bluuebunny/crossref_metadata_2025 huggingface dataset:
Selectively increased trace conditioning under the neurotensin agonist PD 149163 in an aversive procedure in which SR 142948A was without intrinsic effect
Authors: Grimond-Billa SK , Norman C , Bennett GW , Cassaday HJ
Published: February 2008

There is evidence to suggest that neurotensin (NT) may enhance cognitive function. The present study, therefore, examined the role of NT in associative learning between a conditioned stimulus (CS) and an unconditioned stimulus (UCS). This was tested in a trace procedure using conditioned suppression of drinking with a noise CS and foot shock UCS. We compared the effects of an NT agonist (PD 149163, 0.25 and 1 mg/kg) with those of an NT antagonist (SR 142948A, 0.01 and 0.1 mg/kg). Conditioning after drug treatment was followed by drug-free tests of associative learning. At 0.25 but not 1 mg/kg, PD 149163 selectively increased conditioning over the trace interval: there was no such increased conditioning in the 0s group. This increased conditioning over the trace is an effect that is reliably produced by dopamine (DA) agonists in the same procedure. However, dissimilar to the effects of DA agonists, conditioning to box context, was reduced under PD 149163. Doses of SR 142948A, selected on the basis of their effects in similar aversively motivated tests of latent inhibition, were without intrinsic effect in the present procedure. The dose-related dissociation between trace and contextual conditioning effects under PD 149163 is considered as cognitive enhancement.
A meta-analysis of clinical trials comparing mirtazapine with selective serotonin reuptake inhibitors for the treatment of major depressive disorder
Authors: Papakostas GI , Homberger CH , Fava M.
Published: February 2008

Over the past few years, a number of studies have suggested that the treatment of major depressive disorder (MDD) with anti-depressants enhancing both noradrenergic as well as serotonergic neurotransmission may result in higher response or remission rates than treatment with anti-depressants selectively enhancing serotonergic neurotransmission. The objective of this paper was to compare response rates among patients with MDD treated with either mirtazapine, an anti-depressant thought to simultaneously enhance both noradrenergic and serotonergic neurotransmission, or selective serotonin reuptake inhibitors (SSRIs). Medline/Pubmed were searched. No year of publication limits were used. Double-blind, randomized clinical trials comparing mirtazapine with an SSRI for the treatment of MDD. Data were extracted with the use of a pre-coded form. Analyses were performed comparing response rates between the two anti—depressant agents. Data from 10 reports involving a total of 1904 outpatients with MDD were identified and combined using a random-effects model. Patients randomized to treatment with mirtazapine were as likely to experience clinical response as patients randomized to treatment with an SSRI (RR = 1.07; 95% CI: 0.96—1.2, P = 0.181). Simply pooling response rates between the two agents revealed a 67.1% response rate for mirtazapine and a 62.1% response rate for the SSRIs. There was no difference in overall discontinuation rates (RR = 1.1; 95% CI: 0.7—1.5; P = 0.550), discontinuation rates due to adverse events (RR = 0.9; 95% CI: 0.6—1.2; P = 0.497), or discontinuation rates due to lack of efficacy (RR = 0.9; 95% CI: 0.4—2.0; P = 0.871) between the two groups. Fewer mirtazapine-treated patients complained of insomnia (RR = 0.5; 95% CI: 0.3—0.9; P = 0.017), nausea (RR = 0.3; 95% CI: 0.3—0.5; P < 0.0001), whereas fewer SSRI-treated patients complained of fatigue (RR = 1.5; 95% CI: 1.1—2.4; P = 0.028), excessive sleepiness (RR = 1.3; 95% CI: 1.1—1.7; P = 0.020), weight-gain (RR = 3.8; 95% CI: 2.3—6.4; P < 0.0001) or dry mouth (RR = 1.8; 95% CI: 1.3—2.4; P < 0.0001) during the course of treatment. These results suggest that mirtazapine and the SSRIs differ with respect to their side-effect profile but not their overall efficacy in the treatment of MDD.
Pharmacokinetics and time-course of D2 receptor occupancy induced by atypical antipsychotics in stabilized schizophrenic patients
Authors: Catafau AM , Penengo MM , Nucci G. , Bullich S. , Corripio I. , Parellada E. , García-Ribera C. , Gomeni R. , Merlo-Pich E. ,   Barcelona Clinical Imaging in Psychiatry Group
Published: February 2008

The 123I-IBZM SPECT measured D2 receptor occupancy (D2RO) in chronically dosed, stabilized schizophrenic patients and its relationship with antipsychotic (AP) pharmacokinetics (PK) over time is still unclear. The aims of this study were: 1) To define the relationship between striatal D2 receptor occupancy (D 2RO) and plasma concentration ( CP) in stabilized schizophrenic patients on clinically relevant doses using 123I-IBZM SPECT; 2) To investigate the time course of AP-induced D2RO and corresponding CP. Forty-six schizophrenic patients on their clinically required doses of risperidone, olanzapine, clozapine or quetiapine were included. D 2RO and CP were measured over time following a sparse-sampling experimental design, and individual PK and D2RO-time profiles were estimated using a population approach. Observed striatal D2RO and CP ranges were 28—75% and 9.4—60.5 ng/mL for risperidone, 22—84% and 8.6—89.5 ng/mL for olanzapine, 5—53% and 41.6—818.2 ng/mL for clozapine and 0—64% and 37.9—719.6 ng/mL for quetiapine. A PK—D2RO relationship was found for the four APs. D2RO pattern over time was stable for risperidone, olanzapine and clozapine but fluctuating for quetiapine. Stabilized schizophrenic patients show a wide range of both D2RO and CP at clinically effective doses of the four AP, suggesting that clinical response to these AP may be maintained with D2RO below 65%. D2RO patterns over time differ between AP. These results should be considered for accurate interpretation of D2RO measurements, proper design of studies and optimization of drug regimens for patients on AP treatment.
Endogenous cannabinoids in patients with schizophrenia and substance use disorder during quetiapine therapy
Authors: Potvin Stéphane , Kouassi Édouard , Lipp Olivier , Bouchard Roch-Hugo , Roy Marc-André , Demers Marie-France , Gendron Alain , Astarita Giuseppe , Piomelli Daniele , Stip Emmanuel
Published: February 2008

Disturbances in the endogenous cannabinoid (ECB) system in schizophrenia may contribute to their enhanced sensitivity to psychoactive substances, and the beneficial effects of second-generation antipsychotics for substance abuse in schizophrenia may involve modulatory effects on ECB. To verify these two assumptions, 29 patients (24 completers) with schizophrenia and substance use disorders (SUD) were treated with quetiapine for 12 weeks, and peripheral ECB levels were measured, using high-performance liquid chromatography/mass spectrometry, in patients (weeks 0, 6 and 12) and 17 healthy volunteers. Baseline anandamide levels were significantly higher in patients, relative to controls. This result is consistent with studies describing ECB dysfunctions in schizophrenia. SUD parameters improved during treatment, but no changes in ECB occurred over time. Improvements in substance abuse were probably not mediated by modulatory effects of quetiapine on ECB. Lastly, baseline anandamide predicted endpoint SUD scores (alcohol/ cannabis). Anandamide is a potential target for medications aimed at relieving SUD in schizophrenia.
Comparative effects of the dopaminergic agonists piribedil and bromocriptine in three different memory paradigms in rodents
Authors: Marighetto A. , Valerio S. , Philippin JN , Bertaina-Anglade V. , Drieu la Rochelle C. , Jaffard R. , Morain P.
Published: February 2008

The potential memory-enhancing properties of two dopamine agonists currently used in patients with Parkinson's disease, piribedil (1, 10 mg/kg/day, subcutaneously) and bromocriptine (5 mg/kg/day, subcutaneously), were evaluated in three experiments. Although piribedil (10 mg/kg) and bromocriptine equally enhanced spontaneous object recognition in young adult rats (experiment A), only piribedil displayed beneficial effects against aging-related memory impairments in two radial-maze experiments in mice. First (experiment B), a two-stage paradigm of spatial discrimination was used to assess relational/declarative memory in aged mice; piribedil (1 and 10 mg/kg) selectively and significantly improved the performances of aged mice in the critical tests for relational/declarative memory, whereas bromocriptine had no effect. Second, in a novel working memory task (experiment C), vehicle- or bromocriptine-treated aged mice displayed, compared with (vehicle) younger controls, a severe and persistent deficit in short-term retention of successive arm-visits, performing close to chance whichever the retention interval. Performances of piribedil (10 mg/kg) group remarkably improved across testing-days and reached young adults' level. The restoration of specific mnemonic impairments, in aged mice, highlights the memory-enhancing properties of piribedil. The efficacy of this drug in treating cognitive impairment of Parkinson's disease should now be assessed in more specific models.This work was published in an abstract form: ECNP Abstracts, 2005 (P8060 & P8065).
Effect of chewing a single betel-quid on autonomic nervous modulation in healthy young adults
Authors: Chiou S-S. , Kuo C-D.
Published: February 2008

Betel-quid is widely used around the world as a stimulant for the autonomic nervous system. The aim of this study was to assess the effect of betel-quid chewing on autonomic nervous modulation by using spectral heart rate variability (HRV) analysis. Twenty healthy young adults were included in this study. Each subject chewed a single betel-quid containing one betel nut or a piece of chewing-gum for 60 min on different days in random order. Spectral HRV measures were obtained before, and 5, 30 and 60 min after starting to chew betel-quid or gum. Sequential changes in HRV measures were compared between chewing gum and betel-quid. Heart rate was significantly elevated after 5 min chewing betel-quid, but not after chewing gum. The normalized low-frequency power and low-/high-frequency power ratio were elevated after 5 min chewing gum or betel-quid; however, the normalized high-frequency power was reduced after 5 min chewing gum or betel-quid. The percentage changes in total power after 5, 30 and 60 min chewing betel-quid were significantly lower than those after chewing gum. This study confirms that novice chewing of betel-quid modulates autonomic nervous system activity; transiently enhancing sympathetic activity and gradually suppressing vagal activity in healthy young adults.
The Turnover Continuum: A Marxist Analysis of Capitalist Fluctuations
Authors: Saros Daniel E.
Published: February 2008

In volume 2 of Capital, Marx investigates the process of circulation of capital. His analysis reveals that capital assumes three distinct forms throughout the course of its circuit: money capital, productive capital, and commodity capital. When discussing the turnover process of capital in part 2, Marx provides the foundation for a theory of macroeconomic fluctuations that resists formalization by means of conventional methods. This article presents a rigorous interpretation of Marx's discussion of the turnover process of capital with a system of piecewise continuous functions. On the basis of these functions, a computer program is developed using the MAPLE mathematical software program, which is then used to analyze aggregate fluctuations in the three forms of capital given hypothetical data for individual capitalist enterprises. The fluctuations resulting from the turnover process, embedded within complex actual capitalist economies, have the potential to influence the overall health and direction of the credit system. JEL classification: B51, E11
Measuring Victimization Inside Prisons
Authors: Wolff Nancy , Jing Shi  , Bachman Ronet
Published: February 2008

Violence and victimization inside the prison setting are accepted as facts, although the facts about their prevalence remain uncertain. Variation in the methods used to estimate rates of sexual and physical victimization contribute to the wide range in estimates appearing in the prison literature. This article focuses on the questions used in the prison victimization literature to elicit information on victimization from inmates, compared to questions used in the general victimization literature. The questions used in the National Violence Against Women and Men Surveys are used to estimate sexual and physical victimization rates for an entire prison system. Rates of victimization were found to vary significantly by specificity of the question, definition of perpetrator, and clustering of behaviors. Facts about victimization inside prison will become more certain when the methodology becomes more standardized and consistent with definitions of victimization.
Prognostic influence of tumor-infiltrating mast cells in patients with follicular lymphoma treated with rituximab and CHOP
Authors: Taskinen Minna , Karjalainen-Lindsberg Marja-Liisa , Leppä Sirpa
Published: February 2008

Gene expression profiling and immunohistochemical studies have demonstrated that nonmalignant tumor infiltrating inflammatory cells contribute to clinical outcome in patients with follicular lymphoma (FL). Particularly, tumor-associated macrophage (TAM) content correlates with longer survival rates after immunochemotherapy. Here we investigated the prognostic importance of tumor-associated mast cells (MCs) and their relation to TAMs in patients with FL treated with a combination of rituximab (R) and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Of the 98 patients, 70 received R-CHOP at diagnosis and 28 at relapse. According to Kaplan-Meier estimates, the patients with high MC content had a worse 4-year progression-free survival (PFS) than the ones with low MC content after R-CHOP therapy (34% vs 74%, P = .002). The adverse prognostic value of MCs was seen both for the patients treated at diagnosis and at relapse, whereas no such impact on PFS was observed for the control patients treated with chemotherapy only (P = .4). When the TAM-related PFS was analyzed separately in patients with high and low MC contents, the positive prognostic effect of TAM was seen only in patients with few MCs. Taken together, the data demonstrate that a high MC score is associated with unfavorable prognosis and it eliminates the positive prognostic value of TAMs in patients with FL treated with immunochemotherapy.
Mediastinal angiomyolipomas in a male patient affected by tuberous sclerosis
Authors: Warth A. , Herpel E. , Schmähl A. , Hoffmann H. , Herth F. J. F. , Schirmacher P. , Dienemann H. , Schnabel P. A.
Published: February 2008

Classical angiomyolipomas are benign tumours composed of various tissues, including components of fat, abnormal blood vessels and smooth muscle cells. They are often found in association with tuberous sclerosis complex (TSC).

The present study reports a male patient affected by TSC with intermittent, massive chylous pleural effusions, who developed recurrent mediastinal angiomyolipomas. The tumours were characterisedviahistological and immunohistochemical methods.

Although angiomyolipomas frequently occur in the kidneys of TSC patients, this case is the first report of mediastinal angiomyolipomas associated with TSC.

Besides lymphangioleiomyomatosis, this differential diagnosis has to be taken into account in the case of chylous pleural effusions and mediastinal masses in tuberous sclerosis complex patients.
Impact of methicillin resistance on mortality inStaphylococcus aureusVAP: a systematic review
Authors: Athanassa Z. , Siempos I. I. , Falagas M. E.
Published: February 2008

The aim of the present study was to estimate the impact of methicillin resistance on mortality in ventilator-associated pneumonia (VAP) due toStaphylococcus aureus.

PubMed, Scopus and the bibliographies of the eligible studies were searched. The DerSimonian-Laird random effects model was used to determine the effect of methicillin resistance on mortality.

Eight articles were included. Crude in-hospital mortality was higher in patients with VAP due to methicillin-resistantS. aureus(MRSA) than in those with VAP due to methicillin-sensitiveS. aureus(MSSA). This was also the case for crude intensive care unit mortality. However, three of the selected studies, which adjusted for potential confounding factors, including adequacy of empirical treatment and severity of illness, demonstrated no difference in in-hospital mortality between patients with MRSA and MSSA VAP. This was not the case for another eligible study that also made adjustment, but for confounders other than those shown above.

The limited available evidence seems to suggest that methicillin resistance is associated with death among persons acquiringStaphylococcus aureusventilator-associated pneumonia. However, although supported by even more limited data, adjustment for risk factors suggests that this association may not be causal, but probably due to confounders, such as the adequacy of empirical treatment and severity of illness.
HaploSNPer: a web-based allele and SNP detection tool
Authors: Tang Jifeng , Leunissen Jack AM , Voorrips Roeland E , van der Linden C Gerard , Vosman Ben
Published: February 2008

Background

Single nucleotide polymorphisms (SNPs) and small insertions or deletions (indels) are the most common type of polymorphisms and are frequently used for molecular marker development. Such markers have become very popular for all kinds of genetic analysis, including haplotype reconstruction. Haplotypes can be reconstructed for whole chromosomes but also for specific genes, based on the SNPs present. Haplotypes in the latter context represent the different alleles of a gene. The computational approach to SNP mining is becoming increasingly popular because of the continuously increasing number of sequences deposited in databases, which allows a more accurate identification of SNPs. Several software packages have been developed for SNP mining from databases. From these, QualitySNP is the only tool that combines SNP detection with the reconstruction of alleles, which results in a lower number of false positive SNPs and also works much faster than other programs. We have build a web-based SNP discovery and allele detection tool (HaploSNPer) based on QualitySNP.

Results

HaploSNPer is a flexible web-based tool for detecting SNPs and alleles in user-specified input sequences from both diploid and polyploid species. It includes BLAST for finding homologous sequences in public EST databases, CAP3 or PHRAP for aligning them, and QualitySNP for discovering reliable allelic sequences and SNPs. All possible and reliable alleles are detected by a mathematical algorithm using potential SNP information. Reliable SNPs are then identified based on the reconstructed alleles and on sequence redundancy.

Conclusion

Thorough testing of HaploSNPer (and the underlying QualitySNP algorithm) has shown that EST information alone is sufficient for the identification of alleles and that reliable SNPs can be found efficiently. Furthermore, HaploSNPer supplies a user friendly interface for visualization of SNP and alleles. HaploSNPer is available fromhttp://www.bioinformatics.nl/tools/haplosnper/.
Reliability and applications of statistical methods based on oligonucleotide frequencies in bacterial and archaeal genomes
Authors: Bohlin Jon , Skjerve Eystein , Ussery David W
Published: February 2008

Background

The increasing number of sequenced prokaryotic genomes contains a wealth of genomic data that needs to be effectively analysed. A set of statistical tools exists for such analysis, but their strengths and weaknesses have not been fully explored. The statistical methods we are concerned with here are mainly used to examine similarities between archaeal and bacterial DNA from different genomes. These methods compare observed genomic frequencies of fixed-sized oligonucleotides with expected values, which can be determined by genomic nucleotide content, smaller oligonucleotide frequencies, or be based on specific statistical distributions. Advantages with these statistical methods include measurements of phylogenetic relationship with relatively small pieces of DNA sampled from almost anywhere within genomes, detection of foreign/conserved DNA, and homology searches. Our aim was to explore the reliability and best suited applications for some popular methods, which include relative oligonucleotide frequencies (ROF), di- to hexanucleotide zero'th order Markov methods (ZOM) and 2.order Markov chain Method (MCM). Tests were performed on distant homology searches with large DNA sequences, detection of foreign/conserved DNA, and plasmid-host similarity comparisons. Additionally, the reliability of the methods was tested by comparing both real and random genomic DNA.

Results

Our findings show that the optimal method is context dependent. ROFs were best suited for distant homology searches, whilst the hexanucleotide ZOM and MCM measures were more reliable measures in terms of phylogeny. The dinucleotide ZOM method produced high correlation values when used to compare real genomes to an artificially constructed random genome with similar %GC, and should therefore be used with care. The tetranucleotide ZOM measure was a good measure to detect horizontally transferred regions, and when used to compare the phylogenetic relationships between plasmids and hosts, significant correlation (R
2 = 0.4) was found with genomic GC content and intra-chromosomal homogeneity.

Conclusion

The statistical methods examined are fast, easy to implement, and powerful for a number of different applications involving genomic sequence comparisons. However, none of the measures examined were superior in all tests, and therefore the choice of the statistical method should depend on the task at hand.
Rapid detection and curation of conserved DNA via enhanced-BLAT and EvoPrinterHD analysis
Authors: Yavatkar Amarendra S , Lin Yong , Ross Jermaine , Fann Yang , Brody Thomas , Odenwald Ward F
Published: February 2008

Background

Multi-genome comparative analysis has yielded important insights into the molecular details of gene regulation. We have developed EvoPrinter, a web-accessed genomics tool that provides a single uninterrupted view of conserved sequences as they appear in a species of interest. An EvoPrint reveals with near base-pair resolution those sequences that are essential for gene function.

Results

We describe here EvoPrinterHD, a 2nd-generation comparative genomics tool that automatically generates from a single input sequence an enhanced view of sequence conservation between evolutionarily distant species. Currently available for 5 nematode, 3 mosquito, 12 Drosophila, 20 vertebrate, 17 Staphylococcus and 20 enteric bacteria genomes, EvoPrinterHD employs a modified BLAT algorithm [enhanced-BLAT (eBLAT)], which detects up to 75% more conserved bases than identified by the BLAT alignments used in the earlier EvoPrinter program. The new program also identifies conserved sequences within rearranged DNA, highlights repetitive DNA, and detects sequencing gaps. EvoPrinterHD currently holds over 112 billion bp of indexed genomes in memory and has the flexibility of selecting a subset of genomes for analysis. An EvoDifferences profile is also generated to portray conserved sequences that are uniquely lost in any one of the orthologs. Finally, EvoPrinterHD incorporates options that allow for (1) re-initiation of the analysis using a different genome's aligning region as the reference DNA to detect species-specific changes in less-conserved regions, (2) rapid extraction and curation of conserved sequences, and (3) for bacteria, identifies unique or uniquely shared sequences present in subsets of genomes.

Conclusion

EvoPrinterHD is a fast, high-resolution comparative genomics tool that automatically generates an uninterrupted species-centric view of sequence conservation and enables the discovery of conserved sequences within rearranged DNA. When combined with cis-Decoder, a program that discovers sequence elements shared among tissue specific enhancers, EvoPrinterHD facilitates the analysis of conserved sequences that are essential for coordinate gene regulation.
VitisExpDB: A database resource for grape functional genomics
Authors: Doddapaneni Harshavardhan , Lin Hong , Walker M Andrew , Yao Jiqiang , Civerolo Edwin L
Published: February 2008

Background

The family Vitaceae consists of many different grape species that grow in a range of climatic conditions. In the past few years, several studies have generated functional genomic information on different Vitis species and cultivars, including the European grape vine, Vitis vinifera. Our goal is to develop a comprehensive web data source for Vitaceae.

Description

VitisExpDB is an online MySQL-PHP driven relational database that houses annotated EST and gene expression data for V. vinifera and non-vinifera grape species and varieties. Currently, the database stores ~320,000 EST sequences derived from 8 species/hybrids, their annotation (BLAST top match) details and Gene Ontology based structured vocabulary. Putative homologs for each EST in other species and varieties along with information on their percent nucleotide identities, phylogenetic relationship and common primers can be retrieved. The database also includes information on probe sequence and annotation features of the high density 60-mer gene expression chip consisting of ~20,000 non-redundant set of ESTs. Finally, the database includes 14 processed global microarray expression profile sets. Data from 12 of these expression profile sets have been mapped onto metabolic pathways. A user-friendly web interface with multiple search indices and extensively hyperlinked result features that permit efficient data retrieval has been developed. Several online bioinformatics tools that interact with the database along with other sequence analysis tools have been added. In addition, users can submit their ESTs to the database.

Conclusion

The developed database provides genomic resource to grape community for functional analysis of genes in the collection and for the grape genome annotation and gene function identification. The VitisExpDB database is available through our website http://cropdisease.ars.usda.gov/vitis_at/main-page.htm.
Seroprevalence of hepatitis C and associated risk factors in urban areas of Antananarivo, Madagascar
Authors: Ramarokoto Charles E , Rakotomanana Fanjasoa , Ratsitorahina Maherisoa , Raharimanga Vaomalala , Razafindratsimandresy Richter , Randremanana Rindra , Rakoto-Andrianarivelo Mala , Rousset Dominique , Andrianaja Voahangy , Richard Vincent , Soares Jean-Louis , Rabarijaona Leon P
Published: February 2008

Background

The risk factors for the transmission of HCV vary substantially between countries and geographic regions. The overall prevalence in south and east Africa region has been estimated to be 1.6% but limited information about the epidemiology of HCV infection in Madagascar is available

Methods

A cross-sectional survey for hepatitis C antibodies was conducted in 2,169 subjects of the general population of Antananarivo to determine seroprevalence of hepatitis C and associated risk factors.

Results

The overall seroprevalence was 1.2% (25/2,169). The prevalence did not differ significantly according to gender but it increased with age (Chi2 tendency test, p < 10-5). The variable history of hospitalization, previous therapeutic injections, dental treatment, intravenous drug use, and abnormal ALT and AST were statistically significantly related with the presence of HCV antibodies. No relationship with past history of blood transfusion was observed.

Conclusion

HCV prevalence in Madagascar seems to be similar to that in most other east African countries. Age appears to be an important risk factor. Iatrogenic causes of HCV transmission need to be further evaluated because all HCV cases had a history of receiving therapeutic injections and data suggested a cumulative effect in relation with therapeutic injections.
A one-year exercise intervention program in pre-pubertal girls does not influence hip structure
Authors: Alwis Gayani , Linden Christian , Stenevi-Lundgren Susanna , Ahlborg Henrik G , Besjakov Jack , Gardsell Per , Karlsson Magnus K
Published: February 2008

Background

We have previously reported that a one-year school-based exercise intervention program influences the accrual of bone mineral in pre-pubertal girls. This report aims to evaluate if also hip structure is affected, as geometry independent of bone mineral influences fracture risk.

Methods

Fifty-three girls aged 7 – 9 years were included in a curriculum-based exercise intervention program comprising 40 minutes of general physical activity per school day (200 minutes/week). Fifty healthy age-matched girls who participated in the general Swedish physical education curriculum (60 minutes/week) served as controls. The hip was scanned by dual X-ray absorptiometry (DXA) and the hip structural analysis (HSA) software was applied to evaluate bone mineral content (BMC), areal bone mineral density (aBMD), periosteal and endosteal diameter, cortical thickness, cross-sectional moment of inertia (CSMI), section modulus (Z) and cross-sectional area (CSA) of the femoral neck (FN). Annual changes were compared. Group comparisons were done by independent student'st-test between means and analyses of covariance (ANCOVA). Pearson's correlation test was used to evaluate associations between activity level and annual changes in FN. All children remained at Tanner stage 1 throughout the study.

Results

No between-group differences were found during the 12 months study period for changes in the FN variables. The total duration of exercise during the year was not correlated with the changes in the FN traits.

Conclusion

Evaluated by the DXA technique and the HSA software, a general one-year school-based exercise program for 7–9-year-old pre-pubertal girls seems not to influence the structure of the hip.
An experimental hut evaluation of Olyset® nets against anopheline mosquitoes after seven years use in Tanzanian villages
Authors: Malima Robert C , Magesa Stephen M , Tungu Patrick K , Mwingira Victor , Magogo Frank S , Sudi Wema , Mosha Frank W , Curtis Christopher F , Maxwell Caroline , Rowland Mark
Published: February 2008

Background

Long-lasting insecticidal nets (LLINs) are advocated by WHO for protection against malaria. Of the three brands of LLINs currently approved by WHO, Olyset® is the only one currently granted full recommendation. With this type of LLIN, the insecticide (permethrin) is incorporated into the polyethylene fibre during manufacture and diffuses from the core to the surface, thereby maintaining surface concentrations. It has not been determined for how long Olyset nets remain protective against mosquitoes in household use.

Methods

Examples of Olyset nets, which had been in use in Tanzanian villages for seven years, were tested in experimental huts against naturally entering Anopheles gambiae and Anopheles funestus mosquitoes. Performance was compared with new Olyset nets, conventionally treated ITNs (either newly treated with alphacypermethrin or taken from local villages after 1.5 years of use) and untreated nets. All nets were artificially holed except for the seven-year Olyset nets, which had developed holes during prolonged domestic use.

Results

Anopheles funestus and An. gambiae in NE Tanzania are susceptible to pyrethroids. The new Olyset nets caused high mortality against An. funestus (73.9%) and An. gambiae (62.7%) in experimental huts. The seven-year Olyset nets caused 58.9% mortality against An. funestus and 40.0% mortality against An. gambiae. The freshly treated alphacypermethrin nets also caused high mortality against An. funestus (70.6%) and An. gambiae (72.0%); this decreased to 58.4% and 69.6% respectively after 1.5 years of use. The new Olyset nets inhibited blood-feeding by 40–50%. The 7 year Olyset nets showed no feeding inhibition over that shown by the untreated nets. The alphacypermethrin treated nets failed to inhibit blood-feeding after 1.5 years of use. However iHhhdn laboratory tunnel tests samples of all types of treated net including the 7 year Olyset inhibited blood-feeding by more than 95%.

Conclusion

After seven years of use Olyset nets were still strongly insecticidal. Mosquito mortality decreased by only 20–35% over this period. However, Olyset would not provide personal protection after seven years unless it was in good condition and all holes fully repaired.
Transduction of the rat brain by Bovine Herpesvirus 4
Authors: Redaelli Marco , Cavaggioni Andrea , Mucignat-Caretta Carla , Cavirani Sandro , Caretta Antonio , Donofrio Gaetano
Published: February 2008

Bovine herpesvirus 4 (BoHV-4) is a gamma-herpesvirus with no clear disease association. A recombinant BoHV-4 (BoHV-4EGFPΔTK) expressing Green Fluorescent Protein (EGFP), was successfully used to infect F98 rat glioma cells. BoHV-4EGFPΔTK was injected into the lateral ventricle of the rat brain. Histology and immunohistochemistry showed that ependymal and rostral migratory stream cells were transduced while neurons were not. Clinical scores, evaluated for 90 days, indicated that the virus was non neuropathogenic, suggesting this virus is a suitable vector for brain tumor gene therapy.
Scaling, growth and cyclicity in biology: a new computational approach
Authors: Delsanto Pier Paolo , Gliozzi Antonio S , Guiot Caterina
Published: February 2008

Background

The Phenomenological Universalities approach has been developed by P.P. Delsanto and collaborators during the past 2–3 years. It represents a new tool for the analysis of experimental datasets and cross-fertilization among different fields, from physics/engineering to medicine and social sciences. In fact, it allows similarities to be detected among datasets in totally different fields and acts upon them as a magnifying glass, enabling all the available information to be extracted in a simple way. In nonlinear problems it allows the nonscaling invariance to be retrieved by means of suitable redefined fractal-dimensioned variables.

Results

The main goal of the present contribution is to extend the applicability of the new approach to the study of problems of growth with cyclicity, which are of particular relevance in the fields of biology and medicine.

Conclusion

As an example of its implementation, the method is applied to the analysis of human growth curves. The excellent quality of the results (R
2 = 0.988) demonstrates the usefulness and reliability of the approach.
Detection of bone erosions in rheumatoid arthritis wrist joints with magnetic resonance imaging, computed tomography and radiography
Authors: Døhn Uffe Møller , Ejbjerg Bo J , Hasselquist Maria , Narvestad Eva , Møller Jakob , Thomsen Henrik S , Østergaard Mikkel
Published: February 2008

Background

The objectives of the present study were, with multidetector computed tomography (CT) as the reference method, to determine the performance of magnetic resonance imaging (MRI) and radiography for the detection of bone erosions in rheumatoid arthritis wrist bones, and to test whether measuring volumes of erosions on CT and MRI is reproducible and correlated to semiquantitative assessments (scores) of erosions on CT, MRI and radiography.

Methods

Seventeen patients with rheumatoid arthritis and four healthy control individuals underwent CT, MRI and radiography of one wrist, performed on the same day. CT was performed on a Philips Mx8000IDT unit (voxel size 0.4 mm × 0.4 mm × 1 mm) and MRI was performed on a Philips Panorama 0.6T unit (voxel size 0.4 mm × 0.4 mm × 0.4 mm). Images were evaluated separately for erosions in all wrist bones and were scored according to the principles of the Outcome Measures in Rheumatology Rheumatoid Arthritis MRI Scoring System (CT and MRI) and the Sharp/van der Heijde (radiographs) scoring methods. Measurements of erosion volumes of all erosions were performed twice with a 1-week interval.

Results

With CT as the reference method, the overall sensitivity, specificity and accuracy (concordance) of MRI for detecting erosions were 61%, 93% and 77%, respectively, while the respective values were 24%, 99% and 63% for radiography. The intramodality agreements when measuring erosion volumes were high for both CT and MRI (Spearman correlation coefficients 0.92 and 0.90 (both P < 0.01), respectively). Correlations between volumes and scores of individual erosions were 0.96 for CT and 0.99 for MRI, while they were 0.83 (CT) and 0.80 (MRI) for persons' total erosion volume and total score (all P < 0.01).

Conclusion

With CT as the reference method, MRI showed moderate sensitivity and good specificity and accuracy for detection of erosions in rheumatoid arthritis and healthy wrist bones, while radiography showed very low sensitivity. The tested volumetric method was highly reproducible and correlated to scores of erosions.
New classification of HLA-DRB1alleles in rheumatoid arthritis susceptibility: a combined analysis of worldwide samples
Authors: Barnetche Thomas , Constantin Arnaud , Cantagrel Alain , Cambon-Thomsen Anne , Gourraud Pierre-Antoine
Published: February 2008

Introduction

Rheumatoid arthritis (RA) is a complex polygenic disease of unknown etiology. HLA-DRB1 alleles encoding the shared epitope (SE) (RAA amino acid pattern in positions 72 to 74 of the third hypervariable region of the DRβ1 chain) are associated with RA susceptibility. A new classification of HLA-DRB1 SE alleles has been developed by Tezenas du Montcel and colleagues to refine the association between HLA-DRB1 and RA. In the present study, we used RA samples collected worldwide to investigate the relevance of this new HLA-DRB1 classification in terms of RA susceptibility across various Caucasoid and non-Caucasoid patients.

Methods

Eighteen subsamples were defined from a total number of 759 cases and 789 controls and grouped in 10 samples on the basis of their ethnic origin. HLA-DRB1 alleles were divided into five groups (S1, S2, S3D, S3P, and X) according to the new HLA-DRB1 allele classification. The whole analysis was performed by comparing carrier frequencies for the five HLA-DRB1 allele groups between RA patients and controls across the 10 Caucasoid and non-Caucasoid samples. The Mantel-Haenszel method of meta-analysis provided a global odds ratio (OR) estimate with 95% confidence interval (CI).

Results

A positive association with RA susceptibility was found for S2 allele carriers (OR 2.15, 95% CI 1.54 to 3.00; p < 10-5) and S3P allele carriers (OR 2.74, 95% CI 2.01 to 3.74; p < 10-5). A negative association was found for S1 alleles (OR 0.60, 95% CI 0.48 to 0.76; p < 10-4) and X alleles (OR 0.58, 95% CI 0.39 to 0.84; p = 4 × 10-3). No significant association was highlighted for the S3D group of alleles (OR 0.89, 95% CI 0.69 to 1.14; p = 0.89). The complementary genotype analysis fit with the genotype risk hierarchy previously reported in Caucasoid RA patients.

Conclusion

So far, the present study is the first attempt to investigate the relevance of this new HLA-DRB1 classification in terms of RA susceptibility on both Caucasoid and non-Caucasoid samples. Our results support the hypothesis of a differential role played by different HLA-DRB1 allele groups in RA susceptibility across different ethnic backgrounds and confirm the interest of such an HLA-DRB1 classification in differentiating predisposing and protective alleles.
Breast cancer subtypes and survival in patients with brain metastases
Authors: Nam Byung-Ho , Kim Sun Young , Han Hye-Sook , Kwon Youngmee , Lee Keun Seok , Kim Tae Hyun , Ro Jungsil
Published: February 2008

Introduction

Brain metastases (BM) occur in up to one third of patients with metastatic breast cancer (MBC), whose incidences and prognoses by breast cancer subtypes in BM have not been well delineated.

Methods

Retrospective survival analyses were performed in 126 BM patients from 805 MBC patients treated at the National Cancer Center between August 2001 and April 2006, according to clinical characteristics, breast cancer subtypes, and receipt of trastuzumab. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor-2 (HER2) statuses were tested by immunohistochemical (IHC) staining, and HER2 FISH analysis conducted for IHC 2+.

Results

The proportion of HER2+/ER- (29% vs 16%) and triple-negative (37% vs 25%) tumors was higher in the 126 BM patients than those without BM. While median survival after recurrence was longer in patients with luminal A disease (median survival of luminal A vs luminal B vs HER2+/ER- vs triple-negative: p = 0.0246; 39.6 vs 27.4 vs 20.9 vs 15.5 months), survival was shorter from BM to death in luminal A and triple negatives (median survival: p = 0.0113; 4.0 vs 9.2 vs 5.0 vs 3.4 months). Receipt of trastuzumab after BM was a significant variable for survival in HER2+ patients. Multivariate analyses identified ER-negative, HER2-negative, or triple-negative, as well as older age, presence of leptomeningeal disease, and three or more extracranial disease sites, as poor prognostic factors for survival after BM.

Conclusion

MBC patients who developed BM had higher proportions of triple-negative and HER2+/ER- tumor status. Triple receptor status is a useful prognostic marker for predicting survival after BM in metastatic breast cancer patients.
Forkhead box transcription factor FOXO3a suppresses estrogen-dependent breast cancer cell proliferation and tumorigenesis
Authors: Zou Yiyu , Tsai Wen-Bin , Cheng Chien-Jui , Hsu Chiun , Chung Young Min , Li Pao-Chen , Lin Sue-Hwa , Hu Mickey CT
Published: February 2008

Introduction

Estrogen receptors (ERs) play key roles in breast cancer development and influence treatment outcome in breast cancer patients. Identification of molecules that regulate ER function may facilitate development of breast cancer treatment strategies. The forkhead box class O (FOXO) transcription factor FOXO3a has been suggested to function as a tumor suppressor in breast cancer. Using protein-protein interaction screening, we found that FOXO3a interacted with ER-α and ER-β proteins in the human breast carcinoma cell line MCF-7, suggesting that there exists a crosstalk between the FOXO3a and ER signaling pathways in estrogen-dependent breast cancer cells.

Methods

The interaction between FOXO3a and ER was investigated by using co-immunoprecipitation and immunoblotting assays. Inhibition of ER-α and ER-β transactivation activity by FOXO was determined by luciferase reporter assays. Cell proliferation in culture was evaluated by counting cell numbers. Tumorigenesis was assessed in athymic mice that were injected with MCF-7 cell lines over-expressing FOXO3a. Protein expression levels of cyclin-dependent kinase inhibitors, cyclins, ERs, FOXM1, and the proteins encoded by ER-regulated genes in MCF-7 cell lines and breast tumors were examined by immunoblotting analysis and immunohistochemical staining.

Results

We found that FOXO3a interacted with ER-α and ER-β proteins and inhibited 17β-estradiol (E2)-dependent, ER-regulated transcriptional activities. Consistent with these observations, expression of FOXO3a in the ER-positive MCF-7 cells decreased the expression of several ER-regulated genes, some of which play important roles in cell proliferation. Moreover, we found that FOXO3a upregulated the expression of the cyclin-dependent kinase inhibitors p21Cip1, p27Kip1, and p57Kip2. These findings suggest that FOXO3a induces cell growth arrest to effect tumor suppression. FOXO3a repressed the growth and survival of MCF-7 cells in cell culture. In an orthotopic breast cancer xenograft model in athymic mice, over-expression of FOXO3a in MCF-7 cells suppressed their E2-induced tumorigenesis, whereas knockdown of FOXO3a in MCF-7 resulted in the E2-independent growth.

Conclusion

Functional interaction between FOXO3a and ER plays a critical role in suppressing estrogen-dependent breast cancer cell growth and tumorigenesis in vivo. This suggests that agents that activate FOXO3a may be novel therapeutic agents that can inhibit and prevent tumor proliferation and development in breast cancer.
Acute lung injury and the acute respiratory distress syndrome in Ireland: a prospective audit of epidemiology and management
Authors:   The Irish Critical Care Trials Group
Published: February 2008

Introduction

The aim of this study was to describe the epidemiology and management of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) in Ireland.

Methods

As part of a 10-week prospective national audit of patient demographics and organ failure incidence in intensive care in Ireland, all patients with ALI/ARDS in 14 participating centres were prospectively identified using American European Consensus Conference definitions.

Results

There were 1,029 admissions during the study period; of these, 728 patients were invasively ventilated. A total of 196 (19%) patients had ALI/ARDS, and 141 of these (72%) had ALI/ARDS on admission and a further 55 (28%) developed ALI/ARDS after admission. For the patients with ALI/ARDS, the mean (± standard deviation) age was 58 ± 17 years and 62% were male. The most common predisposing risk factors were pneumonia (50%) and nonpulmonary sepsis (26%). Mean (± standard deviation) tidal volume/kg was 7.0 ± 1.7 ml/kg. Median (interquartile range) duration of ventilation was 6.8 (2.0 to 12.8) days. Median (interquartile range) length of stay in the intensive care unit was 10.0 (5.0 to 18.5) days. The overall intensive care unit mortality for ALI/ARDS was 32.3%. Lower baseline arterial oxygen tension/fraction of inspired oxygen ratio and higher Sequential Organ Failure Assessment scores were associated with increased mortality. Although not significant, patients receiving treatment with a statin during admission had a 73% lower odds of death (odds ratio 0.27, 95% confidence interval 0.06 to 1.21; P = 0.09).

Conclusion

The incidence of ALI/ARDS is high and is associated with significant mortality. Protective lung ventilation is used commonly throughout participating centres. With low tidal volume ventilation, the degree of hypoxaemia is associated with outcome. These data will inform future multicentre clinical trials in ALI/ARDS in Ireland.
He who pays the piper
Authors: Sarkar Sameer P.
Published: February 2008

It has been clearly established as a matter of legal principle that the duty of expert witnesses is to the court, and not to the cause of those who instruct them. I will suggest that many experts fail to maintain this neutrality, for both conscious and unconscious reasons. If this is so, there may be real dangers in the use of single joint experts, even if there is the benefit of lower costs. In England and Wales, expert witness practice is now seen as part of medical practice by the General Medical Council: the whole profession needs to engage in a debate about how this should be scrutinised and regulated.
The primary care management of anxiety and depression: a GP's perspective
Authors: Cohen Alan
Published: February 2008

The management of anxiety and depression in primary care presents significant issues for workload and understanding the patient in terms of a bio-psychosocial model. There is no shortage of policy in this area, but finding effective and innovative ways of implementing that guidance is only just beginning. This article discusses some of the ways that implementation is happening for adults of working age.