bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term outcome with intravenous iloprost in pulmonary arterial hypertension
Authors: Hoeper M. M. , Gall H. , Seyfarth H. J. , Halank M. , Ghofrani H. A. , Winkler J. , Golpon H. , Olsson K. M. , Nickel N. , Opitz C. , Ewert R.
Published: February 2009

There is limited data on the long-term efficacy of intravenous iloprost in patients with pulmonary arterial hypertension (PAH).

This retrospective multicentre analysis evaluated the clinical course of patients with PAH treated withi.v.iloprost, in most cases after having received inhaled iloprost as first-line therapy.

Between 1997 and 2001, 79 PAH patients were treated withi.v.iloprost and followed until 2007. These patients had advanced and progressive disease as indicated by a mean pulmonary vascular resistance of 1,533 dyn·s·cm−5at the time of diagnosis and of 1,858 dyn·s·cm−5at the onset ofi.v.iloprost therapy. Introduction ofi.v.iloprost therapy resulted in initial haemodynamic and clinical improvement. At the end of the observation period, however, 50 (61%) patients had died and 21 (26%) required lung transplantation. Transplantation-free survival rates at 1, 3, and 5 yrs were 86%, 59% and 45%, respectively, after the diagnosis of PAH, and 54%, 31% and 15%, respectively, after the introduction ofi.v.iloprost therapy. Predictors of an adverse outcome at baseline were a low 6-min walk distance and a low mixed venous oxygen saturation.

In conclusion, despite initial haemodynamic and clinical improvement, overall long-term survival withi.v.iloprost therapy was limited.
Acute effects of outdoor air pollution on forced expiratory volume in 1 s: a panel study of schoolchildren with asthma
Authors: Dales R. , Chen L. , Frescura A. M. , Liu L. , Villeneuve P. J.
Published: February 2009

Urban air pollution has been associated with morbidity but little information exists on how it affects diurnal variation of lung function in children with asthma. The purpose of this study was to investigate the acute effects of traffic-related pollution on lung function among children with asthma.

We recorded morning and evening forced expiratory volume in 1 s (FEV1) for 28 consecutive days in 182 elementary schoolchildren with physician-diagnosed asthma, and monitored ambient hourly air pollution concentrations.

An interquartile range (IQR) increase (6.0 μg·m−3) in the previous 24-h (20:00 h to 20:00 h) mean concentration of fine particulate matter 2.5 μm in diameter (PM2.5) was associated with a 0.54% (95% confidence interval (CI) 0.06–1.02) decrease in bedtime FEV1(p = 0.027). This association persisted in two-pollutant models with ozone, nitrogen dioxide and sulphur dioxide. An IQR increase in mean daytime (08:00 h to 20:00 h) PM2.5of 6.5 μg·m−3was associated with a 0.73% (95% CI 0.10–1.37) decrease in FEV1over the course of the day expressed as 100×(FEV1bedtime − FEV1morning)/FEV1morning (p = 0.024).

This study suggests that, in children with asthma, relatively low concentrations of urban air pollution worsen lung function over a short period of time, even within a day. Of the pollutants measured, PM2.5appears to be the most important.
Epidemiology and clinical management of XDR-TB: a systematic review by TBNET
Authors: Sotgiu G. , Ferrara G. , Matteelli A. , Richardson M. D. , Centis R. , Ruesch-Gerdes S. , Toungoussova O. , Zellweger J-P. , Spanevello A. , Cirillo D. , Lange C. , Migliori G. B.
Published: February 2009

Extensively drug-resistant tuberculosis (XDR-TB) is present in all regions and poses serious challenges for public health and clinical management. Laboratory diagnosis is difficult and little evidence exists to guide clinicians in treating people with XDR-TB effectively. To summarise the available data on diagnosis and treatment, the current authors performed a systematic review on 13 recent studies of the epidemiology and clinical management of XDR-TB.

Studies that met inclusion criteria were reviewed, in order to assess methodology, treatment regimens and treatment outcomes.

Meta-analysis of currently available data is not possible because of inconsistent definitions and methodologies. Data show that XDR-TB can be successfully treated in up to 65% of patients, particularly those who are not co-infected with HIV. However, treatment duration is longer and outcomes are in general poorer than for non-XDR TB patients.

To strengthen the evidence for extensively drug-resistant tuberculosis diagnosis, treatment and prevention, future studies should: 1) be prospective in design; 2) adopt standardised, internationally accepted definitions; 3) use quality-assured laboratory testing for all first- and second-line drugs; and 4) collect data on an agreed-upon set of standard variables, allowing for comparisons across studies. Early diagnosis and aggressive management of extensively drug-resistant tuberculosis provide the best chance of positive outcome, but prevention is still paramount.
Second-hand smoke exposure in a sample of European hospitals
Authors: Fernández E. , Martínez C. , Fu M. , Martínez-Sánchez J. M. , López M. J. , Invernizzi G. , Ouranou A. , Dautzenberg B. , Nebot M.
Published: February 2009

Smoking in hospitals is banned in many European countries; nevertheless, the level of compliance is diverse, and, in some cases, smoking areas remain. The present study describes the levels of second-hand smoke, as derived from respirable suspended particle measurements, in a sample of European hospitals during the year 2007.

The present study was a multicentric descriptive cross-sectional study carried out in 30 hospitals in seven European countries (Austria, Belgium, France, Germany, Greece, Romania and Spain). Particulate matter with a 50% cut-off aerodynamic diameter of 2.5 μm (PM2.5) concentration was measured by means of a hand-held laser-operated monitor of particle size and mass concentration in six selected indoor locations. Medians and interquartile ranges of PM2.5concentration were computed in order to describe the data by country and location of measurement.

The median PM2.5concentration in all countries and locations was 3.0 μg·m−3, with half of the measurements ranging 2.0–7.0 μg·m−3. PM2.5levels were similar across countries. Eleven (5.5%) measurements were >25.0 μg·m−3, which is the 24-h mean limit recommended by the World Health Organization outdoor air quality guideline.

The present results show that exposure to second-hand smoke in this sample of European hospitals is very low, and can be easily monitored in order to ensure smoke-free legislation compliance.
Inhaled iloprost for the treatment of pulmonary hypertension
Authors: Olschewski H.
Published: February 2009

Prostacyclin and its analogues (prostanoids) are potent vasodilators, and exhibit antithrombotic, antiproliferative and anti-inflammatory properties. Pulmonary arterial hypertension (PAH) is characterised by vasoconstriction, thrombosis and proliferation, and is associated with reduced synthesis of endogenous prostacyclin. This provides a strong rationale for the use of prostanoids to treat PAH, a concept that is now supported by more than two decades of clinical research and experience. Intravenous and subcutaneous prostanoids have clearly demonstrated efficacy in severe PAH, but adverse events related to the drug delivery system, systemic side-effects and tachyphylaxis have driven research into alternative prostanoid treatments.

Iloprost is administered by inhalation, and thus avoids most of the systemic side-effects associated withi.v.or subcutaneous prostanoid infusion. Two randomised controlled 12-week trials in patients with PAH have demonstrated efficacy and a favourable safety profile for iloprost as monotherapy (the AIR trial) and in combination with oral bosentan (STEP). Open-label uncontrolled long-term studies of inhaled iloprost therapy indicate that this treatment may improve long-term outcomes in PAH.
Activated mammalian target of rapamycin is associated with T regulatory cell insufficiency in nasal polyps
Authors: Xu Geng , Xia Jiahong , Hua Xiaoyang , Zhou Han , Yu Chuanzhao , Liu Zheng , Cai Kemin , Shi Jianbo , Li Huabin
Published: February 2009

Background

Decreased infiltration of Foxp3+ T regulatory cell (Treg) is considered to be critical for the Th1/Th2 dysregulation of nasal polyps, while the cellular mechanism underlying Foxp3+ Treg insufficiency is currently not well defined.

Methods

We attempted to investigate the tissue expression of phosphorylated mammalian target of rapamycin (pmTOR) and infiltration of Foxp3+ Tregs in 28 nasal polyps and 16 controls by histological staining. We also evaluated the effects of blocking the mTOR signaling pathway with rapamycin on T cell phenotype selection and Foxp3+CD4+ Tregs expansion in a tissue culture system.

Results

Significantly increased infiltration of pmTOR+ inflammatory cells and decreased infiltration of Foxp3+CD4+ Tregs into nasal polyps was observed, with an inverse association. In the tissue culture system, we detected significantly elevated Foxp3 expression and IL-10 production, as well as an increased percentage of Foxp3+ Tregs in nasal polyps after blocking the mTOR signaling pathway with rapamycin.

Conclusion

Here we demonstrate for the first time that the mTOR signaling pathway is associated with Foxp3+ Tregs insufficiency in nasal polyps. Inhibition of the mTOR signaling pathway may be helpful for enhancement of Foxp3+ Treg expansion, as well as modulation of T cell phenotype imbalances in nasal polyps.
Clustering of cancer among families of cases with Hodgkin Lymphoma (HL), Multiple Myeloma (MM), Non-Hodgkin's Lymphoma (NHL), Soft Tissue Sarcoma (STS) and control subjects
Authors: McDuffie Helen H , Pahwa Punam , Karunanayake Chandima P , Spinelli John J , Dosman James A
Published: February 2009

Background

A positive family history of chronic diseases including cancer can be used as an index of genetic and shared environmental influences. The tumours studied have several putative risk factors in common including occupational exposure to certain pesticides and a positive family history of cancer.

Methods

We conducted population-based studies of Hodgkin lymphoma (HL), Multiple Myeloma (MM), non-Hodgkin's Lymphoma (NHL), and Soft Tissue Sarcoma (STS) among male incident case and control subjects in six Canadian provinces. The postal questionnaire was used to collect personal demographic data, a medical history, a lifetime occupational history, smoking pattern, and the information on family history of cancer. The family history of cancer was restricted to first degree relatives and included relationship to the index subjects and the types of tumours diagnosed among relatives. The information was collected on 1528 cases (HL (n = 316), MM (n = 342), NHL (n = 513), STS (n = 357)) and 1506 age ± 2 years and province of residence matched control subjects. Conditional logistic regression analyses adjusted for the matching variables were conducted.

Results

We found that most families were cancer free, and a minority included two or more affected relatives. HL [(ORadj(95% CI)1.79 (1.33, 2.42)], MM(1.38(1.07, 1.78)), NHL(1.43 (1.15, 1.77)), and STS cases(1.30(1.00, 1.68))had higher incidence of cancer if any first degree relative was affected with cancer compared to control families. Constructing mutually exclusive categories combining "family history of cancer" (yes, no) and "pesticide exposure ≥10 hours per year" (yes, no) indicated that a positive family history was important for HL(2.25(1.61, 3.15)), and for the combination of the two exposures increased risk for MM(1.69(1.14,2.51)). Also, a positive family history of cancer both with(1.72 (1.21, 2.45))and without pesticide exposure(1.43(1.12, 1.83))increased risk of NHL.

Conclusion

HL, MM, NHL, and STS cases had higher incidence of cancer if any first degree relative affected with cancer compared to control families. A positive family history of cancer and/or shared environmental exposure to agricultural chemicals play an important role in the development of cancer.
Overexpression of RRM2 decreases thrombspondin-1 and increases VEGF production in human cancer cells in vitro and in vivo: implication of RRM2 in angiogenesis
Authors: Zhang Keqiang , Hu Shuya , Wu Jun , Chen Linling , Lu Jianming , Wang Xiaochen , Liu Xiyong , Zhou Bingsen , Yen Yun
Published: February 2009

Background

In addition to its essential role in ribonucleotide reduction, ribonucleotide reductase (RNR) small subunit, RRM2, has been known to play a critical role in determining tumor malignancy. Overexpression of RRM2 significantly enhances the invasive and metastatic potential of tumor. Angiogenesis is critical to tumor malignancy; it plays an essential role in tumor growth and metastasis. It is important to investigate whether the angiogenic potential of tumor is affected by RRM2.

Results

We examined the expression of antiangiogenic thrombospondin-1 (TSP-1) and proangiogenic vascular endothelial growth factor (VEGF) in two RRM2-overexpressing KB cells: KB-M2-D and KB-HURs. We found that TSP-1 was significantly decreased in both KB-M2-D and KB-HURs cells compared to the parental KB and mock transfected KB-V. Simultaneously, RRM2-overexpressing KB cells showed increased production of VEGF mRNA and protein. In contrast, attenuating RRM2 expression via siRNA resulted in a significant increased TSP-1 expression in both KB and LNCaP cells; while the expression of VEGF by the two cells was significantly decreased under both normoxia and hypoxia. In comparison with KB-V, overexpression of RRM2 had no significant effect on proliferation in vitro, but it dramatically accelerated in vivo subcutaneous growth of KB-M2-D. KB-M2-D possessed more angiogenic potential than KB-V, as shown in vitro by its increased chemotaxis for endothelial cells and in vivo by the generation of more vascularized tumor xenografts.

Conclusion

These findings suggest a positive role of RRM2 in tumor angiogenesis and growth through regulation of the expression of TSP-1 and VEGF.
Protein evolution on a human signaling network
Authors: Cui Qinghua , Purisima Enrico O , Wang Edwin
Published: February 2009

Background

The architectural structure of cellular networks provides a framework for innovations as well as constraints for protein evolution. This issue has previously been studied extensively by analyzing protein interaction networks. However, it is unclear how signaling networks influence and constrain protein evolution and conversely, how protein evolution modifies and shapes the functional consequences of signaling networks. In this study, we constructed a human signaling network containing more than 1,600 nodes and 5,000 links through manual curation of signaling pathways, and analyzed the d
N/d
S values of human-mouse orthologues on the network.

Results

We revealed that the protein d
N/d
S value decreases along the signal information flow from the extracellular space to nucleus. In the network, neighbor proteins tend to have similar d
N/d
S ratios, indicating neighbor proteins have similar evolutionary rates: co-fast or co-slow. However, different types of relationships (activating, inhibitory and neutral) between proteins have different effects on protein evolutionary rates, i.e., physically interacting protein pairs have the closest evolutionary rates. Furthermore, for directed shortest paths, the more distant two proteins are, the less chance they share similar evolutionary rates. However, such behavior was not observed for neutral shortest paths. Fast evolving signaling proteins have two modes of evolution: immunological proteins evolve more independently, while apoptotic proteins tend to form network components with other signaling proteins and share more similar evolutionary rates, possibly enhancing rapid information exchange between apoptotic and other signaling pathways.

Conclusion

Major network constraints on protein evolution in protein interaction networks previously described have been found for signaling networks. We further uncovered how network characteristics affect the evolutionary and co-evolutionary behavior of proteins and how protein evolution can modify the existing functionalities of signaling networks. These new insights provide some general principles for understanding protein evolution in the context of signaling networks.
Converted-wave resolution
Authors: Meier Mark A. , Lee Paul J.
Published: February 2009

Seismic-resolution theory used in survey design applies to P- and S-wave reflection seismology but is not readily applicable to converted waves. We rederived the theory with sufficient generality to include converted waves explicitly. Generalization of the theory requires that the inherent converted-wave properties of mode change and finite scattering angle be accommodated. The significance of amplitude fidelity in modern seismic applications also affects the resolution description. We considered resolution in the context of a single recorded trace (trace resolution) and an image derived from many traces (image resolution). Trace resolution is governed by wavelet width, which results in a minimum bandwidth requirement, depending on scattering angle and local propagation velocities of incident and scattered modes. Image resolution is governed additionally by the migration acceptance angle and results in minimum aperture and sampling requirements. The requirements for converted-wave surveys generally differ from those of P- and S-wave surveys. Our theory predicts converted-wave reflection seismology resolution and provides the minimum acquisition parameters required to achieve resolution objectives.
Psychogenic amnesia: when memory complaints are medically unexplained
Authors: McKay Gavin C. M. , Kopelman Michael D.
Published: February 2009

The focus of this article is the assessment and management of medically unexplained (‘psychogenic’) amnesia, which we classify here as global or situation specific. Other psychiatric causes for memory disorder and neurological conditions that could cause diagnostic confusion are briefly reviewed, as are forensic aspects of memory complaints. Finally, brain and physiological mechanisms potentially associated with psychogenic amnesia are discussed.
Mental health of regular and reserve military veterans
Authors: Iversen Amy C. , Greenberg Neil
Published: February 2009

The psychiatric problems of combat returnees are a topical and important issue given the ongoing conflicts in Iraq and Afghanistan. Despite the media prominence afforded to post-traumatic stress disorder, the most common disorders in the UK armed forces post-deployment are depression, alcohol misuse and anxiety disorders. Although the majority of service personnel do well after leaving military life, a minority who leave with psychiatric problems appear to be at risk of social exclusion and ongoing ill health. Reserve veterans are at greater risk as they do not have access to the usual support networks of the regular military. Steps to improve the knowledge and expertise of primary care services about veterans' mental health issues and increasing the availability of treatment options are important and are underway.
Depression, cardiac mortality and all-cause mortality
Authors: Seymour Jeremy , Benning Tony B.
Published: February 2009

Depression is an illness that kills. The links between depression and medical illness are well established and bi-directional, but evidence is mounting that depression increases mortality as well as morbidity in adults, particularly older adults. We examine the evidence that the increase in mortality in depression applies to all-cause mortality as well as cardiac mortality, and describe plausible physiological theories for the association. We conclude that excess mortality arising from depression is a major public health problem that is largely unrecognised and needs to be addressed by a range of clinicians.
Combining antidepressants: a review of evidence
Authors: Palaniyappan Lena , Insole Lisa , Ferrier Nicol
Published: February 2009

Sequenced (stepped) treatment approaches are widely endorsed in the management of depression. Combining antidepressants is a recognised step for those failing to respond to monotherapy. Despite the limited evidence base, this strategy is widely used by clinicians in practice. Not every combination used clinically has a sound neuropharmacological rationale and the use of such combinations may increase the side-effect burden without any additional advantage to the patient. Efficacy of various antidepressant combinations along with the data on side-effect profile and toxicity of such combined treatments are reviewed here. The different combinations are considered by each class of antidepressant available in the UK.
Life after therapy: post-termination boundary violations in psychiatry and psychotherapy
Authors: Sarkar Sameer P.
Published: February 2009

Although recent cases of egregious boundary violations in professional relationships in the UK have led to a concerted and robust government response, the issue of doctors having relationships with former patients is relatively sparsely talked about. Publications by the General Medical Council and the Department of Health deal with this tricky and often contentious matter in some depth. This article discusses the abuse of professional relationships and examines the ethics, law and advances in understanding in the area of doctors' relationships with former patients.
The postgraduate curriculum and assessment programme in psychiatry: the underlying principles
Authors: Holsgrove Gareth , Malik Amit , Bhugra Dinesh
Published: February 2009

Assessment is key to the educational process and plays a significant role in looking at the progress trainees make as a result of training and personal development. Recent developments in curricula have led to substantial changes in assessing progress and attainment throughout postgraduate medical education in the UK. This article outlines the framework used to develop the postgraduate curriculum in psychiatry and describes the nature and purpose of the assessment programme that forms part of this new curriculum. The article considers the principles of medical education that are essential for the success of assessments, not only centrally in the development of the assessment system, but also locally in the delivery of these assessments. The overall context of developments in medical education, as well as the relationship between workplace-based assessments (WPBAs) and formal examinations, are described with specific references to developments in psychiatric training, its curriculum and assessments.
Form and mental state: an interpersonal approach to painting
Authors: Green Jonathan
Published: February 2009

This article is based on the idea that paintings carry much of their cultural power by being ways of embodying states of mind in physical material. It follows that the understanding we have of how people infer mental states in others can also be used to address how we respond to visual art: our facility for inferring mental states can help us understand paintings. In pursuing this argument, I discuss first how artists make meaning in paintings by a process that embodies mental states within a formal structure. Second, I support the notion of a link between the formal structure of art and mental states with evidence from my studies of children's drawings. Third, by analogy with the way we relate to another person's mental states, I look in more detail at the process by which we ‘read’ a painting and in consequence develop an aesthetic relationship to it.
Group psychoeducation for stabilised bipolar disorders: 5-year
outcome of a randomised clinical trial
Authors: Colom F. , Vieta E. , Sánchez-Moreno J. , Palomino-Otiniano R. , Reinares M. , Goikolea J. M. , Benabarre A. , Martínez-Arán A.
Published: February 2009

Background

The long-term efficacy of psychological interventions for bipolar
disorders has not been tested.

Aims

This study assessed the efficacy of group psychoeducation to prevent
recurrences and to reduce time spent ill for people with bipolar
disorders.

Method

A randomised controlled trial with masked outcome assessment comparing
group psychoeducation and non-structured group intervention during 5-year
follow-up. One hundred and twenty people with bipolar disorders were
included in the study and 99 completed 5-year follow-up. Time to any
recurrence, number of recurrences, total number of days spent ill,
frequency and length of hospitalisations were the main outcome
measures.

Results

At the 5-year follow-up, time to any recurrence was longer for the
psychoeducation group (log rank=9.953, P<0.002). The
psychoeducation group had fewer recurrences (3.86 v.
8.37, F=23.6, P<0.0001) of any type
and they spent less time acutely ill (154 v. 586 days,
F=31.66, P=0.0001). The median
number of days of hospitalisation per hospitalised participant was also
lower for the psychoeducation group (45 v. 30,
F=4.26, P=0.047).

Conclusions

Six-month group psychoeducation has long-lasting prophylactic effects in
individuals with bipolar disorders. Group psychoeducation is the first
psychological intervention showing such a long-term maintained efficacy
in people with bipolar disorders.
Attention-deficit hyperactivity disorder: treatment
discontinuation in adolescents and young adults
Authors: McCarthy Suzanne , Asherson Philip , Coghill David , Hollis Chris , Murray Macey , Potts Laura , Sayal Kapil , de Soysa Ruwan , Taylor Eric , Williams Tim , Wong Ian C. K.
Published: February 2009

Background

Symptoms of attention-deficit hyperactivity disorder (ADHD) are known to
persist into adulthood in the majority of cases.

Aims

To determine the prevalence of methylphenidate, dexamfetamine and
atomoxetine prescribing and treatment discontinuation in adolescents and
young adults.

Method

A descriptive cohort study using the UK General Practice Research
Database included patients aged 15–21 years from 1999 to 2006 with a
prescription for a study drug.

Results

Prevalence of prescribing averaged across all ages increased 6.23-fold
over the study period. Overall, prevalence decreased with age: in 2006,
prevalence in males dropped 95% from 12.77 per 1000 in 15-year-olds to
0.64 per 1000 in 21-year-olds. A longitudinal analysis of a cohort of 44
patients aged 15 years in 1999 demonstrated that no patient received
treatment after the age of 21 years.

Conclusions

The prevalence of prescribing by general practitioners to patients with
ADHD drops significantly from age 15 to age 21 years. The fall in
prescribing is greater than the reported age-related decrease in
symptoms, raising the possibility that treatment is prematurely
discontinued in some young adults in whom symptoms persist.
Public attitudes towards people with mental illness in England
and Scotland, 1994–2003
Authors: Mehta Nisha , Kassam Aliya , Leese Morven , Butler Georgia , Thornicroft Graham
Published: February 2009

Background

Understanding trends in public attitudes towards people with mental
illness informs the assessment of ongoing severity of stigma and
evaluation of anti-stigma campaigns.

Aims

To analyse trends in public attitudes towards people with mental illness
in England and Scotland using Department of Health Attitudes to Mental
Illness Surveys, 1994–2003.

Method

We analysed trends in attitudes for 2000 respondents in each survey year
(6000 respondents in 1996 and 1997) using quota sampling methods and the
adapted Community Attitudes Toward the Mentally Ill scale.

Results

Comparing 2000 and 2003, there was significant deterioration for 17/25
items in England and for 4/25 items in Scotland. Neither country showed
significant improvements in items between 2000 and 2003.

Conclusions

Public attitudes towards people with mental illness in England and
Scotland became less positive during 1994–2003, especially in 2000–2003,
and to a greater extent in England. The results are consistent with early
positive effects for the ‘see me’ anti-stigma campaign in Scotland.
Mental health and employment: much work still to be
done
Authors: Harvey Samuel B. , Henderson Max , Lelliott Paul , Hotopf Matthew
Published: February 2009

Mental illness is now the leading cause of both sickness absence and
incapacity benefits in most high-income countries. The rising economic and
social costs make health and work an increasing priority for policy makers.
We discuss the findings from Dame Carol Black's recent review of the health
of Britain's working-age population and examine how her recommendations may
impact and challenge mental health services.
Staff attitudes to smoking and the smoking ban
Authors: Praveen Kudlur Thyarappa , Kudlur Swamy Nirvana Chandrappa , Hanabe Rudresh Paramishiyaiah , Egbewunmi Adeyemi Tiwalade
Published: February 2009

Aims and Method

Our aim was to explore attitudes of in-patient mental health staff to smoking and the smoking ban. A questionnaire was distributed to staff (n=450) working at National Health Service psychiatric units in three different locations.

Results

We obtained 308 responses, at a response rate of 68.4%. Staff were generally less permissive towards smoking in mental health units when compared with previous studies. However, most (78.9%) feared that service users' states would deteriorate if they were not allowed to smoke.

Clinical Implications

We found small but noticeable change in staff attitudes following initial reforms in smoking policy. However, there is a need for further significant change in staff attitudes to facilitate implementation of a total smoking ban from July 2008.
Is psychoeducation routinely provided in the UK? Survey of community mental health teams
Authors: Getachew Henok , Dimic Sara , Priebe Stefan
Published: February 2009

Aims and Method

The study aimed to assess the current provision of psychoeducation programmes for patients with mental illness in the UK. A postal questionnaire was sent randomly to 100 community mental health teams regarding the delivery and characteristics of psychoeducation programmes. Non-responders were contacted via telephone after 8 weeks.

Results

The response rate was 87%. Eight services provided group psychoeducation, 40 provided individual psychoeducation within the care programme approach, and 39 did not provide any psychoeducation programme.

Clinical Implications

Patients with mental illnesses have limited access to psychoeducation in routine care. Group programmes should perhaps be more widely implemented as a relatively low-cost intervention.
Cocaine use and dependence in clients attending a drug treatment centre in Dublin
Authors: Thula Mpho Abel
Published: February 2009

Aims and Method

To assess the number of cocaine-dependent clients attending a typical addiction clinic, using urine drug testing for screening and a structured clinical interview for diagnostic assessment.

Results

Of the 419 clients whose urine records were analysed, 38 were regular users of cocaine (9.1%), with at least half of their urine samples positive for cocaine in a 12-week period; 84.2% of these regular users of cocaine satisfied the criteria for cocaine dependence (7.7% of the total number of those attending the clinic).

Clinical Implications

Publicly funded addiction treatment centres in Ireland are mostly designed for the treatment of opiate addiction. There is, however, a significant problem of concomitant cocaine dependence in these centres. Increased availability of psychological/behavioural treatment programmes with proven efficacy in cocaine addiction may help improve overall treatment outcome.
Self-harm in first-episode psychosis
Authors: Patel Kamlesh , Upthegrove Rachel
Published: February 2009

Aims and Method

Suicide in schizophrenia remains frequent. One of the best predictors of suicide, previous self-harm, is increasing in young people. the aim of this case-note review was to investigate the frequency of a history of self-harm for individuals presenting to psychiatric services with a first episode of psychosis in our local area and study their demographic characteristics.

Results

A history of self-harm was found in 32% of the cohort. the predominant method of self-harm was self-laceration. In univariate analyses, age and gender were significant predictors of self-harming behaviour.

Clinical Implications

The rate of self-harm among those with first-episode psychosis is high. Efforts to reduce the rate of completed suicide in psychotic illness need to focus on this risk, which often predates contact with psychiatric services. This emphasises again the need for early detection and intervention in psychotic illness.
Dr Norman Kaye
Authors: Cameron Douglas
Published: February 2009

Norman Kaye was a consultant psychiatrist in Leicestershire, based at Carlton Hayes Hospital, from 1965 until his retirement in 1988.
Use of 5-α-Reductase Inhibitors for Prostate Cancer Chemoprevention: American Society of Clinical Oncology/American Urological Association 2008 Clinical Practice Guideline
Authors: Kramer Barnett S. , Hagerty Karen L. , Justman Stewart , Somerfield Mark R. , Albertsen Peter C. , Blot William J. , Ballentine Carter H. , Costantino Joseph P. , Epstein Jonathan I. , Godley Paul A. , Harris Russell P. , Wilt Timothy J. , Wittes Janet , Zon Robin , Schellhammer Paul
Published: February 2009

Purpose

To develop an evidence-based guideline on the use of 5-α-reductase inhibitors (5-ARIs) for prostate cancer chemoprevention.

Methods

The American Society of Clinical Oncology (ASCO) Health Services Committee (HSC), ASCO Cancer Prevention Committee, and the American Urological Association Practice Guidelines Committee jointly convened a Panel of experts, who used the results from a systematic review of the literature to develop evidence-based recommendations on the use of 5-ARIs for prostate cancer chemoprevention.

Results

The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period prevalence.

Conclusion

Asymptomatic men with a prostate-specific antigen (PSA) ≤ 3.0 ng/mL who are regularly screened with PSA or are anticipating undergoing annual PSA screening for early detection of prostate cancer may benefit from a discussion of both the benefits of 5-ARIs for 7 years for the prevention of prostate cancer and the potential risks (including the possibility of high-grade prostate cancer). Men who are taking 5-ARIs for benign conditions such as lower urinary tract [obstructive] symptoms (LUTS) may benefit from a similar discussion, understanding that the improvement of LUTS relief should be weighed with the potential risks of high-grade prostate cancer from 5-ARIs (although the majority of the Panel members judged the latter risk to be unlikely). A reduction of approximately 50% in PSA by 12 months is expected in men taking a 5-ARI; however, because these changes in PSA may vary across men, and within individual men over time, the Panel cannot recommend a specific cut point to trigger a biopsy for men taking a 5-ARI. No specific cut point or change in PSA has been prospectively validated in men taking a 5-ARI.
Differential Expression and Functional Characterization of Luteinizing Hormone Receptor Splice Variants in Human Luteal Cells: Implications for Luteolysis
Authors: Dickinson Rachel E. , Stewart Alan J. , Myers Michelle , Millar Robert P. , Duncan W. Colin
Published: February 2009

The human LH receptor (LHR) plays a key role in luteal function and the establishment of pregnancy through its interaction with the gonadotropins LH and human chorionic gonadotropin. We previously identified four splice variants of the LHR in human luteinized granulosa cells (LGCs) and corpora lutea (CL). Real-time quantitative PCR revealed that expression of the full-length LHR (LHRa) and the most truncated form (LHRd) changed significantly in CL harvested at different stages of the ovarian cycle (P < 0.01, ANOVA). LHRa expression was reduced in the late luteal CL (P < 0.05). Conversely, an increase in LHRd expression was observed in the late luteal CL (P < 0.01). Chronic manipulation of human chorionic gonadotropin in LGC primary cultures supported the in vivo findings. LHRd encodes a protein lacking the transmembrane and carboxyl terminal domains. COS-7 cells expressing LHRd were unable to produce cAMP in response to LH stimulation. COS-7 cells coexpressing LHRd and LHRa also failed to generate cAMP in response to LH, suggesting that this truncated form has a negative effect on the signaling of LHRa. Immunofluorescence staining of LGC and COS-7 cells implied that there is a reduction in cell surface expression of LHRa when LHRd is present. Overall, these results imply expression of LHR splice variants is regulated in the human CL. Furthermore, during functional luteolysis a truncated variant could modulate the cell surface expression and activity of full-length LHR.
Persistent Oxidative Stress Due to Absence of Uncoupling Protein 2 Associated with Impaired Pancreatic β-Cell Function
Authors: Pi Jingbo , Bai Yushi , Daniel Kiefer W. , Liu Dianxin , Lyght Otis , Edelstein Diane , Brownlee Michael , Corkey Barbara E. , Collins Sheila
Published: February 2009

Uncoupling protein (UCP) 2 is a widely expressed mitochondrial protein whose precise function is still unclear but has been linked to mitochondria-derived reactive oxygen species production. Thus, the chronic absence of UCP2 has the potential to promote persistent reactive oxygen species accumulation and an oxidative stress response. Here, we show that Ucp2−/− mice on three highly congenic (N >10) strain backgrounds (C57BL/6J, A/J, 129/SvImJ), including two independently generated sources of Ucp2-null animals, all exhibit increased oxidative stress. Ucp2-null animals exhibit a decreased ratio of reduced glutathione to its oxidized form in blood and tissues that normally express UCP2, including pancreatic islets. Islets from Ucp2−/− mice exhibit elevated levels of numerous antioxidant enzymes, increased nitrotyrosine and F4/80 staining, but no change in insulin content. Contrary to results in Ucp2−/− mice of mixed 129/B6 strain background, glucose-stimulated insulin secretion in Ucp2−/− islets of each congenic strain was significantly decreased. These data show that the chronic absence of UCP2 causes oxidative stress, including in islets, and is accompanied by impaired glucose-stimulated insulin secretion.
Ammonia transport in cultured gill epithelium of freshwater rainbow trout: the importance of Rhesus glycoproteins and the presence of an apical Na+/NH4+ exchange complex
Authors: Tsui T. K. N. , Hung C. Y. C. , Nawata C. M. , Wilson J. M. , Wright P. A. , Wood C. M.
Published: February 2009

The mechanisms of ammonia excretion at fish gills have been studied for decades but details remain unclear, with continuing debate on the relative importance of non-ionic NH3 or ionic NH4+permeation by various mechanisms. The presence of an apical Na+/NH4+ exchanger has also been controversial. The present study utilized an in vitro cultured gill epithelium (double seeded insert, DSI) of freshwater rainbow trout as a model to investigate these issues. The relationship between basolateral ammonia concentration and efflux to apical freshwater was curvilinear, indicative of a saturable carrier-mediated component (Km=66 μmol l–1) superimposed on a large diffusive linear component. Pre-exposure to elevated ammonia (2000 μmol l–1) and cortisol (1000 ng ml–1) had synergistic effects on the ammonia permeability of DSI, with significantly increased Na+influx and positive correlations between ammonia efflux and Na+uptake. This increase in ammonia permeability was bidirectional. It could not be explained by changes in paracellular permeability as measured by[3H]PEG-4000 flux. The mRNA expressions of Rhbg, Rhcg2,H+-ATPase and Na+/H+ exchanger-2 (NHE-2) were up-regulated in DSI pre-exposed to ammonia and cortisol, CA-2 mRNA was down-regulated, and transepithelial potential became more negative. Bafilomycin (1 μmol l–1), phenamil (10 μmol l–1) and 5-(N,N-hexamethylene)amiloride (HMA, 10μmol l–1) applied to the apical solution significantly inhibited ammonia efflux, indicating that H+-ATPase, Na+channel and NHE-2 pathways on the apical surface were involved in ammonia excretion. Apical amiloride (100 μmol l–1) was similarly effective, while basolateral HMA was ineffective. Pre-treatment with apical freshwater low in [Na+] caused increases in both Rhcg2 mRNA expression and ammonia efflux without change in paracellular permeability. These data suggest that Rhesus glycoproteins are important for ammonia transport in the freshwater trout gill, and may help to explain in vivo data where plasma ammonia stabilized at 50% below water levels during exposure to high environmental ammonia (∼2300 μmol l–1). We propose an apical`Na+/NH4+ exchange complex' consisting of several membrane transporters, while affirming the importance of non-ionic NH3 diffusion in ammonia excretion across freshwater fish gills.
Yolk androgens and the development of avian immunity: an experiment in jackdaws (Corvus monedula)
Authors: Sandell Maria I. , Tobler Michael , Hasselquist Dennis
Published: February 2009

Maternally derived androgens have been shown to influence offspring phenotype in various ways. In birds, the benefits of prenatal androgen exposure, such as increased competitiveness and accelerated growth in nestlings, have been suggested to be balanced by costs, such as reduced immune function. In this study, we used an integrative approach to examine the influence of yolk androgens on the development of immune function in jackdaw(Corvus monedula) nestlings. Specifically, we tested whether the effects of yolk androgens on offspring immunity may extend over the first few days of life and be detectable even after several weeks. We manipulated yolk androgen concentrations in jackdaw eggs and estimated immune responsiveness by challenging the young with different pathogens at different stages of the nestling period. Six-day-old chicks hatched from eggs with elevated yolk androgen levels had lower pre-challenge antibody titres against lipopolysaccharide (LPS) than control chicks. However, antibody titres against LPS did not differ between treatment groups eight days after a challenge with LPS. During the late nestling phase, both humoral (towards diphtheria/tetanus antigens) and cell-mediated (towards phytohaemagglutinin) immune responsiveness were lower in chicks from yolk androgen-treated eggs compared with control chicks. Our experimental study on jackdaw chicks shows that elevated yolk androgen levels result in a general immunosuppression in offspring; this conclusion was based on results for several immunological tests of both humoral and cell-mediated immunity conducted at 1–2 and 3–4 weeks of age.
From cells to coastlines: how can we use physiology to forecast the impacts of climate change?
Authors: Helmuth Brian
Published: February 2009

The interdisciplinary fields of conservation physiology, macrophysiology,and mechanistic ecological forecasting have recently emerged as means of integrating detailed physiological responses to the broader questions of ecological and evolutionary responses to global climate change. Bridging the gap between large-scale records of weather and climate (as measured by remote sensing platforms, buoys and ground-based weather stations) and the physical world as experienced by organisms (niche-level measurements) requires a mechanistic understanding of how `environmental signals' (parameters such as air, surface and water temperature, food availability, water flow) are translated into signals at the scale of the organism or cell (e.g. body temperature, food capture, hydrodynamic force, aerobic capacity). Predicting the impacts of how changing environments affect populations and ecosystems further mandates an understanding of how organisms `filter' these signals via their physiological response (e.g. whether they respond to high or low frequencies, whether there is a time lag in response, etc.) and must be placed within the context of adult movement and the dispersal of larvae and gametes. Recent studies have shown that patterns of physiological stress in nature are far more complex in space and time than previously assumed and challenge the long-held paradigm that patterns of biogeographic distribution can be based on simple environmental gradients. An integrative, systems-based approach can provide an understanding of the roles of environmental and physiological variability in driving ecological responses and can offer considerable insight and predictive capacity to researchers, resource managers and policy makers involved in planning for the current and future effects of climate change.
Locomotor–feeding coupling during prey capture in a lizard(Gerrhosaurus major): effects of prehension mode
Authors: Montuelle Stéphane J. , Herrel Anthony , Libourel Paul-Antoine , Reveret Lionel , Bels Vincent L.
Published: February 2009

In tetrapods, feeding behaviour in general, and prey capture in particular,involves two anatomical systems: the feeding system and the locomotor system. Although the kinematics associated with the movements of each system have been investigated in detail independently, the actual integration between the two systems has received less attention. Recently, the independence of the movements of the jaw and locomotor systems was reported during tongue-based prey capture in an iguanian lizard (Anolis carolinensis), suggesting a decoupling between the two systems. Jaw prehension, on the other hand, can be expected to be dependent on the movements of the locomotor system to a greater degree. To test for the presence of functional coupling and integration between the jaw and locomotor systems, we used the cordyliform lizard Gerrhosaurus major as a model species because it uses both tongue and jaw prehension. Based on a 3-D kinematic analysis of the movements of the jaws, the head, the neck and the forelimbs during the approach and capture of prey, we demonstrate significant correlations between the movements of the trophic and the locomotor systems. However, this integration differs between prehension modes in the degree and the nature of the coupling. In contrast to our expectations and previous data for A. carolinensis,our data indicate a coupling between feeding and locomotor systems during tongue prehension. We suggest that the functional integration between the two systems while using the tongue may be a consequence of the relatively slow nature of tongue prehension in this species.