bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipocalin 2 in the central nervous system host response to systemic lipopolysaccharide administration
Authors: Ip Jacque PK , Noçon Aline L , Hofer Markus J , Lim Sue Ling , Müller Marcus , Campbell Iain L
Published: September 2011

Background

Lipocalin 2 (Lcn2) is a bacteriostatic factor that may also modulate cellular function, however, little is known concerning the expression or role of Lcn2 in CNS inflammation. Therefore, here we investigated the regulation and possible function of Lcn2 in the CNS following peripheral lipopolysaccharide (LPS) injection in mice.

Methods

A murine model for systemic endotoxemia was used in this study. Wild type or Lcn2 KO mice (both genotypes C57BL/6 strain) were given either a single or dual, staggered intraperitoneal injections of purifiedE. coliLPS or vehicle alone. The brain was examined for the expression and location of Lcn2 mRNA and protein and various markers for neuroinflammation were analyzed.

Results

Although undetectable under physiological conditions, both Lcn2 mRNA and protein were induced to high levels in the brain after LPS injection. By contrast, RNA corresponding to the putative Lcn2 (termed 24p3R) receptor was present at high levels in the normal brain and remained unaltered by LPS injection. Differences between Lcn2 and 24p3R mRNA expression were found at the anatomic and cellular level. Endothelial cells, microglia and the choroid plexus but not neurons were identified as the main cellular sources for Lcn2 mRNA in the CNS. By contrast, 24p3R mRNA was detected in neurons and the choroid plexus only. Lcn2 protein was found to have a similar cellular localization as the corresponding RNA transcripts with the exception that subsets of neurons were also strongly positive. Various inflammatory, glial, and iron handling markers were analyzed and found to have similar alterations between WT and Lcn2 KO animals.

Conclusions

1) Lcn2 production is strongly induced in the CNS by systemic LPS injection, 2) in addition to Lcn2 production at key gateways of bacterial entry to the CNS, neurons may be a target for the actions of Lcn2, which is apparently taken up by these cells, and 3) the cellular functions of Lcn2 in the CNS remain enigmatic.
Distinct roles of CD4+T cell subpopulations in retroviral immunity: lessons from the Friend virus mouse model
Authors: Nair Savita , Bayer Wibke , Ploquin Mickaël JY , Kassiotis George , Hasenkrug Kim J , Dittmer Ulf
Published: September 2011

It is well established that CD4+T cells play an important role in immunity to infections with retroviruses such as HIV. However, in recent years CD4+T cells have been subdivided into several distinct populations that are differentially regulated and perform widely varying functions. Thus, it is important to delineate the separate roles of these subsets, which range from direct antiviral activities to potent immunosuppression. In this review, we discuss contributions from the major CD4+T cell subpopulations to retroviral immunity. Fundamental concepts obtained from studies on numerous viral infections are presented along with a more detailed analysis of studies on murine Friend virus. The relevance of these studies to HIV immunology and immunotherapy is reviewed.
First-line antiretroviral therapy and dyslipidemia in people living with HIV-1 in Cameroon: a cross-sectional study
Authors: Pefura Yone Eric Walter , Betyoumin Awa Foueudjeu , Kengne André Pascal , Kaze Folefack François Jérome , Ngogang Jeanne
Published: September 2011

Background

Data on lipid profile derangements induced by antiretroviral treatment in Africa are scarce. The aim of this study was to determine the prevalence and characteristics of lipid profile derangements associated with first-line highly active antiretroviral therapy (ART) among Cameroonians living with human immunodeficiency virus (HIV) infection.

Methods

This cross-sectional study was conducted between November 2009 and January 2010, and involved 138 HIV patients who had never received ART (ART-naive group) and 138 others treated for at least 12 months with first line triple ART regimens that included nevirapine or efavirenz (ART group). Lipid profile was determined after overnight fast and dyslipidemia diagnosed according to the US National Cholesterol Education Program III criteria. Data comparison used chi-square test, Student t-test and logistic regressions.

Results

The prevalence of total cholesterol ≥ 200 mg/dl was 37.6% and 24.6% respectively in ART group and ART-naive groups (p = 0.019). The equivalents for LDL-cholesterol ≥ 130 mg/dl were 46.4% and 21% (p ≤ 0.001). Proportions of patients with total cholesterol/HDL-cholesterol ratio ≥ 5 was 35.5% in ART group and 18.6% in ART-naive group (p ≤ 0.001). The distribution of HDL-cholesterol and triglycerides was similar between the two groups. In multivariable analysis adjusted for age, sex, body mass index, CD4 count and co-infection with tuberculosis, being on ART was significantly and positively associated with raised total cholesterol, LDL-cholesterol and TC/HDL cholesterol. The adjusted odd ratios (95% confidence interval, p-value) ART-treated vs. ART-naïve was 1.82 (1.06-1.12, p = 0.02) for TC ≥ 200 mg/dl; 2.99 (1.74-5.15), p < 0.0001) for LDL-cholesterol ≥ 130 mg/dl and 1.73 (1.04-2.89, p = 0.03) for TC/HDL-cholesterol ≥ 5.

Conclusions

First-line antiretroviral therapy that includes nonnucleoside reverse transcriptase inhibitors is associated with pro-atherogenic adverse lipid profile in people with HIV-1 infection compared to untreated HIV-infected subjects in Yaounde. Lipid profile and other cardiovascular risk factors should be monitored in patients on such therapy so that any untoward effects of treatments can be optimally managed.
Maspin and MCM2 immunoprofiling in salivary gland carcinomas
Authors: Ghazy Shaimaa E , Helmy Iman M , Baghdadi Houry M
Published: September 2011

Background

The pathogenesis of salivary gland carcinomas is very complex and prognostic markers are difficult to find in these carcinomas of which the different subtypes have varying malignant potential. The study was conducted to examine the cellular distribution of maspin and MCM2 in salivary gland carcinomas and their value to predict lymph node metastasis.

Materials and methods

Fifty three paraffin blocks of different lesions (15 muco-epidermoid carcinoma, 14 adenoid cystic carcinoma, 3 epi-myoepithelial carcinoma, 5 salivary duct carcinoma, 5 malignant pleomorphic adenoma, 6 polymorphous low grade adenocarcinoma and 5 acinic cell carcinoma) were prepared for immunohistochemical staining with maspin and MCM2 antibodies. ANOVA and Pearson correlation tests were used for the statistical analysis of the results.

Results

All salivary gland carcinomas express maspin and MCM2 with variable cellular localization. There was a significant difference in the expression of each antibody between mucoepidermoid carcinoma, adenoid cystic carcinoma and polymorphous low grade adenocarcinoma. No association was found between examined markers and lymph node metastasis.

Conclusions

Salivary gland carcinomas express maspin and MCM2 with variable levels and cellular localization, consisting important markers of biological behavior in these tumors. The level of MCM2 expression can be used in the differential diagnosis of adenoid cystic carcinoma and polymorphous low grade adenocarcinoma. Further study with large sample size is recommended to assess their value in prediction of lymph node metastasis.
How yeast re-programmes its transcriptional profile in response to different nutrient impulses
Authors: Dikicioglu Duygu , Karabekmez Erkan , Rash Bharat , Pir Pınar , Kirdar Betul , Oliver Stephen G
Published: September 2011

Background

A microorganism is able to adapt to changes in its physicochemical or nutritional environment and this is crucial for its survival. The yeast, Saccharomyces cerevisiae, has developed mechanisms to respond to such environmental changes in a rapid and effective manner; such responses may demand a widespread re-programming of gene activity. The dynamics of the re-organization of the cellular activities of S. cerevisiae in response to the sudden and transient removal of either carbon or nitrogen limitation has been studied by following both the short- and long-term changes in yeast's transcriptomic profiles.

Results

The study, which spans timescales from seconds to hours, has revealed the hierarchy of metabolic and genetic regulatory switches that allow yeast to adapt to, and recover from, a pulse of a previously limiting nutrient. At the transcriptome level, a glucose impulse evoked significant changes in the expression of genes concerned with glycolysis, carboxylic acid metabolism, oxidative phosphorylation, and nucleic acid and sulphur metabolism. In ammonium-limited cultures, an ammonium impulse resulted in the significant changes in the expression of genes involved in nitrogen metabolism and ion transport. Although both perturbations evoked significant changes in the expression of genes involved in the machinery and process of protein synthesis, the transcriptomic response was delayed and less complex in the case of an ammonium impulse. Analysis of the regulatory events by two different system-level, network-based approaches provided further information about dynamic organization of yeast cells as a response to a nutritional change.

Conclusions

The study provided important information on the temporal organization of transcriptomic organization and underlying regulatory events as a response to both carbon and nitrogen impulse. It has also revealed the importance of a long-term dynamic analysis of the response to the relaxation of a nutritional limitation to understand the molecular basis of the cells' dynamic behaviour.
Toll-like receptor activation by helminths or helminth products to alleviate inflammatory bowel disease
Authors: Sun ShuMin , Wang XueLin , Wu XiuPing , Zhao Ying , Wang Feng , Liu XiaoLei , Song YanXia , Wu ZhiLiang , Liu MingYuan
Published: September 2011

Helminth infection may modulate the expression of Toll like receptors (TLR) in dendritic cells (DCs) and modify the responsiveness of DCs to TLR ligands. This may regulate aberrant intestinal inflammation in humans with helminthes and may thus help alleviate inflammation associated with human inflammatory bowel disease (IBD). Epidemiological and experimental data provide further evidence that reducing helminth infections increases the incidence rate of such autoimmune diseases. Fine control of inflammation in the TLR pathway is highly desirable for effective host defense. Thus, the use of antagonists of TLR-signaling and agonists of their negative regulators from helminths or helminth products should be considered for the treatment of IBD.
DNA Repair Capacity in Peripheral Lymphocytes Predicts Survival of Patients With Non–Small-Cell Lung Cancer Treated With First-Line Platinum-Based Chemotherapy
Authors: Wang Li-E , Yin Ming , Dong Qiong , Stewart David J. , Merriman Kelly W. , Amos Christopher I. , Spitz Margaret R. , Wei Qingyi
Published: September 2011

Purpose

Platinum-based regimens are the standard chemotherapy for patients with advanced non–small-cell lung cancer (NSCLC). DNA repair capacity (DRC) in tumor cells plays an important role in resistance to platinum-based drugs. We have previously reported that efficient DRC, as assessed by an in vitro lymphocyte-based assay, was a determinant of poor survival in patients with NSCLC in a relatively small data set. In this larger independent study of 591 patients with NSCLC, we further evaluated whether DRC in peripheral lymphocytes predicts survival of patients with NSCLC who receive platinum-based chemotherapy.

Patients and Methods

All patients were recruited at The University of Texas MD Anderson Cancer Center and donated blood samples before the start of any chemotherapy. We measured DRC in cultured T lymphocytes by using the host-cell reactivation assay, and we assessed associations between DRC in peripheral lymphocytes and survival of patients with NSCLC who were treated with first-line platinum-based chemotherapy.

Results

We found an inverse association between DRC in peripheral lymphocytes and patient survival. Compared with patients in the low tertile of DRC, patients with NSCLC in the high tertile of DRC had significantly worse overall and 3-year survival (adjusted hazard ratio [HR], 1.33; 95% CI, 1.04 to 1.71; P = .023; and HR, 1.35; 95% CI, 1.04 to 1.76; P = .025, respectively). This trend was more pronounced in patients with early-stage tumors, adenocarcinoma, or squamous cell carcinoma.

Conclusion

We confirmed that DRC in peripheral lymphocytes is an independent predictor of survival for patients with NSCLC treated with platinum-based chemotherapy.
Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update
Authors: Basch Ethan , Prestrud Ann Alexis , Hesketh Paul J. , Kris Mark G. , Feyer Petra C. , Somerfield Mark R. , Chesney Maurice , Clark-Snow Rebecca Anne , Flaherty Anne Marie , Freundlich Barbara , Morrow Gary , Rao Kamakshi V. , Schwartz, Rowena N. , Lyman Gary H.
Published: September 2011

Purpose

To update the American Society of Clinical Oncology (ASCO) guideline for antiemetics in oncology.

Methods

A systematic review of the medical literature was completed to inform this update. MEDLINE, the Cochrane Collaboration Library, and meeting materials from ASCO and the Multinational Association for Supportive Care in Cancer were all searched. Primary outcomes of interest were complete response and rates of any vomiting or nausea.

Results

Thirty-seven trials met prespecified inclusion and exclusion criteria for this systematic review. Two systematic reviews from the Cochrane Collaboration were identified; one surveyed the pediatric literature. The other compared the relative efficacy of the 5-hydroxytryptamine-3 (5-HT3) receptor antagonists.

Recommendations

Combined anthracycline and cyclophosphamide regimens were reclassified as highly emetic. Patients who receive this combination or any highly emetic agents should receive a 5-HT3 receptor antagonist, dexamethasone, and a neurokinin 1 (NK1) receptor antagonist. A large trial validated the equivalency of fosaprepitant, a single-day intravenous formulation, with aprepitant; either therapy is appropriate. Preferential use of palonosetron is recommended for moderate emetic risk regimens, combined with dexamethasone. For low-risk agents, patients can be offered dexamethasone before the first dose of chemotherapy. Patients undergoing high emetic risk radiation therapy should receive a 5-HT3 receptor antagonist before each fraction and for 24 hours after treatment and may receive a 5-day course of dexamethasone during fractions 1 to 5. The Update Committee noted the importance of continued symptom monitoring throughout therapy. Clinicians underestimate the incidence of nausea, which is not as well controlled as emesis.
Determining True HER2 Gene Status in Breast Cancers With Polysomy by Using Alternative Chromosome 17 Reference Genes: Implications for Anti-HER2 Targeted Therapy
Authors: Tse Chun Hing , Hwang Harry C. , Goldstein Lynn C. , Kandalaft Patricia L. , Wiley Jesse C. , Kussick Steven J. , Gown Allen M.
Published: September 2011

Purpose

The ratio of human epidermal growth factor receptor 2 (HER2) to CEP17 by fluorescent in situ hybridization (FISH) with the centromeric probe CEP17 is used to determine HER2 gene status in breast cancer. Increases in CEP17 copy number have been interpreted as representing polysomy 17. However, pangenomic studies have demonstrated that polysomy 17 is rare. This study tests the hypothesis that the use of alternative chromosome 17 reference genes might more accurately assess true HER2 gene status.

Patients and Methods

In all, 171 patients with breast cancer who had HER2 FISH that had increased mean CEP17 copy numbers (> 2.6) were selected for additional chromosome 17 studies that used probes for Smith-Magenis syndrome (SMS), retinoic acid receptor alpha (RARA), and tumor protein p53 (TP53) genes. A eusomic copy number exhibited in one or more of these loci was used to calculate a revised HER2-to-chromosome-17 ratio by using the eusomic gene locus as the reference.

Results

Of 132 cases classified as nonamplified on the basis of their HER2:CEP17 ratios, 58 (43.9%) were scored as amplified by using alternative chromosome 17 reference gene probes, and 13 (92.9%) of 14 cases scored as equivocal were reclassified as amplified. Among the cases with mean HER2 copy number of 4 to 6, 41 (47.7%) of 86 had their HER2 gene status upgraded from nonamplified to amplified, and four (4.7%) of 86 were upgraded from equivocal to amplified.

Conclusion

Our results support the findings of recent pangenomic studies that true polysomy 17 is uncommon. Additional FISH studies that use probes to the SMS, RARA, and TP53 genes are an effective way to determine the true HER2 amplification status in patients with polysomy 17 and they have important potential implications for guiding HER2-targeted therapy in breast cancer.
Prospective Study on Incidence, Risk Factors, and Long-Term Outcome of Osteonecrosis in Pediatric Acute Lymphoblastic Leukemia
Authors: te Winkel Mariël L. , Pieters Rob , Hop Wim C.J. , de Groot-Kruseman Hester A. , Lequin Maarten H. , van der Sluis Inge M. , Bökkerink Jos P.M. , Leeuw Jan A. , Bruin Marrie C.A. , Egeler R. Maarten , Veerman Anjo J.P. , van den Heuvel-Eibrink Marry M.
Published: September 2011

Purpose

We studied cumulative incidence, risk factors, therapeutic strategies, and outcome of symptomatic osteonecrosis in pediatric patients with acute lymphoblastic leukemia (ALL).

Patients and Methods

Cumulative incidence of osteonecrosis was assessed prospectively in 694 patients treated with the dexamethasone-based Dutch Child Oncology Group–ALL9 protocol. Osteonecrosis was defined by development of symptoms (National Cancer Institute grade 2 to 4) during treatment or within 1 year after treatment discontinuation, confirmed by magnetic resonance imaging. We evaluated risk factors for osteonecrosis using logistic multivariate regression. To describe outcome, we reviewed clinical and radiologic information after antileukemic treatment 1 year or more after osteonecrosis diagnosis.

Results

Cumulative incidence of osteonecrosis at 3 years was 6.1%. After adjustment for treatment center, logistic multivariate regression identified age (odds ratio [OR], 1.47; P < .01) and female sex (OR, 2.23; P = .04) as independent risk factors. Median age at diagnosis of ALL in patients with osteonecrosis was 13.5 years, compared with 4.7 years in those without. In 21 (55%) of 38 patients with osteonecrosis, chemotherapy was adjusted. Seven patients (18%) underwent surgery: five joint-preserving procedures and two total-hip arthroplasties. Clinical follow-up of 35 patients was evaluated; median follow-up was 4.9 years. In 14 patients (40%), symptoms completely resolved; 14 (40%) had symptoms interfering with function but not with activities of daily living (ADLs; grade 2); seven (20%) had symptoms interfering with ADLs (grade 3). In 24 patients, radiologic follow-up was available; in six (25%), lesions improved/disappeared; in 13 (54%), lesions remained stable; five (21%) had progressive lesions.

Conclusion

Six percent of pediatric patients with ALL developed symptomatic osteonecrosis during or shortly after treatment. Older age and female sex were risk factors. After a median follow-up of 5 years, 60% of patients had persistent symptoms.
Creation of Nucleophilic Boryl Anions and Their Properties
Authors: Yamashita Makoto
Published: September 2011

A series of anionic boron compounds, possessing a polarized boron–metal bond, were synthesized and structurally characterized. Detailed analyses of these boryl anions using NMR spectroscopy, X-ray crystallography, reactivity with electrophiles, and DFT calculations revealed that these compounds have anionic and nucleophilic character on the boron center in contrast to conventional boron-containing molecules with a Lewis acidic character. Some applications of boryl anions toward organic synthesis, organometallic chemistry, and main group chemistry are also described.
Development of a New System for Photocatalytic Water Splitting into H2 and O2 under Visible Light Irradiation
Authors: Abe Ryu
Published: September 2011

Photocatalytic water splitting using semiconductor materials has attracted considerable interest due to its potential for clean production of H2 from water by utilizing abundant solar light. The developments of water-splitting systems that can efficiently use visible light have been a major challenge for many years in order to realize efficient conversion of solar light. We have developed a new type of photocatalysis system that can split water into H2 and O2 under visible light irradiation, which was inspired by the two-step photoexcitation (Z-scheme) mechanism of natural photosynthesis in green plants. In this system, the water-splitting reaction is broken up into two stages: one for H2 evolution and the other for O2 evolution; these are combined by using a shuttle redox couple (Red/Ox) in the solution. The introduction of a Z-scheme mechanism reduces the energy required to drive each photocatalysis process, extending the usable wavelengths significantly (≈660 nm for H2 evolution and ≈600 nm for O2 evolution) from that in conventional water splitting systems (≈460 nm) based on one-step photoexcitation in single semiconductor material.
Moving out: from sterol transport to drug resistance – the ABCG subfamily of efflux pumps
Authors: Moitra Karobi , Silverton Latoya , Limpert Katy , Im Kate , Dean Michael
Published: September 2011

The ATP binding cassette (ABC) proteins are typically ATP-driven transmembrane pumps that have been evolutionarily conserved from bacteria to humans. In humans these transporters are subdivided into seven subfamilies, ranging from A to G. The ABCG subfamily of transporters is the primary focus of this review. This subfamily of proteins has been conserved throughout evolution and plays a central role in several cellular processes, such as sterol homeostasis and multidrug resistance. Functional polymorphisms/mutations in some of these G-subfamily transporters have clinical consequences in humans.
IGF1/insulin receptor kinase inhibition by BMS-536924 is better tolerated than alloxan-induced hypoinsulinemia and more effective than metformin in the treatment of experimental insulin-responsive breast cancer
Authors: Dool Carly Jade , Mashhedi Haider , Zakikhani Mahvash , David Stéphanie , Zhao Yunhua , Birman Elena , Carboni Joan M , Gottardis Marco , Blouin Marie-José , Pollak Michael
Published: September 2011

Epidemiologic and experimental evidence suggest that a subset of breast cancer is insulin responsive, but it is unclear whether safe and effective therapies that target the insulin receptor (IR), which is homologous to oncogenes of the tyrosine kinase class, can be developed. We demonstrate that both pharmacologic inhibition of IR family tyrosine kinase activity and insulin deficiency have anti-neoplastic activity in a model of insulin-responsive breast cancer. Unexpectedly, in contrast to insulin deficiency, pharmacologic IR family inhibition does not lead to significant hyperglycemia and is well tolerated. We show that pharmacokinetic factors explain the tolerability of receptor inhibition relative to insulin deficiency, as the small molecule receptor kinase inhibitor BMS-536924 does not accumulate in muscle at levels sufficient to block insulin-stimulated glucose uptake. Metformin, which lowers insulin levels only in settings of hyperinsulinemia, had minimal activity in this normoinsulinemic model. These findings highlight the importance of tissue-specific drug accumulation as a determinant of efficacy and toxicity of tyrosine kinase inhibitors and suggest that therapeutic targeting of the IR family for cancer treatment is practical.
Prevalence of Asthma and Its Association With Glycemic Control Among Youth With Diabetes
Authors: Black Mary Helen , Anderson Andrea , Bell Ronny A. , Dabelea Dana , Pihoker Catherine , Saydah Sharon , Seid Michael , Standiford Debra A. , Waitzfelder Beth , Marcovina Santica M. , Lawrence Jean M.
Published: September 2011

OBJECTIVE:

To estimate the prevalence of asthma among youth with types 1 and 2 diabetes and examine associations between asthma and glycemic control.

METHODS:

This was a cross-sectional analysis of data from the SEARCH for Diabetes in Youth study, which included youth diagnosed with type 1 (n = 1683) and type 2 (n = 311) diabetes from 2002 through 2005. Asthma status and medications were ascertained from medical records and self-administered questionnaires, and glycemic control was assessed from hemoglobin A1c measured at the study visit.

RESULTS:

Prevalence of asthma among all youth with diabetes was 10.9% (95% confidence interval [CI]: 9.6%–12.3%). The prevalence was 10.0% (95% CI: 8.6%–11.4%) among youth with type 1 and 16.1% (95% CI: 12.0%–20.2%) among youth with type 2 diabetes and differed according to race/ethnicity. Among youth with type 1 diabetes, those with asthma had higher mean A1c levels than those without asthma, after adjustment for age, gender, race/ethnicity, and BMI (7.77% vs 7.49%; P = .034). Youth with asthma were more likely to have poor glycemic control, particularly those with type 1 diabetes whose asthma was not treated with pharmacotherapy, although this association was attenuated by adjustment for race/ethnicity.

CONCLUSIONS:

Prevalence of asthma may be elevated among youth with diabetes relative to the general US population. Among youth with type 1 diabetes, asthma is associated with poor glycemic control, especially if asthma is untreated. Specific asthma medications may decrease systemic inflammation, which underlies the complex relationship between pulmonary function, BMI, and glycemic control among youth with diabetes.
Infant Growth Before and After Term: Effects on Neurodevelopment in Preterm Infants
Authors: Belfort Mandy B. , Rifas-Shiman Sheryl L. , Sullivan Thomas , Collins Carmel T. , McPhee Andrew J. , Ryan Philip , Kleinman Ken P. , Gillman Matthew W. , Gibson Robert A. , Makrides Maria
Published: September 2011

OBJECTIVE:

To identify sensitive periods of postnatal growth for preterm infants relative to neurodevelopment at 18 months' corrected age.

PATIENTS AND METHODS:

We studied 613 infants born at <33 weeks' gestation who participated in the DHA for Improvement of Neurodevelopmental Outcome trial. We calculated linear slopes of growth in weight, length, BMI, and head circumference from 1 week of age to term (40 weeks' postmenstrual age), term to 4 months, and 4 to 12 months, and we estimated their associations with Bayley Scales of Infant Development, 2nd Edition, Mental (MDI) and Psychomotor (PDI) Development Indexes in linear regression.

RESULTS:

The median gestational age was 30 (range: 2–33) weeks. Mean ± SD MDI was 94 ± 16, and PDI was 93 ± 16. From 1 week to term, greater weight gain (2.4 MDI points per z score [95% confidence interval (CI): 0.8–3.9]; 2.7 PDI points [95% CI: 1.2–.2]), BMI gain (1.7 MDI points [95% CI: 0.4–3.1]; 2.5 PDI points [95% CI: 1.2–3.9]), and head growth (1.4 MDI points [95% CI: −0.0–2.8]; 2.5 PDI points [95% CI: 1.2–3.9]) were associated with higher scores. From term to 4 months, greater weight gain (1.7 points [95% CI: 0.2–3.1]) and linear growth (2.0 points [95% CI: 0.7–3.2]), but not BMI gain, were associated with higher PDI. From 4 to 12 months, none of the growth measures was associated with MDI or PDI score.

CONCLUSIONS:

In preterm infants, greater weight and BMI gain to term were associated with better neurodevelopmental outcomes. After term, greater weight gain was also associated with better outcomes, but increasing weight out of proportion to length did not confer additional benefit.
Molecular Assays in the Diagnosis of Neonatal Sepsis: A Systematic Review and Meta-analysis
Authors: Pammi Mohan , Flores Angela , Leeflang Mariska , Versalovic James
Published: September 2011

BACKGROUND:

Microbial cultures for diagnosis of neonatal sepsis suffer from low sensitivity and reporting delay. Advances in molecular microbiology have fostered new molecular assays that are rapid and may improve neonatal outcomes.

OBJECTIVES:

We assessed whether molecular assays have sufficient sensitivity (>0.98) and specificity (>0.95) to replace microbial cultures in the diagnosis of neonatal sepsis and explored heterogeneity by use of subgroup analyses based on the type of assay, gestational age of the neonate, and type of sepsis onset.

METHODS:

We performed the systematic review as recommended by the Cochrane Diagnostic Test Accuracy Working Group. Electronic bibliographic databases, conference abstracts, personal files, and reference lists of identified articles were searched. We included studies of case-control or consecutive series design, which evaluated molecular assays (index test) in neonates with suspected sepsis (participants) in comparison with microbial cultures (reference standard). Two reviewers independently assessed the methodologic quality of the studies and extracted data.

RESULTS:

A bivariate random-effects model was used for meta-analysis of the 23 included studies, and summary estimates of sensitivity and specificity with 95% confidence intervals (CIs) were generated. Mean sensitivity and specificity were 0.90 (95% CI: 0.78–0.95) and 0.96 (95% CI: 0.94–0.97), respectively. Real-time polymerase chain reaction (PCR) and broad-range conventional PCR had higher sensitivity and specificity than other assays. Sufficient data were not available to evaluate gestational-age and sepsis-type subgroups.

CONCLUSION:

Molecular assays do not have sufficient sensitivity to replace microbial cultures in the diagnosis of neonatal sepsis but may perform well as “add-on” tests.
Pharmacokinetic analysis of high-dose methotrexate treatments in children with hematologic malignancies
Authors: Csordás Katalin , Eipel Olivér , Hegyi Márta , Csóka Monika , Pap Éva , Kovács Gábor
Published: September 2011

Monitoring the pharmacokinetic parameters of different anticancer drugs is necessary because they might have several side effects. Aim: Pharmacokinetic and toxicity evaluation of high-dose methotrexate treatments in children with acute lymphoblastic leukemia. Patients and methods: 43 children (28 boys, 15 girls, mean age: 7.03 years) in 147 cases were treated with 5 g/m2/24h MTX according to ALL-BFM 1995 and 2002 protocols. Methotrexate and 7-hydroxi-methotrexate levels were measured with high pressure liquid chromatography at 24, 36, 48 hours. Authors registered the development of hepatotoxicity, nephrotoxicity, grade III/IV oral mucositis. Results: Therapeutic methotrexate serum concentrations (30-100µmol/l) were achieved in 72.5% of the cases. Repeated treatments resulted similar serum levels. Hepatotoxicity and hypoproteinemia occurred in 17% and in 48.9% of the cases. There was significant correlation between serum 7-hydroxi-methotrexate and creatinine levels (p<0.05). Conclusion: 5 g/m2methotrexate resulted reliable therapeutic serum levels with mild and reversible toxicity. 7-hydroxi-methotexate measurements might be more useful than methotrexate levels to detect toxicity. Orv. Hetil., 2011, 152, 1609–1617.
Atomistically informed continuum model for body centered cubic iron
Authors: Koester Aenne , Ma Anxin , Hartmaier Alexander
Published: September 2011

Plastic deformation in body centered cubic iron is dominated by glide of screw dislocations with non-planar dislocation cores. This causes a strong strain rate and temperature dependence of flow stress, the breakdown of Schmid’s law and a dependence of dislocation mobility on shear stress components that do not contribute to the mechanical driving force for dislocation glide. Based on the framework of crystal plasticity, we developed a constitutive plasticity model that takes all these phenomena into account. To parameterize this continuum plasticity model molecular statics simulations using a semi-empirical potential have been performed. These atomistic calculations yielded quantitative relationships for the influence of all components of the local stress tensor on dislocation mobility. Together with experimental data from the literature on the kinetics of screw dislocations in bcc iron the constitutive relation presented here has been developed. As application example of the model, we calculated the tension compression asymmetry and the strain rate dependence of the hardening behavior within a bcc iron crystal.
Mapping Nanomechanical Properties near Internal Interfaces in Biological Materials
Authors: Zlotnikov Igor , Drezner Haika , Shilo Doron , Aichmayer Barbara , Dauphin Yannicke , Zolotoyabko Emil , Fratzl Peter
Published: September 2011

Modulus mapping using nanoDMA (Dynamic Mechanical Analysis) is a recently developed technique based on a nanoindentation instrument equipped with an AFM-like piezoscanner and dynamic force modulation system. The surface properties, storage and loss moduli are quantified based on the Hertz model for the contact mechanics of the sample-tip configuration. In this approach, the applied load, topography features, and their size may have a pronounced effect on the obtained results. In order to demonstrate that, internal interfaces of deep sea sponge (Monorhaphis chuni), which comprises alternating layers of relatively thick (4 μm in average) biosilica and thin (60 nm) organic material, were characterized using the nanoDMA modulus mapping technique. Experimental data were analyzed in tight interrelation with finite element simulations. This combination allowed us to evaluate elastic modulus of a 60 nm wide organic layers in M. chuni.
Zinc and Zinc Oxide Nanowires Grown on PEDOT:PSS/SiO2 Conductive Polymer Thin Films by Vapor Phase Transport Deposition
Authors: Chamberlin Matthew P. , Constantin Costel
Published: September 2011

Easily available spin coating and vapor phase transport deposition techniques offer tremendous possibilities in fabricating inorganic/organic heterojunctions. We present here preliminary results from different thin film growth mechanisms including: i) PEDOT:PSS/Zn-nanowires/SiO2, ii) Zn-nanowires/PEDOT:PSS/SiO2, and iii) ZnO-nanowires/PEDOT:PSS/SiO2. The preliminary scanning electron microscopy and energy dispersive spectroscopy results show that Zn nanowires bond better to the non-annealed PEDOT:PSS thin films. It was also found that ZnO nanowires grow homogeneously on annealed PEDOT:PSS surfaces with colloidal Au nanoparticles as bonding reaction catalysts.
The effect of the accelerated aging on the mechanical properties of the PMMA denture base materials modified with itaconates
Authors: Spasojevic Pavle , Zrilic Milorad , Stamenkovic Dragoslav , Velickovic Sava
Published: September 2011

This study evaluated the effect of accelerated ageing on the tensile
strength, elongation at break, hardness and Charpy impact strength in
commercial PMMA denture base material modified with di-methyl itaconate (DMI)
and di-n-butyl itaconate (DBI). The samples were prepared by modifying
commercial formulation by addition of itaconates in the amounts of 2.5, 5,
7.5 and 10% by weight. After polymerization samples were characterized by
FT-IR and DSC analysis while residual monomer content was determined by
HPLC-UV. Accelerated ageing was performed at 70?C in water for periods of 7,
15 and 30 days. Tensile measurements were performed using Instron testing
machine while the hardness of the polymerized samples was measured by Shore D
method. The addition of itaconate significantly reduces the residual MMA.
Even at the small amounts of added itaconates (2.5%) the residual MMA content
was reduced by 50%. The increase of itaconate content in the system leads to
the decrease of residual MMA. It has been found that the addition of
di-n-alkyl itaconates decreases the tensile strength, hardness and Charpy
impact strength and increases elongation at break. Samples modified with DMI
had higher values of tensile strength, hardness and Charpy impact strength
compared to the ones modified with DBI. This is explained by the fact that
DBI has longer side chain compared to DMI. After accelerated ageing during a
30 days period the tensile strength decreased for all the investigated
samples. The addition of DMI had no effect on the material ageing and the
values for the tensile strength of all of the investigated samples decreased
around 20%, while for the samples modified with DBI, the increase of the
amount of DBI in the polymerized material leads to the higher decrease of the
tensile strength after the complete accelerated ageing period od 30 days,
aulthough after the first seven days of the accelerated ageing the values of
hardness have increased for all of the investigated samples. Such behavior is
explained as the result of the polymer chain relaxation. The values of Charpy
impact strength decreased after accelerated ageing. The amount of added DMI
have no affect on the decrease of Charpy impact strength after accelerated
ageing, the decrease was similar as for pure PMMA. The decrease of Charpy
impact strength increased as the amount of added DBI increases.
In Vitro Evaluation of the Effect of Delaying Toothbrushing With Toothpaste on Enamel Microhardness Subsequent to Bleaching the Teeth With 15% Carbamide Peroxide
Authors: Navimipour EJ , Kimyai S , Nikazar S , Ghojazadeh M
Published: September 2011

Clinical Relevance

Delaying oral hygiene procedures during bleaching does not seem to cause any change in enamel microhardness.
Treatment of Invasive Cervical Resorption With Sandwich Technique Using Mineral Trioxide Aggregate: A Case Report
Authors: Kqiku L , Ebeleseder KA , Glockner K
Published: September 2011

Clinical Relevance

MTA combined with glass ionomer cement and composite resin in a “sandwich technique” showed a favourable clinical outcome for treatment of invasive cervical resorption lesions.
An innovative image fusion algorithm based on wavelet transform and discrete fast curvelet transform
Authors: Sumathi T. , Hemalatha M.
Published: September 2011

Image fusion is the method of combining relevant information from two or more images into a single image resulting in an image that is more informative than the initial inputs. Methods for fusion include discrete wavelet transform, Laplacian pyramid based transform, curvelet based transform etc. These methods demonstrate the best performance in spatial and spectral quality of the fused image compared to other spatial methods of fusion. In particular, wavelet transform has good time-frequency characteristics. However, this characteristic cannot be extended easily to two or more dimensions with separable wavelet experiencing limited directivity when spanning a one-dimensional wavelet. This paper introduces the second generation curvelet transform and uses it to fuse images together. This method is compared against the others previously described to show that useful information can be extracted from source and fused images resulting in the production of fused images which offer clear, detailed information.
Fitts’ law to the rescue: A comparison of graph tables
Authors: Hedman Anna , Alm Håkan
Published: September 2011

In this paper we investigate image browsing as an interactive method for visualizing line graphs. We have compared two interfaces that both presented exactly identically looking tables, but while one version was an overview+detail interface, the other one was a distortion-oriented interface of bifocal type. We expected there to be no difference in task completion times, and found none in our first statistical evaluation. Users preferred the static overview+detail interface to the distortion-oriented, which was motivated by complaints about the changed appearance of the distortion-oriented table. The empirical results were compared to theoretical results obtained using Fitts’ law, which showed a difference in task completion time for a certain task type. A second statistical analysis included only data from task type for which a difference could be expected. The new results supported the theoretical model, saying that users were faster with the overview+detail interface. In this paper we discuss problems with image browsing tests, and suggest some ideas for future research topics and designs.
Tigecycline attenuates polymorphonuclear leukocyte (PMN) receptors but not functions
Authors: Naess Are , Andreeva Hristina , Sørnes Steinar
Published: September 2011

Tigecycline attenuates polymorphonuclear leukocyte (PMN) receptors but not functions

Tigecycline achieves high intracellular concentrations in polymorphonuclear leukocytes (PMNs). To evaluate the effects of tigecycline on human PMNs, PMNs were incubated with tigecycline dilutions (0.1 to 100 mg L-1). Phagocytosis-associated PMN Fcγ- and complement receptors as well as phagocytosis and oxidative burst induced byStaphylococcus aureuswere measured by flow cytometry. Incubation with tigecycline caused small but significant decreases in the density of complement receptors CD11b and CD35 (all concentrations) and Fcγ receptors CD16 and CD32 (high concentrations), but not in the percentages of receptor-bearing cells, except for small reductions in the proportions of CD16 positive cells at high concentrations. Tigecycline had no effect on phagocytosis or oxidative burst induced byS. aureus. Tigecycline was thus associated with decreased density of PMN complement and (at high concentrations) Fcγ receptors. Although statistically significant, the differences were small and did not influence the PMN function as measured by phagocytosis and oxidative burst.
Simultaneous estimation of ramipril, acetylsalicylic acid and atorvastatin calcium by chemometrics assisted UV-spectrophotometric method in capsules
Authors: Sankar A. , Vetrichelvan Thangarasu , Venkappaya Devashya
Published: September 2011

Simultaneous estimation of ramipril, acetylsalicylic acid and atorvastatin calcium by chemometrics assisted UV-spectrophotometric method in capsules

In the present work, three different spectrophotometric methods for simultaneous estimation of ramipril, aspirin and atorvastatin calcium in raw materials and in formulations are described. Overlapped data was quantitatively resolved by using chemometric methods,viz.inverse least squares (ILS), principal component regression (PCR) and partial least squares (PLS). Calibrations were constructed using the absorption data matrix corresponding to the concentration data matrix. The linearity range was found to be 1-5, 10-50 and 2-10 μg mL-1for ramipril, aspirin and atorvastatin calcium, respectively. The absorbance matrix was obtained by measuring the zero-order absorbance in the wavelength range between 210 and 320 nm. A training set design of the concentration data corresponding to the ramipril, aspirin and atorvastatin calcium mixtures was organized statistically to maximize the information content from the spectra and to minimize the error of multivariate calibrations. By applying the respective algorithms for PLS 1, PCR and ILS to the measured spectra of the calibration set, a suitable model was obtained. This model was selected on the basis of RMSECV and RMSEP values. The same was applied to the prediction set and capsule formulation. Mean recoveries of the commercial formulation set together with the figures of merit (calibration sensitivity, selectivity, limit of detection, limit of quantification and analytical sensitivity) were estimated. Validity of the proposed approaches was successfully assessed for analyses of drugs in the various prepared physical mixtures and formulations.
Effect of formulation parameters on the drug release and floating properties of gastric floating two-layer tablets with acetylsalicylic acid
Authors: Hasçiçek Canan , Yüksel-Tilkan Günseli , Türkmen Berna , Özdemir Nurten
Published: September 2011

Effect of formulation parameters on the drug release and floating properties of gastric floating two-layer tablets with acetylsalicylic acid

Floating dosage forms of acetylsalicylic acid, used for its antithrombotic effect, were developed to prolong gastric residence time and increase bioavailability. In the two-layer tablet formulation, hydroxypropyl methylcellulose (HPMC) of high viscosity and an effervescent mixture of citric acid and sodium bicarbonate formed the floating layer. The release layer contained the drug, direct tableting agent and different types of matrix-forming polymers such as HPMC of low viscosity, sodium carboxymethylcellulose and chitosan. Tablets were prepared using a direct compression technique. The effect of formulation variables on physicochemical and floating properties and the drug release from tablets were investigated. Floating ability was dependent on the amount of effervescent agent and gel-forming polymer of the floating layer. Drug release was prolonged to 8 hours by changing the type and viscosity of the matrix-forming polymer in the drug-loading layer and all formulations showed a diffusion release mechanisms.
Synthesis and biological evaluation of some novel 2-phenyl benzimidazole-1-acetamide derivatives as potential anthelmintic agents
Authors: Sawant Ramesh , Kawade Deepali
Published: September 2011

Synthesis and biological evaluation of some novel 2-phenyl benzimidazole-1-acetamide derivatives as potential anthelmintic agents

The present study describes synthesis of a series of 2-phenyl benzimidazole-1-acetamide derivatives and their evaluation for anthelmintic activity using Indian adult earthworms,Pheretima posthuma.The structure of the title compounds was elucidated by elemental analysis and spectral data. The compounds 4-({[2-(4-nitrophenyl)-1H-benzimidazol-1-yl]acetyl}amino) benzoic acid (3a),N-ethyl-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3c),N-benzyl-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3d),N-(4-hydroxyphenyl)-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3f), 2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl]-N-phenyl acetamide (3h), 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N'-phenylacetohydrazide (3k), 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N-(4-nitrophenyl) acetamide (3n) and 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N-phenyl acetamide (3q) were found better to paralyze worms whereasN-ethyl-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3c), N-(4-nitrophenyl)-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3e), 4-({[2-(4-chlorophenyl)-1H-benzimidazol-1-yl] acetyl}amino) benzoic acid (3j), 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N-ethyl acetamide (31) and 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N-phenyl acetamide (3q) were better to cause death of worms compared to the anthelmintic drug albendazole.
The Town with No Poverty: The Health Effects of a Canadian Guaranteed Annual Income Field Experiment
Authors: Forget Evelyn L.
Published: September 2011

This paper has two purposes. First, it documents the historical context of MINCOME, a Canadian guaranteed annual income field experiment (1974 to 1979). Second, it uses routinely collected health administration data and a quasi-experimental design to document an 8.5 percent reduction in the hospitalization rate for participants relative to controls, particularly for accidents and injuries and mental health. We also found that participant contacts with physicians declined, especially for mental health, and that more adolescents continued into grade 12. We found no increase in fertility, family dissolution rates, or improved birth outcomes. We conclude that a relatively modest GAI can improve population health, suggesting significant health system savings.
Families, Time, and Well-Being in Canada
Authors: Burton Peter , Phipps Shelley
Published: September 2011

We study changes in time and money available to families with children from 1971 to 2006. Increases in incomes at the top of the Canadian income distribution since the mid-1990s have taken place without any significant increases in total family hours of paid work. On the other hand, for families in the middle of the income distribution, family income has stagnated, despite the fact that parents jointly supply significantly higher hours of paid work. If both time and money are valuable resources for the production of well-being for family members, these findings suggest that inequality in well-being has increased even more than inequality of income.