bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of dietary interventions. A simple payoff matrix for display of comparative dietary trials
Authors: Feinman Richard D , Fine Eugene J , Volek Jeff S
Published: August 2008

Objective

To provide a simple method for presentation of data in comparative dietary trials.

Methods

Individual data from each diet are ranked and all possible paired comparisons are made and displayed in a pay-off matrix which can be color-coded according to the magnitude of the differences between the two diets. Probability of outcome can be calculated from the fraction of matrix elements corresponding to specified conditions. The method has the advantage of emphasizing differences and providing the maximum amount of information.

Results

The method was tested with values from the literature and allows intuitive sense of the comparative effectiveness of the two diets. In a test case in which a cross-over study had been performed the matrix derived from theoretical paired comparisons (treating the data as two parallel studies) was consistent with the results from the actual pairing in the cross-over.

Conclusion

The matrix method is a simple way of providing access to the differences between dietary trials. It exaggerates differences but can be used in combination with group statistics that, conversely, provide reliability at the expense of detailed information.
Effects of Krill Oil on serum lipids of hyperlipidemic rats and human SW480 cells
Authors: Zhu Jia-Jin , Shi Jia-Hui , Qian Wen-Bin , Cai Zhen-Zhen , Li Duo
Published: August 2008

Background

Cardiovascular disease (CVD) and colon cancer incidence are known to be closely related to dietary factors. This article evaluated effects of krill oil (KO) on serum lipids of hyperlipidemia rats and human colon cancer cells (SW480). Serum lipids of rats fed with high fat diet (HFD) and different doses of KO were measured by automatic analyzer. Effect of KO on viability of cells was determined by methyl thiazolyl tetrazolium (MTT) assay.

Results

Except for higher dose group, body weights decreased significantly. Total cholesterol (TC), LDL-cholesterol (LDL-C) of all dose groups, Triglycerides (TG) of low and mid dose groups descended significantly, while there were no significant differences of HDL-cholesterol (HDL-C), compared with control group. Treatment of colon cancer cells with KO also resulted in time-dependent inhibition of cell growth.

Conclusion

Our findings indicated that the consumption of KO may provide benefits to control serum lipid levels in certain diseases and inhibit growth of colon cancer cells. Therefore, KO may be a good candidate for development as a functional food and nutraceutical.
Developing a competency-based curriculum in HIV for nursing schools in Haiti
Authors: Knebel Elisa , Puttkammer Nancy , Demes Adrien , Devirois Ruth , Prismy Mona
Published: August 2008

Background

Preparing health workers to confront the HIV/AIDS epidemic is an urgent challenge in Haiti, where the HIV prevalence rate is 2.2% and approximately 10 100 people are taking antiretroviral treatment. There is a critical shortage of doctors in Haiti, leaving nurses as the primary care providers for much of the population. Haiti's approximately 1000 nurses play a leading role in HIV/AIDS prevention, care and treatment. However, nurses do not receive sufficient training at the pre-service level to carry out this important work.

Methods

To address this issue, the Ministry of Health and Population collaborated with the International Training and Education Center on HIV over a period of 12 months to create a competency-based HIV/AIDS curriculum to be integrated into the 4-year baccalaureate programme of the four national schools of nursing.

Results

Using a review of the international health and education literature on HIV/AIDS competencies and various models of curriculum development, a Haiti-based curriculum committee developed expected HIV/AIDS competencies for graduating nurses and then drafted related learning objectives. The committee then mapped these learning objectives to current courses in the nursing curriculum and created an 'HIV/AIDS Teaching Guide' for faculty on how to integrate and achieve these objectives within their current courses. The curriculum committee also created an 'HIV/AIDS Reference Manual' that detailed the relevant HIV/AIDS content that should be taught for each course.

Conclusion

All nursing students will now need to demonstrate competency in HIV/AIDS-related knowledge, skills and attitudes during periodic assessment with direct observation of the student performing authentic tasks. Faculty will have the responsibility of developing exercises to address the required objectives and creating assessment tools to demonstrate that their graduates have met the objectives. This activity brought different administrators, nurse leaders and faculty from four geographically dispersed nursing schools to collaborate on a shared goal using a process that could be easily replicated to integrate any new topic in a resource-constrained pre-service institution. It is hoped that this experience provided stakeholders with the experience, skills and motivation to strengthen other domains of the pre-service nursing curriculum, improve the synchronization of didactic and practical training and develop standardized, competency-based examinations for nursing licensure in Haiti.
Transcriptional responses to biologically relevant doses of UV-B radiation in the model archaeon, Halobacteriumsp. NRC-1
Authors: Boubriak Ivan , Ng Wooi Loon , DasSarma Priya , DasSarma Shiladitya , Crowley David J , McCready Shirley J
Published: August 2008

Background

Most studies of the transcriptional response to UV radiation in living cells have used UV doses that are much higher than those encountered in the natural environment, and most focus on short-wave UV (UV-C) at 254 nm, a wavelength that never reaches the Earth's surface. We have studied the transcriptional response of the sunlight-tolerant model archaeon, Halobacterium sp. NRC-1, to low doses of mid-wave UV (UV-B) to assess its response to UV radiation that is likely to be more biologically relevant.

Results

Halobacterium NRC-1 cells were irradiated with UV-B at doses equivalent to 30 J/m2 and 5 J/m2 of UV-C. Transcriptional profiling showed that only 11 genes were up-regulated 1.5-fold or more by both UV-B doses. The most strongly up-regulated gene was radA1 (vng2473), the archaeal homologue of RAD51/recA recombinase. The others included arj1 (vng779) (recJ-like exonuclease), top6A (vng884) and top6B (vng885) (coding for Topoisomerase VI subunits), and nrdJ (vng1644) (which encodes a subunit of ribonucleotide reductase). We have found that four of the consistently UV-B up-regulated genes, radA1 (vng2473), vng17, top6B (vng885) and vng280, share a common 11-base pair motif in their promoter region, TTTCACTTTCA. Similar sequences were found in radA promoters in other halophilic archaea, as well as in the radA promoter of Methanospirillum hungatei. We analysed the transcriptional response of a repair-deficient ΔuvrA (vng2636) ΔuvrC (vng2381) double-deletion mutant and found common themes between it and the response in repair proficient cells.

Conclusion

Our results show a core set of genes is consistently up-regulated after exposure to UV-B light at low, biologically relevant doses. Eleven genes were up-regulated, in wild-type cells, after two UV-B doses (comparable to UV-C doses of 30 J/m2 and 5 J/m2), and only four genes were up-regulated by all doses of UV-B and UV-C that we have used in this work and previously. These results suggest that high doses of UV-C radiation do not necessarily provide a good model for the natural response to environmental UV. We have found an 11-base pair motif upstream of the TATA box in four of the UV-B up-regulated genes and suggest that this motif is the binding site for a transcriptional regulator involved in their response to UV damage in this model archaeon.
Pentobarbital versus thiopental in the treatment of refractory intracranial hypertension in patients with traumatic brain injury: a randomized controlled trial
Authors: Pérez-Bárcena Jon , Llompart-Pou Juan A , Homar Javier , Abadal Josep M , Raurich Joan M , Frontera Guillem , Brell Marta , Ibáñez Javier , Ibáñez Jordi
Published: August 2008

Introduction

Experimental research has demonstrated that the level of neuroprotection conferred by the various barbiturates is not equal. Until now no controlled studies have been conducted to compare their effectiveness, even though the Brain Trauma Foundation Guidelines recommend that such studies be undertaken. The objectives of the present study were to assess the effectiveness of pentobarbital and thiopental in terms of controlling refractory intracranial hypertension in patients with severe traumatic brain injury, and to evaluate the adverse effects of treatment.

Methods

This was a prospective, randomized, cohort study comparing two treatments: pentobarbital and thiopental. Patients who had suffered a severe traumatic brain injury (Glasgow Coma Scale score after resuscitation ≤ 8 points or neurological deterioration during the first week after trauma) and with refractory intracranial hypertension (intracranial pressure > 20 mmHg) first-tier measures, in accordance with the Brain Trauma Foundation Guidelines.

Results

A total of 44 patients (22 in each group) were included over a 5-year period. There were no statistically significant differences in ' baseline characteristics, except for admission computed cranial tomography characteristics, using the Traumatic Coma Data Bank classification. Uncontrollable intracranial pressure occurred in 11 patients (50%) in the thiopental treatment group and in 18 patients (82%) in the pentobarbital group (P = 0.03). Under logistic regression analysis – undertaken in an effort to adjust for the cranial tomography characteristics, which were unfavourable for pentobarbital – thiopental was more effective than pentobarbital in terms of controlling intracranial pressure (odds ratio = 5.1, 95% confidence interval 1.2 to 21.9; P = 0.027). There were no significant differences between the two groups with respect to the incidence of arterial hypotension or infection.

Conclusions

Thiopental appeared to be more effective than pentobarbital in controlling intracranial hypertension refractory to first-tier measures. These findings should be interpreted with caution because of the imbalance in cranial tomography characteristics and the different dosages employed in the two arms of the study. The incidence of adverse effects was similar in both groups.

Trial Registration

(Trial registration: US Clinical Trials registry NCT00622570.)
The needs of new consultants
Authors: Beezhold Julian
Published: August 2008

This editorial discusses the needs of new consultants with reference to existing research and attempts made to meet these needs both within the Royal College of Psychiatrists and elsewhere. Some future challenges for new consultant psychiatrists are identified and discussed. Initiatives that can help meet their needs on a personal and also on an organisational level are suggested. A call is made for new consultants to take control of their own destiny using tried and tested methods and thereby creating hope for their future.
Atypical antipsychotics in bipolar disorder: the treatment of mania
Authors: Cookson John
Published: August 2008

The development of atypical antipsychotics has stimulated research on the treatment of mania. Several well-established options now exist for monotherapy of mania. None of the atypicals has shown greater efficacy than haloperidol in improving manic symptoms, but they all produce fewer extrapyramidal side-effects and they may differ in their effects on depressive symptoms. Combinations of an antipsychotic with lithium or valproate offer further options, with somewhat greater efficacy in treating mania but also with more side-effects.
Delivering race equality in mental health services
Authors: Lau Annie
Published: August 2008

‘Delivering race equality’ is a 5-year action plan for tackling race inequalities in mental healthcare in England and Wales, based on the main themes of improved services, better community engagement and better information. The perception is that clinical teams have not been sufficiently engaged with the plan and progress is slow. This article shares insights from the author's work across government departments over the past 2 years and explores the potential for linking up different initiatives across the patient care pathway in support of the plan's delivery. A summary of conclusions from a pilot survey of consultant psychiatrists, commissioned by the Department of Health in June 2007, addresses the main controversial areas in the action plan, with suggestions for improvement. Areas for clinical engagement are identified that exploit new funding, investment and policy initiatives. Examples of good practice are offered.
Another step towards understanding recovery?
Authors: Abbott Pat
Published: August 2008

Self-determination theory has been offered as a potential theoretical framework for recovery. It has been argued that a concept as wide-ranging as recovery seems likely to require a number of theoretical frameworks, including self-determination theory, which appears to be particularly applicable to the clinical and social dimensions of this concept. With its emphasis on social competence and environmental support, self-determination theory may be particularly useful as a framework for considering recovery in client groups with higher levels of service need associated with disability or risk.
Anti-stigma films and medical students' attitudes towards mental illness and psychiatry: randomised controlled trial
Authors: Kerby Jane , Calton Tim , Dimambro Ben , Flood Caroline , Glazebrook Cristine
Published: August 2008

Aims and Method

To explore the feasibility of a randomised controlled trial of the effects of two anti-stigma films on medical students' attitudes to serious mental illness and psychiatry. Attitudes to serious mental illness, perceived dangerousness, social distance and psychiatry, were measured before and after watching the films and at 8 weeks.

Results

Intervention films significantly improved general attitudes to serious mental illness and social distance, with a trend towards reducing perceived dangerousness. These effects appeared to attenuate during the students' clinical placements, suggesting a possible interaction with their clinical experiences.

Clinical Implications

Our results suggest both that it may be possible to conduct a substantive trial of the effects of the intervention films on a larger cohort of medical students and that the films may be effective in reducing stigmatising attitudes in medical students.
National service for adolescents and adults with severe obsessive–compulsive and body dysmorphic disorders
Authors: Drummond L. M. , Fineberg N. A. , Heyman I. , Kolb P. J. , Pillay A. , Rani S. , Salkovskis P. , Veale D.
Published: August 2008

Aims and Method

National guidelines for the assessment and treatment of obsessive–compulsive disorder (OCD) and body dysmorphic disorder were published in 2005 by the National Institute for Health and Clinical Excellence (NICE). Local services are unable to treat a small but significant number of the most severely ill patients successfully, and the guidelines recommend that such patients should have access to highly specialised care. From 1 April 2007, the Department of Health decided to centrally fund treatment services for severe, chronic, refractory OCD and BDD. We describe a new National Service for Refractory OCD; its rationale, treatments offered, referral criteria and expected clinical outcomes.

Results

Initial results from one centre show an average 42% reduction in OCD symptoms at the end of treatment.

Clinical Implications

The operational challenges and potential generalisability of this model of healthcare delivery are discussed. We present a summary of the progress made so far in establishing a new, coherent National Service for Refractory OCD, 18 months after the NICE guideline was published. the aim of the paper is to educate clinicians about the service and describe its rationale, treatments offered, referral criteria and expected clinical outcomes.
The repentant sinner: methods to reduce stigmatised attitudes towards mental illness
Authors: Luty Jason , Rao Harish , Arokiadass Sujaa Mary Rajagopal , Easow Joby Maducolil , Sarkhel Arghya
Published: August 2008

Aims and Method

To devise a simple technique to reduce stigmatised attitudes of the general public towards those with mental disorder (schizophrenia and substance misuse). Members of the general public (n=400) completed a questionnaire to measure stigmatised attitudes towards people with schizophrenia and substance misuse disorders. Participants were randomised to receive either a short, ‘upbeat’ leaflet with a description of a patient in remission and a photograph of a man in a business suit; or a simple description of a fictional patient. the 5-item Attitudes to Mental Illness Questionnaire (AMIQ) was used to measure the effect of the various procedures on stigmatised attitudes (score range −10 to +10).

Results

Results were received for 310 (77%) participants. the leaflet produced a large, statistically significant reduction in stigmatised attitudes towards people with opiate dependence (effect size 1.53, CI 1.23–1.82, P < 0.0001; median change 4 units) and alcohol dependence (effect size 1.41, CI 1.12–1.70, P < 0.0001; median change 4 units) but less so towards people with schizophrenia (effect size 0.54, CI 0.27–0.80, P=0.0002; median change 2 units). There was no difference between participants in respect of the control group at 4-week follow-up (233 responses received; 78% response rate).

Clinical Implications

A short illustrated leaflet can be used to reduce stigmatised attitudes towards substance misuse disorders if patients are presented in a positive manner. This is less effective for attitudes towards people with schizophrenia, possibly because people have a more generous attitude towards patients who have overcome substance misuse disorders.
Junior psychiatrists' electrocardiogram interpretation skills
Authors: Collins Noel , Mandal Uttara , Pendlebury Gabrielle , Drife Jenny
Published: August 2008

Aims and Method

We checked whether psychiatric junior doctors could identify common electrocardiogram (ECG) abnormalities. Participants were directly approached at three London sites during induction or teaching programmes.

Results

The survey had a total response rate of 65% (36/55). Psychiatry junior doctors displayed an overall success rate of 97% in detecting whether an ECG is grossly abnormal, but were much less competent in specifying exact ECG diagnoses (success rate of 41%). Accuracy rates for some diagnoses (e.g. paced rhythm) fell to as low as 11%. General practitioners performed no better than psychiatry trainees.

Clinical Implications

There is little consensus about minimum acceptable standards in medical skills such as ECG reporting in junior doctors. These competencies are generally ignored in new curriculums. Questions regarding the appropriate remit of psychiatry doctors in this area are raised and the need for more monitoring and education of these skills is queried.
Is psychiatry torn in different ethical directions?
Authors: Lepping Peter
Published: August 2008

Psychiatry is the only specialty that uses legislation which is torn between utilitarian and rights-focused approaches. Although on the one hand this improves the opportunity for good outcome, on the other it reduces autonomous decision-making. Because psychiatry is the only medical speciality in this situation, this may cause stigmatisation and an inappropriate expectation on psychiatry to fulfil some kind of social policing role.
Abortion and mental health
Authors: Fergusson David M.
Published: August 2008

A recent Royal College of Psychiatrists' statement concluded that current evidence on abortion and mental health is inconclusive. This contribution examines the background to the Royal College of Psychiatrists' statement and the issues it raises. It is concluded that the best route to resolving such issues is through further and better research.
Defects of Prostate Development and Reproductive System in the Estrogen Receptor-α Null Male Mice
Authors: Chen Ming , Hsu Iawen , Wolfe Andrew , Radovick Sally , Huang KuoHsiang , Yu Shengqiang , Chang Chawnshang , Messing Edward M. , Yeh Shuyuan
Published: August 2008

The estrogen receptor-α knockout (ERαKO, ERα−/−) mice were generated via the Cre-loxP system by mating floxed ERα mice with β-actin (ACTB)-Cre mice. The impact of ERα gene deletion in the male reproductive system was investigated. The ACTB-Cre/ERα−/− male mice are infertile and have lost 90% of epididymal sperm when compared with wild-type mice. Serum testosterone levels in ACTB-Cre/ERα−/− male mice are 2-fold elevated. The ACTB-Cre/ERα−/− testes consist of atrophic and degenerating seminiferous tubules with less cellularity in the disorganized seminiferous epithelia. Furthermore, the ventral and dorsal-lateral prostates of ACTB-Cre/ERα−/− mice display reduced branching morphogenesis. Loss of ERα could also be responsible for the decreased fibroblast proliferation and changes in the stromal content. In addition, we found bone morphogenetic protein, a mesenchymal inhibitor of prostatic branching morphogenesis, is significantly up-regulated in the ACTB-Cre/ERα−/− prostates. Collectively, these results suggest that ERα is required for male fertility, acts through a paracrine mechanism to regulate prostatic branching morphogenesis, and is involved in the proliferation and differentiation of prostatic stromal compartment.

Newly generated ACTB-Cre/Estrogen receptor alpha knockout (ERα-/-) male mice show that ERα acts through a paracrine mechanism to regulate prostatic branching morphogenesis and is involved in the proliferation and differentiation of prostatic stoma.
Gonadotropin-Releasing Hormone Inhibits Pituitary Adenylyl Cyclase-Activating Polypeptide Coupling to 3′,5′-Cyclic Adenosine-5′-Monophosphate Pathway in LβT2 Gonadotrope Cells through Novel Protein Kinase C Isoforms and Phosphorylation of Pituitary Adenylyl Cyclase-Activating Polypeptide Type I Receptor
Authors: Larivière Sigolène , Garrel-Lazayres Ghislaine , Simon Violaine , Shintani Norihito , Baba Akemichi , Counis Raymond , Cohen-Tannoudji Joëlle
Published: August 2008

Gonadotrope cells are primarily regulated by GnRH but are also targets of the pituitary adenylyl cyclase-activating polypeptide (PACAP). Although it has been reported that reciprocal interactions between both neuropeptides contribute to regulation of gonadotrope function, the underlying mechanisms remain poorly understood. In this study, we reevaluated PACAP coupling to the cAMP pathway in LβT2 gonadotrope cells and analyzed GnRH effect on PACAP signaling. We established that PACAP38 markedly increases intracellular cAMP levels (EC50 of 4.7 ± 1.3 nm) through the PACAP type 1 receptor (PAC1-R), as evidenced by pharmacological and RT-PCR studies. Interestingly, although GnRH couples to cAMP pathway in LβT2 cells, the effects of both neuropeptides were not synergistic. Instead, the GnRH agonist (GnRHa) triptorelin rapidly and strongly inhibited (70% inhibition as early as 5 min) PACAP38-induced cAMP production. Inhibition was calcium independent, mimicked by the phorbol ester phorbol 12-myristate 13-acetate, and blocked by the protein kinase C (PKC) inhibitor bisindoylmaleimide, indicating that GnRHa inhibitory action relies on PKC. Selective down-regulation of both conventional and novel PKC prevented a GnRHa effect, whereas pharmacological inhibition of conventional PKC only was ineffective, strongly suggesting the involvement of novel PKC isoforms. GnRHa did not inhibit forskolin- or cholera toxin-stimulated cAMP accumulation, suggesting that PAC1-R is the predominant target of GnRH. Accordingly, we demonstrated for the first time that GnRH increases PAC1-R phosphorylation through PKC, providing a potential molecular mechanism which may account for GnRH inhibitory effect.
Effects of Prenatal Dexamethasone Treatment on Physical Growth, Pituitary-Adrenal Hormones, and Performance of Motor, Motivational, and Cognitive Tasks in Juvenile and Adolescent Common Marmoset Monkeys
Authors: Hauser Jonas , Knapman Alana , Zürcher Nicole R. , Pilloud Sonia , Maier Claudia , Diaz-Heijtz Rochellys , Forssberg Hans , Dettling Andrea , Feldon Joram , Pryce Christopher R.
Published: August 2008

Synthetic glucocorticoids such as dexamethasone (DEX) are commonly used to prevent respiratory distress syndrome in preterm infants, but there is emerging evidence of subsequent neurobehavioral abnormalities (e.g. problems with inattention/hyperactivity). In the present study, we exposed pregnant common marmosets (Callithrix jacchus, primates) to daily repeated DEX (5 mg/kg by mouth) during either early (d 42–48) or late (d 90–96) pregnancy (gestation period of 144 days). Relative to control, and with a longitudinal design, we investigated DEX effects in offspring in terms of physical growth, plasma ACTH and cortisol titers, social and maintenance behaviors, skilled motor reaching, motivation for palatable reward, and learning between infancy and adolescence. Early DEX resulted in reduced sociability in infants and increased motivation for palatable reward in adolescents. Late DEX resulted in a mild transient increase in knee-heel length in infants and enhanced reversal learning of stimulus-reward association in adolescents. There was no effect of either early or late DEX on basal plasma ACTH or cortisol titers. Both treatments resulted in impaired skilled motor reaching in juveniles, which attenuated in early DEX but persisted in late DEX across test sessions. The increased palatable-reward motivation and decreased social motivation observed in early DEX subjects provide experimental support for the clinical reports that prenatal glucocorticoid treatment impairs social development and predisposes to metabolic syndrome. These novel primate findings indicate that fetal glucocorticoid overexposure can lead to abnormal development of motor, affective, and cognitive behaviors. Importantly, the outcome is highly dependent upon the timing of glucocorticoid overexposure.
Dual roles of Incenp crucial to the assembly of the acentrosomal metaphase spindle in female meiosis
Authors: Colombié Nathalie , Cullen C. Fiona , Brittle Amy L. , Jang Janet K. , Earnshaw William C. , Carmena Mar , McKim Kim , Ohkura Hiroyuki
Published: August 2008

Spindle formation in female meiosis differs from mitosis in many animals,as it takes place independently of centrosomes, and the molecular requirements of this pathway remain to be understood. Here, we report two crucial roles of Incenp, an essential subunit of the chromosomal passenger complex (the Aurora B complex), in centrosome-independent spindle formation in Drosophilafemale meiosis. First, the initial assembly of spindle microtubules is drastically delayed in an incenp mutant. This clearly demonstrates,for the first time, a crucial role for Incenp in chromosome-driven spindle microtubule assembly in living oocytes. Additionally, Incenp is necessary to stabilise the equatorial region of the metaphase I spindle, in contrast to mitosis, where the equivalent function becomes prominent after anaphase onset. Our analysis suggests that Subito, a kinesin-6 protein, cooperates with Incenp for this latter function, but not in microtubule assembly. We propose that the two functions of Incenp are part of the mechanisms that compensate for the lack of centrosomes during meiotic spindle formation.
Insulin receptor substrate 1 is an effector of sonic hedgehog mitogenic signaling in cerebellar neural precursors
Authors: Parathath Susana R. , Mainwaring Lori Anne , Fernandez-L Africa , Campbell Dane Ohlosson , Kenney Anna Marie
Published: August 2008

Sonic hedgehog (SHH) and insulin-like growth factor (IGF) signaling are essential for development of many tissues and are implicated in medulloblastoma, the most common solid pediatric malignancy. Cerebellar granule neuron precursors (CGNPs), proposed cells-of-origin for specific classes of medulloblastomas, require SHH and IGF signaling for proliferation and survival during development of the cerebellum. We asked whether SHH regulates IGF pathway components in proliferating CGNPs. We report that SHH-treated CGNPs showed increased levels of insulin receptor substrate 1(IRS1) protein, which was also present in the germinal layer of the developing mouse cerebellum and in mouse SHH-induced medulloblastomas. Previous roles for IRS1, an oncogenic protein that is essential for IGF-mediated proliferation in other cell types, have not been described in SHH-mediated CGNP proliferation. We found that IRS1 overexpression can maintain CGNP proliferation in the absence of SHH. Furthermore, lentivirus-mediated knock down experiments have shown that IRS1 activity is required for CGNP proliferation in slice explants and dissociated cultures. Contrary to traditional models for SHH signaling that focus on gene transcription, SHH stimulation does not regulate Irs1 transcription but rather stabilizes IRS1 protein by interfering with mTOR-dependent IRS1 turnover and possibly affects Irs1 mRNA translation. Thus, we have identified IRS1 as a novel effector of SHH mitogenic signaling that may serve as a future target for medulloblastoma therapies. Our findings also indicate a previously unreported interaction between the SHH and mTOR pathways, and provide an example of a non-classical means for SHH-mediated protein regulation during development.
In vivo birthdating by BAPTISM reveals that trigeminal sensory neuron diversity depends on early neurogenesis
Authors: Caron Sophie J. C. , Prober David , Choy Margaret , Schier Alexander F.
Published: August 2008

Among sensory systems, the somatic sense is exceptional in its ability to detect a wide range of chemical, mechanical and thermal stimuli. How this sensory diversity is established during development remains largely elusive. We devised a method (BAPTISM) that uses the photoconvertible fluorescent protein Kaede to simultaneously analyze birthdate and cell fate in live zebrafish embryos. We found that trigeminal sensory ganglia are formed from early-born and late-born neurons. Early-born neurons give rise to multiple classes of sensory neurons that express different ion channels. By contrast,late-born neurons are restricted in their fate and do not form chemosensory neurons expressing the ion channel TrpA1b. Accordingly, larvae lacking early-born neurons do not respond to the TrpA1b agonist allyl isothiocyanate. These results indicate that the multimodal specification and function of trigeminal sensory ganglia depends on the timing of neurogenesis.
Go West: surgical fellowships in the US
Authors: Freudmann Matt , Wales Lucy
Published: August 2008

As a final-year trainee in vascular surgery, I was working at the West London Renal and Transplant Centre for Professor Nadey Hakim and Vassilios Papalois. I am very grateful to both of them for encouraging me to apply for a visiting fellowship to the United States, enabling me to experience some of the benefits of surgical training abroad and to broaden my perspectives in transplantation. I was awarded a visiting fellowship to the University of Minnesota Transplant Center by Professor David Sutherland, head of the division of transplant surgery.
Keeping the future in safe hands
Authors: Extance-Vaughan Nicola
Published: August 2008

Each year legacies generously left to the College support all areas of our work including education, research and heritage. Although unrestricted legacies allow us the flexibility to allocate the funds where the need is greatest, those who choose to leave a bequest to the specific needs of the education department go a long way in enabling us to ensure comprehensive training for the surgeons of tomorrow.
College response to Darzi Review
Authors: Edwards Simon
Published: August 2008

No new targets and a focus on quality of care were the two main messages coming from Lord Darzi's Next Stage Review final report, published at the end of June to coincide with the celebration of the 60th anniversary of the NHS. The review provides a vision for the new foundations for the health service of empowered staff and patient choice but with little detail on the delivery frame work. This vision is the star t of the next stage of NHS reform for the coming ten years.
Consultants and the EWTD
Authors: Horrocks Michael , Cripps Jo
Published: August 2008

The deadline for full implementation of the European Working Time Directive (EWTD) is fast approaching. By now we should all know the requirements for trainees but what does the EWTD mean for consultant surgeons? In this article we outline the position of consultants and discuss what full implementation of the directive might mean for them.
Continuing professional development: advice for surgeons
Authors: Clarke Ray
Published: August 2008

This article is written on behalf of the chairman and members of the pan-specialty recertification project board continuing professional development subgroup. The author would like to thank Professor Graham Layer (chairman), Chris Chilton, Professor Louise Higgins, Patrick Magennis, Professor Peter McCollum, Alan McKay, David Limb, Joe O'Donoghue, Professor John Pepper, Dr Alistair Thomson and David Hanson for their contribution.
The College library: 'a public benefit and an honour'
Authors: Knight Thalia
Published: August 2008

Visitors to the College have the chance to see the elegant library reading room designed by Sir Charles Barry, architect of the Houses of Parliament, and rebuilt between 1834 and 1836. Together with the 1828 portico and the main entrance it is the only part of the College to survive the 1941 bombing and is listed as Grade II* by English Heritage. During Open House, which takes place on 20 September in 2008 (see http://www.openhouse.org.uk/london/home.html), members of the public will also have the opportunity to view the room. It is still recognisably the same as in the photograph taken in the early 1890s (top of article). The day-to-day services have, however, changed enormously in line with the evolution of medical education and the practice of surgery.
DCP registration: the challenge of meeting new educational needs
Authors: Hunter Sally
Published: August 2008

One of the major issues to impact on the dental profession in the UK in recent years has been the introduction of mandatory registration with the General Dental Council (GDC) for dental care professionals (DCPs). Sally Hunter looks at the educational opportunities and challenges that DCP registration has presented.
Laminin-511 but Not -332, -111, or -411 Enables Mouse Embryonic Stem Cell Self-Renewal In Vitro
Authors: Domogatskaya Anna , Rodin Sergey , Boutaud Ariel , Tryggvason Karl
Published: August 2008

We tested specific laminin (LN) isoforms for their ability to serve as substrata for maintaining mouse embryonic stem (ES) cells pluripotent in vitro in the absence of leukemia inhibitory factor or any other differentiation inhibitors or feeder cells. Recombinant human LN-511 alone was sufficient to enable self-renewal of mouse ES cells for up to 169 days (31 passages). Cells cultured on LN-511 maintained expression of pluripotency markers, such as Oct4, Sox2, Tert, UTF1, and Nanog, during the entire period, and cells cultured for 95 days (17 passages) were used to generate chimeric mice. LN-332 enabled ES cells proliferation but not pluripotency. In contrast, under the same conditions LN-111, Matrigel, and gelatin caused rapid differentiation, whereas LN-411 and poly-d-lysine did not support survival. ES cells formed a thin monolayer on LN-511 that differed strikingly from typical dense cluster ES cell morphology. However, expression of pluripotency markers was not affected by morphological changes. The effect was achieved at low ES cell density (<200 cell/mm2). The ability of LN-511 and LN-332 to support ES cell proliferation correlated with increased cell contact area with those adhesive substrata. ES cells interacted with LN-511 via β1-integrins, mostly α6β1 and αVβ1. This is the first demonstration that certain extracellular matrix molecules can support ES cell self-renewal in the absence of differentiation inhibitors and at low cell density. The results suggest that recombinant laminin isoforms can provide a basis for defined surface coating systems for feeder-free maintenance of undifferentiated mammalian ES cells in vitro.

Disclosure of potential conflicts of interest is found at the end of this article.
A Cross-Talk Between Stromal Cell-Derived Factor-1 and Transforming Growth Factor-β Controls the Quiescence/Cycling Switch of CD34+ Progenitors Through FoxO3 and Mammalian Target of Rapamycin
Authors: Chabanon Aurélie , Desterke Christophe , Rodenburger Emilie , Clay Denis , Guerton Bernadette , Boutin Laetitia , Bennaceur-Griscelli Annelise , Pierre-Louis Olivier , Uzan Georges , Abecassis Lucile , Bourgeade Marie-Françoise , Lataillade Jean-Jacques , Le Bousse-Kerdilès Marie-Caroline
Published: August 2008

Cell cycle regulation plays a fundamental role in stem cell biology. A balance between quiescence and proliferation of hematopoietic stem cells in interaction with the microenvironment is critical for sustaining long-term hematopoiesis and for protection against stress. We analyzed the molecular mechanisms by which stromal cell-derived factor-1 (SDF-1) exhibited a cell cycle-promoting effect and interacted with transforming growth factor-β (TGF-β), which has negative effects on cell cycle orchestration of human hematopoietic CD34+ progenitor cells. We demonstrated that a low concentration of SDF-1 modulated the expression of key cell cycle regulators such as cyclins, cyclin-dependent kinase inhibitors, and TGF-β target genes, confirming its cell cycle-promoting effect. We showed that a cross-talk between SDF-1- and TGF-β-related signaling pathways involving phosphatidylinositol 3-kinase (PI3K)/Akt phosphorylation participated in the control of CD34+ cell cycling. We demonstrated a pivotal role of two downstream effectors of the PI3K/Akt pathway, FoxO3a and mammalian target of rapamycin, as connectors in the SDF-1-/TGF-β-induced control of the cycling/quiescence switch and proposed a model integrating a dialogue between the two molecules in cell cycle progression. Our data shed new light on the signaling pathways involved in SDF-1 cell cycle-promoting activity and suggest that the balance between SDF-1- and TGF-β-activated pathways is critical for the regulation of hematopoietic progenitor cell cycle status.

Disclosure of potential conflicts of interest is found at the end of this article.
Enhanced Reprogramming of Xist by Induced Upregulation of Tsix and Dnmt3a
Authors: Do Jeong Tae , Han Dong Wook , Gentile Luca , Sobek-Klocke Inge , Stehling Martin , Schöler Hans R.
Published: August 2008

Reactivation of Oct4 gene expression occurs within 2 days of fusion of somatic cells with pluripotent stem cells and within 9 days of postinfection of four transcription factors. We sought to determine whether somatic genome reprogramming is completed by the onset of Oct4 reactivation. The complex regulation of the reactivation of inactive X chromosome (Xi) serves as a model for studying reprogramming of chromatin domains. A time-course analysis of the DNA methylation, gene expression, and X inactivation-specific transcript (Xist)/Tsix RNA fluorescence in situ hybridization revealed that expression of pluripotency- and tissue-specific marker genes was reset to the level of pluripotent stem cells within 2 days of fusion, whereas reprogramming of Xist/reactivation of Xi took at least 9 days. We found that trichostatin A, which normally activates gene expression, results in downregulation of Xist. This is due to activation of Dnmt3a and Tsix, two negative regulators of Xist. Moreover, delayed reprogramming of Xist/reactivation of inactive X chromosome after cell fusion was accelerated by DNA methylation and histone deacetylation of Xist, which follow upregulation of Dnmt3a and Tsix.

Disclosure of potential conflicts of interest is found at the end of this article.
Don't Look: Growing Clonal Versus Nonclonal Neural Stem Cell Colonies
Authors: Coles-Takabe Brenda L.K. , Brain Ian , Purpura Kelly A. , Karpowicz Phillip , Zandstra Peter W. , Morshead Cindi M. , van der Kooy Derek
Published: August 2008

Recent reports have challenged the clonality of the neurosphere assay in assessing neural stem cell (NSC) numbers quantitatively. We tested the clonality of the neurosphere assay by culturing mixtures of differently labeled neural cells, watching single neural cells proliferate using video microscopy, and encapsulating single NSCs and their progeny. The neurosphere assay gave rise to clonal colonies when using primary cells plated at 10 cells/μl or less; however, when using passaged NSCs, the spheres were clonal only if plated at 1 cell/μl. Most important, moving the plates during the growth phase (to look at cultures microscopically) greatly increased the incidence of nonclonal colonies. To ensure clonal sphere formation and investigate nonautonomous effects on clonal sphere formation frequencies, single NSCs were encapsulated in agarose and proliferated as clonal free-floating spheres. We demonstrate that clonal neurospheres can be grown by avoiding movement-induced aggregation, by single-cell tracking, and by encapsulation of single cells.

Disclosure of potential conflicts of interest is found at the end of this article.
The role of JUN in the regulation of PRKCC-mediated STAR expression and steroidogenesis in mouse Leydig cells
Authors: Manna Pulak R , Stocco Douglas M
Published: August 2008

Activator protein 1 (JUN) transcription factors (JUN and FOS) play critical roles in a wide variety of signaling processes including those in the protein kinase C (PRKCC) pathway, a pathway that is instrumental in the expression of the steroidogenic acute regulatory (STAR) protein. In the present study, we determined the functional involvement of one of the key JUN family members, JUN, in the regulation of PRKCC-dependent STAR expression and steroidogenesis. MA-10 mouse Leydig tumor cells treated with an activator of PRKCC, phorbol 12-myristate 13-acetate (PMA), demonstrated increases in the expression of the STAR and CYP11A1 proteins and progesterone synthesis, which coincided with the expression and phosphorylation of JUN (P-JUN). PMA was also capable of enhancing the cAMP analog, (Bu)2cAMP, which stimulated JUN, STAR, P-STAR and progesterone levels. The induction of Jun mRNA expression and steroid synthesis by PMA requires de novo protein synthesis. Chromatin immunoprecipitation studies revealed the association of P-JUN with the STAR proximal promoter and that PMA specifically enhanced in vivo P-JUN–DNA interaction. Electrophoretic mobility shift assays and reporter gene analyses demonstrated that JUN binds to the JUN motif (−81/−75 bp) in the STAR promoter, and that JUN–DNA-binding activity was highly correlated with the induction of JUN by PRKCC signaling. Overexpression of JUN increased the PMA-mediated transcription of the Star gene, an event markedly decreased by TAM-67, a dominant negative mutant of JUN. Targeted silencing of endogenous JUN, by small interfering RNA, was correlated with the repression of basal- and PMA-mediated STAR expression and progesterone synthesis. These findings describe the mechanisms by which JUN influences PRKCC signaling and provide additional and novel insight into the regulation of the steroidogenic machinery in mouse Leydig cells.
Acute effects of endocannabinoid anandamide and CB1 receptor antagonist, AM251 in the regulation of thyrotropin secretion
Authors: da Veiga Marco Aurélio Liberato Costa , Fonseca Bloise Flávia , Costa-e-Sousa Ricardo Henrique , Souza Luana Lopes , Almeida Norma Aparecida dos Santos , Oliveira Karen Jesus , Pazos-Moura Carmen Cabanelas
Published: August 2008

We examined the acute effects of endocannabinoid, anandamide, and of synthetic cannabinoid receptor antagonist, AM251[N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide], on TSH, thyroxine (T4), and triiodothyronine (T3) secretions. Euthyroid male rats showed a 42% decrease in serum TSH, 2 h after a single i.p. injection of 0.02, but not 0.2 mg/kg body weight (BW), anandamide, accompanied by a 39% reduction in serum T4, without alteration in serum T3. At 0.5 and 1 h, these serum hormones showed no significant change. Hypothyroid rats showed a 35% reduction in serum TSH (P<0.01), 2 h after anandamide injection, which had no effect on hyperthyroid rats. In both thyroid states, no modification of serum thyroid hormones was observed. Intraperitoneal injection of 0.17 or 1.7 mg/kg BW AM251 in euthyroid rats caused, 1.5 h later, 1.7-fold or 4.3-fold increase in serum TSH respectively, without changing thyroid hormones. Stimulatory effect of 0.17 mg/kg BW AM251 and inhibitory effect of anandamide was abolished in the group injected with AM251 followed by an anandamide injection, 30 min later. Intracerebroventricular injection of 20 ng (but not 200 ng) anandamide induced a decrease in serum TSH at 60 min after injection, which tended to disappear at 120 min. Anterior pituitary explants presented significant reduction in TSH release in the presence of 10−7 M anandamide in incubation medium, which was blocked by 10−7 M AM251. In conclusion, anandamide has the ability to acutely inhibit TSH release in eu- and hypothyroid rats, acting at the hypothalamus–pituitary axis. Since, in addition, the cannabinoid receptor antagonist AM251 increased TSH release, we suggest that endocannabinoid system has a role as negative regulator of TSH secretion.
Application of the Experiential Learning Cycle in Learning from a Business Simulation Game
Authors: Ahn Jung-Hoon
Published: August 2008

The purpose of this study was to investigate the effects of engaging students in Kolb's experiential learning cycle on facilitating students' simulation game performance and knowledge application skills in learning with a business simulation game. A sample was drawn from a population of business-major undergraduate students at the School of Business at Yonsei University in Seoul, Korea. A total of 57 subjects, who were enrolled in the entrepreneurship course in the fall semester of the 2006 school year, participated in the study. This study used two different types of prompt questions – the strategy question and the knowledge application questions – to engage subjects in the reflective observation step and the abstract conceptualisation step of Kolb's experiential learning cycle respectively. The results of data analysis revealed that subjects, who were engaged both in the reflective observation step and the abstract conceptualisation step of Kolb's experiential learning cycle, scored higher in the knowledge application posttest, and performed better in the business simulation game than subjects who were engaged only in the reflective observation step. Data analysis also found that subjects' knowledge application skills were positively correlated with their simulation game performance scores. The survey results indicated that subjects who were engaged both in the reflective observation step and the abstract conceptualisation step of Kolb's experiential learning cycle perceived their learning experience more positively than subjects who were engaged only in the reflective observation step did, and furthermore, subjects' positive perceptions of their learning experience were positively correlated with their simulation game performance scores.
Tech Writing, Meet Tomb Raider: Video and Computer Games in the Technical Communication Classroom
Authors: Vie Stephanie
Published: August 2008

This article examines the common genre of the usability study in technical communication courses and proposes the incorporation of computer and video games to ensure a rhetorical focus to this genre. As games are both entertaining and educational, their use in the technical communication classroom provides a new perspective on multimodal literacies that is appropriate to meet the needs of twenty-first-century learners. This article both describes a theoretical rationale for the inclusion of video and computer games in the classroom and also offers suggestions for their practical pedagogical incorporation.