bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the Preservice Practicum Experience of Undergraduate Music Education Majors— Exploring Connections and Dispositions Through Multiple Perspectives A Critical Grounded Theory
Authors: Abrahams Frank
Published: August 2009

This grounded theory study explores the relationship between the college methods class and the off-campus practicum experience. The study included nine undergraduate music education majors enrolled in a methods course designed to prepare them to teach music in secondary schools. Also included were three in-service teachers who served in the role of cooperating teachers for the practicum portion of the experience. Content for the on-campus methods class was altered to accommodate the programs where students would be working. Data included reflections from the students during a weekly on-campus seminar, informal interviews with the cooperating teachers, observations of the students at the practicum sites, and written evaluations of the students by the cooperating teachers. As a result of open, focused, and axial coding, several themes emerged that confirmed the literature stating that despite best efforts, the on-campus course and off-campus practicums do not connect.
Band and Orchestra Teachers’ Rankings of General Pedagogical Knowledge and Skill
Authors: Si Millican J.
Published: August 2009

Classroom management, presentation, and organization skills are significant predictors in the success or failure of teachers regardless of subject. Elements of this type have been categorized in the literature as general pedagogical knowledge (GPK). The purpose of this quantitative study is to determine if a relationship exists between music teachers’ rankings of importance for GPK variables and the variables related to primary teaching assignment, grade level, teaching experience, and school size. Band and orchestra directors ( N = 173) ranked the variables organize and plan instruction; develop rules, routines, procedures, handbooks, etc.; enforce classroom rules promptly and consistently; and develop relationships with students highest of all GPK variables. Some of the findings in this study suggest that band and orchestra directors may approach their time in classrooms differently based on their teaching assignment and grade level. Results give an insight into the specific nature of classroom management as it relates to music settings.
Relation of Soluble Endothelial Protein C Receptor and Cytokines After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Azik Fatih Mehmet , Ertem Mehmet , Ileri Talia , Ince Elif Unal , Uysal Zumrut , Egin Yonca , Akar Nejat
Published: August 2009

Aim: The objective of this study was to elucidate the effects of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), interleukin 2 (IL-2), interleukin 6 (IL-6), and interleukin 8 (IL-8) on the expression of soluble endothelial protein C receptor (sEPCR) in the pathogenesis of thrombotic complications after hematopoietic stem cell transplantation (HSCT).

Methods: The relationship between plasma concentrations of proinflammatory cytokines (TNF-α, IL-1β, IL-2, IL-6, and IL-8) and sEPCR was evaluated in 32 consecutive allogeneic hematopoietic stem cell—transplanted patients prior to conditioning regimen and randomly once between +5 and +30 days after transplantation and compared these results with 20 healthy controls.

Results: Soluble endothelial protein C receptor levels did not indicate any significant difference between pre- and posttransplantation period, and sEPCR levels showed a significantly negative correlation between IL-6 and IL-8 (sEPCR and IL-6, r = —.43, P < .01; sEPCR and IL-8, r = —.57, P < .01). There was no correlation between sEPCR levels and TNF-α, IL-1β, or IL-2 (sEPCR and TNF-α, r = —.13, P > .05; sEPCR and IL-1β, r = —.1, P ≥ .05; sEPCR and IL-2, r = —.07, P > .05).

Conclusions: Our results suggest that the production of sEPCR was not affected by allogeneic HSCT. Soluble endothelial protein C receptor did not show any positive correlation between these proinflammatory cytokines (TNF-α, IL-1β, IL-2, IL-6, and IL-8), on the contrary a significantly negative correlation was determined between sEPCR and either IL-6 or IL-8. This negative correlation may be a protective mechanism in the pathway of protein C activation.
Tissue Factor Pathway Inhibitor and P-Selectin as Markers of Sepsis-Induced Non-overt Disseminated Intravascular Coagulopathy
Authors: Mosad Eman , Elsayh Khalid I. , Eltayeb Azza A.
Published: August 2009

Inflammation and coagulation occur concomitantly in sepsis. Thrombin activates platelet that leads to P-selectin translocation, which upregulate tissue factor (TF) generation. Tissue factor pathway inhibitor (TFPI) is an anticoagulant that modulates coagulation induced by TF. The term non-overt disseminated intravascular coagulation (DIC) refers to a state of affairs prevalent before the occurrence of overt DIC. It was suggested that an initiation of treatment in non-overt DIC has better outcome than overt DIC. This study investigated the role of TFPI level, P-selectin, and thrombin activation markers in non-overt and overt DIC induced by sepsis and its relationship to outcome and organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score. It included 176 patients with sepsis. They were admitted to the pediatric intensive care unit (ICU).They included 144 cases of non-overt DIC and 32 cases of overt DIC. There was a significant difference in hemostatic markers, platelet count, partial thromboplastin time (PTT), P-selectin, thrombin activation markers, TFPI, and DIC score between overt and non-overt DIC in both groups. It was noticed that P-selectin was positively correlated with DIC score, fibrinogen consumption, fibrinolysis (D-dimer), thrombin activation markers, and TFPI. Tissue factor pathway inhibitor was significantly correlated with fibrinolysis, DIC score, and prothrombin fragment 1+2. Sequential Organ Failure Assessment score was correlated with DIC score and other hemostatic markers in patients with overt DIC. To improve the outcome of patients with DIC, there is a need to establish more diagnostic criteria for non-overt-DIC. Plasma levels of TFPI and P-selectin may be helpful in this respect.
The Domestic Foodscapes of Young Low-Income Women in Montreal: Cooking Practices in the Context of an Increasingly Processed Food Supply
Authors: Engler-Stringer Rachel
Published: August 2009

Over the course of the past century, the quantity of prepackaged, pre-prepared foods available in the North American context has increased dramatically. This study examines the shifts in food practices that are taking place through an exploration of the day-to-day cooking practices of a group of young, low-income women in Montreal and considers how these contribute to health problems such as obesity and nutritional deficiencies in addition to health inequalities within populations. The participatory study uses data from five focus groups with a total of 22 participants to contribute to our understanding of how social and physical food environments (the “foodscape”) shape daily food and cooking practices. Aspects of these environments that were discussed include household roles and responsibilities that require complex management, personal food choice and skill, as well as health, learning, and access to food.
Attitudes and Beliefs Associated With Mammography in a Multiethnic Population in Israel
Authors: Baron-Epel Orna
Published: August 2009

This article highlights beliefs, attitudes, and barriers that are associated with mammography use in four distinct cultural and ethnic groups in Israel: veteran, ultra-orthodox, and immigrant Jewish and Arab women. A random telephone survey of 1,550 women was performed. Information from claims records concerning mammography use was obtained for each woman from Maccabi Health Services. Of the barriers studied, no one barrier was associated with mammography performance in all population groups. However, the combined measure was associated with mammography use in all groups. Subjective norms, fatalism, fear of breast cancer, and perceived effectiveness were associated with mammography in some of the population groups but not in others. Each population seems to have a unique set of variables predicting mammography use. It is not possible to generalize from one population to another and it implies that information concerning beliefs and attitudes should be studied in each subpopulation before planning interventions.
Multiple sclerosis, immunomodulators, and pregnancy outcome: a prospective observational study
Authors: Weber-Schoendorfer C , Schaefer C
Published: August 2009

Background

There is still uncertainty about the management of pregnant women exposed to immunomodulatory therapy for treatment of multiple sclerosis (MS) in pregnancy.

Objective

To assess the safety of interferon (IFN)-β1a, IFN-β1b, and glatiramer acetate (GA) for treatment of MS during pregnancy.

Methods

A prospective observational cohort study was performed with patients enrolled through a drug risk assessment by the Teratology Information Service (TIS), Berlin, from 1996 to 2007. Pregnancy outcomes for four groups of women were compared: two exposed groups (IFN, n = 69; GA, n = 31), MS patients without exposure to IFN or GA ( n = 64) and a healthy comparative group ( n = 1556).

Results

Spontaneous abortion rates were in normal range for all groups except the small subgroup of IFN-β1b exposed ( n = 21), where 28% aborted spontaneously. There were two major birth defects in the GA group (club feet and atrioventricular canal) and none in the IFN cohort. Preterm delivery was not significantly different between exposed cohorts and healthy controls. The adjusted mean birth weight was in normal range in all groups (>3200 g), but newborns exposed to IFN had a significantly lower birth weight.

Conclusion

Our findings suggest that neither GA nor IFN constitutes a major risk for prenatal developmental toxicity.
Review: Angiogenesis inhibitors in the treatment of non-small cell lung cancer
Authors: Lind Joline S.W. , Smit Egbert F.
Published: August 2009

A therapeutic plateau seems to have been reached with the standard treatment of cytotoxic chemotherapy alone for advanced stage non-small cell lung cancer (NSCLC) and new treatment options are urgently needed. Recent insight into the molecular biology of cancer has identified angiogenesis as one of the key biological processes. The major player in tumor angiogenesis is the vascular endothelial growth factor (VEGF) pathway. VEGF is expressed in the majority of NSCLC and overexpression is associated with a poor prognosis. The VEGF pathway can be inhibited in two main ways: targeting VEGF directly or inhibiting the VEGF receptors. The development of angiogenesis inhibitors has shown great promise in the treatment of NSCLC. Bevacizumab, an anti-VEGF antibody, has been approved for the treatment of advanced NSCLC and other drugs are undergoing phase III investigation. However, a number of unresolved issues remain. In this review, we discuss the main angiogenesis inhibitors in development for the treatment of NSCLC focusing on the VEGF pathway.
Review: Adjuvant therapy for resected non-small cell lung cancer
Authors: Wozniak Antoinette J. , Gadgeel Shirish M.
Published: August 2009

Surgery remains the initial treatment for patients with early-stage non-small cell lung cancer (NSCLC). The frequent occurrence of distant metastases and local regional failure after surgical resection would indicate that additional treatment is necessary. Early trials of adjuvant chemotherapy and postoperative radiation were often plagued by small patient sample size, inadequate surgical staging, and ineffective or antiquated treatment. A 1995 meta-analysis found a nonsignificant reduction in risk of death for postoperative cisplatin-based chemotherapy. This was followed by a new generation of randomized phase III trials some of which have reported a benefit for chemotherapy in the adjuvant setting. Based on the results of these trials, platin-based chemotherapy has become the standard of care for resected stages II and IIIA NSCLC. The role of postoperative radiation therapy remains to be defined. In the future, improvement in survival outcomes from adjuvant treatment is likely to result from the evaluation of novel agents, identification of tumor markers predictive of disease relapse, and definition of factors that determine sensitivity to therapeutic agents. Some of the molecularly targeted agents such as the angiogenesis and epidermal growth factor receptor inhibitors are being incorporated into clinical trials. Gene expression profiles and proteomics are techniques being used to create prediction models to identify patients at risk for disease relapse. Molecular markers such as ERCC1 may determine response to treatment. Increasing the understanding of the molecular makeup of lung cancer will hopefully increase cure rates for patients by maximizing the efficacy of the adjuvant therapy.
Review: Risk stratification in the hormonal treatment of patients with prostate cancer
Authors: Uhlman Matthew A. , Moul Judd W. , Tang Ping , Stackhouse Danielle A. , Sun Leon
Published: August 2009

Prostate cancer (PCa) is the most common type of cancer found in American men, other than skin cancer. The American Cancer Society estimates that there will be 186,320 new cases of prostate cancer in the United States in 2008. About 28,660 men will die of this disease this year and PCa remains the second-leading cause of cancer death in men. One in six men will get PCa during his lifetime and one in 35 will die of the disease. Today, more than 2 million men in the United States who have had PCa are still alive. The death rate for PCa continues to decline, chiefly due to early detection and treatment, and improved salvage therapy such as hormone therapy (HT). HT continues to be a mainstay for primary-recurrent PCa and locally-advanced PCa. However, HT is associated with many undesirable side effects including sexual dysfunction, osteoporosis and hot flashes, all of which can lead to decreased quality of life (QOL). These risks are seen in both long- and short-term HT regimens. Additionally, research in recent years has revealed trends related to clinico pathological variables and their predictive ability in HT outcomes. Awareness of the potential adverse effects, the risks associated with HT and the prognostic ability of clinical and pathological variables is important in determining optimal therapy for individual patients. A rigorous evaluation of the current scientific literature associated with HT was conducted with the goal of identifying the most favorable balance of benefits and risks associated with HT.
Review: Cooperative group trials — Southwest Oncology Group (SWOG) innovations in advanced prostate cancer
Authors: Dorff Tanya B. , Tangen Cathy M. , Crawford E. David , Petrylak Daniel P. , Higano Celestia S. , Raghavan Derek , Quinn David I. , Vogelzang Nicholas J. , Thompson Ian M.
Published: August 2009

The major goals of the Southwest oncology genitourinary (SWOG-GU) committee in the area of advanced prostate cancer are to improve the survival and quality of life (QOL) of patients with advanced prostate cancer. SWOG trials have examined the role of combined androgen blockade, intermittent androgen deprivation, and the early application of chemotherapy in castration-naïve disease. In addition, they have contributed to advancing the current chemotherapy standard of docetaxel plus prednisone, and ongoing trials seek to improve upon that standard. Finally, surrogate endpoints have been identified and markers of treatment response or resistance with novel technology are under active investigation. This review highlights findings from recent SWOG clinical trials for advanced prostate cancer, emphasizing the clinical impact and future applications of the data.
Plasmacytoid dendritic cells express TRAIL and induce CD4+ T-cell apoptosis in HIV-1 viremic patients
Authors: Stary Georg , Klein Irene , Kohlhofer Sabine , Koszik Frieder , Scherzer Thomas , Müllauer Leonhard , Quendler Heribert , Kohrgruber Norbert , Stingl Georg
Published: August 2009

Artificial Toll-like receptor 7/8 (TLR7/8) ligands can endow plasmacytoid dendritic cells (pDCs) with tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–dependent lytic properties. Keeping in mind that ssRNA serves as natural TLR7/8 ligand, we searched for TRAIL-expressing cells in persons infected with HIV and identified TRAIL+ pDCs in HIV-1 viremic persons, but not in nonviremic and healthy persons. TRAIL expression on pDCs was directly correlated with individual viral loads. Conversely, HIV-1 viremia was found to be associated with the up-regulation of the apoptosis-transmitting receptor TRAIL R1 on activated CD4+ T cells. As a consequence, the latter became susceptible to TRAIL-dependent pDC-mediated killing. In contrast, initiation of antiretroviral therapy led to the up-regulation of apoptosis-inhibiting TRAIL R4 on CD4+ T cells, which subsequently became resistant against pDC-mediated cellular injury. Definition of pDCs as killers of CD4+ T cells implies a new mechanism of disease progression in HIV infection.
Altered fibrin clot structure/function in patients with idiopathic venous thromboembolism and in their relatives
Authors: Undas Anetta , Zawilska Krystyna , Ciesla-Dul Mariola , Lehmann-Kopydłowska Agata , Skubiszak Agnieszka , Ciepłuch Katarzyna , Tracz Wiesława
Published: August 2009

We tested the hypothesis that fibrin structure/function is unfavorably altered in patients after idiopathic venous thromboembolism (VTE) and their relatives. Ex vivo plasma fibrin clot permeability, turbidimetry, and efficiency of fibrinolysis were investigated in 100 patients with first-ever VTE, including 34 with pulmonary embolism (PE), 100 first-degree relatives, and 100 asymptomatic controls with no history of thrombotic events. Known thrombophilia, cancer, trauma, and surgery were exclusion criteria. VTE patients and their relatives were characterized by lower clot permeability (P < .001), lower compaction (P < .001), higher maximum clot absorbancy (P < .001), and prolonged clot lysis time (P < .001) than controls, with more pronounced abnormalities, except maximum clot absorbance, in the patients versus relatives (all P < .01). Fibrin clots obtained for PE patients were more permeable, less compact, and were lysed more efficiently compared with deep-vein thrombosis patients (all P < .05) with no differences in their relatives. Being VTE relative, fibrinogen, and C-reactive protein were independent predictors of clot permeability and fibrinolysis time in combined analysis of controls and relatives. We conclude that altered fibrin clot features are associated with idiopathic VTE with a different profile of fibrin variables in PE. Similar features can be detected in VTE relatives. Fibrin properties might represent novel risk factors for thrombosis.
Involvement of potential pathways in malignant transformation from Oral Leukoplakia to Oral Squamous Cell Carcinoma revealed by proteomic analysis
Authors: Wang Zhi , Feng Xiaodong , Liu Xinyu , Jiang Lu , Zeng Xin , Ji Ning , Li Jing , Li Longjiang , Chen Qianming
Published: August 2009

Background

Oral squamous cell carcinoma (OSCC) is one of the most common forms of cancer associated with the presence of precancerous oral leukoplakia. Given the poor prognosis associated with oral leukoplakia, and the difficulties in distinguishing it from cancer lesions, there is an urgent need to elucidate the molecular determinants and critical signal pathways underlying the malignant transformation of precancerous to cancerous tissue, and thus to identify novel diagnostic and therapeutic target.

Results

We have utilized two dimensional electrophoresis (2-DE) followed by ESI-Q-TOF-LC-MS/MS to identify proteins differentially expressed in six pairs of oral leukoplakia tissues with dysplasia and oral squamous cancer tissues, each pair was collected from a single patient. Approximately 85 differentially and constantly expressed proteins (> two-fold change, P < 0.05) were identified, including 52 up-regulated and 33 down-regulated. Gene ontological methods were employed to identify the biological processes that were over-represented in this carcinogenic stage. Biological networks were also constructed to reveal the potential links between those protein candidates. Among them, three homologs of proteosome activator PA28 a, b and g were shown to have up-regulated mRNA levels in OSCC cells relative to oral keratinocytes.

Conclusion

Varying levels of differentially expressed proteins were possibly involved in the malignant transformation of oral leukoplakia. Their expression levels, bioprocess, and interaction networks were analyzed using a bioinformatics approach. This study shows that the three homologs of PA28 may play an important role in malignant transformation and is an example of a systematic biology study, in which functional proteomics were constructed to help to elucidate mechanistic aspects and potential involvement of proteins. Our results provide new insights into the pathogenesis of oral cancer. These differentially expressed proteins may have utility as useful candidate markers of OSCC.
Effect of CAR activation on selected metabolic pathways in normal and hyperlipidemic mouse livers
Authors: Režen Tadeja , Tamasi Viola , Lövgren-Sandblom Anita , Björkhem Ingemar , Meyer Urs A , Rozman Damjana
Published: August 2009

Background

Detoxification in the liver involves activation of nuclear receptors, such as the constitutive androstane receptor (CAR), which regulate downstream genes of xenobiotic metabolism. Frequently, the metabolism of endobiotics is also modulated, resulting in potentially harmful effects. We therefore used 1,4-Bis [2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) to study the effect of CAR activation on mouse hepatic transcriptome and lipid metabolome under conditions of diet-induced hyperlipidemia.

Results

Using gene expression profiling with a dedicated microarray, we show that xenobiotic metabolism, PPARα and adipocytokine signaling, and steroid synthesis are the pathways most affected by TCPOBOP in normal and hyperlipidemic mice. TCPOBOP-induced CAR activation prevented the increased hepatic and serum cholesterol caused by feeding mice a diet containing 1% cholesterol. We show that this is due to increased bile acid metabolism and up-regulated removal of LDL, even though TCPOBOP increased cholesterol synthesis under conditions of hyperlipidemia. Up-regulation of cholesterol synthesis was not accompanied by an increase in mature SREBP2 protein. As determined by studies in CAR -/- mice, up-regulation of cholesterol synthesis is however CAR-dependent; and no obvious CAR binding sites were detected in promoters of cholesterogenic genes. TCPOBOP also affected serum glucose and triglyceride levels and other metabolic processes in the liver, irrespective of the diet.

Conclusion

Our data show that CAR activation modulates hepatic metabolism by lowering cholesterol and glucose levels, through effects on PPARα and adiponectin signaling pathways, and by compromising liver adaptations to hyperlipidemia.
Association of hypoxia inducible factor-1 alpha gene polymorphism with both type 1 and type 2 diabetes in a Caucasian (Hungarian) sample
Authors: Nagy Geza , Kovacs-Nagy Reka , Kereszturi Eva , Somogyi Aniko , Szekely Anna , Nemeth Nora , Hosszufalusi Nora , Panczel Pal , Ronai Zsolt , Sasvari-Szekely Maria
Published: August 2009

Background

Hypoxia inducible factor-1 alpha (HIF-1α) is a transcription factor that plays an important role in neo-vascularisation, embryonic pancreas beta-cell mass development, and beta cell protection. Recently a non synonymous single nucleotide polymorphism (g.C45035T SNP, rs11549465) of HIF-1α gene, resulting in the p.P582S amino acid change has been shown to be associated with type 2 diabetes (T2DM) in a Japanese population. Our aim was to replicate these findings on a Caucasian (Hungarian) population, as well as to study whether this genetic effect is restricted to T2DM or can be expanded to diabetes in general.

Methods

A large Caucasian sample (N = 890) was recruited including 370 T2DM, 166 T1DM and 354 healthy subjects. Genotyping was validated by two independent methods: a restriction fragment analysis (RFLP) and a real time PCR using TaqMan probes. An overestimation of heterozygotes by RFLP was observed as a consequence of a nearby SNP (rs34005929). Therefore genotyping results of the justified TaqMan system were accepted. The measured genotype distribution corresponded to Hardy-Weinberg equilibrium (P = 0.740)

Results

As the TT genotype was extremely rare in the population (0.6% in clinical sample and 2.5% in controls), the genotypes were grouped as T absent (CC) and T present (CT and TT). Genotype-wise analysis showed a significant increase of T present group in controls (24.0%) as compared to patients (16.8%, P = 0.008). This genetic effect was demonstrated in the separated samples of type 1 (15.1%, P = 0.020), and also in type 2 (17.6%, P = 0.032) diabetes. Allele-wise analysis gave identical results showing a higher frequency of the T allele in the control sample (13.3%) than in the clinical sample (8.7%, P = 0.002) with similar results in type 1 (7.8%, P = 0.010) and type 2 (9.1%, P = 0.011) diabetes. The odds ratio for diabetes (either type 1 or 2) was 1.56 in the presence of the C allele.

Conclusion

We confirmed the protective effect of a rare genetic variant of HIF-1α gene against type 2 diabetes in a Caucasian sample. Moreover we demonstrated a genetic contribution of the same polymorphism in type 1 diabetes as well, supporting a possible overlap in pathomechanism for T2DM and a T1DM.
Self-reported pediatricians' management of the well-appearing young child with fever without a source: first survey in an European country in the anti-pneumococcal vaccine era
Authors: Chiappini Elena , Galli Luisa , Bonsignori Francesca , Venturini Elisabetta , Principi Nicola , de Martino Maurizio
Published: August 2009

Background

Recent studies suggest a substantially reduced risk of invasive bacterial infection in children vaccinated with heptavalent pneumococcal conjugate vaccine (PCV). To investigate whether the introduction of PCV might affect clinical decision making, we conducted a cross-sectional survey aimed at Italian Pediatric physicians.

Results

The study included 348 (46.5%) primary care pediatricians; 251 (36.4%) hospital pediatricians, and 139 (20.1%) pediatric residents. In an hypothetical scenario, a well-appearing 12-month-old child with fever without source would be sent home with no therapy by 60.7% (419/690) of physicians if the child was not vaccinated with PCV. The proportion increased to 74.2% (512/690) if the child had received PCV (P < 0.0001). Also, physicians would obtain blood tests less frequently in the vaccinated than in unvaccinated children (139/690 [20.1%] vs. 205/690 [29.7%]; P < 0.0001), and started empiric antibiotic therapy less frequently (3.0% vs. 7.5%; P < 0.0001). In the hypothetical event that white blood cell count was 17,500/μL, a significantly lower proportion of physicians would ask for erythrocyte sedimentation rate (P < 0.017), C reactive protein (P < 0.0001), blood culture (P = 0.022), and urine analysis or dipstick (P = 0.028), if the child had received PCV. Only one third of participants routinely recommended PCV.

Conclusion

Our data suggest that implementation of educational programs regarding the proper management of the febrile child is needed.
T-cell-based diagnosis of tuberculosis infection in children in Lithuania: a country of high incidence despite a high coverage with bacille Calmette-Guerin vaccination
Authors: Hansted Edita , Andriuskeviciene Angele , Sakalauskas Raimundas , Kevalas Rimantas , Sitkauskiene Brigita
Published: August 2009

Background

Lithuania is a country with a high incidence of tuberculosis (TB), despite a high coverage with bacille Calmette-Guerin (BCG) vaccination. Until now the only method used to detect latent TB infection was the tuberculin skin test (TST). However, TST may have a cross reactivity to the BCG vaccine and to environmental mycobacteria. The aim of this study was to conduct assessments of the diagnostic accuracy of the T-cell based test (T SPOT TB) for TB in children who had previously been BCG vaccinated and compare these with the results of the TST.

Methods

Between January 2005 and February 2007, children with bacteriologically confirmed TB, children having contacts with a case of infectious pulmonary TB and children without any known risk for TB were tested with both the TST and T SPOT TB.

Results

The TST and T SPOT TB tests were positive for all patients in the „culture-confirmed TB“ group. Whereas, in the „high risk for TB“ group, the TST was positive for 60%, but the T SPOT TB test, only for 17.8%. Meanwhile the results for the „low risk for TB“ group were 65.4% and 9.6%, respectively. A correlation between the TST and T SPOT TB was obtained in the "culture-confirmed TB" group where the TST ≥15 mm (r = 0.35, p < 0.001).

Conclusion

The T-cell based method is more objective than the TST for identifying latent TB infection in children who had been previously BCG vaccinated. This method could be useful in countries like Lithuania where there is a high incidence of TB despite a high coverage with BCG vaccination. It may also help to avoid unnecessary chemoprophylaxis when TST reactions are false-positive.
pRb2/p130 protein expression and RBL2 mutation analysis in Burkitt lymphoma from Uganda
Authors: Kalungi Sam , Steine Solrun J , Wabinga Henry , Bostad Leif , Molven Anders
Published: August 2009

Background

The members of the retinoblastoma protein family, pRb, p107 and pRb2 (p130), are central players in controlling the cell cycle. Whereas disturbed function of pRb is commonly seen in human cancers, it is still an open question whether pRb2 is involved in tumorigenic processes. However, altered subcellular localization of pRb2 and mutations in the pRb2-encoding gene RBL2 have been described for some tumours, including Burkitt lymphomas (BL).

Methods

We retrieved 51 biopsy specimens of endemic BL cases from Uganda. The expression of pRb2 was determined by immunohistochemistry. Exons 19-22 of the RBL2 gene, the region known to contain a nuclear localization signal, were screened for mutations by PCR amplification and direct DNA sequencing.

Results

Nearly all of our cases (84.0%) were positive for pRb2 protein expression although this protein is a marker for growth arrest and Burkitt lymphoma is characterized by a high proliferation rate. Of the positive cases, 73.8% were scored as expressing the protein at a high level. Subcellular pRb2 localization was predominantly nuclear and no cases with expression restricted to the cytoplasm were observed. We did not detect any RBL2 mutations in the part of the gene that encodes the C-terminal end of the protein.

Conclusion

The majority of endemic BL cases from Uganda express pRb2, but somatic RBL2 mutations affecting the protein's nuclear localization signal appear to be rare.
Gender-based reciprocal expression of transforming growth factor-β1 and the inducible nitric oxide synthase in a rat model of cyclophosphamide-induced cystitis
Authors: Tyagi Pradeep , Tyagi Vikas , Yoshimura Naoki , Witteemer Erich , Barclay Derek , Loughran Patricia A , Zamora Ruben , Vodovotz Yoram
Published: August 2009

Background

The pluripotent cytokine transforming growth factor-β1 (TGF-β1) is the central regulator of inducible Nitric Oxide Synthase (iNOS) that is responsible for nitric oxide (NO) production in inflammatory settings. Previous studies have implicated a role for NO, presumably derived from iNOS, in cyclophosphamide (CYP)-induced cystitis in the bladder. TGF-β1 is produced in latent form and requires dissociation from the latency-associated peptide (LAP) to act as primary anti-inflammatory and pro-healing modulator following tissue injury in the upper urinary tract. Since the role of TGF-β1 in lower urinary tract inflammation is currently unknown, and since gender-based differences exist in the setting of interstitial cystitis (IC), the present study examined the relationship between TGF-β1 and iNOS/NO in the pathogenesis of CYP-induced cystitis in both male and female rats.

Methods

Sprague-Dawley rats, 4 months of age, of either gender were given 150 mg/kg CYP intraperitoneally. Urinary and bladder tissue TGF-β1 and NO reaction products (NO2-/NO3-) were quantified as a function of time following CYP. Expression of active and latent TGF-β1 as well as iNOS in harvested bladder tissue was assessed by immunohistochemistry.

Results

Female rats had significantly higher levels of NO2-/NO3-in urine even at baseline as compared to male rats (p < 0.001), whereas there was no gender based significant difference in urine levels of active or latent TGF-β1 prior to CYP injection. Inflammatory and cytotoxic changes were induced by CYP in the bladder of both sexes that were accompanied by differences in the urine levels of NO2-/NO3-and TGF-β1. Male rats responded to CYP with significantly lower levels of NO2-/NO3-and significantly higher levels of TGF-β1 in urine (p < 0.05) as compared to females at all time points after CYP. The urine levels of NO2-/NO3-after CYP were inversely correlated to latent and active TGF-β1 (Pearson coefficient of -0.72 and -0.69 in females and -0.89 and -0.76 in males, respectively; p < 0.01). Bladder tissue of male rats exhibited significantly higher levels of both latent and active TGF-β1 (p < 0.01) compared to female rats after CYP. TGF-β1 and iNOS protein was mostly localized in the urothelium.

Conclusion

The results of this study suggest that there exists an inverse relationship between the expression of TGF-β1 and iNOS/NO2-/NO3-in CYP-inflamed bladder. The gender of the animal appears to magnify the differences in urine levels of TGF-β1 and NO2-/NO3-in this inflammatory setting. These results support the hypothesis that TGF-β1 can suppress iNOS expression associated with bladder inflammation and reduce systemic levels of NO2-/NO3-, and further suggest that this feature of TGF-β1 can be harnessed for therapy and diagnosis of interstitial cystitis.
Environmental supportiveness for physical activity in English schoolchildren: a study using Global Positioning Systems
Authors: Jones Andrew P , Coombes Emma G , Griffin Simon J , van Sluijs Esther MF
Published: August 2009

Background

There is increasing evidence that the environment plays a role in influencing physical activity in children and adults. As children have less autonomy in their behavioural choices, neighbourhood environment supportiveness may be an important determinant of their ability to be active. Yet we know rather little about the types of environment that children use for bouts of physical activity. This study uses accelerometery and global positioning system technologies to identify the charactieristics of environments being used for bouts of continuous moderate to vigorous physical activity (MVPA) in a sample of English schoolchildren.

Methods

The study used a convenience sample of 100 children from SPEEDY (Sport, Physical activity and Eating behaviour: Environmental Determinants in Young people), a cohort of 2064 9–10 year-olds from Norfolk, England, recruited in 2007. Children wore an ActiGraph GT1M accelerometer and a Garmin Forerunner 205 GPS unit over four consecutive days. Accelerometery data points were matched to GPS locations and bouts (5 minutes or more) of MVPA were identified. Bout locations were overlaid with a detailed landcover dataset developed in a GIS to identify the types of environment supporting MVPA. Findings are presented using descriptive statistics.

Results

Boys were also more active than girls, spending an average of 20 (SD 23) versus 11 (SD 15) minutes per day in MVPA bouts. Children who spent more time outside the home were more active (p = 0.002), especially girls and children living in rural locations (both p < 0.05). Children tended to be active close to home, with 63% of all bout time occurring inside neighbourhoods, although boys (p = 0.05) and rural children (p = 0.01) were more likely to roam outside their neighbourhood. Amongst urban children, gardens (28% of bout time) and the street environment (20%) were the most commonly used environments for MVPA bouts. Amongst rural children farmland (22%) and grassland (18%) were most frequently used.

Conclusion

The study has developed a new methodology for the identification of environments in which bouts of continuous physical activity are undertaken. The results highlight the importance of the provision of urban gardens and greenspaces, and the maintenance of safe street environments as places for children to be active.
Control of chicken CR1 retrotransposons is independent of Dicer-mediated RNA interference pathway
Authors: Lee Sung-Hun , Eldi Preethi , Cho Soo-Young , Rangasamy Danny
Published: August 2009

Background

Dicer is an RNase III-ribonuclease that initiates the formation of small interfering RNAs as a defence against genomic parasites such as retrotransposons. Despite intensive characterization in mammalian species, the biological functions of Dicer in controlling retrotransposable elements of the non-mammalian vertebrate are poorly understood. In this report, we examine the role of chicken Dicer in controlling the activity of chicken CR1 retrotransposable elements in a chicken-human hybrid DT40 cell line employing a conditional loss-of-Dicer function.

Results

Retrotransposition is detrimental to host genome stability and thus eukaryotic cells have developed mechanisms to limit the expansion of retrotransposons by Dicer-mediated RNAi silencing pathways. However, the mechanisms that control the activity and copy numbers of transposable elements in chicken remain unclear. Here, we describe how the loss of Dicer in chicken cells does not reactivate endogenous chicken CR1 retrotransposons with impaired RNAi machinery, suggesting that the control of chicken CR1 is independent of Dicer-induced RNAi silencing. In contrast, upon introduction of a functionally active human L1 retrotransposable element that contains an active 5' UTR promoter, the Dicer-deficient chicken cells show a strong increase in the accumulation of human L1 transcripts and retrotransposition activity, highlighting a major difference between chicken CR1 and other mammalian L1 retrotransposons.

Conclusion

Our data provide evidence that chicken CR1 retrotransposons, unlike their mammalian L1 counterparts, do not undergo retrotransposition because most CR1 retrotransposons are truncated or mutated at their 5'UTR promoters and thus are not subjected to Dicer-mediated RNAi-silencing control.
Safety and effectiveness of bariatric surgery: Roux-en-y gastric bypass is superior to gastric banding in the management of morbidly obese patients: a reply to the response by Bhoyrul et al
Authors: Guller Ulrich , Klein Lazar V , Hagen John A
Published: August 2009

Background

We have read the letter by Bhoyrul et al. in response to our recently published article "Safety and effectiveness of bariatric surgery: Roux-en-Y gastric bypass is superior to gastric banding in the management of morbidly obese patients". We strongly disagree with the content of the letter.

Results and discussion

Bhoyrul et al. base their letter mostly on low level evidence such as single-institutional case series (level IV evidence) and expert opinion (level V evidence). Surprisingly, they do not comment on the randomized controlled trial, which clearly favours gastric bypass over gastric banding.

Conclusion

The letter by Bhoyrul et al. is based on low level evidence and is itself biased, unsubstantiated, and not supported by the current literature.
The paediatric flat foot proforma (p‐FFP): improved and abridged following a reproducibility study
Authors: Evans Angela Margaret , Nicholson Hollie , Zakarias Noami
Published: August 2009

Background

Concern about a child's flat foot posture is a common reason for frequent clinical consultations for an array of health care and medical professionals. The recently developed paediatric flatfoot clinical‐care pathway (FFP) has provided an evidence based approach to diagnosis and management. The intra and inter‐rater/measurer reliability of the FFP has been investigated in this study.

Methods

From a study population of 140 children aged seven to 10 years, a sample with flat feet was identified by screening with the Foot posture index (FPI‐6). Subjects who scored ≥ 6 on the FPI‐6 for both feet became the study's flat foot sample. A same subject, repeated measure research design was used for this study which examined the reliability of the FFP in 31 children aged seven to 10 years, as rated by three examiners.

Results

Approximately half of the items of the FFP showed less‐than‐desirable inter‐rater reliability, arbitrarily set at the conventional 0.7 level (intra‐class correlations). Removal of the unreliable items has produced a shorter; more relevant instrument designated the paediatric flat foot proforma (p‐FFP).

Conclusion

The p‐FFP is a reliable instrument for the assessment and resulting treatment actions for children with flat feet. Findings indicate that the simplified p‐FFP is a reproducible instrument for the clinical assessment of flat foot in mid‐childhood.
Sedation improves early outcome in severely septic Sprague Dawley rats
Authors: Qiao Hong , Sanders Robert D , Ma Daqing , Wu Xinmin , Maze Mervyn
Published: August 2009

Introduction

Sepsis, a systemic inflammatory response to infective etiologies, has a high mortality rate that is linked both to excess cytokine activity and apoptosis of critical immune cells. Dexmedetomidine has recently been shown to improve outcome in a septic cohort of patients when compared to patients randomized to a benzodiazepine-based sedative regimen. We sought to compare the effects of dexmedetomidine and midazolam, at equi-sedative doses, on inflammation and apoptosis in an animal model of severe sepsis.

Methods

After central venous access, Sprague Dawley rats underwent cecal ligation and intestinal puncture (CLIP) with an 18 G needle without antibiotic cover and received either saline, or an infusion of comparable volume of saline containing midazolam (0.6 mg.kg-1.h-1) or dexmedetomidine (5 ug.kg-1.h-1) for 8 hours. Following baseline measurements and CLIP, blood was sampled for cytokine measurement (tumour necrosis factor (TNF)-alpha and interleukin (IL)-6; n = 4-6 per group) at 2, 4 and 5 hours, and animal mortality rate (MR) was monitored (n = 10 per group) every 2 hours until 2 hours had elapsed. In addition, spleens were harvested and apoptosis was assessed by immunoblotting (n = 4 per group).

Results

The 24 hour MR in CLIP animals (90%) was significantly reduced by sedative doses of either dexmedetomidine (MR = 20%) or midazolam (MR = 30%). While both sedatives reduced systemic levels of the inflammatory cytokine TNF-alpha (P < 0.05); only dexmedetomidine reduced the IL-6 response to CLIP, though this narrowly missed achieving significance (P = 0.05). Dexmedetomidine reduced splenic caspase-3 expression (P < 0.05), a marker of apoptosis, when compared to either midazolam or saline.

Conclusions

Sedation with midazolam and dexmedetomidine both improve outcome in polymicrobial severely septic rats. Possible benefits conveyed by one sedative regimen over another may become evident over a more prolonged time-course as both IL-6 and apoptosis were reduced by dexmedetomidine but not midazolam. Further studies are required to evaluate this hypothesis.
Could spaceflight-associated immune system weakening preclude the expansion of human presence beyond Earth’s orbit?
Authors: Guéguinou Nathan , Huin-Schohn Cécile , Bascove Matthieu , Bueb Jean-Luc , Tschirhart Eric , Legrand-Frossi Christine , Frippiat Jean-Pol
Published: August 2009

Review describes hazards present as humans explore space and focuses on the effects of spaceflight on immunity.

This year, we celebrate the 40th birthday of the first landing of humans on the moon. By 2020, astronauts should return to the lunar surface and establish an outpost there that will provide a technical basis for future manned missions to Mars. This paper summarizes major constraints associated with a trip to Mars, presents immunological hazards associated with this type of mission, and shows that our current understanding of the immunosuppressive effects of spaceflight is limited. Weakening of the immune system associated with spaceflight is therefore an area that should be considered more thoroughly before we undertake prolonged space voyages.
Retinal astrocytes respond to IL-17 differently than retinal pigment epithelial cells
Authors: Ke Yan , Jiang Guomin , Sun Deming , Kaplan Henry J , Shao Hui
Published: August 2009

Differential responses to IL-17 released by uveitogenic Th17 T cells by retinal astrocytes vs. retinal pigmental epithelial cells.

IL-17+ T cells make up the majority of the infiltrating cells in the inflamed eye during the development of EAU. However, the role of IL-17 in ocular inflammation is poorly defined. Given that the primary target cells for IL-17 are parenchymal cells of the tissue, we investigated the in vitro effect of IL-17 on mouse RACs and RPE cells. Our results showed that although RACs and RPE cells expressed the IL-17R, RACs responded to IL-17 by producing increased amounts of proinflammatory cytokines and chemokines, leading to increased migration of granulocytes, whereas RPE cells responded to the same concentration of IL-17 by expressing increased levels of SOCS proteins, resulting in only limited production of proinflammatory cytokines and chemokines and an increased amount of suppressive cytokines, such as LIF. The combination of IL-17 and IFN-γ had a synergistic effect on cell migration with RACs but an antagonistic effect with RPE. In addition, specific inhibitors of the PI3K/Akt signaling pathway completely blocked inflammatory cell migration induced by chemokines released by IL-17-stimulated RACs. Our results demonstrate that IL-17 can induce a pro- or anti-inflammatory effect in the eye, depending on the parenchymal cells stimulated.
Mechanisms for transcellular diapedesis: probing and pathfinding by `invadosome-like protrusions'
Authors: Carman Christopher V.
Published: August 2009

Immune-system functions require that blood leukocytes continuously traffic throughout the body and repeatedly cross endothelial barriers (i.e. diapedese) as they enter (intravasate) and exit (extravasate) the circulation. The very earliest studies to characterize diapedesis directly in vivo suggested the coexistence of two distinct migratory pathways of leukocytes: between (paracellular pathway) and directly through (transcellular pathway) individual endothelial cells. In vivo studies over the past 50 years have demonstrated significant use of the transcellular diapedesis pathway in bone marrow, thymus, secondary lymphoid organs, various lymphatic structures and peripheral tissues during inflammation and across the blood-brain barrier and blood-retinal barrier during inflammatory pathology. Recently, the first in vitro reports of transcellular diapedesis have emerged. Together, these in vitro and in vivo observations suggest a model of migratory pathfinding in which dynamic `invadosome-like protrusions' formed by leukocytes have a central role in both identifying and exploiting endothelial locations that are permissive for transcellular diapedesis. Such `probing' activity might have additional roles in this and other settings.