bluuebunny/crossref_metadata_2025 huggingface dataset:
Recognizing protein–protein interfaces with empirical potentials and reduced amino acid alphabets
Authors: Launay Guillaume , Mendez Raul , Wodak Shoshana , Simonson Thomas
Published: August 2007

Background

In structural genomics, an important goal is the detection and classification of protein–protein interactions, given the structures of the interacting partners. We have developed empirical energy functions to identify native structures of protein–protein complexes among sets of decoy structures. To understand the role of amino acid diversity, we parameterized a series of functions, using a hierarchy of amino acid alphabets of increasing complexity, with 2, 3, 4, 6, and 20 amino acid groups. Compared to previous work, we used the simplest possible functional form, with residue–residue interactions and a stepwise distance-dependence. We used increased computational ressources, however, constructing 290,000 decoys for 219 protein–protein complexes, with a realistic docking protocol where the protein partners are flexible and interact through a molecular mechanics energy function. The energy parameters were optimized to correctly assign as many native complexes as possible. To resolve the multiple minimum problem in parameter space, over 64000 starting parameter guesses were tried for each energy function. The optimized functions were tested by cross validation on subsets of our native and decoy structures, by blind tests on series of native and decoy structures available on the Web, and on models for 13 complexes submitted to the CAPRI structure prediction experiment.

Results

Performance is similar to several other statistical potentials of the same complexity. For example, the CAPRI target structure is correctly ranked ahead of 90% of its decoys in 6 cases out of 13. The hierarchy of amino acid alphabets leads to a coherent hierarchy of energy functions, with qualitatively similar parameters for similar amino acid types at all levels. Most remarkably, the performance with six amino acid classes is equivalent to that of the most detailed, 20-class energy function.

Conclusion

This suggests that six carefully chosen amino acid classes are sufficient to encode specificity in protein–protein interactions, and provide a starting point to develop more complicated energy functions.
3'-UTR SIRF: A database for identifying clusters of short interspersed repeats in 3' untranslated regions
Authors: Andken Benjamin B , Lim In , Benson Gary , Vincent John J , Ferenc Matthew T , Heinrich Bianca , Jarzylo Larissa A , Man Heng-Ye , Deshler James O
Published: August 2007

Background

Short (~5 nucleotides) interspersed repeats regulate several aspects of post-transcriptional gene expression. Previously we developed an algorithm (REPFIND) that assigns P-values to all repeated motifs in a given nucleic acid sequence and reliably identifies clusters of short CAC-containing motifs required for mRNA localization inXenopusoocytes.

Description

In order to facilitate the identification of genes possessing clusters of repeats that regulate post-transcriptional aspects of gene expression in mammalian genes, we used REPFIND to create a database of all repeated motifs in the 3' untranslated regions (UTR) of genes from the Mammalian Gene Collection (MGC). The MGC database includes seven vertebrate species: human, cow, rat, mouse and three non-mammalian vertebrate species. A web-based application was developed to search this database of repeated motifs to generate species-specific lists of genes containing specific classes of repeats in their 3'-UTRs. This computational tool is called 3'-UTR SIRF (ShortInterspersedRepeatFinder), and it reveals that hundreds of human genes contain an abundance of short CAC-rich and CAG-rich repeats in their 3'-UTRs that are similar to those found in mRNAs localized to the neurites of neurons. We tested four candidate mRNAs for localization in rat hippocampal neurons byin situhybridization. Our results show that two candidate CAC-rich (Syntaxin 1BandTubulin β4) and two candidate CAG-rich (Sec61αandSyntaxin 1A) mRNAs are localized to distal neurites, whereas two control mRNAs lacking repeated motifs in their 3'-UTR remain primarily in the cell body.

Conclusion

Computational data generated with 3'-UTR SIRF indicate that hundreds of mammalian genes have an abundance of short CA-containing motifs that may direct mRNA localization in neurons.In situhybridization shows that four candidate mRNAs are localized to distal neurites of cultured hippocampal neurons. These data suggest that short CA-containing motifs may be part of a widely utilized genetic code that regulates mRNA localization in vertebrate cells. The use of 3'-UTR SIRF to search for new classes of motifs that regulate other aspects of gene expression should yield important information in future studies addressingcis-regulatory information located in 3'-UTRs.
Computer-aided identification of polymorphism sets diagnostic for groups of bacterial and viral genetic variants
Authors: Price Erin P , Inman-Bamber John , Thiruvenkataswamy Venugopal , Huygens Flavia , Giffard Philip M
Published: August 2007

Background

Single nucleotide polymorphisms (SNPs) and genes that exhibit presence/absence variation have provided informative marker sets for bacterial and viral genotyping. Identification of marker sets optimised for these purposes has been based on maximal generalized discriminatory power as measured by Simpson's Index of Diversity, or on the ability to identify specific variants. Here we describe the Not-N algorithm, which is designed to identify small sets of genetic markers diagnostic for user-specified subsets of known genetic variants. The algorithm does not treat the user-specified subset and the remaining genetic variants equally. Rather Not-N analysis is designed to underpin assays that provide 0% false negatives, which is very important for e.g. diagnostic procedures for clinically significant subgroups within microbial species.

Results

The Not-N algorithm has been incorporated into the "Minimum SNPs" computer program and used to derive genetic markers diagnostic for multilocus sequence typing-defined clonal complexes, hepatitis C virus (HCV) subtypes, and phylogenetic clades defined by comparative genome hybridization (CGH) data forCampylobacter jejuni,Yersinia enterocoliticaandClostridium difficile.

Conclusion

Not-N analysis is effective for identifying small sets of genetic markers diagnostic for microbial sub-groups. The best results to date have been obtained with CGH data from several bacterial species, and HCV sequence data.
A systematic screen for genes expressed in definitive endoderm by Serial Analysis of Gene Expression (SAGE)
Authors: Hou Juan , Charters Anita M , Lee Sam C , Zhao Yongjun , Wu Mona K , Jones Steven JM , Marra Marco A , Hoodless Pamela A
Published: August 2007

Background

The embryonic definitive endoderm (DE) gives rise to organs of the gastrointestinal and respiratory tract including the liver, pancreas and epithelia of the lung and colon. Understanding how DE progenitor cells generate these tissues is critical to understanding the cause of visceral organ disorders and cancers, and will ultimately lead to novel therapies including tissue and organ regeneration. However, investigation into the molecular mechanisms of DE differentiation has been hindered by the lack of early DE-specific markers.

Results

We describe the identification of novel as well as known genes that are expressed in DE using Serial Analysis of Gene Expression (SAGE). We generated and analyzed three longSAGE libraries from early DE of murine embryos: early whole definitive endoderm (0–6 somite stage), foregut (8–12 somite stage), and hindgut (8–12 somite stage). A list of candidate genes enriched for expression in endoderm was compiled through comparisons within these three endoderm libraries and against 133 mouse longSAGE libraries generated by the Mouse Atlas of Gene Expression Project encompassing multiple embryonic tissues and stages. Using whole mountin situhybridization, we confirmed that 22/32 (69%) genes showed previously uncharacterized expression in the DE. Importantly, two genes identified,Pyyand5730521E12Rik, showed exclusive DE expression at early stages of endoderm patterning.

Conclusion

The high efficiency of this endoderm screen indicates that our approach can be successfully used to analyze and validate the vast amount of data obtained by the Mouse Atlas of Gene Expression Project. Importantly, these novel early endoderm-expressing genes will be valuable for further investigation into the molecular mechanisms that regulate endoderm development.
Phenoxodiol protects against Cisplatin induced neurite toxicity in a PC-12 cell model
Authors: Klein Reuben , Brown David , Turnley Ann M
Published: August 2007

Background

Many commonly used chemotherapeutic agents, such as Cisplatin, are restricted in their potential anti-neoplastic effectiveness by their side effects, with one of the most problematic being induction of peripheral neuropathy. Although a number of different neurotrophic, neuroprotective or anti-oxidant treatments have been tried in order to prevent or treat the neuropathies, to date they have met with limited success. Phenoxodiol is a new chemotherapeutic agent that has anti-proliferative and apoptotic effects on a range of cancer cells. PC12 cells are a commonly used neuronal cell model for examination of neurite outgrowth. In this study we examined whether phenoxodiol could protect against Cisplatin induced neurite inhibition in PC12 cells as an indication of the potential to protect against neuropathy.

Results

Using the PC12 neuronal cell line, concentrations of Cisplatin were chosen that induced moderate or strong neurite toxicity within 24 hrs but were not cytotoxic. The effect of Phenoxodiol on Cisplatin induced neurite toxicity was assessed by measurement of neurite outgrowth. Addition of phenoxodiol at 100 nM or 1 μM showed no cytotoxicity and blocked the Cisplatin induced neurite toxicity, while phenoxodiol at 10 μM was cytotoxic and enhanced neurite toxicity of Cisplatin. When Cisplatin was added for 24 hrs, then washed out and the cells allowed to recover for 48 hrs, neurite outgrowth was not restored and addition of phenoxodiol did not further promote recovery or restore the Cisplatin treated cells.

Conclusion

In addition to its potential as a chemotherapeutic agent Phenoxodiol may thus also have the potential to be used in conjunction with Cisplatin chemotherapy to prevent induction of neuropathy.
Inducible gene inactivation in neurons of the adult mouse forebrain
Authors: Erdmann Gitta , Schütz Günther , Berger Stefan
Published: August 2007

Background

The analysis of the role of genes in important brain functions like learning, memory and synaptic plasticity requires gene inactivation at the adult stage to exclude developmental effects, adaptive changes or even lethality. In order to achieve temporally controlled somatic mutagenesis, the Cre/loxP-recombination system has been complemented with the tamoxifen-inducible fusion protein consisting of Cre recombinase and the mutated ligand binding domain of the human estrogen receptor (CreERT2). To induce recombination of conditional alleles in neurons of the adult forebrain, we generated a bacterial artificial chromosome-derived transgene expressing the CreERT2 fusion protein under control of the regulatory elements of the CaMKIIα gene (CaMKCreERT2 transgene).

Results

We established three mouse lines harboring one, two and four copies of the CaMKCreERT2 transgene. The CaMKCreERT2 transgene displayed reliable and copy number-dependent expression of Cre recombinase specifically in neurons of the adult forebrain. Using Cre reporter mice we show very low background activity of the transgene in absence of the ligand and efficient induction of recombination upon tamoxifen treatment in all three lines. In addition, we demonstrate in mice harboring two conditional glucocorticoid receptor (GR) alleles and the CaMKCreERT2 transgene spatially restricted loss of GR protein expression in neurons of the adult forebrain upon tamoxifen treatment.

Conclusion

This is to our knowledge the first approach allowing highly efficient inducible gene inactivation in neurons of the adult mouse forebrain. This new approach will be a useful tool to dissect the function of specific genes in the adult forebrain. Effects of gene inactivation on pre- and postnatal brain development and compensatory mechanisms elicited by an early onset of gene inactivation can now be excluded.
Design of a randomized controlled trial on the effects of Counseling of mental health problems by Occupational Physicians on return to work: the CO-OP-study
Authors: Rebergen David S , Bruinvels David J , van der Beek Allard J , van Mechelen Willem
Published: August 2007

Background

Mental health problems often lead to prolonged sick leave. In primary care, the usual approach towards these patients was the advice to take rest and not return to work before all complaints had disappeared. When complaints persist, these patients are often referred to psychologists from primary and specialized secondary care. As an alternative, ways have been sought to activate the Dutch occupational physician (OP) in primary care. Early 2000, the Dutch Association of Occupational Physicians (NVAB) published a guideline concerning the management by OPs of employees with mental health problems. The guideline received positive reactions from employees, employers and Dutch OPs. This manuscript describes the design of a study, which aims to assess the effects of the guideline, compared with usual care.

Methods/Design

In a randomized controlled trial (RCT), subjects in the intervention group were treated according to the guideline. The control group received usual care, with minimal involvement of the OP and easy access to a psychologist. Subjects were recruited from two Dutch police departments. The primary outcomes of the study are return to work and treatment satisfaction by the employee, employer, and OP. A secondary outcome is cost-effectiveness of the intervention, compared with usual care. Furthermore, prognostic measures are taken into account as potential confounders. A process evaluation will be done by means of performance indicators, based on the guideline.

Discussion

In this pragmatic trial, effectiveness instead of efficacy is studied. We will evaluate what is possible in real clinical practice, rather than under ideal circumstances. Many requirements for a high quality trial are being met. Results of this study will contribute to treatment options in occupational health practice for employees on sick leave due to mental health problems. Additionally, they may contribute to new and better-suited guidelines and stepped care. Results will become available during 2007.

Trial registration

Current Controlled Trials ISRCTN34887348
Evidence based practice in postgraduate healthcare education: A systematic review
Authors: Flores-Mateo Gemma , Argimon Josep M
Published: August 2007

Background

Training in Evidence-Based Practice (EBP) has been widely implemented throughout medical school and residency curricula. The aim of this study is to systematically review studies that assessed the effectiveness of EBP teaching to improve knowledge, skills, attitudes and behavior of postgraduate healthcare workers, and to describe instruments available to evaluate EBP teaching.

Methods

The design is a systematic review of randomized, non-randomized, and before-after studies. The data sources were MEDLINE, Cochrane Library, EMBASE, CINAHL and ERIC between 1966 and 2006. Main outcomes were knowledge, skills, attitudes and behavior towards EBP. Standardized effect sizes (E-S) were calculated. The E-S was categorized as small (E-S < 0.2), small to moderate (E-S between 0.2 and 0.5), moderate to large (E-S between 0.51 and 0.79), large (E-S > 0.79). Reliability and validity of instruments for evaluating education were assessed. Studies excluded were those that were not original, performed in medical students, focused on prescribing practices, specific health problems, theoretical reviews of different components of EBP, continuing medical education, and testing the effectiveness of implementing guidelines.

Results

Twenty-four studies met our inclusion criteria. There were 15 outcomes within the 10 studies for which E-S could be calculated. The E-S ranged from 0.27 (95%CI: -0.05 to 0.59) to 1.32 (95%CI: 1.11 to 1.53). Studies assessing skills, behavior and/or attitudes had a "small to moderate" E-S. Only 1 of the 2 studies assessing knowledge had E-S of 0.57 (95 CI: 0.32 to 0.82) and 2 of the 4 studies that assessed total test score outcomes had "large" E-S. There were 22 instruments used, but only 10 had 2 or more types of validity or reliability evidence.

Conclusion

Small improvements in knowledge, skills, attitudes or behavior are noted when measured alone. A large improvement in skills and knowledge in EBP is noted when measured together in a total test score. Very few studies used validated measures tests.
Health equity issues at the local level: Socio-geography, access, and health outcomes in the service area of the Hôpital Albert Schweitzer-Haiti
Authors: Perry Henry B , King-Schultz Leslie W , Aftab Asma S , Bryant John H
Published: August 2007

Background

Although health equity issues at regional, national and international levels are receiving increasing attention, health equity issues at the local level have been virtually overlooked. Here, we describe here a comprehensive equity assessment carried out by the Hôpital Albert Schweitzer-Haiti (HAS) in 2003. HAS has been operating health and development programs in the Artibonite Valley of Haiti for 50 years.

Methods

We reviewed all available information arising from a comprehensive evaluation of the programs of HAS carried out in 1999 and 2000. As part of this evaluation, two demographic and health surveys were carried out. We carried out exit interviews with clients receiving primary health care, observations within health facilities, interviews with households related to quality of care, and focus group discussions with community-based health workers. A special study was carried out in 2003 to assess factors determining the use of prenatal care services. Finally, selected findings were obtained from the HAS information system.

Results

We found markedly reduced access to health services in the peripheral mountainous areas compared to the central plains. The quality of services was more deficient and the coverage of key services was lower in the mountains. Finally, health status, as measured by under-five mortality rates and levels of childhood malnutrition, was also worse in the mountains.

Conclusion

These findings indicate that local health programs need to give attention to monitoring the health status as well as the quality and coverage of basic services among marginalized groups within the program service area. Health inequities will not be overcome until such monitoring occurs and leaders of health programs ensure that inequities identified are addressed in the local programming of activities. It is quite likely that, within relatively small geographic areas in resource-poor settings around the world, similar, if not even greater, levels of health inequities exist. These inequities need to be measured and addressed in order for health programs to achieve equity and maximum improvement in health status within the population.
Major HGF-mediated regenerative pathways are similarly affected in human and canine cirrhosis
Authors: Spee Bart , Arends Brigitte , van den Ingh Ted SGAM , Roskams Tania , Rothuizen Jan , Penning Louis C
Published: August 2007

Background

The availability of non-rodent animal models for human cirrhosis is limited. We investigated whether privately-owned dogs (Canis familiaris) are potential model animals for liver disease focusing on regenerative pathways. Several forms of canine hepatitis were examined: Acute Hepatitis (AH), Chronic Hepatitis (CH), Lobular Dissecting Hepatitis (LDH, a specific form of micronodulair cirrhosis), and Cirrhosis (CIRR). Canine cirrhotic samples were compared to human liver samples from cirrhotic stages of alcoholic liver disease (hALC) and chronic hepatitis C infection (hHC).

Results

Canine specific mRNA expression of the regenerative hepatocyte growth factor (HGF) signaling pathway and relevant down-stream pathways were measured by semi-quantitative PCR and Western blot (STAT3, PKB, ERK1/2, and p38-MAPK). In all canine groups, levels of c-MET mRNA (proto-oncogenic receptor for HGF) were significantly decreased (p < 0.05). Surprisingly, ERK1/2 and p38-MAPK were increased in CH and LDH. In the human liver samples Western blotting indicated a high homology of down-stream pathways between different etiologies (hALC and hHC). Similarly activated pathways were found in CIRR, hALC, and hHC.

Conclusion

In canine hepatitis and cirrhosis the major regenerative downstream pathways were activated. Signaling pathways are similarly activated in human cirrhotic liver samples, irrespective of the differences in etiology in the human samples (alcohol abuse and HCV-infection). Therefore, canine hepatitis and cirrhosis could be an important clinical model to evaluate novel interventions prior to human clinical trials.
Differential mortality in Iran
Authors: Khosravi Ardeshir , Taylor Richard , Naghavi Mohsen , Lopez Alan D
Published: August 2007

Background

Among the available data provided by health information systems, data on mortality are commonly used not only as health indicators but also as socioeconomic development indices. Recognizing that in Iran accurate data on causes of death were not available, the Deputy of Health in the Ministry of Health and Medical Education (MOH&ME) established a new comprehensive system for death registration which started in one province (Bushehr) as a pilot in 1997, and was subsequently expanded to include all other provinces, except Tehran province. These data can be used to investigate the nature and extent of differences in mortality in Iran. The objective of this paper is to estimate provincial differences in the level of mortality using this death registration system.

Methods

Data from the death registration system for 2004 for each province were evaluated for data completeness, and life tables were created for provinces after correction for under-enumeration of death registration. For those provinces where it was not possible to adjust the data on adult deaths by using the Brass Growth Balance method, adult mortality was predicted based on adult literacy using information from provinces with reliable data.

Results

Child mortality (risk of a newborn dying before age 5, or 5q0) in 2004 varied between 47 per 1000 live births for both sexes in Sistan and Baluchistan province, and 25 per 1000 live births in Tehran and Gilan provinces. For adults, provincial differences in mortality were much greater for males than females. Adult mortality (risk of dying between ages 15 and 60, or 45q15) for females varied between 0.133 in Kerman province and 0.117 in Tehran province; for males the range was from 0.218 in Kerman to 0.149 in Tehran province. Life expectancy for females was highest in Tehran province (73.8 years) and lowest in Sistan and Baluchistan (70.9 years). For males, life expectancy ranged from 65.7 years in Sistan and Baluchistan province to 70.9 years in Tehran.

Conclusion

Substantial differences in survival exist among the provinces of Iran. While the completeness of the death registration system operated by the Iranian MOH&ME appears to be acceptable in the majority of provinces, further efforts are needed to improve the quality of data on mortality in Iran, and to expand death registration to Tehran province.
Analysis of the cellular centrosome in fine-needle aspirations of the breast
Authors: Guo Hui-qin , Gao Meixia , Ma Jinfang , Xiao Ting , Zhao Lin-lin , Gao Yanning , Pan Qin-jing
Published: August 2007

Background

The purpose of the present investigation is to determine whether centrosome amplifications are present in breast tumor cells, whether there are differences of centrosome amplification between benign breast lesions and breast carcinomas, and whether centrosomal analysis can be of value in the diagnosis and prognosis of breast carcinoma.

Methods

Using immunofluorescence analysis with an antibody against γ-tubulin, we analyzed centrosome abnormalities in fine-needle aspirations of 100 breast lesions (25 cases with benign lesions and 75 cases with carcinomas).

Results

We found that centrosome amplifications, including numerical centrosome amplification and structural centrosome amplification, were present in most breast tumors. Cells with numerical centrosome amplification were found in 23 of 25 benign lesions, and in all 75 cases of breast carcinomas. Cells with structural centrosome amplification were found in three of 25 benign lesions, and in 69 of 75 breast carcinomas. The breast carcinomas showed a mean percentage of cells with numerical centrosome amplification of 4.86% and a mean percentage of cells with structural centrosome amplification of 3.98%. These percentages were significantly higher than those in benign lesions, with a numerical centrosome amplification of 2.77% and a structural centrosome amplification of 0.10%. Furthermore, the mean percentage of cells with structural centrosome amplification was significantly associated with HER2/neu overexpression (P < 0.05) and with negative estrogen receptor status (P < 0.05), and had a borderline association with negative progesterone receptor status (P = 0.056) in breast carcinomas.

Conclusion

Structural centrosome amplification may bear a close relationship with breast carcinoma and may be a potential biomarker for diagnosis and prognosis of breast carcinoma.
Quantifying the major mechanisms of recent gene duplications in the human and mouse genomes: a novel strategy to estimate gene duplication rates
Authors: Pan Deng , Zhang Liqing
Published: August 2007

Background

The rate of gene duplication is an important parameter in the study of evolution, but the influence of gene conversion and technical problems have confounded previous attempts to provide a satisfying estimate. We propose a new strategy to estimate the rate that involves separate quantification of the rates of two different mechanisms of gene duplication and subsequent combination of the two rates, based on their respective contributions to the overall gene duplication rate.

Results

Previous estimates of gene duplication rates are based on small gene families. Therefore, to assess the applicability of this to families of all sizes, we looked at both two-copy gene families and the entire genome. We studied unequal crossover and retrotransposition, and found that these mechanisms of gene duplication are largely independent and account for a substantial amount of duplicated genes. Unequal crossover contributed more to duplications in the entire genome than retrotransposition did, but this contribution was significantly less in two-copy gene families, and duplicated genes arising from this mechanism are more likely to be retained. Combining rates of duplication using the two mechanisms, we estimated the overall rates to be from approximately 0.515 to 1.49 × 10-3 per gene per million years in human, and from approximately 1.23 to 4.23 × 10-3 in mouse. The rates estimated from two-copy gene families are always lower than those from the entire genome, and so it is not appropriate to use small families to estimate the rate for the entire genome.

Conclusion

We present a novel strategy for estimating gene duplication rates. Our results show that different mechanisms contribute differently to the evolution of small and large gene families.
Differences in neurogenic potential in floor plate cells along an anteroposterior location: midbrain dopaminergic neurons originate from mesencephalic floor plate cells
Authors: Ono Yuichi , Nakatani Tomoya , Sakamoto Yoshimasa , Mizuhara Eri , Minaki Yasuko , Kumai Minoru , Hamaguchi Akiko , Nishimura Miyuki , Inoue Yoko , Hayashi Hideki , Takahashi Jun , Imai Toshio
Published: August 2007

Directed differentiation and purification of mesencephalic dopaminergic(mesDA) neurons from stem cells are crucial issues for realizing safe and efficient cell transplantation therapies for Parkinson's disease. Although recent studies have identified the factors that regulate mesDA neuron development, the mechanisms underlying mesDA neuron specification are not fully understood. Recently, it has been suggested that mesencephalic floor plate (FP) cells acquire neural progenitor characteristics to generate mesDA neurons. Here, we directly examined this in a fate mapping experiment using fluorescence-activated cell sorting (FACS) with an FP cell-specific surface marker, and demonstrate that mesencephalic FP cells have neurogenic activity and generate mesDA neurons in vitro. By contrast, sorted caudal FP cells have no neurogenic potential, as previously thought. Analysis of dreher mutant mice carrying a mutation in the Lmx1a locus and transgenic mice ectopically expressing Otx2 in caudal FP cells demonstrated that Otx2 determines anterior identity that confers neurogenic activity to FP cells and specifies a mesDA fate, at least in part through the induction of Lmx1a. We further show that FACS can isolate mesDA progenitors, a suitable transplantation material, from embryonic stem cell-derived neural cells. Our data provide insights into the mechanisms of specification and generation of mesDA neurons, and illustrate a useful cell replacement approach for Parkinson's disease.
Genitourinary medicine clinic KC60 coding for first episode genital herpes: a lesson from north of the border?
Authors: Challenor R , Theobald N , Pinsent S , Mullan H ,   Genitourinary Medicine Non-Consultant Career Grade Group of the British Association for Sexual Health and HIV
Published: August 2007

A survey of the accuracy of applying the KC60 diagnostic code for genital herpes: first attack (C10A) was undertaken by non-consultant career-grade doctors working in genitourinary (GU) medicine in England, Wales and Northern Ireland. In total, 148 forms were returned (58% response). Overall, 88/148, 59.5% (95% confidence interval 51.5–67.4%) applied the correct codes for all the clinical scenarios presented. Of doctors who personally assigned codes to clinical episodes, 57/104 (54.8%), were correct compared with 31/44 (70.5%) who did not personally apply codes. There was no difference between these two groups ( P=0.08). The main error was assigning code C10A on clinical grounds only when there was no laboratory confirmation of herpes simplex virus. The authors suggest that the KC60 C10A code for first attack genital herpes should be simplified to accept a clinical diagnosis rather than insisting on viral confirmation. Alternatively, consideration could also be given to adopting a more comprehensive system (such as the Scottish example) for first attack genital herpes. We believe that either option would help improve the accuracy of GU clinic data relating to genital herpes.
Genetic analysis of the E site during RF2 programmed frameshifting
Authors: Sanders Christina L. , Curran James F.
Published: July 2007

The roles of the ribosomal E site are not fully understood. Prior evidence suggests that deacyl-tRNA in the E site can prevent frameshifting. We hypothesized that if the E-site codon must dissociate from its tRNA to allow for frameshifting, then weak codon:anticodon duplexes should allow for greater frameshifting than stronger duplexes. Using the well-characterized Escherichia coli RF2 (prfB) programmed frameshift to study frameshifting, we mutagenized the E-site triplet to all Unn and Cnn codons. Those variants should represent a very wide range of duplex stability. Duplex stability was estimated using two different methods. Frameshifting is inversely correlated with stability, as estimated by either method. These findings indicate that pairing between the deacyl-tRNA and the E-site codon opposes frameshifting. We discuss the implications of these findings on frame maintenance and on the RF2 programmed frameshift mechanism.
Position of the acetabular component determines the fate of femoral head autografts in total hip replacement for acetabular dysplasia
Authors: Atilla B. , Ali H. , Aksoy M. C. , Caglar O. , Tokgozoglu A. M. , Alpaslan M.
Published: August 2007

We have reviewed 54 patients who had undergone 61 total hip replacements using bulk femoral autografts to augment a congenitally dysplastic acetabulum. There were 52 women and two men with a mean age of 42.4 years (29 to 76) at the time of the index operation. A variety of different prostheses was used: 28 (45.9%) were cemented and 33 (54.1%) uncemented. The graft technique remained unchanged throughout the series.

Follow-up was at a mean of 8.3 years (3 to 20). The Hospital for Special Surgery hip score improved from a mean of 10.7 (4 to 18) pre-operatively to a mean of 35 (28 to 38) at follow-up.

The position of the acetabular component was anatomical in 37 hips (60.7%), displaced less than 1 cm in 20 (32.7%) and displaced more than 1 cm in four (6.6%). Its cover was between 50% and 75% in 34 hips (55.7%) and less than 50% in 25 (41%). In two cases (3.3%), it was more than 75%.

There was no graft resorption in 36 hips (59%), mild resorption in 21 (34%) and severe resorption in four (6%).

Six hips (9.8%) were revised for aseptic loosening. The overall rate of loosening and revision was 14.8%. Overall survival at 8.3 years was 93.4%.

The only significant factor which predicted failure was the implantation of the acetabular component more than 1 cm from the anatomical centre of rotation of the hip.
The relationship of the angle of immobilisation of the knee to the force applied to the extensor mechanism when partially weight-bearing
Authors: Khan W. S. , Nokes L. , Jones R. K. , Johnson D. S.
Published: August 2007

We describe the influence of the angle of immobilisation during partial weight-bearing on the forces across the extensor mechanism of the knee. Gait analysis was performed on eight healthy male subjects with the right knee in an orthotic brace locked at 0°, 10°, 20° and 30°, with the brace unlocked and also without a brace. The ground reaction force, the angle of the knee and the net external flexion movement about the knee were measured and the extensor mechanism force was calculated.

The results showed a direct non-linear relationship between the angle of knee flexion and the extensor mechanism force. When a brace was applied, the lowest forces occurred when the brace was locked at 0°. At 30° the forces approached the failure strength of some fixation devices. We recommend that for potentially unstable injuries of the extensor mechanism, when mobilising with partial weight-bearing, the knee should be flexed at no more than 10°.
Genetic influences in the aetiology of anteromedial osteoarthritis of the knee
Authors: McDonnell S. M. , Sinsheimer J. , Price A. J. , Carr A. J.
Published: August 2007

We report a study of 112 patients with primary anteromedial osteoarthritis of the knee and their families. Sibling risk was determined using randomly selected single siblings. Spouses were used as controls. The presence of symptomatic osteoarthritis was determined using an Oxford knee score of ≥ 29 supported by a Kellgren and Lawrence radiological score of II or greater.

Using Fisher’s exact test we found that there was a significant increased risk of anteromedial osteoarthritis (OA) relative to the control group (p = 0.031). The recurrence risk of anteromedial OA to siblings was 3.21 (95% confidence interval 1.12 to 9.27).

These findings imply that genetic factors may play a major role in the development of anteromedial OA of the knee.
Reinforcement sensitivity of sex offenders and non‐offenders: An experimental and psychometric study of reinforcement sensitivity theory
Authors: Leue Anja , Brocke Burkhard , Hoyer Jürgen
Published: July 2007

This study tested predictions of Gray's Reinforcement Sensitivity Theory (RST) in subgroups of sex offenders and male non‐offenders using an experimental choice task consisting of a reward and a non‐reward phase. In addition, RST‐related psychometric measures were used. Both experimental and psychometric data were of interest to determine whether sex offenders could be reliably differentiated from non‐offenders. Paraphilic (N=50) and impulse control‐disordered (N=48) sex offenders showed greater sensitivity to continuous reward than male non‐offenders (N=51). Impulse control‐disordered sex offenders showed less behavioural adaptation under non‐reward than both paraphilic sex offenders and male non‐offenders. In addition, reward sensitivity, rash‐spontaneous impulsivity, and anxiety measures discriminated sex offenders from male non‐offenders. The results suggest that reinforcement sensitivity is a promising personality trait for differentiating subgroups of sex offenders from non‐offenders. The experimental and psychometric results illustrate that predictive accuracy in forensic settings could be improved by combining several types of data.
Certification of Creatinine in a Human Serum Reference Material by GC-MS and LC-MS
Authors: Dodder Nathan G , Tai Susan S-C , Sniegoski Lorna T , Zhang Nien F , Welch Michael J
Published: July 2007

Background: To meet recommendations given by the Laboratory Working Group of the National Kidney Disease Education Program for improving serum creatinine measurements, NIST developed standard reference material (SRM) 967 Creatinine in Frozen Human Serum. SRM 967 is intended for use by laboratories and in vitro diagnostic equipment manufacturers for the calibration and evaluation of routine clinical methods.

Methods: The SRM was produced from 2 serum pools with different creatinine concentrations. The concentrations were certified using a higher-order isotope-dilution GC-MS method and an isotope-dilution LC-MS method. The LC-MS method is a potential higher-order reference measurement procedure.

Results: The GC-MS mean (CV) concentrations were 67.0 (0.9%) μmol/L for serum pool 1 and 346.1 (0.45%) μmol/L for serum pool 2. The LC-MS results were 66.1 (0.2%) μmol/L and 346.3 (0.2%) μmol/L, respectively. For serum pool 1, there was a 1.4% difference between the mean GC-MS and LC-MS measurements, and a 0.10% difference for serum pool 2. The results from the 2 methods were combined to give the certified concentrations and expanded uncertainties.

Conclusions: The certified concentration (expanded uncertainty) of SRM 967 was 66.5 (1.8) μmol/L for serum pool 1 (a value close to the diagnostically important concentration of 88.4 μmol/L) and 346.2 (7.4) μmol/L for serum pool 2 (a concentration corresponding to that expected in a patient with chronic kidney disease).
Corrosion resistance of thermally sprayed high-boron iron-based amorphous-metal coatings: Fe49.7Cr17.7Mn1.9Mo7.4W1.6B15.2C3.8Si2.4
Authors: Farmer J.C. , Haslam J.J. , Day S.D. , Lian T. , Saw C.K. , Hailey P.D. , Choi J-S. , Rebak R.B. , Yang N. , Payer J.H. , Perepezko J.H. , Hildal K. , Lavernia E.J. , Ajdelsztajn L. , Branagan D.J. , Buffa E.J. , Aprigliano L.F.
Published: August 2007

An iron-based amorphous metal, Fe49.7Cr17.7Mn1.9Mo7.4W1.6B15.2C3.8Si2.4 (SAM2X5), with very good corrosion resistance has been developed. This material was prepared as a melt-spun ribbon, as well as gas atomized powder and a thermal-spray coating. During electrochemical testing in several environments, including seawater at 90 °C, the passive film stability was found to be comparable to that of high-performance nickel-based alloys and superior to that of stainless steels, based on electrochemical measurements of the passive film breakdown potential and general corrosion rates. This material also performed very well in standard salt fog tests. Chromium (Cr), molybdenum (Mo), and tungsten (W) provided corrosion resistance, and boron (B) enabled glass formation. The high boron content of this particular amorphous metal made it an effective neutron absorber and suitable for criticality control applications. This material and its parent alloy maintained corrosion resistance up to the glass transition temperature and remained in the amorphous state during exposure to relatively high neutron doses.
Use of Piecewise Nonlinear Models to Estimate Variable Size-Related Mortality Rates
Authors: Maceina Michael J.
Published: August 2007

I present a method and examples of a piecewise function in nonlinear regression to estimate size-related differential mortality using age- and length-based models for data collected from a Tennessee River (Alabama) population of blue catfish Ictalurus furcatus. The model is similar to catch curve regression but computes two slope coefficients that can be used to estimate mortality; these slopes meet at a joint (or knot) that estimates the age or length at which differences in mortality occur. The model is described as loge(Ni) = b0 − (b1 + b2)ti, where Ni is the number of fish collected for the ith age or length interval; ti is the age or relative age of the ith age or length interval; b0 is the intercept coefficient; b1 is the slope coefficient and is equal to b*1 when ti is less than or equal to the knot and 0 otherwise; b2 is a second slope coefficient and is equal to b*1 − b*2 when ti is greater than the knot and 0 otherwise; and b*1 and b*2 are estimated by the model. For these data, fish ranged in age from 3 to 25 years and ranged in total length (TL) from 301 to 1,291 mm. With this piecewise nonlinear approach, the fit between age or length and loge(Ni) improved over that determined with linear catch curves. For both age- and length-based structure data, annual mortality for small blue catfish ranged from 0.41 to 0.49 for younger and smaller fish (age ≤ 10 years; TL ≤ 684 mm). For larger, older fish (age = 11–25 years; TL > 685 mm), annual mortality estimates ranged from 0.08 to 0.16. Observations of the fishery indicated that anglers harvested smaller blue catfish (<562 mm TL); harvest of larger fish was nil, which probably accounted for the size-related differences in mortality. I provide a computer program to derive estimates of size-related mortality using piecewise nonlinear regression.
Effect of Relative Volume on Radio Transmitter Expulsion in Subadult Common Carp
Authors: Penne Christopher R. , Ahrens Nicholas L. , Summerfelt Robert C. , Pierce Clay L.
Published: August 2007

Expulsion of surgically implanted radio transmitters is a problem in some fish telemetry studies. We conducted a 109-d experiment to test the hypothesis that variation in relative volume of transmitters surgically implanted in subadult common carp Cyprinus carpio would affect transmitter expulsion. We also necropsied fish at the end of the experiment to evaluate histological evidence for the mechanism of expulsion. Survival rate was high during our experiment; all control fish and 88% of the fish subjected to the implantation surgery survived. Expulsion rate was low; of the 23 fish that received transmitters and survived the experiment, only two (9%) expelled the transmitters. One of these expulsions occurred through a rupture of the incision and the other occurred via the intestine. Retained transmitters were all encapsulated by tissue, and most exhibited multiple adhesions to the intestine, gonads, and body wall. Adhesions were more numerous in fish that received larger transmitters.
Linking Adult Reproduction and Larval Density of Invasive Carp in a Large River
Authors: DeGrandchamp Kelly L. , Garvey James E. , Csoboth Laura A.
Published: August 2007

Identifying how temporal variation in the environment affects reproductive success of invasive alien species will aid in predicting future establishment and tracking dynamics of established populations. Asian carp Hypophthalmichthys spp. have become a nuisance in recent years in the Mississippi River basin. Their populations are apparently expanding, indicating favorable conditions for reproduction. During 2004 and 2005, we quantified mean density of Asian carp larvae, mean monthly gonadosomatic index (GSI) of adult males and females, and number of eggs within mature females in the lower Illinois River, a major tributary of the Mississippi River. A flood (water velocity ≥ 0.7 m/s) and drought (<0.2 m/s) occurred during apparent spawning in 2004 and 2005, respectively. During 2004, Asian carp larvae were found during 32% of sampling weeks; mean GSI and fecundity were relatively low for adults, probably reflecting partially spawned individuals and perhaps low reproductive investment. During the drought of 2005, larval stages were present during only one (5%) of the sampling weeks, whereas mean GSI and fecundity of adults were high through summer. Females resorbed their eggs instead of spawning during this year. Spawning conditions during low water periods appear to be unsuitable for Asian carps, inhibiting adult spawning and yielding few larvae. Spawning conditions during 2004 were better but still yielded low densities of larvae relative to native fishes. Reproduction in the lower Illinois River appears to be linked to river flow and its impact on adult spawning decisions, but conditions for strong year‐class production (i.e., high larval densities) may be rarer than previously expected.
Some Aspects of the Endocrine Profile and Management of Hormone-Dependent Male Breast Cancer
Authors: Dimitrov Nikolay V. , Colucci Philomena , Nagpal Sunil
Published: August 2007

Learning Objectives

After completing this course, the reader will be able to: Identify some differences in the endocrine profiles of male and female breast cancer patients.Describe the importance of the endocrine profile in the management of male breast cancer.Assess different points of the endocrine profile for tailoring individual therapy.

CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Nitrous Oxide Fluxes from Cultivated Areas and Rangeland: U.S. High Plains
Authors: Weeks Edwin P. , McMahon Peter B.
Published: August 2007

Concentration profiles of N2O, a greenhouse gas, and the conservative trace gases SF6 and the chlorofluorocarbons CFC‐11, CFC‐12, CFC‐113, and were measured periodically through thick vadose zones at nine sites in the U.S. High Plains. The CFC and SF6 measurements were used to calibrate a one‐dimensional gas diffusion model, using the parameter identification program UCODE. The calibrated model was used with N2O measurements to estimate average annual N2O flux from both the root zone and the deep vadose zone to the atmosphere. Estimates of root‐zone N2O fluxes from three rangeland sites ranged from near 0 to about 0.2 kg N2O‐N ha−1 yr−1, values near the low end of the ranges determined for native grass from other studies. Estimates of root‐zone N2O fluxes from two fields planted to corn (Zea mays L.) of about 2 to 6 kg N2O‐N ha−1 yr−1 are similar to those determined for corn in other studies. Estimates of N2O flux from Conservation Reserve grassland converted from irrigated corn indicate that production of N2O is substantially reduced following conversion from cropland. Small N2O fluxes from the water table or from deep in the vadose zone occurred at three sites, ranging from 0.004 to 0.02 kg N2O‐N ha−1 yr−1. Our estimates of N2O flux represent space‐ and time‐averaged values that should be useful to more fully evaluate the significance of instantaneous point flux measurements.