bluuebunny/crossref_metadata_2025 huggingface dataset:
Soluble guanylate cyclase stimulation: an emerging option in pulmonary hypertension therapy
Authors: Ghofrani H. A. , Grimminger F.
Published: February 2009

The prognosis for patients with pulmonary hypertension remains poor despite recent treatment advances, and there is a need for therapies with new modes of action. Nitric oxide (NO) is an endogenous vasodilator, the levels of which are regulated throughout the lung to ensure preferential perfusion of well-ventilated regions. Drugs that act in synergy with endogenous NO would therefore promote pulmonary vasodilation while maintaining optimal gas exchange.

Riociguat is an oral stimulator of the NO receptor soluble guanylate cyclase. It synergises with NO and has demonstrated vasodilatory and antiremodelling properties in preclinical studies. Riociguat has been shown to have a favourable safety profile in healthy volunteers and in patients with pulmonary hypertension. Pharmacokinetic analyses have revealed substantial interindividual variation, suggesting that individual dose titration will be required.

In a proof-of-concept study of patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension, riociguat improved cardiopulmonary haemodynamics from baseline. It also caused systemic vasodilation, which was well tolerated but should be monitored in future studies. Dose titration of riociguat should promote pulmonary vasodilation while maintaining control of systemic effects, and has been investigated in a phase-II study of patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Preliminary results indicate that phase-III trials are warranted.
Fatal rupture of pulmonary arteriovenous malformation in hereditary haemorrhagic telangiectasis and severe PAH
Authors: Montani D. , Price L. C. , Girerd B. , Chinet T. , Lacombe P. , Simonneau G. , Humbert M.
Published: February 2009

A 29-yr-old patient with hereditary haemorrhagic telangiectasia was referred to the present authors’ centre with progressive exertional dyspnoea.

Pulmonary arterial hypertension (PAH) was suspected on Doppler echocardiography and confirmed by right heart catheterisation demonstrating severe PAH. Genetic analysis found an activin receptor-like kinase-1 gene missense mutation. Chest radiography and computed tomodensitometry of the chest revealed a pulmonary arteriovenous malformation with a 5-mm diameter feeding artery in the right lower lobe. Embolisation of the arteriovenous malformation was discussed, but was considered a very high-risk procedure that could aggravate PAH and was therefore not performed. Haemodynamics were improved by dual endothelin receptor antagonist and inhaled iloprost but the patient subsequently died suddenly of a rupture of the arteriovenous malformation into the pleural cavity.

Severe PAH is generally considered a contraindication to performing pulmonary arteriovenous malformation embolisation because of the risk of worsening of PAH. However, given the significant risk of rupture, paradoxical embolism and haemoptysis, and the lack of data regarding the evolution of pulmonary pressure after embolisation in PAH, pulmonary arteriovenous malformation embolisation should not be absolutely contraindicated and might be considered in patients with stable PAH.
The conserved WW-domain binding sites in Dystroglycan C-terminus are essential but partially redundant for Dystroglycan function
Authors: Yatsenko AS , Kucherenko MM , Pantoja M , Fischer KA , Madeoy J , Deng W-M , Schneider M , Baumgartner S , Akey J , Shcherbata HR , Ruohola-Baker H
Published: February 2009

Background

Dystroglycan (Dg) is a transmembrane protein that is a part of the Dystrophin Glycoprotein Complex (DGC) which connects the extracellular matrix to the actin cytoskeleton. The C-terminal end of Dg contains a number of putative SH3, SH2 and WW domain binding sites. The most C-terminal PPXY motif has been established as a binding site for Dystrophin (Dys) WW-domain. However, our previous studies indicate that both Dystroglycan PPXY motives, WWbsI and WWbsII can bind Dystrophin protein in vitro.

Results

We now find that both WW binding sites are important for maintaining full Dg function in the establishment of oocyte polarity in Drosophila. If either WW binding site is mutated, the Dg protein can still be active. However, simultaneous mutations in both WW binding sites abolish the Dg activities in both overexpression and loss-of-function oocyte polarity assays in vivo. Additionally, sequence comparisons of WW binding sites in 12 species of Drosophila, as well as in humans, reveal a high level of conservation. This preservation throughout evolution supports the idea that both WW binding sites are functionally required.

Conclusion

Based on the obtained results we propose that the presence of the two WW binding sites in Dystroglycan secures the essential interaction between Dg and Dys and might further provide additional regulation for the cytoskeletal interactions of this complex.
Full sib pens of pigs are not suitable to identify variance component of associative effect: a simulation study using Gibbs Sampling
Authors: Cheng Jiqiu , Janssens Steven , Buys Nadine
Published: February 2009

Background

Accounting for and quantifying the associative effect of each animal could improve both welfare of animals and response to selection. Because of the limitation of REML, Gibbs Sampling could be an alternative technique to estimate the variance component of the associative effect. The objective of this study was to investigate the estimation accuracy of the variance component of associative effect by using simulation via Gibbs Sampling. The simulated data comprised five generations of pigs. The breeding animals of each generation were selected randomly. In the simulation, variations were introduced for the methods of assigning pens (random, mixed sib and full sib), the number of pigs per pen (5 or 10), the number of breeding animals per generation (162 or 324) and the correlation between genetic direct effect and genetic associative effect (-0.5, 0.1 or +0.5). Each set of simulation was run for 30 replications.

Results

Random assignment or mixed sib assignment resulted in bias of estimated variance components in only 3 of 24 combinations. Furthermore, these 3 cases occurred with 162 breeding animals. With full sib assignment, 9 out of 12 groups of estimates significantly deviated from the true parameter value. The Root Mean Square Errors obtained with the full sib assignment were higher than with the other two methods of pen assignment in most of the cases. The Root Mean Square Errors obtained with datasets with 324 breeding animals were notably smaller than the datasets from 162 breeding animals. Within each method of pen assignment, the relative bias of the associative effect was significantly smaller with group size 10 than with group size 5.

Conclusion

Full sib assignment caused difficulties to estimate variance components in most of the cases, due to a lack of identifiability. With random and mixed assignment, most data structures yielded unbiased results but increasing the number of breeding animals or group size improves the estimation. Thus to get identifiable and unbiased estimates of the genetic associative effect, it is recommended to avoid close genetic relationship between animals within one pen and to use sufficient numbers of breeding animals and sufficient group sizes.
Two mechanisms of the enhanced antibody-dependent cellular cytotoxicity (ADCC) efficacy of non-fucosylated therapeutic antibodies in human blood
Authors: Iida Shigeru , Kuni-Kamochi Reiko , Mori Katsuhiro , Misaka Hirofumi , Inoue Miho , Okazaki Akira , Shitara Kenya , Satoh Mitsuo
Published: February 2009

Background

Antibody-dependent cellular cytotoxicity (ADCC) has recently been identified as one of the critical mechanisms underlying the clinical efficacy of therapeutic antibodies, especially anticancer antibodies. Therapeutic antibodies fully lacking the core fucose of the Fc oligosaccharides have been found to exhibit much higher ADCC in humans than their fucosylated counterparts. However, data which show how fully non-fucosylated antibodies achieve such a high ADCC in human whole blood have not yet been disclosed. The precise mechanisms responsible for the high ADCC mediated by fully non-fucosylated therapeutic antibodies, even in the presence of human plasma, should be explained based on direct evidence of non-fucosylated antibody action in human blood.

Methods

Using a humanex vivoB-cell depletion assay with non-fucosylated and fucosylated anti-CD20 IgG1s rituximab, we monitored the binding of the therapeutic agents both to antigens on target cells (target side interaction) and to leukocyte receptors (FcγR) on effector cells (effector side interaction), comparing the intensities of ADCC in human blood.

Results

In the target side interaction, down-modulation of CD20 on B cells mediated by anti-CD20 was not observed. Simple competition for binding to the antigens on target B cells between fucosylated and non-fucosylated anti-CD20s was detected in human blood to cause inhibition of the enhanced ADCC of non-fucosylated anti-CD20 by fucosylated anti-CD20. In the effector side interaction, non-fucosylated anti-CD20 showed sufficiently high FcγRIIIa binding activity to overcome competition from plasma IgG for binding to FcγRIIIa on natural killer (NK) cells, whereas the binding of fucosylated anti-CD20 to FcγRIIIa was almost abolished in the presence of human plasma and failed to recruit NK cells effectively. The core fucosylation levels of individual serum IgG1 from healthy donors was found to be so slightly different that it did not affect the inhibitory effect on the ADCC of fucosylated anti-CD20.

Conclusion

Our results demonstrate that removal of fucosylated antibody ingredients from antibody therapeutics elicits high ADCC in human blood by two mechanisms: namely, by evading the inhibitory effects both of plasma IgG on FcγRIIIa binding (effector side interaction) and of fucosylated antibodies on antigen binding (target side interaction).
Comparison between the HCV IRES domain IV RNA structure and the Iron Responsive Element
Authors: Tumban Ebenezer , Painter Jenna M , Lott William B
Published: February 2009

Background

Serum ferritin and hepatic iron concentrations are frequently elevated in patients who are chronically infected with the hepatitis C virus (HCV), and hepatic iron concentration has been used to predict response to interferon therapy, but these correlations are not well understood. The HCV genome contains an RNA structure resembling an iron responsive element (IRE) in its internal ribosome entry site (IRES) structural domain IV (dIV). An IRE is a stem loop structure used to control the expression of eukaryotic proteins involved in iron homeostasis by either inhibiting ribosomal binding or protecting the mRNA from nuclease degradation. The HCV structure, located within the binding site of the 40S ribosomal subunit, might function as an authentic IRE or by an IRE-like mechanism.

Results

Electrophoretic mobility shift assays showed that the HCV IRES domain IV structure does not interact with the iron regulatory protein 1 (IRP1)in vitro. Systematic HCV IRES RNA mutagenesis suggested that IRP1 cannot accommodate the shape of the wild type HCV IRES dIV RNA structure.

Conclusion

The HCV IRES dIV RNA structure is not an authentic IRE. The possibility that this RNA structure is responsible for the observed correlations between intracellular iron concentration and HCV infection parameters through an IRE-likemechanism in response to some other cellular signal remains to be tested.
Smells like home: Desert ants, Cataglyphis fortis, use olfactory landmarks to pinpoint the nest
Authors: Steck Kathrin , Hansson Bill S , Knaden Markus
Published: February 2009

Background

Cataglyphis fortis ants forage individually for dead arthropods in the inhospitable salt-pans of Tunisia. Locating the inconspicuous nest after a foraging run of more than 100 meters demands a remarkable orientation capability. As a result of high temperatures and the unpredictable distribution of food, Cataglyphis ants do not lay pheromone trails. Instead, path integration is the fundamental system of long-distance navigation. This system constantly informs a foraging ant about its position relative to the nest. In addition, the ants rely on visual landmarks as geocentric navigational cues to finally pinpoint the nest entrance.

Results

Apart from the visual cues within the ants' habitat, we found potential olfactory landmark information with different odour blends coupled to various ground structures. Here we show that Cataglyphis ants can use olfactory information in order to locate their nest entrance. Ants were trained to associate their nest entrance with a single odour. In a test situation, they focused their nest search on the position of the training odour but not on the positions of non-training odours. When trained to a single odour, the ants were able to recognise this odour within a mixture of four odours.

Conclusion

The uniform salt-pans become less homogenous if one takes olfactory landmarks into account. As Cataglyphis ants associate environmental odours with the nest entrance they can be said to use olfactory landmarks in the vicinity of the nest for homing.
Mice with Cisplatin and Oxaliplatin-Induced Painful Neuropathy Develop Distinct Early Responses to Thermal Stimuli
Authors: Ta Lauren E , Low Philip A , Windebank Anthony J
Published: February 2009

Background

Cisplatin has been in use for 40 years for treatment of germ line and other forms of cancer. Oxaliplatin is approved for treatment of metastatic colorectal cancer. Thirty to forty percent of cancer patients receiving these agents develop pain and sensory loss. Oxaliplatin induces distinctive cold-associated dysesthesias in up to 80% of patients.

Results

We have established mouse models of cisplatin and oxaliplatin-induced neuropathy using doses similar to those used in patients. Adult male C57BL6J mice were treated with daily intraperitoneal injection for 5 days, followed by 5 days of rest, for two cycles. Total cumulative doses of 23 mg/kg cisplatin and 30 mg/kg oxaliplatin were used. Behavioral evaluations included cold plate, von Frey, radiant heat, tail immersion, grip strength and exploratory behavior at baseline and at weekly intervals for 8 weeks. Following two treatment cycles, mice in the cisplatin and oxaliplatin treatment groups demonstrated significant mechanical allodynia compared to control mice. In addition, the cisplatin group exhibited significant thermal hyperalgesia in hind paws and tail, and the oxaliplatin group developed significant cold hyperalgesia in hind paws.

Conclusion

We have therefore established a model of platinum drug-induced painful peripheral neuropathy that reflects the differences in early thermal pain responses that are observed in patients treated with either cisplatin or oxaliplatin. This model should be useful in studying the molecular basis for these different pain responses and in designing protective therapeutic strategies.
Adenomatous polyposis coli is required for early events in the normal growth and differentiation of the developing cerebral cortex
Authors: Ivaniutsin Uladzislau , Chen Yijing , Mason John O , Price David J , Pratt Thomas
Published: February 2009

Background

Adenomatous polyposis coli (Apc) is a large multifunctional protein known to be important for Wnt/β-catenin signalling, cytoskeletal dynamics, and cell polarity. In the developing cerebral cortex, Apc is expressed in proliferating cells and its expression increases as cells migrate to the cortical plate. We examined the consequences of loss of Apc function for the early development of the cerebral cortex.

Results

We used Emx1
Cre
to inactivate Apc specifically in proliferating cerebral cortical cells and their descendents starting from embryonic day 9.5. We observed reduction in the size of the mutant cerebral cortex, disruption to its organisation, and changes in the molecular identity of its cells. Loss of Apc leads to a decrease in the size of the proliferative pool, disrupted interkinetic nuclear migration, and increased apoptosis. β-Catenin, pericentrin, and N-cadherin proteins no longer adopt their normal high concentration at the apical surface of the cerebral cortical ventricular zone, indicating that cell polarity is disrupted. Consistent with enhanced Wnt/β-catenin signalling resulting from loss of Apc we found increased levels of TCF/LEF-dependent transcription and expression of endogenous Wnt/β-catenin target genes (Axin2 (conductin), Lef1, and c-myc) in the mutant cerebral cortex. In the Apc mutant cerebral cortex the expression of transcription factors Foxg1, Pax6, Tbr1, and Tbr2 is drastically reduced compared to normal and many cells ectopically express Pax3, Wnt1, and Wt1 (but not Wnt2b, Wnt8b, Ptc, Gli1, Mash1, Olig2, or Islet1). This indicates that loss of Apc function causes cerebral cortical cells to lose their normal identity and redirect to fates normally found in more posterior-dorsal regions of the central nervous system.

Conclusion

Apc is required for multiple aspects of early cerebral cortical development, including the regulation of cell number, interkinetic nuclear migration, cell polarity, and cell type specification.
Moxibustion and other acupuncture point stimulation methods to treat breech presentation: a systematic review of clinical trials
Authors: Li Xun , Hu Jun , Wang Xiaoyi , Zhang Huirui , Liu Jianping
Published: February 2009

Background

Moxibustion, acupuncture and other acupoint stimulations are commonly used for the correction of breech presentation. This systematic review aims to evaluate the efficacy and safety of moxibustion and other acupoint stimulations to treat breech presentation.

Methods

We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on moxibustion, acupuncture or any other acupoint stimulating methods for breech presentation in pregnant women. All searches in PubMed, the Cochrane Library (2008 Issue 2), China National Knowledge Information (CNKI), Chinese Scientific Journal Database (VIP) and WanFang Database ended in July 2008. Two authors extracted and analyzed the data independently.

Results

Ten RCTs involving 2090 participants and seven CCTs involving 1409 participants were included in the present study. Meta-analysis showed significant differences between moxibustion and no treatment (RR 1.35, 95% CI 1.20 to 1.51; 3 RCTs). Comparison between moxibustion and knee-chest position did not show significant differences (RR 1.30, 95% CI 0.95 to 1.79; 3 RCTs). Moxibustion plus other therapeutic methods showed significant beneficial effects (RR 1.36, 95% CI 1.21 to 1.54; 2 RCTs). Laser stimulation was more effective than assuming the knee-chest position plus pelvis rotating. Moxibustion was more effective than no treatment (RR 1.29, 95% CI 1.17 to 1.42; 2 CCTs) but was not more effective than the knee-chest position treatment (RR 1.22, 95% CI 1.11 to 1.34; 2 CCTs). Laser stimulation at Zhiyin (BL67) was more effective than the knee-chest position treatment (RR 1.30, 95% CI 1.10 to 1.54; 2 CCTs,).

Conclusion

Moxibustion, acupuncture and laser acupoint stimulation tend to be effective in the correction of breech presentation.
Cardiovascular risk factors and acute-phase response in idiopathic ascending aortitis: a case control study
Authors: Chowdhary Vaidehi R , Crowson Cynthia S , Liang Kimberly P , Michet Clement J , Miller Dylan V , Warrington Kenneth J , Matteson Eric L
Published: February 2009

Introduction

Idiopathic aortitis is a rare condition characterized by giant cell or lymphoplasmacytic inflammation of the aorta. The purpose of this study was to describe risk factors for the development of idiopathic aortitis.

Methods

We conducted a case control study of 50 patients who were age-matched with two control subjects with non-inflammatory ascending aortic aneurysms. We examined whether the prevalences of gender, hypertension, hyperlipidemia, diabetes mellitus, smoking, family history of any aortic aneurysms, and elevated inflammatory markers differed between cases and controls.

Results

The mean age of cases was 71.6 ± 8.9 years and that of controls was 71.1 ± 8.9 years. We found female gender (odds ratio [OR] 2.41, 95% confidence interval [CI] 1.20 to 4.85; P = 0.014) and active smoking (OR 3.37, 95% CI 1.12 to 10.08; P = 0.03) to be associated with idiopathic aortitis. The association with smoking persisted after adjustment for gender (OR 3.24, 95% CI 1.05 to 9.96; P = 0.04). There was a trend toward lower prevalence of diabetes mellitus in cases (OR 0.39, 95% CI 0.11 to 1.43; P = 0.16) but no difference in prevalences of other risk factors. The median pre-operative erythrocyte sedimentation rate (ESR) was 20 mm/hour in cases (n = 13) and 9 mm/hour in controls (n = 22). The median pre-operative C-reactive protein (CRP) levels were 12 mg/L in cases (n = 8) and 3 mg/L in controls (n = 6) (normal: <8 mg/L). A higher proportion of cases versus controls had elevations in ESR (38% versus 9%; P = 0.075) and CRP (62% versus 0%; P = 0.031).

Conclusions

Gender and smoking may interact in complex mechanisms with immune and proteolytic pathways in older, less distensible thoracic aortas. Elevated acute-phase reactants as a marker of systemic inflammation may be present in some patients.
Performance of piezoelectric transducers in terms of amplitude and waveform
Authors: Buddensiek Maike L. , Krawczyk Charlotte M. , Kukowski Nina , Oncken Onno
Published: February 2009

For seismic physical modeling, piezoelectric transducers (PETs) usually are used as sources and receivers. Their properties affect data significantly, especially if data are processed as seismic data: (1) Strong resonance at one frequency causes a ringy signal and a narrow frequency band; (2) the pronounced directionality effectively limits the offsets at which energy arrives; and (3) because the dimension of the [Formula: see text] transducer is larger than the wavelength [Formula: see text], the recorded waveform changes with offset. To reduce the pronounced directionality of the transducers at ultrasonic frequencies, we designed PETs that have a smaller effective diameter than do traditional ones. To test their applicability for laboratory seismic profiling, we tested their frequency sensitivity, their directionality, and the change of waveform as a function of offset caused by their size relative to the wavelengths. The experiments showed that the PETs produce their best-quality data at frequencies of [Formula: see text] and source-receiver offsets of [Formula: see text]. For these frequencies, the amplitudes decay to ringing-noise level at incidence angles of [Formula: see text]; for a reflector [Formula: see text] deep, that results in a [Formula: see text] source-receiver offset. For these frequencies and offsets, the spacious dimension of the PETs does not cause the waveform to change such that further processing is compromised. We also developed an analytic solution to the changing-waveform problem that predicts the temporal divergence of the signal as an additional resolution limit to the Fresnel effect; the loss of high frequencies is caused not by by attenuation alone, but also by the spacious dimension of the sensors.
Management of bulimia nervosa and other binge eating problems
Authors: Cooper Zafra , Fairburn Christopher G.
Published: February 2009

Binge eating occurs across the entire range of eating disorders. It is required for a diagnosis of bulimia nervosa but it is also seen in some cases of anorexia nervosa and in many cases of eating disorder not otherwise specified (usually referred to as eating disorder NOS or atypical eating disorder). This article focuses on the management of those eating disorders in which binge eating is a prominent feature.
Childhood temperament and long-term sickness absence in adult life
Authors: Henderson Max , Hotopf Matthew , Leon David A.
Published: February 2009

Background

Little is known as to whether childhood temperament is associated with long-term sickness absence in adult life.

Aims

To explore the associations between childhood temperament and long-term sickness absence in middle age.

Method

The Aberdeen Children of the 1950s study is comprised of 12 150 children born in Aberdeen 1950–55. Teachers completed the Aberdeen–London Child Behaviour Scale (Rutter B) for all participants in 1964. Current employment status was ascertained for 7183 (63.7%) in 2001.

Results

Five and a half per cent of responders classified themselves as ‘permanently sick or disabled’ at follow-up. ‘Often complains of aches and pains’ (OR=6.75, 95% CI 1.28–35.5) and ‘Often appears miserable or unhappy’ (OR=3.81, 95% CI 1.01–14.4) were strongly associated with being permanently sick or disabled following adjustment for year of birth, gender, IQ and father's social class.

Conclusions

Childhood temperament is strongly associated with sickness absence in middle age.
Prevalence, correlates and course of behavioural and psychological symptoms of dementia in the population
Authors: Savva George M. , Zaccai Julia , Matthews Fiona E. , Davidson Julie E. , McKeith Ian , Brayne Carol
Published: February 2009

Background

Behavioural and psychological symptoms of dementia (BPSD) are major contributors to the burden of dementia.

Aims

To describe the prevalence, correlates and course of BPSD in the population of England and Wales.

Method

The prevalence of 12 symptoms was estimated in 587 participants with dementia and 2050 participants without dementia as part of a population-based longitudinal study of ageing. The effect of risk factors and the factor structure were estimated using 1782 interviews provided by participants with dementia throughout the study.

Results

Each symptom apart from sleeping problems was more common in the population with dementia. The co-occurrence of the symptoms was explained by a four-factor solution, corresponding to psychosis/apathy, depression/anxiety, irritability/persecution and wandering/sleep problems. Psychosis occurred more frequently with declining cognition. Anxiety and depression were more common in younger individuals and in those with poor self-reported health. Persistence varied between symptoms.

Conclusions

Behavioural and psychological symptoms of dementia affect nearly all people with dementia. Symptoms co-occur, and the symptoms that affected individuals experience are related to their socio-demographic and clinical characteristics.
Neuropsychological status of bipolar I disorder: impact of
psychosis
Authors: Savitz Jonathan , van der Merwe Lize , Stein Dan J. , Solms Mark , Ramesar Rajkumar
Published: February 2009

Background

The presence of schizotypal personality traits in some people with
bipolar disorder, together with reports of greater cognitive dysfunction
in patients with a history of psychotic features compared with patients
without such a history, raises questions about the nosological
relationship between bipolar disorder with psychotic features and bipolar
disorder without psychotic features.

Aims

To test the impact of a history of DSM–IV-defined psychosis on the
neuropsychological status of participants with bipolar disorder while
statistically controlling for confounding factors such as mood,
medication, alcohol misuse/dependence and childhood abuse, and to
evaluate the impact of schizotypal personality traits (and thus potential
vulnerability to psychotic illness) on the cognitive performance of
people with bipolar disorder and their healthy relatives.

Method

Neuropsychological data were obtained for 25 participants with type I
bipolar disorder and a history of psychosis, 24 with type I bipolar
disorder but no history of psychosis and 61 unaffected relatives.
Schizotypal traits were measured with the Schizotypal Personality Scale
(STA). Childhood trauma was measured with the Childhood Trauma
Questionnaire.

Results

The group with a history of psychosis performed significantly worse than
the healthy relatives on measures of verbal working memory, cognitive
flexibility and declarative memory. Nevertheless, the two bipolar
disorder groups did not differ significantly from each other on any
cognitive measure. Scores on the STA were negatively associated with
verbal working and declarative memory, but positively associated with
visual recall memory.

Conclusions

‘Psychotic’ and ‘non-psychotic’ subtypes of bipolar disorder may lie on a
nosological continuum that is most clearly defined by verbal memory
impairment.
Stroop-test interference in bipolar disorder
Authors: Kravariti Eugenia , Schulze Katja , Kane Fergus , Kalidindi Sridevi , Bramon Elvira , Walshe Muriel , Marshall Nicolette , Hall Mei-Hua , Georgiades Anna , McDonald Colm , Murray Robin M.
Published: February 2009

We analysed Stroop (neuropsychological screening test) measures of response
inhibition in 18 twin pairs discordant for bipolar I disorder compared with
17 healthy control pairs, as well as 40 singletons with bipolar disorder
with psychotic features and a family history of psychosis, 46 of their
first-degree relatives without bipolar disorder or psychosis and 48
controls. In both studies, individuals with bipolar disorder showed Stroop
deficits and their first-degree relatives showed intact performance. In the
twin patients, an interference score was associated with depressive
symptoms. Having a first-degree relative with bipolar disorder, even a
familial, psychotic form, did not confer risk for enhanced susceptibility to
interference in our studies.
Psychopathic traits and deception: functional magnetic resonance
imaging study
Authors: Fullam Rachael S. , McKie Shane , Dolan Mairead C.
Published: February 2009

Background

There is relatively little existing information regarding the neural
correlates of deception in individuals with psychopathic traits.

Aims

To investigate the relationship between neural responses during deception
and psychopathic personality traits in a sample of male participants
drawn from the normal population.

Method

Twenty-four male participants carried out a simple deception paradigm
while undergoing functional magnetic resonance imaging. Psychopathic
traits were assessed in the sample using the Psychopathic Personality
Inventory (PPI).

Results

Mean response times were greater for the lie than truth condition. Lie
responses resulted in enhanced activation of the ventrolateral prefrontal
cortex. The PPI sub-scales, coldheartedness, fearlessness, Machiavellian
egocentricity, social potency and stress immunity were found to be
correlated with activation patterns in the brain circuitry implicated in
both deception and related processes such as behavioural restraint and
social cognition.

Conclusions

This is a novel technology that may prove useful in our understanding of
some of the key components of the psychopathy construct in both clinical
and non-clinical contexts.
White matter microstructure in schizophrenia: effects of
disorder, duration and medication
Authors: Kanaan Richard , Barker Gareth , Brammer Michael , Giampietro Vincent , Shergill Sukhwinder , Woolley James , Picchioni Marco , Toulopoulou Timothea , McGuire Philip
Published: February 2009

Background

Diffusion tensor magnetic resonance imaging studies in schizophrenia to
date have been largely inconsistent. This may reflect variation in
methodology, and the use of small samples with differing illness duration
and medication exposure.

Aims

To determine the extent and location of white matter microstructural
changes in schizophrenia, using optimised diffusion tensor imaging in a
large patient sample, and to consider the effects of illness duration and
medication exposure.

Method

Scans from 76 patients with schizophrenia and 76 matched controls were
used to compare fractional anisotropy, a measure of white matter
microstructural integrity, between the groups.

Results

We found widespread clusters of reduced fractional anisotropy in
patients, affecting most major white matter tracts. These reductions did
not correlate with illness duration, and there was no difference between
age-matched chronically and briefly medicated patients.

Conclusions

The finding of widespread fractional anisotropy reductions in our larger
sample of patients with schizophrenia may explain some of the
inconsistent findings of previous, smaller studies.
Differential efficacy of escitalopram and nortriptyline on
dimensional measures of depression
Authors: Uher Rudolf , Maier Wolfgang , Hauser Joanna , Marušič Andrej , Schmael Christine , Mors Ole , Henigsberg Neven , Souery Daniel , Placentino Anna , Rietschel Marcella , Zobel Astrid , Dmitrzak-Weglarz Monika , Petrovic Ana , Jorgensen Lisbeth , Kalember Petra , Giovannini Caterina , Barreto Mara , Elkin Amanda , Landau Sabine , Farmer Anne , Aitchison Katherine J. , McGuffin Peter
Published: February 2009

Background

Tricyclic antidepressants and serotonin reuptake inhibitors are
considered to be equally effective, but differences may have been
obscured by internally inconsistent measurement scales and inefficient
statistical analyses.

Aims

To test the hypothesis that escitalopram and nortriptyline differ in
their effects on observed mood, cognitive and neurovegetative symptoms of
depression.

Method

In a multicentre part-randomised open-label design (the Genome Based
Therapeutic Drugs for Depression (GENDEP) study) 811 adults with moderate
to severe unipolar depression were allocated to flexible dosage
escitalopram or nortriptyline for 12 weeks. The weekly Montgomery–Åsberg
Depression Rating Scale, Hamilton Rating Scale for Depression, and Beck
Depression Inventory were scored both conventionally and in a more novel
way according to dimensions of observed mood, cognitive symptoms and
neurovegetative symptoms.

Results

Mixed-effect linear regression showed no difference between escitalopram
and nortriptyline on the three original scales, but symptom dimensions
revealed drug-specific advantages. Observed mood and cognitive symptoms
improved more with escitalopram than with nortriptyline. Neurovegetative
symptoms improved more with nortriptyline than with escitalopram.

Conclusions

The three symptom dimensions provided sensitive descriptors of
differential antidepressant response and enabled identification of
drug-specific effects.
Another nail in the coffin of the cognitive paradigm of
dementia
Authors: Burns Alistair
Published: February 2009

An emerging appreciation by practitioners and researchers, long held by
patients and carers, is that neuropsychiatric features of dementia and the
challenges they present are as important as those of cognitive losses.
Developing a policy to deal with sexual assault on psychiatric in-patient wards
Authors: Lawn Tara , McDonald Elizabeth
Published: February 2009

Sexual harassment and assault on psychiatric wards is an ongoing concern. A number of incidents have been reported in the media. This paper focuses on a policy drafted to deal with allegations of sexual assault or rape on an in-patient psychiatric ward. We aimed to produce a practical, easy-to-follow guide for junior doctors and ward staff who may face complex and possibly contentious issues surrounding consent, capacity to consent and police involvement.
E-learning for psychiatrists
Authors: Hare Elizabeth E.
Published: February 2009

E-learning is an expanding field in which many psychiatrists are active through teaching, training and pursuing their continuing professional development. Much of the benefits of e-learning are due to the implementation of educational principles rather than the medium itself. the College has invested in its own e-learning website as a service for members. However, it should not entirely replace face-to-face lectures, tutoring and mentorship.
Selective Response to Insulin Versus Insulin-Like Growth Factor-I and -II and Up-Regulation of Insulin Receptor Splice Variant B in the Differentiated Mouse Mammary Epithelium
Authors: Berlato Chiara , Doppler Wolfgang
Published: February 2009

The terminal differentiation of the mouse mammary gland epithelium during lactation has been shown to require IGFs and/or superphysiological levels of insulin. It has been suggested that IGF receptor I (IGF-IR), in addition to its well-established role in the mammary gland during puberty and pregnancy, serves as the principal mediator of IGFs at this stage of development. However, our analysis of the expression levels of IGF-IR and the two insulin receptor (IR) splice variants, IR-A and IR-B, has revealed a 3- to 4-fold up-regulation of IR-B transcripts and a 6-fold down-regulation of IGF-IR transcripts and protein during terminal differentiation in the developing mammary gland. IR-B expression was also more than 10-fold up-regulated in murine mammary epithelial cell line HC11 during differentiation in vitro. As already described for the human form, murine IR-B cloned from HC11 exhibited selectivity for insulin as compared with IGFs. When differentiated HC11 cells were stimulated by 10 nm insulin, a concentration that is unable to activate IGF-IR, induction of milk protein and lipid synthetic enzyme gene expression, lactate production, and phosphorylation of Akt were observed. In contrast, on differentiated HC11 cells 10 nm IGF-I or 10 nm IGF-II were able to exert growth-promoting effects only. The lack of response of differentiated cells to low levels of IGFs could not be explained by inactivation of IGFs by IGF binding proteins. Our results suggest a previously unrecognized predominant role for IR-B in the differentiated mammary epithelium.
Vasopressin Administration into the Paraventricular Nucleus Normalizes Plasma Oxytocin and Corticosterone Levels in Brattleboro Rats
Authors: Zelena Dóra , Langnaese Kristina , Domokos Ágnes , Pintér Ottó , Landgraf Rainer , Makara Gábor B. , Engelmann Mario
Published: February 2009

Adult male rats of the Brattleboro strain were used to investigate the impact of the congenital absence of vasopressin on plasma adrenocorticotropin, corticosterone, and oxytocin concentrations as well as the release pattern of oxytocin within the hypothalamic paraventricular nucleus (PVN), in response to a 10-min forced swimming session. Measurement of adrenocorticotropin in plasma samples collected via chronically implanted jugular venous catheters revealed virtually identical stress responses for vasopressin-lacking Brattleboro (KO) and intact control animals. In contrast, plasma corticosterone and oxytocin levels were found to be significantly elevated 105 min after onset of the stressor in KO animals only. Microdialysis samples collected from the extracellular fluid of the PVN showed significantly higher levels of oxytocin both under basal conditions and in response to stressor exposure in KO vs. intact control animals accompanied by elevated oxytocin mRNA levels in the PVN of KO rats. These findings suggest that the increased oxytocin levels in the PVN caused by the congenital absence of vasopressin may contribute to normal adrenocorticotropin stress responses in KO animals. However, whereas the stressor-induced elevation of plasma oxytocin in KO rats may be responsible for their maintained corticosterone levels, oxytocin seems unable to fully compensate for the lack of vasopressin. This hypothesis was tested by retrodialyzing synthetic vasopressin into the PVN area concomitantly with blood sampling in KO animals. Indeed, this treatment normalized plasma oxytocin and corticosterone levels 105 min after forced swimming. Thus, endogenous vasopressin released within the PVN is likely to act as a paracrine signal to facilitate the return of plasma oxytocin and corticosterone to basal levels after acute stressor exposure.
Advanced Glycation End Products Inhibit Glucose-Stimulated Insulin Secretion through Nitric Oxide-Dependent Inhibition of Cytochrome c Oxidase and Adenosine Triphosphate Synthesis
Authors: Zhao Zhengshan , Zhao Chunying , Zhang Xu Hannah , Zheng Feng , Cai Weijing , Vlassara Helen , Ma Zhongmin Alex
Published: February 2009

Advanced glycation end products (AGEs) are implicated in diabetic complications. However, their role in β-cell dysfunction is less clear. In this study we examined the effects of AGEs on islet function in mice and in isolated islets. AGE-BSA or BSA was administered ip to normal mice twice a day for 2 wk. We showed that AGE-BSA-treated mice exhibited significantly higher glucose levels and lower insulin levels in response to glucose challenge than did BSA-treated mice, although there were no significant differences in insulin sensitivity and islet morphology between two groups. Glucose-stimulated insulin secretion by islets of the AGE-BSA-treated mice or AGE-BSA-treated normal islets was significantly lower than that by islets isolated from the BSA-treated mice or BSA-treated normal islets. Furthermore, AGE treatment of islet β-cells inhibited ATP production, and glimepiride, a sulfonylurea derivative, restored glucose-stimulated insulin secretion. Further investigation indicated that AGEs inhibited cytochrome c oxidase activity by inducing the expression of inducible nitric oxide synthase (iNOS). Blocking the formation of nitric oxide with an iNOS selective inhibitor aminoguanidine reversed the inhibitory effects of AGEs on ATP production and insulin secretion. We conclude that AGEs inhibit cytochrome c oxidase and ATP production, leading to the impairment of glucose-stimulated insulin secretion through iNOS-dependent nitric oxide production.
Echolocation by two foraging harbour porpoises (Phocoena phocoena)
Authors: Verfuß Ursula K. , Miller Lee A. , Pilz Peter K. D. , Schnitzler Hans-Ulrich
Published: February 2009

Synchronized video and high-frequency audio recordings of two trained harbour porpoises searching for and capturing live fish were used to study swimming and echolocation behaviour. One animal repeated the tasks blindfolded. A splash generated by the fish being thrown into the pool or– in controls – by a boat hook indicated prey and stimulated search behaviour. The echolocation sequences were divided into search and approach phases. In the search phase the porpoises displayed a clear range-locking behaviour on landmarks, indicated by a distance-dependent decrease in click interval. Only in trials with fish was the search phase followed by an approach phase. In the initial part of the approach phase the porpoises used a rather constant click interval of around 50 ms. The terminal part started with a sudden drop in click interval at distances around 2–4 m. Close to the prey the terminal part ended with a buzz,characterized by constant click intervals around 1.5 ms. The lag time in the search and the initial part of the approach phase seems to be long enough for the porpoise to process echo information before emitting the next click (pulse mode). However, we assume that during the buzz lag times are too short for pulse mode processing and that distance information is perceived as a `pitch'with a `frequency' corresponding to the inverse of the two-way transit time(pitch mode). The swimming speed of the animal was halved when it was blindfolded, while the click intervals hardly changed, resulting in more clicks emitted per metre swum.
Ametabolic embryos of Artemia franciscana accumulate DNA damage during prolonged anoxia
Authors: McLennan Alexander G.
Published: February 2009

Encysted embryos of the brine shrimp Artemia franciscana are able to survive prolonged periods of anoxia even when fully hydrated. During this time there is no metabolism, raising the question of how embryos tolerate spontaneous, hydrolytic DNA damage such as depurination. When incubated at 28°C and 40°C for several weeks, hydrated anoxic embryos were found to accumulate abasic sites in their DNA with k=5.8×10–11s–1 and 2.8×10–10s–1, respectively. In both cases this is about 3-fold slower than expected from published observations on purified DNA. However, purified calf thymus DNA incubated under similar anoxic conditions at pH 6.3, the intracellular pH of anoxic cysts, also depurinated more slowly than predicted(about 1.7-fold), suggesting that cysts may in fact accumulate abasic sites only slightly more slowly than purified DNA. Upon reoxygenation of cysts stored under N2 for 30 weeks at 28°C, the number of abasic sites per 104 bp DNA fell from 21.1±4.0 to 9.8±2.0 by 12 h and to 6.2±2.1 by 24 h. Larvae hatched after 48 h and 72 h had only 0.59±0.17 and 0.48±0.07 abasic sites per 104 bp,respectively, suggesting that repair of these lesions had largely taken place before hatching commenced. Thus, unlike bacterial spores, Artemiacysts appear to have no specific protective mechanism beyond what might be afforded by chromatin structure to limit spontaneous depurination, and rely on the repair of accumulated lesions during the period between reoxygenation and hatching.
Costs and benefits of increased weapon size differ between sexes of the slender crayfish,Cherax dispar
Authors: Wilson Robbie S. , James Rob S. , Bywater Candice , Seebacher Frank
Published: February 2009

Unreliable signals of weapon strength are considered to be problematic for signalling theory and reliable signals are predicted to be the dominant form of signalling among conspecifics in nature. Previous studies have shown that males of the Australian freshwater crayfish (Cherax dispar) routinely use unreliable signals of strength whereas females use reliable signals of weapon strength. In this study, we examined the performance benefits of increased weapon (chela) size for both males and females of C. dispar. In addition, we investigated the possibility of functional trade-offs in weapon size by assessing the relationship between chela size and maximum escape swimming performance. We found males possessed larger and stronger chelae than females and the variance in chela force was greater for males than females. By contrast, females possessed greater absolute and body length-specific escape swimming speeds than males. Swimming speed was also negatively correlated with chela size for males but not females, suggesting that a functional trade-off exists for males only. Decreases in swimming speed with increases in weapon size suggest there could be important fitness costs associated with larger chelae. Larger weaponry of males may then act as a handicap ensuring large chelae are reliable signals of quality.
Seawater Ca2+ concentration influences solar orientation inTalitrus saltator(Crustacea, Amphipoda)
Authors: Ugolini Alberto , Ungherese Giuseppe , Mercatelli Luca , Saer Doumett , Lepri Luciano
Published: February 2009

The role of salinity in the ecophysiology of many intertidal invertebrates has been extensively investigated. Calcium (Ca2+), magnesium(Mg2+), potassium (K+) and sodium (Na+) are the major constituents of seawater and it has been demonstrated that sandhoppers tested under the sun in diluted seawater (3.5‰) head seaward, instead of going landward as expected. Therefore, the variation in seawater salinity (from 35‰ to 3.5‰) influences their directional choice. This paper investigates the contribution of different cations to the sea–land directional choice of Talitrus saltator(Crustacea, Amphipoda) by the sun compass orientation mechanism. Results of releases carried out in basic seawater selectively deprived of Ca2+, Mg2+ or K+ and containing the same concentration of Na+ indicate that only the reduction in Ca2+ concentration affects the capacity of solar orientation. The pH does not influence the directional choice of sandhoppers and nor do small variations in salinity in the range 32–39‰. Moreover, the clear photopositive tendency registered in experiments of phototaxis in Ca2+-deprived seawater indicates that the absence of Ca2+ does not affect the normal functioning of the visual cells. Therefore, our results show that Ca2+ seawater concentration is important for the correct functioning of one of the principal mechanisms of orientation in supralittoral amphipods and it could affect their survival in the field.