromatin. Our results collectively demonstrate that binding of TFIIIC is necessary for insulation but binding of TFIIIB along with TFIIIC likely improves the probability of complex formation at an insulator. Insulation by this transcription factor occurs in the absence of RNA polymerase III or polymerase II but requires specific histone acetylases and chromatin remodelers. This analysis identifies a minimal set of factors required for insulation.
Transporting Children With Special Health Care Needs: Comparing Recommendations and Practice
Authors: O'Neil Joseph , Yonkman Janell , Talty Judith , Bull Marilyn J.
Published: July 2009

OBJECTIVE: We compare the use of the American Academy of Pediatrics (AAP) guidelines for the safe transportation of children with special health care needs (CSHCN) with reported and observed practices.

METHODS: This observational study was based on a convenience sample of vehicles exiting the garage of a tertiary children's hospital. Certified child passenger safety technicians with a health care background and specialized training in the transportation of CSHCN gathered the driver's demographic information and the child's reported medical condition, weight, age, clinic visited, and relation to the driver. The safety technicians observed the car safety seat (CSS) type, vehicle seating position, and if the child required postural support.

RESULTS: During the study, 275 drivers transporting 294 CSHCN were observed. Overall, most drivers complied with AAP recommendations by using a standard CSS seat (75.4%). Among the seats evaluated, 241 (82.0%) were the appropriate choice, but only 75 (26.8%) of 280 assessed had no misuses. Approximately 24% of the drivers modified the CSS, and 19.4% of the children would have benefited from additional body-positioning support. Only 8% of medical equipment was properly secured.

CONCLUSIONS: Although most drivers seemed to choose the appropriate seat, many had at least 1 misuse. Drivers complied with most AAP recommendations; however, some deviated to facilitate care of the child during transport. Discussions with parents or caregivers about the proper transportation of CSHCN and referrals to child passenger safety technicians with special training may improve safety, care, and comfort in the vehicle.
Mental Health Treatment Patterns in Perinatally HIV-Infected Youth and Controls
Authors: Chernoff Miriam , Nachman Sharon , Williams Paige , Brouwers Pim , Heston Jerry , Hodge Janice , Di Poalo Vinnie , Deygoo Nagamah Sandra , Gadow Kenneth D. ,   IMPAACT P1055 Study Team
Published: July 2009

BACKGROUND: Youths perinatally infected with HIV often receive psychotropic medication and behavioral treatment for emotional and behavioral symptoms. We describe patterns of intervention for HIV-positive youth and youth in a control group in the United States.

METHODS: Three hundred nineteen HIV-positive youth and 256 controls, aged 6 to 17 years, enrolled in the International Maternal Adolescent AIDS Clinical Trials 1055, a prospective, 2-year observational study of psychiatric symptoms. One hundred seventy-four youth in the control group were perinatally exposed to HIV, and 82 youth were uninfected children living in households with HIV-positive members. Youth and their primary caregivers completed Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition–referenced symptom-rating scales. Children's medication and behavioral psychiatric intervention histories were collected at entry. We evaluated the association of past or current psychiatric treatment with HIV status, baseline symptoms, and impairment by using multiple logistic regression, controlling for potential confounders.

RESULTS: HIV-positive youth and youth in the control group had a similar prevalence of psychiatric symptoms (61%) and impairment (14% to 15%). One hundred four (18%) participants received psychotropic medications (stimulants [14%], antidepressants [6%], and neuroleptic agents [4%]), and 127 (22%) received behavioral treatment. More HIV-positive youth than youth in the control group received psychotropic medication (23% vs 12%) and behavioral treatment (27% vs 17%). After adjusting for symptom class and confounders, HIV-positive children had twice the odds of children in the control group of having received stimulants and >4 times the odds of having received antidepressants. Caregiver-reported symptoms or impairment were associated with higher odds of intervention than reports by children alone.

CONCLUSIONS: HIV-positive children are more likely to receive mental health interventions than control-group children. Pediatricians and caregivers should consider available mental health treatment options for all children living in families affected by HIV.
Empiric Use of Potassium Citrate Reduces Kidney-Stone Incidence With the Ketogenic Diet
Authors: McNally Melanie A. , Pyzik Paula L. , Rubenstein James E. , Hamdy Rana F. , Kossoff Eric H.
Published: July 2009

OBJECTIVE: Kidney stones are an adverse event with the ketogenic diet (KD), occurring in ∼6% of children who are started on this therapy for intractable epilepsy. Potassium citrate (Polycitra K) is a daily oral supplement that alkalinizes the urine and solubilizes urine calcium, theoretically reducing the risk for kidney stones.

METHODS: Children who started the KD from 2000 to 2008 at Johns Hopkins Hospital, with at least 1 month of follow-up, were evaluated (N = 313). From 2000 to 2005, children were treated with daily Polycitra K at 2 mEq/kg per day only in the setting of identified hypercalciuria, whereas, since 2006, it has been started for all children empirically at KD onset.

RESULTS: Polycitra K was administered to 198 children preventatively overall, 4 (2.0%) of whom developed kidney stones, compared with 11 (10.5%) of 105 who did not receive Polycitra K (P = .003). Two children since 2006 refused Polycitra K, 1 of whom developed a kidney stone. Successful empiric administration of Polycitra K at KD onset resulted in a kidney-stone incidence of 0.9% (1 of 106) compared with administration only because of hypercalciuria, 6.7% (13 of 195; P = .02). Polycitra K resulted in less acidic urine (mean pH: 6.8 vs 6.2; P = .002) but not reduced serum acidosis. No adverse effects of oral citrates were reported.

CONCLUSIONS: Oral potassium citrate is an effective preventive supplement against kidney stones in children who receive the KD, achieving its goal of urine alkalinization. Universal supplementation is warranted.
Management of women with chronic renal disease in pregnancy
Authors: Kapoor Nisha , Makanjuola David , Shehata Hassan
Published: July 2009

A multidisciplinary team should manage pregnancy in women with chronic renal disease.

The outcome is dependent upon prepregnancy renal function and the presence of hypertension and proteinuria.

Women on dialysis and renal transplant recipients form a special group that needs expert care during pregnancy.

Learning objectives:

To understand the basic principles in prepregnancy counselling of women with chronic renal disease.

To be aware of the risks to the pregnancy as well as to long‐term renal function.

Ethical issues:

The risks of serious complications and adverse effects on long‐term health raise complex ethical issues for the health professionals who counsel women with chronic renal disease and look after them during pregnancy.

Please cite this article as: Kapoor N, Makanjuola D, Shehata H. Management of women with chronic renal disease in pregnancy. The Obstetrician & Gynaecologist 2009;11:185–191.
Vulnerability and self-perceived health status among light and heavy smokers: the relationship to short-term fear appeal tobacco control messages
Authors: Szklo André Salem , Coutinho Evandro Silva Freire
Published: July 2009

It is important to stimulate smokers to acquire some level of risk perception associated with their current behavior in order to motivate smoking cessation. The present article attempts to understand how the content of short-term fear appeal government tobacco messages may interact with different levels of daily cigarette consumption in order to affect smokers' vulnerabilities, expressed by self-perceived health status. A Poisson model was used to estimate the prevalence ratio of fair or poor self-perceived health status (FPHS) according to daily cigarette consumption. We also calculated the proportions of smokers who stated that selected health warning pictures on cigarette packets encourage people to quit smoking, stratified by self-perceived health status and daily cigarette consumption. The proportion of smokers with FPHS was 25% higher among those who smoked > 20 cigarettes/day (p = 0.01). Among smokers with FPHS, heavy smokers showed the highest proportions of responses in favor of selected warning pictures most closely related to losses in ordinary daily living, such as shortness of breath and being bothered by cigarette addiction. Short-term loss-framed tobacco control messages seem to have raised awareness of vulnerability among heavier smokers.
Changing Social Ethos is the Key
Authors: Roemer John E
Published: July 2009

As we consider rewriting financial regulation, John Roemer of Yale asks: is it too big a task to implement reasonable outcomes in a world of greed?
A Test of the Selection-Socialization Theory in Moral Reasoning of CPAs in Industry Practice
Authors: Abdolmohammadi Mohammad J. , Ariail Donald L.
Published: July 2009

ABSTRACT: This paper investigates the Selection-Socialization Theory (SST) and its related Inverted-U Phenomenon (IUP) in the moral reasoning of Certified Public Accountants (CPAs) in industry and public practice. This is an extension of the literature that has primarily focused on CPAs in public practice and has reported mixed results. We do not find significant differences in moral reasoning (as measured by the P-score of the Defining Issues Test) between various professional ranks of practicing accountants. This result suggests an absence of SST or IUP in promotions of CPAs to higher ranks in industry or public practice. Investigation of control variables indicates that gender and ethical training do not have significant effects on the P-score. However, as expected, CPAs with graduate degrees have higher P-scores than those with only an undergraduate degree, and politically moderate or liberal CPAs score higher than conservatives.
The Influence of Incentive Structure on Group Performance in Assembly Lines and Teams
Authors: Libby Theresa , Thorne Linda
Published: July 2009

ABSTRACT: Modern manufacturing settings increasingly rely upon workgroups; however, evidence concerning the best fit among incentive structure, production environment, and group performance has been mixed. Young et al. (1993) examine the effect of group incentives on group performance in cooperative and noncooperative environments. Although theory and evidence from practice indicate that group incentives combined with cooperation should result in higher group performance, their results were contrary to this prediction. To further explore this issue, we examine the effect of individual, group, and mixed incentive structures on group performance in assembly lines and teams. We find no difference in group performance depending on incentive structure for assembly lines; however, group performance is higher under group incentives for teams. Supplemental analysis indicates group incentives support the teams’ ability to implement beneficial task strategies and although mixed incentives are theoretically appealing, they may send confusing signals to employees about where to direct their effort.
Prey and Prey‐Age Preference by the Iberian WolfCanis Lupus Signatusin a Multiple‐Prey Ecosystem
Authors: Barja Isabel
Published: July 2009

In many regions of the Iberian Peninsula, wild ungulates have disappeared and wolvesCanis lupusoften depend on garbage dumps and domestic animals. This paper represents an example of wild ungulate preferences of the Iberian wolfCanis lupus signatusin an environment with no human‐wildlife conflicts, because wolves rarely predate on livestock. I studied the patterns of prey selection by the Iberian wolf during May 1998‐October 2002 in northwestern Spain, in an area which supports a diverse community of wild ungulates and in which also domestic ungulates are present. My analysis of 593 wolf scats showed that wild ungulates were consumed preferentially over other prey (i.e. domestic ungulates, carnivores and lagomorphs). Roe deerCapreolus capreoluswas the most important prey species followed by red deerCervus elaphusand wild boarSus scrofa. Domestic ungulates were poorly represented in the wolf diet. Predation frequencies of domestic and wild ungulates varied seasonally and between years. The consumption of roe deer and wild boar increased during the birthing season, probably because of the higher vulnerability of newly born animals; wolves predate mainly on juvenile roe deer and wild boar.
Does the Use of Playback Affect the Estimates of Numbers of Grey Partridge Perdix perdix?
Authors: Kasprzykowski Zbigniew , Goławski Artur
Published: July 2009

Methods of estimating bird numbers differ with regard to the results obtained and time required. A usual method of counting grey partridge Perdix perdix consists in counting calling males in the period with their highest vocal activity. This method was tested in our study with the additional use of playback. The number of males calling after playback was significantly higher than before playback. We found a positive relationship between the increase in the number of males calling after playback and their maximum numbers at the study site. However, after playback, the mean number of recorded males was significantly smaller in sites with the presence of red fox Vulpes vulpes burrows than in locations where this predator was absent. Without playback, there was no difference in the number of males between these two types of sites. The results of this study show that the use of playback improves the ability to detect grey partridges (as was similarly found with many other species). The use of playback in estimating the numbers of grey partridge may also allow further analyses, on e.g. site selectivity.
Can Supplemental Feeding of Red Foxes Vulpes vulpes Increase Roe Deer Capreolus capreolus Recruitment in the Boreal Forest?
Authors: Nordström Jonas , Kjellander Petter , Andrén Henrik , Mysterud Atle
Published: July 2009

Red fox Vulpes vulpes predation on roe deer Capreolus capreolus fawns is regarded as a very important factor affecting recruitment of roe deer. Therefore from a hunting management perspective, it is of interest to find efficient ways to reduce predation. Because predator removal during summer is highly controversial and banned by law in Scandinavia, supplemental feeding of red foxes during the short, critical fawning period of roe deer has been proposed as a means to relieve predation on fawns. We performed a two‐year study of providing red fox vixens with food, supplied as close to active dens as possible, and monitored recruitment of radio‐marked roe deer in the vicinity of these dens at a realistic management scale (i.e. the size of a large hunting area; ∼65 km2). Even though red foxes found and consumed the food supplied, we found no tendency towards increased recruitment of roe deer. We conclude that supplemental feeding of red foxes during the fawning period is not a solution to this management problem, at least not at the chosen management scale and with the current red fox predation levels.
Generation of Expression Clone Set for Functional Proteomics of Human Gastric and Liver Cancers
Authors: Oh Nang-Soo , Park Ji-Seon , Jeon Yeo-Jin , Oh Jung-Hwa , Jeong So-Young , Yang Jin-Ok , Park Yong-Won , Yoo Hyang-Sook , Kim Nam-Soon
Published: July 2009

Two thousand sixty-eight multi-purpose expression clones for the 326 candidate genes related to gastric or liver cancers were constructed using the Gateway system. These clones can be expressed as His, Glutathione-S-transferase (GST) or Enhanced version of the green fluorescent protein (EGFP) fusion proteins in E. coli, insect cells or mammalian cells. For the 246 E. coli expression clones, the GST fusion proteins had greater expression efficiency and solubility than the His fusion proteins. Approximately 20% of the expressed proteins had unexpected molecular weights. A detailed sequence analysis of these clones revealed frameshift mutations resulting from insertion, deletion or substitution of nucleotides. The results indicate that these changes in the candidate genes may affect the occurrence of gastric or liver cancers. In addition, when 105 proteins, which were expressed in E. coli at very low or undetectable levels, were expressed in insect cells, 76% of the proteins were expressed very well and most were soluble. We also found that most of the 30 proteins prepared using EGFP mammalian expression clones were localized to cellular compartments expected by Gene ontology (GO) and this localization was unaffected if the EGFP-fusion was at the N-terminal or C-terminal region of the protein. Antibody production and subcellular localization analysis of the candidate genes as well as a screen of genes involved in carcinogenesis pathways are currently in progress using these expression clones. These studies provide a valuable resource for developing a better understanding of the molecular mechanism of carcinogenesis in both gastric and liver cancer and would be very helpful in diagnosis and therapeutic predictions.
Engineering Nanomaterial Surfaces for Biomedical Applications
Authors: Wang Xin , Liu Li-Hong , Ramström Olof , Yan Mingdi
Published: July 2009

Nanomaterials, possessing unique physical and chemical properties, have attracted much interest and generated wide varieties of applications. Recent investigations of functionalized nanomaterials have expanded into the biological area, providing a versatile platform in biomedical applications such as biomolecular sensing, biological imaging, drug delivery and disease therapy. Bio-functions and bio-compatibility of nanomaterials are realized by introducing synthetic ligands or natural biomolecules onto nanomaterials, and combining ligand-receptor biological interactions with intrinsic nanomaterial properties. Common strategies of engineering nanomaterial surfaces involve physisorption or chemisorption of desired ligands. We developed a photochemically initiated surface coupling chemistry, bringing versatility and simplicity to nanomaterial functionalization. The method was applied to attach underivatized carbohydrates efficiently on gold and iron oxide nanoparticles, and the resulting glyconanoparticles were successfully used as a sensitive biosensing system probing specific interactions between carbohydrates and proteins as well as bacteria.
Anti-tuberculosis Drug Resistance Pattern among Different Category of Tuberculosis Patients
Authors: Rahman Mostafizur , Kamal SM Mostafa , Mohammed Fazle Rabbi , Alam Md Billal , Ahasan HAM Nazmul
Published: July 2009

Background: Anti-Tuberculosis (TB) drug resistance is emerging as a new global health problem. No national data on drug resistance is available in Bangladesh. The absolute number of multidrug resistant TB (MDR-TB) is expected to be high considering high TB burden. This study was aimed to determine the resistance pattern of mycobacterium tuberculosis (MTB) isolates among different category of patient. Method: A total 1123 randomly selected patients having clinical and or radiological features of tuberculosis attending out patients department of NIDCH were enrolled in this study during January to December, 2008. Sputum were collected and processed for culture by digestion, decontamination and concentration following modified Petroff's method and were inoculated on to two slopes of Lowenstein- Jensen (L-J) media for six weeks. The identity of the isolates was made by growth rate, colony morphology, P-nitrobenzoic acid (PNB) susceptibility, catalase and nitrate reduction tests. Ultimately drug susceptibility testing (DST) were performed. Result: Drug susceptibility testing for Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB) and Streptomycin (SM) was done among 363 cases. Resistance rates for INH, RIF, EMB and SM were 76.03%, 71.63%, 27.55% and 55.65% respectively. According to DST report, total 221 cases were detected as multi drug resistant TB (MDR-TB). Among them, 87% cases were MDR-TB in category II (CAT - II) failure and 13% were MDR-TB in category I (CAT - I) failure and it was 0% in new cases. Conclusion: Pattern of anti TB drug resistance was identified in this study. More surveillance and immediate therapeutic interventions should be performed in order to combat the threat of MDR-TB to the general population. Keywords: Tuberculosis, Multi drug resistance, Drug susceptibility testing.   doi: 10.3329/jom.v10i2.2812 J MEDICINE 2009; 10 : 45-47