bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection strategy and the design of hybrid oligonucleotide primers for RACE-PCR: cloning a family of toxin-like sequences from Agelena orientalis
Authors: Pan Zhensheng , Barry Richard , Lipkin Alexey , Soloviev Mikhail
Published: May 2007

Background

the use of specific but partially degenerate primers for nucleic acid hybridisations and PCRs amplification of known or unknown gene families was first reported well over a decade ago and the technique has been used widely since then.

Results

here we report a novel and successful selection strategy for the design of hybrid partially degenerate primers for use with RT-PCR and RACE-PCR for the identification of unknown gene families. The technique (named PaBaLiS) has proven very effective as it allowed us to identify and clone a large group of mRNAs encoding neurotoxin-like polypeptide pools from the venom of Agelena orientalis species of spider. Our approach differs radically from the generally accepted CODEHOP principle first reported in 1998. Most importantly, our method has proven very efficient by performing better than an independently generated high throughput EST cloning programme. Our method yielded nearly 130 non-identical sequences from Agelena orientalis, whilst the EST cloning technique yielded only 48 non-identical sequences from 2100 clones obtained from the same Agelena material. In addition to the primer design approach reported here, which is almost universally applicable to any PCR cloning application, our results also indicate that venom of Agelena orientalis spider contains a much larger family of related toxin-like sequences than previously thought.

Conclusion

with upwards of 100,000 species of spider thought to exist, and a propensity for producing diverse peptide pools, many more peptides of pharmacological importance await discovery. We envisage that some of these peptides and their recombinant derivatives will provide a new range of tools for neuroscience research and could also facilitate the development of a new generation of analgesic drugs and insecticides.
Pre-apoptotic response to therapeutic DNA damage involves protein modulation of Mcl-1, Hdm2 and Flt3 in acute myeloid leukemia cells
Authors: Wergeland Line , Sjøholt Gry , Haaland Ingvild , Hovland Randi , Bruserud Øystein , Gjertsen Bjørn Tore
Published: May 2007

Background

Acute myeloid leukemia (AML) cells are characterized by non-mutated TP53, high levels of Hdm2, and frequent mutation of the Flt3 receptor tyrosine kinase. The juxtamembrane mutation of FLT3 is the strongest independent marker for disease relapse and is associated with elevated Bcl-2 protein and p53 hyper-phosphorylation in AML. DNA damage forms the basic mechanism of cancer cell eradication in current therapy of AML.

Hdm2 and pro-apoptotic Bcl-2 members are among the most intensely induced genes immediately after chemotherapy and Hdm2 is proposed a role in receptor tyrosine kinase regulation. Thus we examined the DNA damage related modulation of these proteins in relation to FLT3 mutational status and induction of apoptosis.

Results

Within one hour after exposure to ionizing radiation (IR), the AML cells (NB4, MV4-11, HL-60, primary AML cells) showed an increase in Flt3 protein independent of mRNA levels, while the Hdm2 protein decreased. The FLT3 mutant MV4-11 cells were resistant to IR accompanied by presence of both Mcl-1 and Hdm2 protein three hours after IR. In contrast, the FLT3 wild type NB4 cells responded to IR with apoptosis and pre-apoptotic Mcl-1 down regulation. Daunorubicin (DNR) induced continuing down regulation of Hdm2 and Mcl-1 in both cell lines followed by apoptosis.

Conclusion

Both IR and DNR treatment resulted in concerted protein modulations of Mcl-1, Hdm2 and Flt3. Cell death induction was associated with persistent attenuation of Mcl-1 and Hdm2. These observations suggest that defining the pathway(s) modulating Flt3, Hdm2 and Mcl-1 may propose new strategies to optimize therapy for the relapse prone FLT3 mutated AML patients.
Helicobacter pylori in colorectal neoplasms: is there an aetiological relationship?
Authors: Jones Mary , Helliwell Peter , Pritchard Colin , Tharakan Joseph , Mathew Joseph
Published: May 2007

Background

This pilot study was carried out to determine whether Helicobacter pylori can be detected in normal colon or in association with colorectal neoplasia.

Methods

Paraffin processed colonic tissue blocks of normal colonic mucosa (n = 60), and patients diagnosed as adenoma (n = 60), and adenocarcinoma (n = 60) were retrieved from our archive; the adenoma group included tubular (n = 20), tubulovillous (n = 20) and villous adenomas (n = 20). 4 μm sections were stained by immunohistochemical methods using anti-Helicobacter pylori antibodies (polyclonal NCL-HPp and monoclonal NCL-C-jejuni).

Results

Significant numbers of Helicobacter pylori were identified in tubular adenomas (OR = 11.13; 95%CI = 1.62–76.70), tubulovillous adenomas (OR = 10.45; 95%CI = 1.52–71.52) and adenocarcinomas (OR = 8.13; 95%CI = 1.40–46.99) compared to controls: there was no association in numbers of Helicobacter pylori and villous adenomas (OR = 2.95; 95%CI = 0.29–9.96).

Conclusion

We conclude that although, in this pilot study, there appears to be an association in the prevalence of Helicobacter pylori with some, but not all, colorectal neoplasms, we can not infer causality from these results. These findings need to be further substantiated with a prospective study and the use of molecular biological techniques to determine a causal association.
Worksite environment physical activity and healthy food choices: measurement of the worksite food and physical activity environment at four metropolitan bus garages
Authors: Shimotsu Scott T , French Simone A , Gerlach Anne F , Hannan Peter J
Published: May 2007

Background

The present research describes a measure of the worksite environment for food, physical activity and weight management. The worksite environment measure (WEM instrument) was developed for the Route H Study, a worksite environmental intervention for weight gain prevention in four metro transit bus garages in Minneapolis-St. Paul.

Methods

Two trained raters visited each of the four bus garages and independently completed the WEM. Food, physical activity and weight management-related items were observed and recorded on a structured form. Inter-rater reliability was computed at the item level using a simple percentage agreement.

Results

The WEM showed high inter-rater reliability for the number and presence of food-related items. All garages had vending machines, microwaves and refrigerators. Assessment of the physical activity environment yielded similar reliability for the number and presence/absence of fitness items. Each garage had a fitness room (average of 4.3 items of fitness equipment). All garages had at least one stationary bike and treadmill. Three garages had at least one weighing scale available. There were no designated walking areas inside or outside. There were on average < 1 food stores or restaurants within sight of each garage. Few vending machine food and beverage items met criteria for healthful choices (15% of the vending machine foods; 26% of the vending machine beverages). The garage environment was perceived to be not supportive of healthy food choices, physical activity and weight management; 52% reported that it was hard to get fruits and vegetables in the garages, and 62% agreed that it was hard to be physically active in the garages.

Conclusion

The WEM is a reliable measure of the worksite nutrition, physical activity, and weight management environment that can be used to assess changes in the work environment.
Differential affinity of mammalian histone H1 somatic subtypes for DNA and chromatin
Authors: Orrego Mary , Ponte Imma , Roque Alicia , Buschati Natascha , Mora Xavier , Suau Pedro
Published: May 2007

Background

Histone H1 is involved in the formation and maintenance of chromatin higher order structure. H1 has multiple isoforms; the subtypes differ in timing of expression, extent of phosphorylation and turnover rate. In vertebrates, the amino acid substitution rates differ among subtypes by almost one order of magnitude, suggesting that each subtype might have acquired a unique function. We have devised a competitive assay to estimate the relative binding affinities of histone H1 mammalian somatic subtypes H1a-e and H1° for long chromatin fragments (30–35 nucleosomes) in physiological salt (0.14 M NaCl) at constant stoichiometry.

Results

The H1 complement of native chromatin was perturbed by adding an additional amount of one of the subtypes. A certain amount of SAR (scaffold-associated region) DNA was present in the mixture to avoid precipitation of chromatin by excess H1. SAR DNA also provided a set of reference relative affinities, which were needed to estimate the relative affinities of the subtypes for chromatin from the distribution of the subtypes between the SAR and the chromatin. The amounts of chromatin, SAR and additional H1 were adjusted so as to keep the stoichiometry of perturbed chromatin similar to that of native chromatin. H1 molecules freely exchanged between the chromatin and SAR binding sites. In conditions of free exchange, H1a was the subtype of lowest affinity, H1b and H1c had intermediate affinities and H1d, H1e and H1° the highest affinities. Subtype affinities for chromatin differed by up to 19-fold. The relative affinities of the subtypes for chromatin were equivalent to those estimated for a SAR DNA fragment and a pUC19 fragment of similar length. Avian H5 had an affinity ~12-fold higher than H1e for both DNA and chromatin.

Conclusion

H1 subtypes freely exchangein vitrobetween chromatin binding sites in physiological salt (0.14 M NaCl). The large differences in relative affinity of the H1 subtypes for chromatin suggest that differential affinity could be functionally relevant and thus contribute to the functional differentiation of the subtypes. The conservation of the relative affinities for SAR and non-SAR DNA, in spite of a strong preference for SAR sequences, indicates that differential affinity alone cannot be responsible for the heterogeneous distribution of some subtypes in cell nuclei.
Media and education play a tremendous role in mounting AIDS awareness among married couples in Bangladesh
Authors: Rahman Mohammad Shafiqur , Rahman Mohammad Lutfor
Published: May 2007

Background

To quarantine the spreading possibility of HIV virus to general population boosting public awareness is must. But the proper awareness level is substantially low in Bangladesh. This paper aims to identify the factors associated with the awareness regarding HIV/AIDS through a bivariate and multivariate analysis using the data extracted from Bangladesh Demography and Health Survey (BDHS) 1999–2000.

Results

The findings of both techniques show that education, occupation, socioeconomic status, status of household food consumption, area of residence and media exposure have significant (p < 0.001) contribution in determining HIV/AIDS awareness level. It also reveals that media, particularly TV, and education play the leading role regarding this issue while the others have an indirect relationship. The odds of awareness among higher educated women and men were 4.69 and 77.73 times of no educated women and men respectively. In addition, both women and men those who regularly watch TV were 8.6 times more likely to be aware about AIDS compared to those who never watch TV. This phenomenon holds true for both women and men.

Conclusion

At this instant it is urgent to give emphasis on education, alleviation of poverty, ensuring electronic media exposure, head to head communication program, institutional based sex education and necessary information to learn about HIV/AIDS for the young, adult and adolescents all over the country.
Early efforts in modeling the incubation period of infectious diseases with an acute course of illness
Authors: Nishiura Hiroshi
Published: May 2007

The incubation period of infectious diseases, the time from infection with a microorganism to onset of disease, is directly relevant to prevention and control. Since explicit models of the incubation period enhance our understanding of the spread of disease, previous classic studies were revisited, focusing on the modeling methods employed and paying particular attention to relatively unknown historical efforts. The earliest study on the incubation period of pandemic influenza was published in 1919, providing estimates of the incubation period of Spanish flu using the daily incidence on ships departing from several ports in Australia. Although the study explicitly dealt with an unknown time of exposure, the assumed periods of exposure, which had an equal probability of infection, were too long, and thus, likely resulted in slight underestimates of the incubation period.

After the suggestion that the incubation period follows lognormal distribution, Japanese epidemiologists extended this assumption to estimates of the time of exposure during a point source outbreak. Although the reason why the incubation period of acute infectious diseases tends to reveal a right-skewed distribution has been explored several times, the validity of the lognormal assumption is yet to be fully clarified. At present, various different distributions are assumed, and the lack of validity in assuming lognormal distribution is particularly apparent in the case of slowly progressing diseases. The present paper indicates that (1) analysis using well-defined short periods of exposure with appropriate statistical methods is critical when the exact time of exposure is unknown, and (2) when assuming a specific distribution for the incubation period, comparisons using different distributions are needed in addition to estimations using different datasets, analyses of the determinants of incubation period, and an understanding of the underlying disease mechanisms.
First introduction of highly pathogenic H5N1 avian influenza A viruses in wild and domestic birds in Denmark, Northern Europe
Authors: Bragstad Karoline , Jørgensen Poul H , Handberg Kurt , Hammer Anne S , Kabell Susanne , Fomsgaard Anders
Published: May 2007

Background

Since 2005 highly pathogenic (HP) avian influenza A H5N1 viruses have spread from Asia to Africa and Europe infecting poultry, humans and wild birds. HP H5N1 virus was isolated in Denmark for the first time in March 2006. A total of 44 wild birds were found positive for the HP H5N1 infection. In addition, one case was reported in a backyard poultry flock.

Results

Full-genome characterisation of nine isolates revealed that the Danish H5N1 viruses were highly similar to German H5N1 isolates in all genes from the same time period. The haemagglutinin gene grouped phylogenetically in H5 clade 2 subclade 2 and closest relatives besides the German isolates were isolates from Croatia in 2005, Nigeria and Niger in 2006 and isolates from Astrakhan in Russia 2006. The German and Danish isolates shared unique substitutions in the NA, PB1 and NS2 proteins.

Conclusion

The first case of HP H5N1 infection of wild and domestic birds in Denmark was experienced in March 2006. This is the first full genome characterisation of HP H5N1 avian influenza A virus in the Nordic countries. The Danish viruses from this time period have their origin from the wild bird strains from Qinghai in 2005. These viruses may have been introduced to the Northern Europe through unusual migration due to the cold weather in Eastern Europe at that time.
A hierarchical approach employing metabolic and gene expression profiles to identify the pathways that confer cytotoxicity in HepG2 cells
Authors: Li Zheng , Srivastava Shireesh , Yang Xuerui , Mittal Sheenu , Norton Paul , Resau James , Haab Brian , Chan Christina
Published: May 2007

Background

Free fatty acids (FFA) and tumor necrosis factor alpha (TNF-α) have been implicated in the pathogenesis of many obesity-related metabolic disorders. When human hepatoblastoma cells (HepG2) were exposed to different types of FFA and TNF-α, saturated fatty acid was found to be cytotoxic and its toxicity was exacerbated by TNF-α. In order to identify the processes associated with the toxicity of saturated FFA and TNF-α, the metabolic and gene expression profiles were measured to characterize the cellular states. A computational model was developed to integrate these disparate data to reveal the underlying pathways and mechanisms involved in saturated fatty acid toxicity.

Results

A hierarchical framework consisting of three stages was developed to identify the processes and genes that regulate the toxicity. First, discriminant analysis identified that fatty acid oxidation and intracellular triglyceride accumulation were the most relevant in differentiating the cytotoxic phenotype. Second, gene set enrichment analysis (GSEA) was applied to the cDNA microarray data to identify the transcriptionally altered pathways and processes. Finally, the genes and gene sets that regulate the metabolic responses identified in step 1 were identified by integrating the expression of the enriched gene sets and the metabolic profiles with a multi-block partial least squares (MBPLS) regression model.

Conclusion

The hierarchical approach suggested potential mechanisms involved in mediating the cytotoxic and cytoprotective pathways, as well as identified novel targets, such as NADH dehydrogenases, aldehyde dehydrogenases 1A1 (ALDH1A1) and endothelial membrane protein 3 (EMP3) as modulator of the toxic phenotypes. These predictions, as well as, some specific targets that were suggested by the analysis were experimentally validated.
Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration
Authors: Le Maitre Christine Lyn , Freemont Anthony John , Hoyland Judith Alison
Published: May 2007

Current evidence implicates intervertebral disc degeneration as a major cause of low back pain, although its pathogenesis is poorly understood. Numerous characteristic features of disc degeneration mimic those seen during ageing but appear to occur at an accelerated rate. We hypothesised that this is due to accelerated cellular senescence, which causes fundamental changes in the ability of disc cells to maintain the intervertebral disc (IVD) matrix, thus leading to IVD degeneration. Cells isolated from non-degenerate and degenerate human tissue were assessed for mean telomere length, senescence-associated β-galactosidase (SA-β-gal), and replicative potential. Expression of P16
INK4A
(increased in cellular senescence) was also investigated in IVD tissue by means of immunohistochemistry. RNA from tissue and cultured cells was used for real-time polymerase chain reaction analysis for matrix metalloproteinase-13, ADAMTS 5 (a disintegrin and metalloprotease with thrombospondin motifs 5), and P16
INK4A
. Mean telomere length decreased with age in cells from non-degenerate tissue and also decreased with progressive stages of degeneration. In non-degenerate discs, there was an age-related increase in cellular expression of P16
INK4A
. Cells from degenerate discs (even from young patients) exhibited increased expression of P16
INK4A
, increased SA-β-gal staining, and a decrease in replicative potential. Importantly, there was a positive correlation between P16
INK4A
and matrix-degrading enzyme gene expression. Our findings indicate that disc cell senescence occurs in vivo and is accelerated in IVD degeneration. Furthermore, the senescent phenotype is associated with increased catabolism, implicating cellular senescence in the pathogenesis of IVD degeneration.
Cooling and hemodynamic management in heatstroke: practical recommendations
Authors: Bouchama Abderrezak , Dehbi Mohammed , Chaves-Carballo Enrique
Published: May 2007

Introduction

Although rapid cooling and management of circulatory failure are crucial to the prevention of irreversible tissue damage and death in heatstroke, the evidence supporting the optimal cooling method and hemodynamic management has yet to be established.

Methods

A systematic review of all clinical studies published in Medline (1966 to 2006), CINAHL (Cumulative Index to Nursing & Allied Health Literature) (1982 to 2006), and Cochrane Database was performed using the OVID interface without language restriction. Search terms included heatstroke, sunstroke, and heat stress disorders.

Results

Fourteen articles reported populations subjected to cooling treatment for classic or exertional heatstroke and included data on cooling time, neurologic morbidity, or mortality. Five additional articles described invasive monitoring with central venous or pulmonary artery catheters. The four clinical trials and 15 observational studies covered a total of 556 patients. A careful analysis of the results obtained indicated that the cooling method based on conduction, namely immersion in iced water, was effective among young people, military personnel, and athletes with exertional heatstroke. There was no evidence to support the superiority of any one cooling technique in classic heatstroke. The effects of non-invasive, evaporative, or conductive-based cooling techniques, singly or combined, appeared to be comparable. No evidence of a specific endpoint temperature for safe cessation of cooling was found. The circulatory alterations in heatstroke were due mostly to a form of distributive shock associated with relative or absolute hypovolemia. Myocardial failure was found to be rare.

Conclusion

A systematic review of the literature failed to identify reliable clinical data on the optimum treatment of heatstroke. Nonetheless, the findings of this study could serve as a framework for preliminary recommendations in cooling and hemodynamic management of heatstroke until more evidence-based data are generated.
Genome-wide identification of novel expression signatures reveal distinct patterns and prevalence of binding motifs for p53, nuclear factor-κB and other signal transcription factors in head and neck squamous cell carcinoma
Authors: Yan Bin , Yang Xinping , Lee Tin-Lap , Friedman Jay , Tang Jun , Van Waes Carter , Chen Zhong
Published: May 2007

Background

Differentially expressed gene profiles have previously been observed among pathologically defined cancers by microarray technologies, including head and neck squamous cell carcinomas (HNSCCs). However, the molecular expression signatures and transcriptional regulatory controls that underlie the heterogeneity in HNSCCs are not well defined.

Results

Genome-wide cDNA microarray profiling of ten HNSCC cell lines revealed novel gene expression signatures that distinguished cancer cell subsets associated with p53 status. Three major clusters of over-expressed genes (A to C) were defined through hierarchical clustering, Gene Ontology, and statistical modeling. The promoters of genes in these clusters exhibited different patterns and prevalence of transcription factor binding sites for p53, nuclear factor-κB (NF-κB), activator protein (AP)-1, signal transducer and activator of transcription (STAT)3 and early growth response (EGR)1, as compared with the frequency in vertebrate promoters. Cluster A genes involved in chromatin structure and function exhibited enrichment for p53 and decreased AP-1 binding sites, whereas clusters B and C, containing cytokine and antiapoptotic genes, exhibited a significant increase in prevalence of NF-κB binding sites. An increase in STAT3 and EGR1 binding sites was distributed among the over-expressed clusters. Novel regulatory modules containing p53 or NF-κB concomitant with other transcription factor binding motifs were identified, and experimental data supported the predicted transcriptional regulation and binding activity.

Conclusion

The transcription factors p53, NF-κB, and AP-1 may be important determinants of the heterogeneous pattern of gene expression, whereas STAT3 and EGR1 may broadly enhance gene expression in HNSCCs. Defining these novel gene signatures and regulatory mechanisms will be important for establishing new molecular classifications and subtyping, which in turn will promote development of targeted therapeutics for HNSCC.
An annotation infrastructure for the analysis and interpretation of Affymetrix exon array data
Authors: Okoniewski Michał J , Yates Tim , Dibben Siân , Miller Crispin J
Published: May 2007

Affymetrix exon arrays contain probesets intended to target every known and predicted exon in the entire genome, posing significant challenges for high-throughput genome-wide data analysis. X:MAP http://xmap.picr.man.ac.uk, an annotation database, and exonmap http://www.bioconductor.org/packages/2.0/bioc/html/exonmap.html, a BioConductor/R package, are designed to support fine-grained analysis of exon array data. The system supports the application of standard statistical techniques, prior to the use of genome scale annotation to provide gene-, transcript- and exon-level summaries and visualization tools.
Tin-Free Radical Carbon–Carbon Bond-Forming Reactions Based on α-Scission of Alkylsulfonyl Radicals
Authors: Kim Sunggak , Kim Sangmo
Published: May 2007

Tin-free radical reactions based on α-scission of alkylsulfonyl radicals are very useful for the formation of carbon–carbon bonds and include allylation, acylation, cyanation, vinylation, and carbonylation. For secondary, tertiary, and benzylic radicals, it is possible to use the corresponding iodides as precursors but the primary radicals still require the use of phenyl tellurides or alkyl allyl sulfones. Especially, alkyl allyl sulfones are highly efficient and most reliable primary alkyl radical precursors for the further formation of carbon–carbon bonds. The present approach is very useful for introducing various functional groups such as carbonyl and alkenyl groups under tin-free conditions.
Radiation-Induced Cross-Linking of Gelatin by Using γ-Rays: Insoluble Gelatin Hydrogel Formation
Authors: Bessho Masahiko , Kojima Takao , Okuda Shuichi , Hara Masayuki
Published: May 2007

Gelatin hydrogels with various concentrations were cross-linked by the irradiation with 60Co γ-rays, and we investigated the radiation-induced cross-linking of gelatin hydrogels by estimating the physical properties of irradiated hydrogels. In case of the 1, 5, and 10% (w/v) gelatin solutions, the specific water content of the irradiated hydrogels, the index showing the extent of cross-linking depended on the absorbed dose, and that of the irradiated gelatin hydrogels with the lower concentration decreased drastically. The breaking strength correlated to the absorbed dose, irrespective of the initial gelatin concentration. More than 8 kGy irradiation induced insolubility due to the cross-linking of the gelatin hydrogels. Besides, γ-ray irradiation to gelatin with free amino acids revealed that amino acids, which have side chains of hydrocarbon groups that are more than two carbon atoms, obstructed the cross-linking of gelatin hydrogels. It is thought that the hydrocarbon groups, such as an alkyl or a phenyl group of the side chains, are the cross-linking sites of gelatin hydrogels.
Management of premature menopause
Authors:   Writing Group for the British Menopause Society Council
Published: May 2007

There has been some confusion among women and health professionals since the publication of the Women's Health Initiative and Million Women studies about the management of premature ovarian failure (POF). Both studies were undertaken in women aged 50 and over, and cannot be extrapolated to their younger counterparts, who would normally be producing their endogenous estrogen, since they have functioning ovaries. Estrogen-based replacement therapy is the main stay of treatment for women with POF and is recommended at least until the average age of natural menopause (52 years in the UK). This view is endorsed by regulatory bodies such as the Committee on Safety of Medicines (now the Commission on Human Medicines) in the UK. No evidence shows that estrogen replacement increases the risk of breast cancer to a level greater than that found in normally menstruating women, and women with POF do not need to start mammographic screening early unless other risk factors are present, such as family history.
Thyroid dysfunction in perimenopausal and postmenopausal women
Authors: Pearce Elizabeth N
Published: May 2007

Thyroid dysfunction is common, especially among women over the age of 50. In caring for peri- and post-menopausal women, it is important to recognize the changing clinical manifestations of thyroid disease with age. Postmenopausal women are at increased risk of both osteoporosis and cardiovascular disease, and untreated thyroid disease may exacerbate these risks. Screening for thyroid dysfunction in asymptomatic individuals is controversial, but aggressive case-finding should be pursued, especially in older women. Women with overt thyroid dysfunction should be treated. Therapy for women with subclinical thyroid dysfunction is more controversial, although women with levels of thyroid stimulating hormone (TSH) ≥10 mU/L should be treated, and treatment may be considered in symptomatic women with subclinical hypothyroidism and TSH values <10 mU/L, and in women with subclinical hyperthyroidism who have TSH values consistently <0.1 mU/L. In women who are treated with thyroxine, careful dose titration and monitoring are required in order to prevent the adverse consequences of iatrogenic subclinical hyperthyroidism or hypothyroidism. Finally, caution is required in diagnosing and treating thyroid dysfunction in women who are taking oral estrogens or selective estrogen receptor modulators.
Calcium and vitamin D – for whom and when
Authors: Prince Richard L
Published: May 2007

The basis of 'nutritional' interventions for the prevention of postmenopausal osteoporosis and osteoporotic fracture is a large topic with much genetic and biochemical evidence, as well as the results of randomized controlled trials, to guide the investigator and clinician. The efficacy of treatment with calcium and vitamin D was once controversial, but with the advent of controlled clinical trials using bone mineral density as an endpoint it has become clear that calcium with or without vitamin D therapy can lead to reductions in the rate of bone loss in postmenopausal women of all ages. Furthermore, with certain caveats, calcium with vitamin D therapy in the older postmenopausal woman can lead to useful reductions infracture rates and falls, especially in populations with reduced exposure to sunlight, which is potentially the majority of postmenopausal women in both developed and developing countries. However, estrogen, selective estrogen receptor modulators (SERMs) and bisphosphonates (especially when given in combination with calcium and vitamin D) are more efficacious in preventing fracture, particularly in postmenopausal patients with impaired bone structure.
Medical management of perimenopausal menorrhagia: an evidence-based approach
Authors: Duckitt Kirsten
Published: May 2007

About one-third of women report heavy menstrual bleeding at some time in their lives. Menstrual blood loss increases with age. Menorrhagia is usually defined as heavy but regular menstrual bleeding of over 80 ml/cycle. Complaints of menorrhagia are common. Several medical therapies are suitable for perimenopausal women with either regular or irregular heavy bleeding. The most effective is intrauterine levonorgestrel. Other options are oral progestogens, the combined oral contraceptive pill, tranexamic acid, mefenamic acid, danazol and gonadotrophin-releasing hormone (GnRH) analogues. Systematic reviews and randomized controlled trials are discussed.
The future of the new selective estrogen receptor modulators
Authors: Palacios Santiago
Published: May 2007

Selective estrogen receptor modulators (SERMs) are compounds that display mixed estrogen agonist/antagonist activity. Currently, four SERMs are licensed for clinical use: tamoxifen, toremifene, clomifene and raloxifene. The STAR and RUTH trials have provided useful data about the potential role of SERMs in the primary prevention of breast cancer and cardiovascular disease in postmenopausal women. New-generation SERMs, such as bazedoxifene, arzoxifene, lasofoxifene and ospemifene, are currently being evaluated. The aim is to find a SERM that conserves the skeleton and prevents breast cancer without increasing the risk of endometrial cancer and venous thromboembolism, and without inducing hot flushes. Technological advances in the study of estrogen receptor activation will provide key information for drug development.
Advances in the surgical management of prolapse
Authors: Slack Alex , Jackson Simon
Published: May 2007

Prolapse is an extremely common condition, for which 11% of women will have a surgical procedure at some point in their lives. The recurrence rate after most of the traditional surgical procedures is high and upto 29% of women who have had surgery for prolapse will require a further operation. In order to improve the surgical outcome, there is currently much interest in the use of grafts to augment traditional repairs and new procedures have been developed using specifically developed grafts. These have been combined with minimally invasive surgical techniques in an attempt to reduce surgical morbidity. These procedures may improve the outcome of surgery for prolapse. However, there is currently a lack of long-term data from randomized trials to demonstrate their effectiveness and safety.
Diagnosis of cardiovascular disease in women
Authors: Schenck-Gustafsson Karin
Published: May 2007

Cardiovascular disease (CVD, comprising coronary heart disease and stroke) is the leading cause of death in both sexes in developed countries. Although women are nine times more likely to die from CVD than they are from breast cancer, there is a general public belief that the most common cause of death is cancer. The symptoms of acute myocardial infarction and acute coronary syndromes differ between the sexes. Women are less likely to experience chest pain and may have non-specific symptoms. Normal or non-obstructive coronary disease, as detected by angiography, is more common in women. Scintigraphy improves the detection of coronary disease in women. There is an urgent need to increase awareness of both coronary heart disease in women and the limitationsof commonly used diagnostic tools.
Delivering group psychoeducational CBT in Primary Care: Comparing outcomes with individual CBT and individual psychodynamic‐interpersonal psychotherapy
Authors: Kellett Stephen , Clarke Suzanne , Matthews Linda
Published: May 2007

Within psychological services in Primary Care, service providers are expected and required to deliver clinical services that are prompt, safe and effective. However, long wait‐times for treatment are common, with attendant clinical chronicity and risk issues. Evaluations of group‐based treatments in Primary Care, which are clinically more efficient than individual treatments, are extremely scarce. The current evaluation attempted to appraise the effectiveness of a service innovation of introducing group‐based psychoeducational cognitive‐behaviour therapy (CBT; N=43), by comparing outcomes with clients treated in individual CBT (N=68) and individual psychodynamic‐interpersonal psychotherapy (N=65). Group psychoeducational participants completed validated scales of psychological functioning (Beck Depression Inventory – 2, BDI‐2; Brief Symptom Inventory, BSI; Inventory of Interpersonal Problems, IIP‐32; and General Health Questionnaire, GHQ‐12) at assessment, start of group, termination of group and 3‐month follow‐up, whereas participants in the individual therapies completed measures only at initiation and termination of treatment. The results indicate broad similarities between the outcomes achieved by the three services, with rates of clinically significant improvements and deteriorations comparable in the main across services. The results are discussed in terms of identified methodological limitations, service implications and models of service delivery for the psychological therapies in Primary Care.
The role of maladaptive appraisals in child acute stress reactions
Authors: Salmon Karen , Sinclair Emma , Bryant Richard A.
Published: May 2007

Objective To test the prediction of cognitive models of trauma that negative, catastrophic appraisals central to the development of psychopathological stress reactions.

Design A cross‐sectional, concurrent design was used.

Methods Sixty‐six children (aged 7–13 years), who were hospitalized after traumatic injury were assessed within 4 weeks of their trauma for acute stress disorder, depression, and administered the Child Post‐traumatic Cognitions Inventory (cPTCI). Parental acute stress was also assessed.

Results Children's negative appraisals of their ongoing vulnerability accounted for 44% of the variance of acute stress reactions in children. Injury severity, depression, age, and parental acute stress levels did not account for significant additional variance.

Conclusions The findings provide support for cognitive models of trauma adaptation and highlight the importance of assessing children's appraisals of their traumatic experience in order to develop effective interventions.
Relationships between the personality beliefs questionnaire and self‐rated personality disorders
Authors: Jones Steven H. , Burrell‐Hodgson Gerrard , Tate Graham
Published: May 2007

Objectives To examine relationships between specific dysfunctional beliefs and self‐reported personality disorder types.

Design Cross‐sectional.

Method One hundred and sixty‐four clinical psychology out‐patients completed the Personality Beliefs Questionnaire (PBQ) and Millon Multiaxial Clinical Inventory‐III (MCMI‐III): 155 completed both. Avoidant, dependent, passive‐aggressive and schizoid PDs, and relevant PBQ subscales were studied.

Results Presence or absence of PD was predicted by scores on the index PBQ subscale.

Conclusions This pattern has previously been reported for PDs diagnosed by structured interview only. PBQ relationships with passive‐aggressive and schizoid PD have not previously been reported.
Low specificity of symptoms on the post‐traumatic stress disorder (PTSD) symptom scale: A comparison of individuals with PTSD, individuals with other anxiety disorders and individuals without psychopathology
Authors: Engelhard Iris M. , Arntz Arnoud , Van den Hout Marcel A.
Published: May 2007

Objectives Screening for post‐traumatic stress disorder (PTSD) takes place in clinical and research settings where diagnostic interviews are not feasible, and typically relies on self‐report instruments like the PTSD symptom scale (PSS). Concerns have been raised about the specificity of PTSD symptoms assessed by questionnaires. This study examined whether the PSS distinguishes between patients with PTSD and those with other anxiety disorders or healthy controls.

Design A between‐participants design was employed.

Methods The participants were 65 individuals with PTSD, 40 individuals with other anxiety disorders and 40 healthy controls. They completed the PSS with respect to a range of stressful life‐events.

Results Using this instrument, 86% of individuals with PTSD and 5% of healthy controls endorsed sufficient symptoms to meet the PTSD diagnosis. This was also the case for 43% of individuals with other anxiety disorders, and self‐reported symptoms related to traumatic events and aversive events that are generally not considered traumatic.

Conclusions The findings suggest that many people screened positive for PTSD may actually be suffering from another anxiety disorder.
Fidgetin-Like 1 Gene Inhibited by Basic Fibroblast Growth Factor Regulates the Proliferation and Differentiation of Osteoblasts
Authors: Park Su Jin , Kim Su Jin , Rhee Yumie , Byun Ji Hyun , Kim Seong Hwan , Kim Myoung Hee , Lee Eun Jig , Lim Sung-Kil
Published: May 2007

The FIGNL1 gene was proven to be a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). In this in vitro study, the AAA proteins inhibited osteoblast proliferation and stimulated osteoblast differentiation. We showed that FIGNL1 may play some regulatory role in osteoblastogenesis.

Introduction: The fidgetin-like 1 (FIGNL1) gene encodes a new subfamily member of ATPases associated with diverse cellular activities (AAA proteins). Although the FIGNL1 protein localizes to both the nucleus and cytoplasm, the function of FIGNL1 remains unknown. In a previous study, we identified several genes that mediate the anabolic effects of basic fibroblast growth factor (bFGF) on bone by using microarray data. FIGNL1 was one of the genes that downregulated >2-fold in MC3T3-E1 cells after treatment with bFGF. Therefore, this study was aimed to identify and confirm the function of FIGNL1 on osteoblastogenesis.

Materials and Methods: We examined the effect of the FIGNL1 gene on proliferation, differentiation, and apoptosis in mouse osteoblast cells (MC3T3-E1 and mouse primary calvarial cells) using flow cytometry, RT-PCR, cell proliferation assay, and cell death assay. MC3T3-E1 cells and mouse calvarial cells were transfected with small interfering RNA (siRNA) directed against the FIGNL1 or nontargeting control siRNA and examined by cell proliferation and cell death assays. Also, FIGNL1 was fused to enhance green fluorescent protein (EGFP), and the EGFP-fused protein was transiently expressed in MC3T3-E1 cells.

Results: Reduced expression of FIGNL1 by bFGF and TGF-β1 treatment was verified by RT-PCR analysis. Overexpression of FIGNL1 reduced the proliferation of MC3T3-E1 and calvarial cells, more than the mock transfected control cells did. In contrast, siFIGNL1 transfection significantly increased the proliferation of osteoblasts, whereas overexpression of FIGNL1 did not seem to alter apoptosis in osteoblasts. Meanwhile, overexpression of FIGNL1 enhanced the mRNA expression of alkaline phosphatase (ALP) and osteocalcin (OCN) in osteoblasts. In contrast, siFIGNL1 decreased the expression of ALP and OCN. A pEGFP-FIGNL1 transfected into MCT3-E1 cells had an initially ubiquitous distribution and rapidly translocated to the nucleus 1 h after bFGF treatment.

Conclusions: From these results, we proposed that FIGNL1, a subfamily member of the AAA family of proteins, might play some regulatory role in osteoblast proliferation and differentiation. Further analyses of FIGNL1 will be needed to better delineate the mechanisms contributing to the inhibition of proliferation and stimulation of osteoblast differentiation.
Managing Nitrogen Contaminated Soils:Benefits of N2–Fixing Alfalfa
Authors: Russelle Michael P. , Lamb JoAnn F. S. , Turyk Nancy B. , Shaw Byron H. , Pearson Bill
Published: May 2007

Perennial forage crops offer an effective, low‐cost method for remediating excess soil N. Where it is agronomically adapted, alfalfa (Medicago sativa L.) is a particularly desirable species for remediation of excess soil N because it has high dry matter (DM) yield and N uptake potential, it can absorb nitrate (NO3) from depths beyond those attainable by most annual crops, and its market value is usually higher than grass forages. On the basis of previous research, we hypothesized that non‐N2–fixing alfalfa would remove more inorganic soil N than standard, N2–fixing alfalfa and tested this hypothesis at an abandoned barnyard on a Richford sandy loam (mixed, mesic Psammentic Hapludalfs) in central Wisconsin, USA. Duplicate plots (30 by 60 m) of both N2–fixing and nonfixing alfalfa were seeded in August 1998 and 1999. Nonfixing alfalfa produced lower DM and N yield and showed greater variability than standard, N2–fixing alfalfa. Yield, N concentration, and stand declined in the nonfixing type where inorganic N supply was inadequate. Average maximum estimated recovery of soil and manure N was about 200 kg N ha−1 annually for plots seeded with N2–fixing alfalfa. During 2 yr when inorganic N uptake was estimated by the 15N natural abundance technique, N2–fixing alfalfa removed nearly 60% more soil and manure N than nonfixing alfalfa, but weeds in the nonfixing alfalfa plots made up the difference. Neither alfalfa prevented ground water contamination by NO3 and concentrations increased similarly under both alfalfas. Because declines in yield and protein concentration may be expected for nonfixing alfalfa on sites with patchy available N distribution, economic remediation of these sites will be promoted by using an adapted cultivar of N2–fixing alfalfa.
Empirical Analysis of Weaning and Pasture Rotation Frequency with Implications for Retained Ownership
Authors: Popp Michael , Coffey K. , Coblentz W. , Johnson Z. , Scarbrough D. , Humphry J. , Smith T. , Hubbell D. , Turner J.
Published: May 2007

The economic impact of rotation frequency (twice weekly vs. twice monthly until time of weaning) and time of weaning (early April vs. 56 d later) was examined for fall‐calving cows using a modified put and take grazing strategy implemented to maintain equal grazing pressure across production systems. Cow and/or calf death losses resulted in replacements with either bred cows or cow–calf pairs. While the analysis on heifer calves was limited to sale at time of weaning, steer calves were tracked through the feedlot stage to determine if the time of sale would alter production system recommendations. For the conditions presented in this study, cow–calf producers may be advised that (i) relative to late weaning, early weaned calves did not regain their weight disadvantage observed at time of weaning; (ii) more intensive pasture management (rotating twice weekly rather than twice monthly) was not worth the effort because partial return results for late‐weaned steer and heifer calves did not differ statistically by rotation frequency, regardless of sale time; (iii) partial returns were highest for steer calves retained through the finishing stage at the feedlot (regardless of production system) compared with sale at the time of weaning or at the time of placement in the feedlot; (iv) the range of returns or financial risk exposure increased with length of calf ownership. However, use of long‐term average prices excluded input price risk from the analysis and output price risk was only partially addressed.
Temporal and Vertical Distribution of Nonstructural Carbohydrate, Fiber, Protein, and Digestibility Levels in Orchardgrass Swards
Authors: Griggs Thomas C. , MacAdam Jennifer W. , Mayland Henry F. , Burns Joseph C.
Published: May 2007

Herbage nonstructural carbohydrates (NC) contribute to livestock performance and silage fermentation. Knowledge of the distribution patterns of NC and other nutritional constituents in orchardgrass (Dactylis glomerata L.) swards could support harvest management decisions. Our objective was to determine diurnal and vertical patterns of total NC (TNC), crude protein (CP), and neutral detergent fiber (NDF) concentrations, and in vitro true dry matter digestibility (IVTDMD) and NDF digestibility (NDFD) in orchardgrass swards in October, June, and August. Herbage was sampled at 6‐h intervals between 0100 and 1900 h from horizons positioned 40 to 27, 27 to 18, 18 to 12, and 12 to 8 cm above soil surface. Herbage composition varied among horizons in all months, and diurnally only in June and August. In June and August, only TNC with maxima of 109 to 123 g kg−1 at 1900 h exhibited consistent diurnal patterns. Swards harvested to residual heights of 18, 12, or 8 cm exhibited little spatial variation in TNC during June and August, but CP, NDF, and IVTDMD varied with harvest depth on all dates. As swards were harvested to successively greater depths, TNC increased in October, but not in June and August. In contrast, CP and IVTDMD decreased, and NDF increased, for harvests to successively greater depths in all months. For harvests in June and August, manipulation of depth would capture more variation in CP, NDF, and IVTDMD, but manipulation of time of day of harvest would capture more variation in TNC to meet animal performance and silage fermentation requirements.