bluuebunny/crossref_metadata_2025 huggingface dataset:
Microarray analysis of Shigella flexneri-infected epithelial cells identifies host factors important for apoptosis inhibition
Authors: Faherty Christina S , Merrell D Scott , Semino-Mora Cristina , Dubois Andre , Ramaswamy Aishwarya V , Maurelli Anthony T
Published: April 2010

Background

Shigella flexneri inhibits apoptosis in infected epithelial cells. In order to understand the pro-survival effects induced by the bacteria, we utilized apoptosis-specific microarrays to analyze the changes in eukaryotic gene expression in both infected and uninfected cells in the presence and absence of staurosporine, a chemical inducer of the intrinsic pathway of apoptosis. The goal of this research was to identify host factors that contribute to apoptosis inhibition in infected cells.

Results

The microarray analysis revealed distinct expression profiles in uninfected and infected cells, and these changes were altered in the presence of staurosporine. These profiles allowed us to make comparisons between the treatment groups. Compared to uninfected cells, Shigella- infected epithelial cells, both in the presence and absence of staurosporine, showed significant induced expression of JUN, several members of the inhibitor of apoptosis gene family, nuclear factor κB and related genes, genes involving tumor protein 53 and the retinoblastoma protein, and surprisingly, genes important for the inhibition of the extrinsic pathway of apoptosis. We confirmed the microarray results for a selection of genes using in situ hybridization analysis.

Conclusion

Infection of epithelial cells with S. flexneri induces a pro-survival state in the cell that results in apoptosis inhibition in the presence and absence of staurosporine. The bacteria may target these host factors directly while some induced genes may represent downstream effects due to the presence of the bacteria. Our results indicate that the bacteria block apoptosis at multiple checkpoints along both pathways so that even if a cell fails to prevent apoptosis at an early step, Shigella will block apoptosis at the level of caspase-3. Apoptosis inhibition is most likely vital to the survival of the bacteria in vivo. Future characterization of these host factors is required to fully understand how S. flexneri inhibits apoptosis in epithelial cells.
A jackknife-like method for classification and uncertainty assessment of multi-category tumor samples using gene expression information
Authors: Zhang Wensheng , Robbins Kelly , Wang Yupeng , Bertrand Keith , Rekaya Romdhane
Published: April 2010

Background

The use of gene expression profiling for the classification of human cancer tumors has been widely investigated. Previous studies were successful in distinguishing several tumor types in binary problems. As there are over a hundred types of cancers, and potentially even more subtypes, it is essential to develop multi-category methodologies for molecular classification for any meaningful practical application.

Results

A jackknife-based supervised learning method called paired-samples test algorithm (PST), coupled with a binary classification model based on linear regression, was proposed and applied to two well known and challenging datasets consisting of 14 (GCM dataset) and 9 (NC160 dataset) tumor types. The results showed that the proposed method improved the prediction accuracy of the test samples for the GCM dataset, especially when t-statistic was used in the primary feature selection. For the NCI60 dataset, the application of PST improved prediction accuracy when the numbers of used genes were relatively small (100 or 200). These improvements made the binary classification method more robust to the gene selection mechanism and the size of genes to be used. The overall prediction accuracies were competitive in comparison to the most accurate results obtained by several previous studies on the same datasets and with other methods. Furthermore, the relative confidence R(T) provided a unique insight into the sources of the uncertainty shown in the statistical classification and the potential variants within the same tumor type.

Conclusion

We proposed a novel bagging method for the classification and uncertainty assessment of multi-category tumor samples using gene expression information. The strengths were demonstrated in the application to two bench datasets.
Salmo salar and Esox lucius full-length cDNA sequences reveal changes in evolutionary pressures on a post-tetraploidization genome
Authors: Leong Jong S , Jantzen Stuart G , von Schalburg Kristian R , Cooper Glenn A , Messmer Amber M , Liao Nancy Y , Munro Sarah , Moore Richard , Holt Robert A , Jones Steven JM , Davidson William S , Koop Ben F
Published: April 2010

Background

Salmonids are one of the most intensely studied fish, in part due to their economic and environmental importance, and in part due to a recent whole genome duplication in the common ancestor of salmonids. This duplication greatly impacts species diversification, functional specialization, and adaptation. Extensive new genomic resources have recently become available for Atlantic salmon (Salmo salar), but documentation of allelic versus duplicate reference genes remains a major uncertainty in the complete characterization of its genome and its evolution.

Results

From existing expressed sequence tag (EST) resources and three new full-length cDNA libraries, 9,057 reference quality full-length gene insert clones were identified for Atlantic salmon. A further 1,365 reference full-length clones were annotated from 29,221 northern pike (Esox lucius) ESTs. Pairwise dN/dS comparisons within each of 408 sets of duplicated salmon genes using northern pike as a diploid out-group show asymmetric relaxation of selection on salmon duplicates.

Conclusions

9,057 full-length reference genes were characterized in S. salar and can be used to identify alleles and gene family members. Comparisons of duplicated genes show that while purifying selection is the predominant force acting on both duplicates, consistent with retention of functionality in both copies, some relaxation of pressure on gene duplicates can be identified. In addition, there is evidence that evolution has acted asymmetrically on paralogs, allowing one of the pair to diverge at a faster rate.
Using epitope predictions to evaluate efficacy and population coverage of the Mtb72f vaccine for tuberculosis
Authors: McNamara Lucy A , He Yongqun , Yang Zhenhua
Published: April 2010

Background

The Mtb72f subunit vaccine for tuberculosis, currently in clinical trials, is hoped to provide improved protection compared to the current BCG vaccine. It is not clear, however, whether Mtb72f would be equally protective in the different human populations suffering from a high burden of tuberculosis. Previous work by Hebert and colleagues demonstrated that the PPE18 protein of Mtb72f had significant variability in a sample of clinical M. tuberculosis isolates. However, whether this variation might impact the efficacy of Mtb72f in the context of the microbial and host immune system interactions remained to be determined. The present study assesses Mtb72f's predicted efficacy in people with different DRB1 genotypes to predict whether the vaccine will protect against diverse clinical strains of M. tuberculosis in a diverse host population.

Results

We evaluated the binding of epitopes in the vaccine to different alleles of the human DRB1 Class II MHC protein using freely available epitope prediction programs and compared protein sequences from clinical isolates to the sequences included in the Mtb72f vaccine. This analysis predicted that the Mtb72f vaccine would be less effective for several DRB1 genotypes, due either to limited vaccine epitope binding to the DRB1 proteins or to binding primarily by unconserved PPE18 epitopes. Furthermore, we found that these less-protective DRB1 alleles are found at a very high frequency in several populations with a high burden of tuberculosis.

Conclusion

Although the Mtb72f vaccine candidate has shown promise in animal and clinical trials thus far, it may not be optimally effective in some genotypic backgrounds. Due to variation in both M. tuberculosis protein sequences and epitope-binding capabilities of different HLA alleles, certain human populations with a high burden of tuberculosis may not be optimally protected by the Mtb72f vaccine. The efficacy of the Mtb72f vaccine should be further examined in these particular populations to determine whether additional protective measures might be necessary for these regions.
Mental health in the aged: prevalence, covariates and related neuroendocrine, cardiovascular and inflammatory factors of successful aging
Authors: Lacruz Maria E , Emeny Rebecca T , Bickel Horst , Cramer Barbara , Kurz Alexander , Bidlingmaier Martin , Huber Dorothea , Klug Günther , Peters Annette , Ladwig Karl H
Published: April 2010

Background

Although aging is accompanied by diminished functioning, many elderly individuals preserve a sense of well-being. While the concept of "successful aging" has been popular for many decades, little is known about its psycho-physiologic and endocrine underpinnings. KORA-Age is a population-based, longitudinal study designed to determine the prevalence of successfully aged men and women between 65 and 94 years old in the MONICA/KORA Augsburg cohort of randomly selected inhabitants. Specifically, we aim to identify predictors of successful aging and to elucidate bio-psychosocial mechanisms that maintain mental health and successful adaptation despite adverse experiences of life and aging.

Methods/Design

Components of successful aging were assessed in a telephone survey of 4,127 participants (2008-2009) enrolled in the MONICA/KORA cohort, on average, 13 years earlier. Psychosocial, somatic and behavioural predictors are used to determine factors that contribute to successful aging. An age-stratified random sub-sample (n = 1,079) participated in a personal interview where further psychological mechanisms that may underlie successful adaptation (resilience, social support, attachment) were examined. The interactions among neuroendocrine systems in the aging process are investigated by studying the cortisol/dehydroepiandrosterone-sulfate ratio, the level of insulin-like growth factor I, and oxytocin.

Discussion

Longitudinal determinants of successful aging can be assessed based on a follow-up of an average of 13 years. A comprehensive analysis of biological as well as physio-psychological information provides a unique opportunity to investigate relevant outcomes such as resilience and frailty in the elderly population.
Who will increase their physical activity? Predictors of change in objectively measured physical activity over 12 months in the ProActive cohort
Authors: Simmons Rebecca K , van Sluijs Esther MF , Hardeman Wendy , Sutton Stephen , Griffin Simon J ,   the ProActive project team
Published: April 2010

Background

The aim was to identify predictors of change in objectively measured physical activity over 12 months in the ProActive cohort to improve understanding of factors influencing change in physical activity.

Methods

ProActive is a physical activity promotion trial that took place in Eastern England (1999-2004). 365 offspring of people with type 2 diabetes underwent measurement of physical activity energy expenditure (PAEE) using heart rate monitoring, fitness, and anthropometric and biochemical status at baseline and 1 year (n = 321). Linear regression was used to quantify the associations between baseline demographic, clinical, psychosocial and behavioural variables and change in PAEE over 12 months. This study is registered as ISRCTN61323766.

Results

ProActive participants significantly increased their PAEE by 0.6 kj/min (SD 4.2, p = 0.006) over one year, the equivalent of around 20 minutes brisk walking/day. Male sex and higher fitness at baseline predicted increase in PAEE. No significant associations were found for any other variables. Very few baseline demographic, clinical, psychosocial and behavioural predictors were associated with change in objectively measured physical activity.

Conclusions

Traditional baseline determinants of self-reported physical activity targeted by behavioural interventions may be relatively weak predictors of change in objectively measured physical activity. Further research is needed to improve our understanding of factors influencing change in physical activity to inform the development and targeting of interventions.
Mentoring programs for medical students - a review of the PubMed literature 2000 - 2008
Authors: Frei Esther , Stamm Martina , Buddeberg-Fischer Barbara
Published: April 2010

Background

Although mentoring is acknowledged as a key to successful and satisfying careers in medicine, formal mentoring programs for medical students are lacking in most countries. Within the framework of planning a mentoring program for medical students at Zurich University, an investigation was carried out into what types of programs exist, what the objectives pursued by such programs are, and what effects are reported.

Methods

A PubMed literature search was conducted for 2000 - 2008 using the following keywords or their combinations: mentoring, mentoring program, medical student, mentor, mentee, protégé, mentorship. Although a total of 438 publications were identified, only 25 papers met the selection criteria for structured programs and student mentoring surveys.

Results

The mentoring programs reported in 14 papers aim to provide career counseling, develop professionalism, increase students' interest in research, and support them in their personal growth. There are both one-to-one and group mentorships, established in the first two years of medical school and continuing through graduation. The personal student-faculty relationship is important in that it helps students to feel that they are benefiting from individual advice and encourages them to give more thought to their career choices. Other benefits are an increase in research productivity and improved medical school performance in general. Mentored students also rate their overall well-being as higher. - The 11 surveys address the requirements for being an effective mentor as well as a successful mentee. A mentor should empower and encourage the mentee, be a role model, build a professional network, and assist in the mentee's personal development. A mentee should set agendas, follow through, accept criticism, and be able to assess performance and the benefits derived from the mentoring relationship.

Conclusion

Mentoring is obviously an important career advancement tool for medical students. In Europe, more mentoring programs should be developed, but would need to be rigorously assessed based on evidence of their value in terms of both their impact on the career paths of juniors and their benefit for the mentors. Medical schools could then be monitored with respect to the provision of mentorships as a quality characteristic.
Aqueous extract of Piper sarmentosum decreases atherosclerotic lesions in high cholesterolemic experimental rabbits
Authors: Amran Adel A , Zakaria Zaiton , Othman Faizah , Das Srijit , Raj Santhana , Nordin Nor-Anita M M
Published: April 2010

Background

Piper sarmentosum (P.s) has flavonoid component in its leaves which has antioxidative effect. To date, its effect on atherosclerosis has not been studied histologically.

Aim

The study aimed to investigate the effect of P.s on atherosclerotic changes in hypercholesterolemic rabbits.

Methods

Forty two male New Zealand white rabbits were divided into seven groups. C - control group fed normal rabbit chow, CH - cholesterol diet (1% cholesterol), W1 - 1% cholesterol with water extract of P.s (62.5 mg/kg), W2 - 1% cholesterol with water extract of P.s (125 mg/kg), W3 - 1% cholesterol with water extract of P.s (250 mg/kg), W4 - 1% cholesterol with water extract of P.s (500 mg/kg) and Smv - 1% cholesterol supplemented with simvistatin drug (1.2 mg/kg). All rabbits were treated for 10 weeks. Following 10 weeks of supplementation, the animals were sacrificed and the aortic tissue was taken for histological study.

Results

Rabbits fed only with high cholesterol diet 1% cholesterol (CH) showed focal fatty streak lesions compared to the C group and 1% cholesterol supplemented with simvistatin drug (Smv) group. Atherosclerotic lesions in the 1% cholesterol group supplemented with P.s (500 mg/kg) i.e. W4 group showed significant reduction (30 ± 6.0%, p < 0.05) in fatty streak compared to the high cholesterol group (85.6 ± 4.1%) under Sudan IV stain. The atherosclerotic lesions under transmission electron microscope showed reduction in foam cells in the treatment groups compared to the CH groups.

Conclusion

Administration of P.s extract has protective effect against atheroscleros
A health economic model for evaluating a vaccine for the prevention of herpes zoster and post-herpetic neuralgia in the UK
Authors: Moore Lee , Remy Vanessa , Martin Monique , Beillat Maud , McGuire Alistair
Published: April 2010

Background

A live-attenuated vaccine aimed at preventing herpes zoster (HZ) and its main complication, post-herpetic neuralgia (PHN) is available in Europe for immunocompetent adults aged 50 years and more. The study objective is to assess the cost effectiveness of a vaccination program for this population in the UK.

Methods

A state-transition Markov model has been developed to simulate the natural history of HZ and PHN and to estimate the lifetime effects of vaccination in the UK. Several health states are defined including good health, HZ, PHN, and death. HZ and PHN health states are further divided to reflect pain severity.

Results

The model predicts that a vaccination strategy for those aged over 50 years would lead to an incremental cost-effectiveness ratio of £13,077 per QALY gained from the NHS perspective, when compared to the current strategy of no vaccination. Age-group analyses show that the lowest ICERs (£10,984 and £10,275 for NHS) are observed when vaccinating people between 60-64 and 65-69 years of age. Sensitivity analyses showed that results are sensitive to the duration of vaccine protection, discount rate, utility decrements and pain severity split used.

Conclusions

Using the commonly accepted threshold of £30,000 per QALY gained in the UK, most scenarios of vaccination programmes preventing HZ and PHN, including the potential use of a repeat dose, may be considered cost-effective by the NHS, especially within the 60 to 69 age-groups.
Clinical significance of EGFR, Her-2 and EGF in oral squamous cell carcinoma: a case control study
Authors: Bernardes Vanessa F , Gleber-Netto Frederico O , Sousa Sílvia F , Silva Tarcília A , Aguiar Maria Cássia F
Published: April 2010

Background

The erbB receptors and their ligands are involved in the pathogenesis and progression of oral squamous cell carcinoma (OSCC). Although EGFR and Her-2 are frequently overexpressed in OSCC, few studies evaluated these proteins in saliva and their association with the tumor, which may represent potential usefulness in a clinical setting.

Methods

The levels of EGFR, Her-2, and EGF were evaluated in saliva of 46 patients with OSCC before and after the surgical removal of the lesion, as well as in matched healthy controls. The relationship of salivary levels and EGFR and Her-2 immunoexpression in tumor samples with clinicopathological features was analyzed.

Results

EGFR and Her-2 salivary levels did not show difference between to pre-surgery and control groups, however, both demonstrated an increase after surgical removal of the tumor. No association was detectable among receptor salivary levels, tissue expression and clinicopathological features. EGF levels in pre-surgery group were significantly lower when compared to the control group.

Conclusions

EGFR and Her-2 were not considered to be valuable salivary tumor markers in OSCC, however, lower levels of EGF in saliva may suggest a higher susceptibility for OSCC development.
Investigation of post-transcriptional gene regulatory networks associated with autism spectrum disorders by microRNA expression profiling of lymphoblastoid cell lines
Authors: Sarachana Tewarit , Zhou Rulun , Chen Guang , Manji Husseini K , Hu Valerie W
Published: April 2010

Background

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by abnormalities in reciprocal social interactions and language development and/or usage, and by restricted interests and repetitive behaviors. Differential gene expression of neurologically relevant genes in lymphoblastoid cell lines from monozygotic twins discordant in diagnosis or severity of autism suggested that epigenetic factors such as DNA methylation or microRNAs (miRNAs) may be involved in ASD.

Methods

Global miRNA expression profiling using lymphoblasts derived from these autistic twins and unaffected sibling controls was therefore performed using high-throughput miRNA microarray analysis. Selected differentially expressed miRNAs were confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis, and the putative target genes of two of the confirmed miRNA were validated by knockdown and overexpression of the respective miRNAs.

Results

Differentially expressed miRNAs were found to target genes highly involved in neurological functions and disorders in addition to genes involved in gastrointestinal diseases, circadian rhythm signaling, as well as steroid hormone metabolism and receptor signaling. Novel network analyses of the putative target genes that were inversely expressed relative to the relevant miRNA in these same samples further revealed an association with ASD and other co-morbid disorders, including muscle and gastrointestinal diseases, as well as with biological functions implicated in ASD, such as memory and synaptic plasticity. Putative gene targets (ID3 and PLK2) of two RT-PCR-confirmed brain-specific miRNAs (hsa-miR-29b and hsa-miR-219-5p) were validated by miRNA overexpression or knockdown assays, respectively. Comparisons of these mRNA and miRNA expression levels between discordant twins and between case-control sib pairs show an inverse relationship, further suggesting that ID3 and PLK2 are in vivo targets of the respective miRNA. Interestingly, the up-regulation of miR-23a and down-regulation of miR-106b in this study reflected miRNA changes previously reported in post-mortem autistic cerebellum by Abu-Elneel et al. in 2008. This finding validates these differentially expressed miRNAs in neurological tissue from a different cohort as well as supports the use of the lymphoblasts as a surrogate to study miRNA expression in ASD.

Conclusions

Findings from this study strongly suggest that dysregulation of miRNA expression contributes to the observed alterations in gene expression and, in turn, may lead to the pathophysiological conditions underlying autism.
Resisting psychotropic medicines: a synthesis of qualitative studies of medicine-taking
Authors: Britten Nicky , Riley Ruth , Morgan Myfanwy
Published: April 2010

This article reports the results of a synthesis of qualitative research articles about lay perspectives on prescribed psychotropic medicines. It updates and elaborates on a model of medicine-taking developed by Pound and colleagues. In this model, the concept of resistance refers to the various ways in which people take prescribed medicines while trying to minimise their intake. The synthesis included 12 papers published since 1992. The findings are presented at the societal level, in terms of the social meanings of mental health problems and medication, and at the individual level; the latter covers active engagement and lay evaluation, as well as the outcomes of evaluation, including the doctor–patient relationship. Although it can be difficult to achieve in the current clinical environment, there is much scope for developing more concordant relationships with patients in relation to prescribing and using psychotropic medicines.
Psychiatric and behavioural manifestations of Huntington's disease
Authors: Jauhar Sameer , Ritchie Stuart
Published: April 2010

Patients with Huntington's disease can be a challenge to psychiatrists and to psychiatric services. We present a patient whose case history illustrates this and underlines the need for prompt and adequate treatment of psychiatric problems in this population. We discuss the psychiatric and behavioural manifestations of the illness, the treatments available and the role of psychiatric services in providing care for people with Huntington's disease.
Different laws, same principles: mental health and incapacity legislation across the UK
Authors: Lyons Donald
Published: April 2010

England and Wales, Scotland and Northern Ireland are all at different stages in developing their mental health legislation. All jurisdictions have encountered problems in interpretation and operation of the various acts. As an introduction to a series of articles to appear in Advances on mental health and incapacity law, this editorial offers a commentary on some of the critical issues and suggests some key principles that everyone should follow in order to provide care and treatment that accords with best legal and ethical practice.
From the Editor's desk
Authors: Tyrer Peter
Published: April 2010

Place counts

Practitioners in all branches of mental health quickly become aware of the importance of time and place as they develop their craft. The value of guidelines for good practice can be considerable, but if they become echoing mantras that are applied indiscriminately, they can impair good care. Psychiatry does not lend itself easily to sound-bites because so much of what we say and do has to be put into a context that is more complex than most other parts of clinical medicine. When giving a talk about the fundamentals of community psychiatry recently in a country with limited resources I was simply told after I had finished with a flourish, ‘this wouldn't work here’, and, after first feeling affronted, had to acknowledge in discussion that what I took for granted as universal, was clearly wrong.
Efficacy and safety of bupropion for smoking cessation and reduction in schizophrenia: systematic review and meta-analysis
Authors: Tsoi Daniel Tai-yin , Porwal Mamta , Webster Angela Claire
Published: April 2010

Background

The benefits and harms of bupropion as an aid for smoking cessation in schizophrenia remain uncertain.

Aims

To summarise the current evidence for efficacy and safety of bupropion as treatment for nicotine dependence in schizophrenia.

Method

Systematic review and random-effects meta-analysis of randomised controlled trials (RCTs) comparing bupropion with placebo or alternative therapeutic control in adult smokers with schizophrenia.

Results

Twenty-one reports from seven RCTs were included. Biochemically verified self-reported smoking cessation rates after bupropion were significantly higher than placebo at the end of treatment (risk ratio (RR) = 2.57,P= 0.004) and at 6 months (RR = 2.78,P= 0.05). Expired carbon monoxide level was significantly lower with bupropion at the end of therapy (P= 0.002) but not at 6 months (P= 0.37). There was no significant difference in positive (P= 0.28) or negative symptoms (P= 0.49) between the bupropion and the placebo group.

Conclusions

Bupropion increases the rates of smoking abstinence in smokers with schizophrenia, without jeopardising their mental state.
Auditory hallucinations and brain structure in schizophrenia: voxel-based morphometric study
Authors: Nenadic Igor , Smesny Stefan , Schlösser Ralf G. M. , Sauer Heinrich , Gaser Christian
Published: April 2010

We applied voxel-based morphometry to high-resolution magnetic resonance images of 99 participants with schizophrenia. Voxel-wise correlations with a score of auditory hallucination severity identified areas in the left and right superior temporal cortex (including Heschl's gyrus), left supramarginal/angular gyrus, left postcentral gyrus and left posterior cingulate cortex. This study extends previous region-of-interest studies demonstrating main effects of auditory hallucinations related to modality-specific superior temporal areas including primary and secondary auditory cortices.
An effective intervention delivered at sub-therapeutic dose becomes an ineffective intervention
Authors: Latimer Eric
Published: April 2010

Evidence to date indicates that the individual placement and support model of supported employment helps people with mental illness to obtain competitive jobs. The study by Howard et al (this issue) is the first unsuccessful trial of this model. Vocational workers had far fewer contacts with clients and employers than normal.
Psychiatric journals as the mirror of the dominant psychiatric model
Authors: Kecmanovic Dusan , Hadzi-Pavlovic Dusan
Published: April 2010

Aims and method

Historical trends in the conceptual domains underlying articles published in psychiatric journals are indicators of major psychiatric concerns and practices. Articles inThe American Journal of PsychiatryandThe British Journal of Psychiatryduring the periods 1947–51, 1967–71 and 2002–6 were classified into either a biomedical, psychological or social conceptual domain to determine which domains, if any, were dominant.

Results

InThe American Journal of Psychiatryone or two domains were dominant for two of the three periods. No domain was dominant inThe British Journal of Psychiatry.

Clinical implications

Examined against various scientific and social developments, American psychiatry appears more responsive to current social, scientific and commercial trends and impulses than British psychiatry.
Two consultants for one patient: service users' and service providers' views on ‘New Ways’
Authors: Singhal Ankush , Garg Deepak , Rana Alok Kumar , Naheed Miriam
Published: April 2010

Aims and method

To investigate, through a semi-qualitative survey at three geographical sites, health professionals' and service users' opinion about the impact of providing separate consultants for in-patient and community settings. It looked at the perceived affect on various issues such as the course of the illness, service delivery, patients' satisfaction as well as the skills and training of psychiatrists.

Results

Opinion was divided about the level of satisfaction, advantages, consultants' skills and success of this model. The most consistent theme related to the problems with the continuation of care and therapeutic relationship. Most of the respondents were not fully informed about this change. An overwhelming majority believed that in-patient psychiatry is not a separate specialty.

Clinical implications

Communication and the sharing of information between the two consultants is the key to success in this model.
Changing futures: premature discharges of alcohol or opioid detoxification in-patients, service improvement
Authors: Parry Mark , Woodthorpe Nicholas , Gunawardena Priyanthi
Published: April 2010

Aims and method

We retrospectively audited premature discharges of in-patients undergoing alcohol or opioid detoxification. Recommendations for good practice aimed at reducing premature discharge rates were implemented, following which a prospective audit was completed.

Results

The retrospective phase of the audit cycle showed a premature discharge rate of 30.8%, compared with a rate of 13.2% for the prospective phase. The difference in these rates is both clinically and statistically significant at the 5% level, with Fisher's exact test producing a two-sidedP= 0.0119.

Clinical implications

Implementing good practice guidelines improved outcomes, with more patients successfully completing detoxifications and a more effective use of resources.
Race and prescribing
Authors: Connolly Anne
Published: April 2010

Treatment of mental illness in Black and minority ethnic groups differs from that in the White majority. Large differences in admission, detention and seclusion rates have been recorded. These disparities extend into the physical healthcare setting, particularly in the USA but also within the UK National Health Service. There are many influences on prescribing of psychotropic medication, not least the metabolising capacity of the individual. Ethnic differences do occur, particularly for East Asian peoples. However, these differences are broadly similar across ethnic groups, particularly for the cytochrome P450 enzymes responsible for metabolising psychotropic medicines. Psychotropic medication prescribing also differs by ethnicity. Specifically, antipsychotic dose, type and route of administration may differ. However, most data originate in the USA and UK studies have not replicated these findings, even after controlling for multiple confounding factors. Similarly, antidepressant prescribing and access to treatment may differ by ethnicity. These differences may have complex causes that are not well understood. Overall, prescribing of antipsychotics appears to be broadly equitable in Black and minority ethnic groups.
Open access community support groups for people with personality disorder: attendance and impact on use of other services
Authors: Miller Steve , Crawford Mike J.
Published: April 2010

Aims and method

To describe a new open access community service for people with personality disorder and to explore interim service utilisation and outcomes. Routine data were analysed together with those from a cross-sectional survey.

Results

During the first 16 months of the service, 171 people attended, of whom 142 (83.0%) returned on at least one other occasion. The median number of attendances was seven (IQR = 3.0–22.0). Over 90% of responders to the survey met criteria for ‘probable personality disorder’ and levels of social dysfunction were high. Presentations to emergency services, contacts with other services and in-patient admissions were reduced. Social functioning improved.

Clinical implications

This service attracted a large number of people with significant health and social problems. Use of the service was associated with improved social functioning and reduced use of other services.
Apparent role of Tribolium orthodenticle in anteroposterior blastoderm patterning largely reflects novel functions in dorsoventral axis formation and cell survival
Authors: Kotkamp Kay , Klingler Martin , Schoppmeier Michael
Published: April 2010

In the short-germ beetle Tribolium castaneum, the head gap gene orthodenticle (Tc-otd) has been proposed to functionally substitute for bicoid, the anterior morphogen unique to higher dipterans. In this study we reanalyzed the function of Tc-otd. We obtained a similar range of cuticle phenotypes as in previously described RNAi experiments; however, we noticed unexpected effects on blastodermal cell fates. First, we found that Tc-otd is essential for dorsoventral patterning. RNAi depletion results in lateralized embryos, a fate map change that by itself can explain the observed loss of the anterior head, which is a ventral anlage in Tribolium. We find that this effect is due to diminished expression of short gastrulation (sog), a gene essential for establishment of the Decapentaplegic (Dpp) gradient in this species. Second, we found that gnathal segment primordia in Tc-otd RNAi embryos are shifted anteriorly but otherwise appear patterned normally. This anteroposterior (AP) fate map shift might largely be due to diminished zen-1 expression and is not responsible for the severe segmentation defects observed in some Tc-otd RNAi embryos. As neither Tc-sog nor Tc-zen-1 probably requires Otd gradient-mediated positional information, we posit that the blastoderm function of Tc-Otd depends on its initial homogeneous maternal expression and that this maternal factor does not provide significant positional information for Tribolium blastoderm embryos.
How the python heart separates pulmonary and systemic blood pressures and blood flows
Authors: Jensen Bjarke , Nielsen Jan M. , Axelsson Michael , Pedersen Michael , Löfman Carl , Wang Tobias
Published: April 2010

The multiple convergent evolution of high systemic blood pressure among terrestrial vertebrates has always been accompanied by lowered pulmonary pressure. In mammals, birds and crocodilians, this cardiac separation of pressures relies on the complete division of the right and left ventricles by a complete ventricular septum. However, the anatomy of the ventricle of most reptiles does not allow for complete anatomical division, but the hearts of pythons and varanid lizards can produce high systemic blood pressure while keeping the pulmonary blood pressure low. It is also known that these two groups of reptiles are characterised by low magnitudes of cardiac shunts. Little, however, is known about the mechanisms that allow for this pressure separation. Here we provide a description of cardiac structures and intracardiac events that have been revealed by ultrasonic measurements and angioscopy. Echocardiography revealed that the atrioventricular valves descend deep into the ventricle during ventricular filling and thereby greatly reduce the communication between the systemic (cavum arteriosum) and pulmonary (cavum pulmonale) ventricular chambers during diastole. Angioscopy and echocardiography showed how the two incomplete septa, the muscular ridge and the bulbuslamelle – ventricular structures common to all squamates – contract against each other in systole and provide functional division of the anatomically subdivided ventricle. Washout shunts are inevitable in the subdivided snake ventricle, but we show that the site of shunting, the cavum venosum, is very small throughout the cardiac cycle. It is concluded that the python ventricle is incapable of the pronounced and variable shunts of other snakes, because of its architecture and valvular mechanics.
The myosin light chain 1 isoform associated with masticatory myosin heavy chain in mammals and reptiles is embryonic/atrial MLC1
Authors: Reiser Peter J. , Bicer Sabahattin , Patel Radhika , An Ying , Chen Qun , Quan Ning
Published: April 2010

We recently reported that masticatory myosin heavy chain (MHC-M) is expressed as the exclusive or predominant MHC isoform in masseter and temporalis muscles of several rodent species, contrary to the prevailing dogma that rodents express almost exclusively MHC isoforms that are typically found in fast limb muscles and not masticatory myosin. We also reported that the same rodent species express the embryonic/atrial isoform of myosin light chain 1 (MLC1E/A) in jaw-closing muscles and not a unique masticatory MLC1 isoform that others have reported as being expressed in jaw-closing muscles of carnivores that express MHC-M. The objective of this study was to test the hypothesis that MLC1E/A is consistently expressed in jaw-closing muscles whenever MHC-M is expressed as the predominant or exclusive MHC isoform. Jaw-closing muscles, fast and slow limb muscles, and cardiac atria and ventricles of 19 species (six Carnivora species, one Primates species, one Chiroptera species, five marsupial species, an alligator and five turtle species) were analyzed using protein gel electrophoresis, immunoblotting, mass spectrometry and RNA sequencing. Gel electrophoresis and immunoblotting indicate that MHC-M is the exclusive or predominant MHC isoform in the jaw-closing muscles of each of the studied species. The results from all of the approaches collectively show that MLC1E/A is exclusively or predominantly expressed in jaw-closing muscles of the same species. We conclude that MLC1E/A is the exclusive or predominant MLC1 isoform that is expressed in jaw-closing muscles of vertebrates that express MHC-M, and that a unique masticatory isoform of MLC1 probably does not exist.
Stretch-activated cation channel from larval bullfrog skin
Authors: Hillyard Stanley D. , Willumsen Niels J. , Marrero Mario B.
Published: April 2010

Cell-attached patches from isolated epithelial cells from larval bullfrog skin revealed a cation channel that was activated by applying suction (−1 kPa to −4.5 kPa) to the pipette. Activation was characterized by an initial large current spike that rapidly attenuated to a stable value and showed a variable pattern of opening and closing with continuing suction. Current–voltage plots demonstrated linear or inward rectification and single channel conductances of 44–56 pS with NaCl or KCl Ringer's solution as the pipette solution, and a reversal potential (−Vp) of 20–40 mV. The conductance was markedly reduced with N-methyl-D-glucamide (NMDG)-Cl Ringer's solution in the pipette. Neither amiloride nor ATP, which are known to stimulate an apical cation channel in Ussing chamber preparations of larval frog skin, produced channel activation nor did these compounds affect the response to suction. Stretch activation was not affected by varying the pipette concentrations of Ca2+ between 0 mmol l−1 and 4 mmol l−1 or by varying pH between 6.8 and 8.0. However, conductance was reduced with 4 mmol l−1 Ca2+. Western blot analysis of membrane homogenates from larval bullfrog and larval toad skin identified proteins that were immunoreactive with mammalian TRPC1 and TRPC5 (TRPC, canonical transient receptor potential channel) antibodies while homogenates of skin from newly metamorphosed bullfrogs were positive for TRPC1 and TRPC3/6/7 antibodies. The electrophysiological response of larval bullfrog skin resembles that of a stretch-activated cation channel characterized in Xenopus oocytes and proposed to be TRPC1. These results indicate this channel persists in all life stages of anurans and that TRP isoforms may be important for sensory functions of their skin.
Stimulation of −1 programmed ribosomal frameshifting by a metabolite-responsive RNA pseudoknot
Authors: Chou Ming-Yuan , Lin Szu-Chieh , Chang Kung-Yao
Published: May 2010

Specific recognition of metabolites by functional RNA motifs within mRNAs has emerged as a crucial regulatory strategy for feedback control of biochemical reactions. Such riboswitches have been demonstrated to regulate different gene expression processes, including transcriptional termination and translational initiation in prokaryotic cells, as well as splicing in eukaryotic cells. The regulatory process is usually mediated by modulating the accessibility of specific sequence information of the expression platforms via metabolite-induced RNA conformational rearrangement. In eukaryotic systems, viral and the more limited number of cellular decoding −1 programmed ribosomal frameshifting (PRF) are commonly promoted by a 3′ mRNA pseudoknot. In addition, such −1 PRF is generally constitutive rather than being regulatory, and usually results in a fixed ratio of products. We report here an RNA pseudoknot capable of stimulating −1 PRF whose efficiency can be tuned in response to the concentration ofS-adenosylhomocysteine (SAH), and the improvement of its frameshifting efficiency by RNA engineering. In addition to providing an alternative approach for small-molecule regulation of gene expression in eukaryotic cells, such a metabolite-responsive pseudoknot suggests a plausible mechanism for metabolite-driven translational regulation of gene expression in eukaryotic systems.
Bunyamwera virus can repair both insertions and deletions during RNA replication
Authors: Walter Cheryl T. , Barr John N.
Published: April 2010

The genomic termini of RNA viruses contain essential cis-acting signals for such diverse functions as packaging, genome translation, mRNA transcription, and RNA replication, and thus preservation of their sequence integrity is critical for virus viability. Sequence alteration can arise due to cellular mechanisms that add or remove nucleotides from terminal regions, or, alternatively, from introduction of sequence errors through nucleotide misincorporation by the error-prone viral RNA-dependent RNA polymerase (RdRp). To preserve template function, many RNA viruses utilize repair mechanisms to prevent accumulation of terminal alterations. Here we show that Bunyamwera virus (BUNV), the prototype of the Bunyaviridae family of segmented negative-sense RNA viruses, also can repair its genomic termini. When an intact nontranslated region (NTR) was added to the anti-genomic 3′ end, it was precisely removed, to restore both length and RNA synthesis function of the wild-type template. Furthermore, when nucleotides were removed from the anti-genome 3′ end, and replaced with a duplicate and intact NTR, both the external NTR were removed, and the missing nucleotides were restored, thus, indicating that the BUNV RdRp can both remove and add nucleotides to the template. We show that the mechanism for repair of terminal extensions is likely that of internal entry of the viral RdRp during genome synthesis. Possible mechanisms for repair of terminal deletions are discussed.
Circularization of the HIV-1 genome facilitates strand transfer during reverse transcription
Authors: Beerens Nancy , Kjems Jørgen
Published: April 2010

Two obligatory DNA strand transfers take place during reverse transcription of a retroviral RNA genome. The first strand transfer involves a jump from the 5′ to the 3′ terminal repeat (R) region positioned at each end of the viral genome. The process depends on base pairing between the cDNA synthesized from the 5′ R region and the 3′ R RNA. The tertiary conformation of the viral RNA genome may facilitate strand transfer by juxtaposing the 5′ R and 3′ R sequences that are 9 kb apart in the linear sequence. In this study, RNA sequences involved in an interaction between the 5′ and 3′ ends of the HIV-1 genome were mapped by mutational analysis. This interaction appears to be mediated mainly by a sequence in the extreme 3′ end of the viral genome and in the gag open reading frame. Mutation of 3′ R sequences was found to inhibit the 5′–3′ interaction, which could be restored by a complementary mutation in the 5′ gag region. Furthermore, we find that circularization of the HIV-1 genome does not affect the initiation of reverse transcription, but stimulates the first strand transfer during reverse transcription in vitro, underscoring the functional importance of the interaction.
Optimality of Affine Policies in Multistage Robust Optimization
Authors: Bertsimas Dimitris , Iancu Dan A. , Parrilo Pablo A.
Published: May 2010

In this paper, we prove the optimality of disturbance-affine control policies in the context of one-dimensional, constrained, multistage robust optimization. Our results cover the finite-horizon case, with minimax (worst-case) objective, and convex state costs plus linear control costs. We develop a new proof methodology, which explores the relationship between the geometrical properties of the feasible set of solutions and the structure of the objective function. Apart from providing an elegant and conceptually simple proof technique, the approach also entails very fast algorithms for the case of piecewise-affine state costs, which we explore in connection with a classical inventory management application.
Generalized Domino-Parity Inequalities for the Symmetric Traveling Salesman Problem
Authors: Cook William J. , Espinoza Daniel G. , Goycoolea Marcos
Published: May 2010

We extend the work of Letchford [Letchford, A. N. 2000. Separating a superclass of comb inequalities in planar graphs. Math. Oper. Res. 25 443–454] by introducing a new class of valid inequalities for the traveling salesman problem, called the generalized domino-parity (GDP) constraints. Just as Letchford's domino-parity constraints generalize comb inequalities, GDP constraints generalize the most well-known multiple-handle constraints, including clique-tree, bipartition, path, and star inequalities. Furthermore, we show that a subset of GDP constraints containing all of the clique-tree inequalities can be separated in polynomial time, provided that the support graph G* is planar, and provided that we bound the number of handles by a fixed constant h.