bluuebunny/crossref_metadata_2025 huggingface dataset:
Physician Counseling and Longer Term Physical Activity
Authors: Spink Kevin S. , Wilson Kathleen S.
Published: September 2010

While physician counseling has been suggested as a strategy to promote physical activity, there is insufficient evidence to support its effectiveness at present. The purpose of this study was to examine the effect of brief physician counseling (modified PACE protocol) and telephone follow-ups on changes in the energy expenditure levels of patients over a 20-month period. Forty-five participants completed physical activity questionnaires at both baseline and 20 months. Following brief physician counseling (modified PACE protocol), patients were randomized into a counseling-only group or an enhanced counseling group that included 3 telephone follow-ups. Energy expenditure significantly increased from baseline (1.5 kcal/kg/d [KKD]) to 20 months (2.2 KKD, P < .05) in both groups. Neither the group nor group-by-time interaction was significant ( P > .05). In line with the counseling provided by physicians, participants showed an increase in moderate intensity activities and a decrease in light intensity activities ( Ps < .001). These findings provide support for the effectiveness of brief physician counseling. However, the additional telephone support did not appear to enhance the physician counseling.
Challenges to Accessing Pediatric Health Care in the Mississippi Delta
Authors: Grant Roy , Ramgoolam Andres , Betz Ryan , Ruttner Laura , Green John J.
Published: September 2010

Background: Increases in hospital emergency department use have been driven by insured patients with problems accessing primary care services. Access problems are especially pronounced in rural communities with health professional shortages. This qualitative study explored reasons for nonurgent pediatric emergency department use in the Mississippi Delta. Method: Using a community-based participatory research framework, a semistructured survey was administered face-to-face in a hospital emergency department waiting room with parents/caregivers who brought their children. Interviews were done over 144 hours in 2-hour blocks covering regular “business hours” and “after hours” (evenings/weekends). Open-ended items allowed qualitative data to be gathered describing reasons for emergency department use and perceptions of urgency of the visit in the parents’/caregivers’ own words. Results: There were 112 children, with a response rate of 87%. The mean child age was 5.7 years; 52% were male; 95% were African American and 5% white; 80.6% had Medicaid/SCHIP, 7.8% commercial, and 3.9% other insurance; 7.8% were uninsured. Most (88%) had a usual source of pediatric care. Only 24.3% tried to obtain care before emergency department visit; 23.2% said their children required “urgent” care. Mean distance from home to usual source of care was 10 miles. Ten percent cited transportation as a barrier to keeping health care appointments; 5.5% cited insurance or cost. Families who used the emergency department during evening/weekends were significantly more likely to have cited clinic hours of operation as a reason care was not sought previously than were “business hours” users, who emphasized convenience. Conclusion: Nonurgent pediatric emergency department use could be reduced by extending clinic hours, adding a walk-in service, and making transportation more available.
Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells
Authors: Tanizaki Hideaki , Egawa Gyohei , Inaba Kayo , Honda Tetsuya , Nakajima Saeko , Moniaga Catharina Sagita , Otsuka Atsushi , Ishizaki Toshimasa , Tomura Michio , Watanabe Takeshi , Miyachi Yoshiki , Narumiya Shuh , Okada Takaharu , Kabashima Kenji
Published: September 2010

Dendritic cells (DCs) are essential for the initiation of acquired immune responses through antigen acquisition, migration, maturation, and T-cell stimulation. One of the critical mechanisms in this response is the process actin nucleation and polymerization, which is mediated by several groups of proteins, including mammalian Diaphanous-related formins (mDia). However, the role of mDia in DCs remains unknown. Herein, we examined the role of mDia1 (one of the isoforms of mDia) in DCs. Although the proliferation and maturation of bone marrow-derived DCs were comparable between control C57BL/6 and mDia1-deficient (mDia1−/−) mice, adhesion and spreading to cellular matrix were impaired in mDia1−/− bone marrow–derived DCs. In addition, fluorescein isothiocyanate-induced cutaneous DC migration to draining lymph nodes in vivo and invasive migration and directional migration to CCL21 in vitro were suppressed in mDia1−/− DCs. Moreover, sustained T-cell interaction and T-cell stimulation in lymph nodes were impaired by mDia1 deficiency. Consistent with this, the DC-dependent delayed hypersensitivity response was attenuated by mDia1-deficient DCs. These results suggest that actin polymerization, which is mediated by mDia1, is essential for several aspects of DC-initiated acquired immune responses.
Loss of tonic T-cell receptor signals alters the generation but not the persistence of CD8+ memory T cells
Authors: Wiehagen Karla R. , Corbo Evann , Schmidt Michelle , Shin Haina , Wherry E. John , Maltzman Jonathan S.
Published: September 2010

The requirements for tonic T-cell receptor (TCR) signaling in CD8+ memory T-cell generation and homeostasis are poorly defined. The SRC homology 2 (SH2)-domain–containing leukocyte protein of 76 kDa (SLP-76) is critical for proximal TCR-generated signaling. We used temporally mediated deletion of SLP-76 to interrupt tonic and activating TCR signals after clearance of the lymphocytic choriomeningitis virus (LCMV). SLP-76–dependent signals are required during the contraction phase of the immune response for the normal generation of CD8 memory precursor cells. Conversely, LCMV-specific memory CD8 T cells generated in the presence of SLP-76 and then acutely deprived of TCR-mediated signals persist in vivo in normal numbers for more than 40 weeks. Tonic TCR signals are not required for the transition of the memory pool toward a central memory phenotype, but the absence of SLP-76 during memory homeostasis substantially alters the kinetics. Our data are consistent with a model in which tonic TCR signals are required at multiple stages of differentiation, but are dispensable for memory CD8 T-cell persistence.
Formin INF2 regulates MAL-mediated transport of Lck to the plasma membrane of human T lymphocytes
Authors: Andrés-Delgado Laura , Antón Olga M. , Madrid Ricardo , Byrne Jennifer A. , Alonso Miguel A.
Published: September 2010

Expression of the src-family kinase lymphocyte-specific protein tyrosine kinase (Lck) at the plasma membrane is essential for it to fulfill its pivotal role in signal transduction in T lymphocytes. MAL, an integral membrane protein expressed in specific types of lymphoma, has been shown to play an important role in targeting Lck to the plasma membrane. Here we report that MAL interacts with Inverted Formin2 (INF2), a formin with the atypical property of promoting not only actin polymerization but also its depolymerization. In Jurkat T cells, INF2 colocalizes with MAL at the cell periphery and pericentriolar endosomes and along microtubules. Videomicroscopic analysis revealed that the MAL+ vesicles transporting Lck to the plasma membrane move along microtubule tracks. Knockdown of INF2 greatly reduced the formation of MAL+ transport vesicles and the levels of Lck at the plasma membrane and impaired formation of a normal immunologic synapse. The actin polymerization and depolymerization activities of INF2 were both required for efficient Lck targeting. Cdc42 and Rac1, which bind to INF2, regulate Lck transport in both Jurkat and primary human T cells. Thus, INF2 collaborates with MAL in the formation of specific carriers for targeting Lck to the plasma membrane in a process regulated by Cdc42 and Rac1.
The DNA relaxation activity and covalent complex accumulation of Mycobacterium tuberculosis topoisomerase I can be assayed in Escherichia coli: application for identification of potential FRET-dye labeling sites
Authors: Narula Gagandeep , Becker Jennifer , Cheng Bokun , Dani Neil , Abrenica Maria V , Tse-Dinh Yuk-Ching
Published: September 2010

Background

Mycobacterium tuberculosis topoisomerase I (MtTOP1) and Escherichia coli topoisomerase I have highly homologous transesterification domains, but the two enzymes have distinctly different C-terminal domains. To investigate the structure-function of MtTOP1 and to target its activity for development of new TB therapy, it is desirable to have a rapid genetic assay for its catalytic activity, and potential bactericidal consequence from accumulation of its covalent complex.

Results

We show that plasmid-encoded recombinant MtTOP1 can complement the temperature sensitive topA function of E. coli strain AS17. Moreover, expression of MtTOP1-G116 S enzyme with the TOPRIM mutation that inhibits DNA religation results in SOS induction and loss of viability in E. coli. The absence of cysteine residues in the MtTOP1 enzyme makes it an attractive system for introduction of potentially informative chemical or spectroscopic probes at specific positions via cysteine mutagenesis. Such probes could be useful for development of high throughput screening (HTS) assays. We employed the AS17 complementation system to screen for sites in MtTOP1 that can tolerate cysteine substitution without loss of complementation function. These cysteine substitution mutants were confirmed to have retained the relaxation activity. One such mutant of MtTOP1 was utilized for fluorescence probe incorporation and fluorescence resonance energy transfer measurement with fluorophore-labeled oligonucleotide substrate.

Conclusions

The DNA relaxation and cleavage complex accumulation of M. tuberculosis topoisomerase I can be measured with genetic assays in E. coli, facilitating rapid analysis of its activities, and discovery of new TB therapy targeting this essential enzyme.
Wound contraction and macro-deformation during negative pressure therapy of sternotomy wounds
Authors: Torbrand Christian , Ugander Martin , Engblom Henrik , Arheden Håkan , Ingemansson Richard , Malmsjö Malin
Published: September 2010

Background

Negative pressure wound therapy (NPWT) is believed to initiate granulation tissue formation via macro-deformation of the wound edge. However, only few studies have been performed to evaluate this hypothesis. The present study was performed to investigate the effects of NPWT on wound contraction and wound edge tissue deformation.

Methods

Six pigs underwent median sternotomy followed by magnetic resonance imaging in the transverse plane through the thorax and sternotomy wound during NPWT at 0, -75, -125 and -175 mmHg. The lateral width of the wound and anterior-posterior thickness of the wound edge was measured in the images.

Results

The sternotomy wound decreased in size following NPWT. The lateral width of the wound, at the level of the sternum bone, decreased from 39 ± 7 mm to 30 ± 6 mm at -125 mmHg (p = 0.0027). The greatest decrease in wound width occurred when switching from 0 to -75 mmHg. The level of negative pressure did not affect wound contraction (sternum bone: 32 ± 6 mm at -75 mmHg and 29 ± 6 mm at -175 mmHg, p = 0.0897). The decrease in lateral wound width during NPWT was greater in subcutaneous tissue (14 ± 2 mm) than in sternum bone (9 ± 2 mm), resulting in a ratio of 1.7 ± 0.3 (p = 0.0423), suggesting macro-deformation of the tissue. The anterior-posterior thicknesses of the soft tissue, at 0.5 and 2.5 cm laterally from the wound edge, were not affected by negative pressure.

Conclusions

NPWT contracts the wound and causes macro-deformation of the wound edge tissue. This shearing force in the tissue and at the wound-foam interface may be one of the mechanisms by which negative pressure delivery promotes granulation tissue formation and wound healing.
Editorial: Pattern recognition receptors and factor B: “complement”ary pathways converge
Authors: Prakash Arun , Hellman Judith
Published: September 2010

Discussion on data from Kaczorowski et al. revealing that LPS and Poly I:C up-regulate macrophage expression of complement factor B in vivo and in vitro.
Particle swarm optimization applied to solving and appraising the streaming-potential inverse problem
Authors: Fernández-Martínez Juan Luis , García-Gonzalo Esperanza , Naudet Véronique
Published: September 2010

Water flow in the subsoil generates electrical currents measurable at the ground surface with the self-potential (SP) method. These measured potentials, which result from hydroelectric coupling, are called streaming potentials and are well correlated with the geometry of the water table. The particle swarm algorithm can be used to estimate the water-table elevation from SP data measured at the ground surface. The basic idea behind particle swarm optimization (PSO) is that each model searches the model space according to its misfit history and the misfit of the other models (particles) of the swarm. PSO is a simple, robust, and versatile algorithm with a very good convergence rate (typically before 3000 forward runs), and it can explore a large model space without being time consuming. Based on samples gathered in a low-misfit area, we have computed a fast approximation of the posterior distribution of the water table, the electrokinetic coupling constant, and the reference hydraulic head. Although PSO is a stochastic search technique, our convergence results, based on the stability of particle trajectories, specify clear criteria to tune PSO parameters.
Delineating a road-salt plume in lakebed sediments using electrical resistivity, piezometers, and seepage meters at Mirror Lake, New Hampshire, U.S.A
Authors: Toran Laura , Johnson Melanie , Nyquist Jonathan , Rosenberry Donald
Published: September 2010

Electrical-resistivity surveys, seepage meter measurements, and drive-point piezometers have been used to characterize chloride-enriched groundwater in lakebed sediments of Mirror Lake, New Hampshire, U.S.A. A combination of bottom-cable and floating-cable electrical-resistivity surveys identified a conductive zone [Formula: see text] overlying resistive bedrock [Formula: see text] beneath the lake. Shallow pore-water samples from piezometers in lakebed sediments have chloride concentrations of [Formula: see text], and lake water has a chloride concentration of [Formula: see text]. The extent of the plume was estimated and mapped using resistivity and water-sample data. The plume ([Formula: see text] wide and at least [Formula: see text] thick) extends nearly the full length and width of a small inlet, overlying the top of a basin formed by the bedrock. It would not have been possible to mapthe plume’s shape without the resistivity surveys because wells provided only limited coverage. Seepage meters were installed approximately [Formula: see text] from the mouth of a small stream discharging at the head of the inlet in an area where the resistivity data indicated lake sediments are thin. These meters recorded in-seepage of chloride-enriched groundwater at rates similar to those observed closer to shore, which was unexpected because seepage usually declines away from shore. Although the concentration of road salt in the northeast inlet stream is declining, the plume map and seepage data indicate the groundwater contribution of road salt to the lake is not declining. The findings demonstrate the benefit of combining geophysical and hydrologic data to characterize discharge of a plume beneath Mirror Lake. The extent of the plume in groundwater beneath the lake and stream indicate there will likely be a long-term source of chloride to the lake from groundwater.
Improved hydrogeophysical characterization and monitoring through parallel modeling and inversion of time-domain resistivity andinduced-polarization data
Authors: Johnson Timothy C. , Versteeg Roelof J. , Ward Andy , Day-Lewis Frederick D. , Revil André
Published: September 2010

Electrical geophysical methods have found wide use in the growing discipline of hydrogeophysics for characterizing the electrical properties of the subsurface and for monitoring subsurface processes in terms of the spatiotemporal changes in subsurface conductivity, chargeability, and source currents they govern. Presently, multichannel and multielectrode data collections systems can collect large data sets in relatively short periods of time. Practitioners, however, often are unable to fully utilize these large data sets and the information they contain because of standard desktop-computer processing limitations. These limitations can be addressed by utilizing the storage and processing capabilities of parallel computing environments. We have developed a parallel distributed-memory forward and inverse modeling algorithm for analyzing resistivity and time-domain induced polar-ization (IP) data. The primary components of the parallel computations include distributed computation of the pole solutions in forward mode, distributed storage and computation of the Jacobian matrix in inverse mode, and parallel execution of the inverse equation solver. We have tested the corresponding parallel code in three efforts: (1) resistivity characterization of the Hanford 300 Area Integrated Field Research Challenge site in Hanford, Washington, U.S.A., (2) resistivity characterization of a volcanic island in the southern Tyrrhenian Sea in Italy, and (3) resistivity and IP monitoring of biostimulation at a Superfund site in Brandywine, Maryland, U.S.A. Inverse analysis of each of these data sets would be limited or impossible in a standard serial computing environment, which underscores the need for parallel high-performance computing to fully utilize the potential of electrical geophysical methods in hydrogeophysical applications.
Self-potential monitoring of a salt plume
Authors: Martínez-Pagán P. , Jardani A. , Revil A. , Haas A.
Published: September 2010

Nonintrusively monitoring the spread of contaminants in real time with a geophysical method is an important task in hydrogeophysics. We have developed a sandbox experiment showing that the self-potential method can locate both the source of leakage and the front of a contaminant plume. We monitored the leakage of a plume of salty water from a hole at the bottom of a small tank located at the top of a main sandbox. Initially, the sand was saturated by tap water. At a given time, a hole was opened at the bottom of the tank, allowing the salty water to migrate by diffusion and buoyancy-driven flow in the main sandbox. The bottom of the sandbox contained a network of 32 nonpolarizing silver-silver chloride electrodes with amplifiers, connected to a multichannel voltmeter. The self-potential response associated withthe migration of the salt plume in the sandbox was recorded over time. A self-potential anomaly was observed with amplitude varying from a few millivolts at the start of the leak to a few tens of millivolts after a few minutes. The self-potential data were inverted using a time-lapse tomographic algorithm to reconstruct the position of the volumetric source current density over time. A positive volumetric source current density was associated with the position of the leak at the bottom of the leaking tank, whereas a negative volumetric source current density was associated with the salinity front moving down inside the sandbox. These poles were well reproduced by performing a finite-element simulation of the problem. Using this information, we estimated the speed of the salt plume sinking inside the sandbox. Therefore, the self-potential method can be used to track, in real time, the position of the front of a contaminant plume in a porous material.
A comparative study of in-river geophysical techniques to define variations in riverbed salt load and aid managing river salinization
Authors: Hatch Michael , Munday Tim , Heinson Graham
Published: September 2010

Increased interest in the character of sediments at the base of waterways, for the purpose of managing river salinization, has led to the application of several geophysical techniques for collecting information from this zone. These instream methods are based on established ground and airborne electrical and electromagnetic technologies, including towed transient electromagnetic systems, towed direct current resistivity array systems, and frequency-domain helicopter electromagnetic systems. Although these systems are individually successful, a systematic examination of their relative effectiveness for identifying variations in substrate conductivity for a common stretch of a river remains lacking. We have compared results obtained from data collected using three instream geophysical techniques for a common stretch of the Murray River in southeastern Australia. The Murray River is an important water resource for drinking and agricultural purposes. Data from these surveys were acquired tolocate areas of significant saltwater accession to the Murray from a saline regional groundwater system that discharges into it. The three methods indirectly inform on those reaches that most likely contribute to higher salt loads in the river, and they do this through the identification of a conductive substrate (a gaining reach). For a [Formula: see text] stretch of the river, the methods identified similar variations in the conductivity structure of sediment substrate, although differences were observed in the modeled response relating to intrinsic differences between each system, including the sampling interval and resolution. The helicopter electromagnetic (EM) system is capable of acquiring hundreds of kil-ometers of data in a day, under any river flow condition, from near the river surface to depths in excess of [Formula: see text]. The other two techniques require safe river flow conditions for acquisition, with as much as 50 river km of data per day possible. The ground-based methods had enhanced lateral and vertical resolving capabilities relative to the helicopter EM system, but their depth of investigation was less (usually only [Formula: see text]).
How reliable are scientific studies?
Authors: Munafò Marcus R. , Flint Jonathan
Published: September 2010

There is growing concern that a substantial proportion of scientific research may in fact be false. A number of factors have been proposed as contributing to the presence of a large number of false-positive results in the literature, one of which is publication bias. We discuss empirical evidence for these factors.
How Law 180 in Italy has reshaped psychiatry after 30 years: past attitudes, current trends and unmet needs
Authors: Altamura A. Carlo , Goodwin Guy M.
Published: September 2010

Law 180 eliminated psychiatric hospitals for the care of people with chronic psychosis in Italy. After 30 years, we review the consequences for the practice of psychiatry in Italy and parallels for England and Wales. We argue that the substitution of legal/political direction for clinical leadership means psychiatrists may cease to merit the privileges and responsibilities of being doctors.
Cost-effectiveness of therapist-delivered online cognitive–behavioural therapy for depression: randomised controlled trial
Authors: Hollinghurst Sandra , Peters Tim J. , Kaur Surinder , Wiles Nicola , Lewisand Glyn , Kessler David
Published: September 2010

Background

Therapist-delivered online cognitive–behavioural therapy (CBT) has been found to be effective for depression in primary care.

Aims

To determine the cost-effectiveness of online CBT compared with usual care.

Method

Economic evaluation at 8 months alongside a randomised controlled trial. Cost to the National Health Service (NHS), personal costs, and the value of lost productivity, each compared with outcomes based on the Beck Depression Inventory and quality-adjusted life-years (QALYs). Incremental analysis indicated the NHS cost per QALY gain.

Results

Online CBT was more expensive than usual care, although the outcomes for the CBT group were better. Cost per QALY gain based on complete case data was £17 173, and £10 083 when missing data were imputed.

Conclusions

Online CBT delivered by a therapist in real time is likely to be cost-effective compared with usual care if society is willing to pay at least £20 000 per QALY; it could be a useful alternative to face-to-face CBT.
Effects of severe mental illness on survival of people with diabetes
Authors: Vinogradova Yana , Coupland Carol , Hippisley-Cox Julia , Whyte Seán , Penny Catherine
Published: September 2010

Background

People with mental health problems are more likely to die prematurely than the general population but no study has examined this in individuals with diabetes.

Aims

To compare survival rates in people with diabetes with and without schizophrenia or bipolar disorder.

Method

A total of 43 992 people with diabetes were drawn from the QRESEARCH database population of over 9 million patients. Survival rates during the study period, between 1 April 2000 and 1 April 2005, and hazard ratios for deaths associated with schizophrenia and bipolar disorder were adjusted by age and gender and additionally for socioeconomic status, obesity, smoking and use of statins.

Results

Among the participants, we identified 257 people diagnosed with schizophrenia, 159 with bipolar disorder and 14 with both conditions. Although crude survival rates did not show significant differences between the groups during the study period, people with schizophrenia or bipolar disorder and diabetes, compared with those with diabetes alone, had a significantly increased risk of death after adjusting for age and gender, with hazard ratios for schizophrenia of 1.84 (95% CI 1.42–2.40) and for bipolar disorder of 1.51 (95% CI 1.10–2.07). After adjusting for the other factors, hazard ratios were 1.52 (95 CI 1.17–1.97) for schizophrenia and 1.47 (95% CI 1.07–2.02) for bipolar disorder.

Conclusions

People with schizophrenia or bipolar disorder in addition to diabetes have a relatively higher mortality rate. This suggests that diabetes either progresses more rapidly or is more poorly controlled in these individuals, or that they have higher levels of comorbidity and so are more likely to die of other causes.
Psychiatric disorders in male prisoners who made near-lethal suicide attempts: case–control study
Authors: Rivlin Adrienne , Hawton Keith , Marzano Lisa , Fazel Seena
Published: September 2010

Background

Although male prisoners are five times more likely to die by suicide than men of a similar age in the general population, the contribution of psychiatric disorders is not known.

Aims

To investigate the association of psychiatric disorders with near-lethal suicide attempts in male prisoners.

Method

A matched case–control study of 60 male prisoners who made near-lethal suicide attempts (cases) and 60 prisoners who had never carried out near-lethal suicide attempts in prison (controls) was conducted. Psychiatric disorders were identified with the Mini International Neuropsychiatric Interview (MINI), and information on sociodemographic characteristics and criminal history was gathered using a semi-structured interview.

Results

Psychiatric disorders were present in all cases and 62% of controls. Most current psychiatric disorders were associated with near-lethal suicide attempts, including major depression (odds ratio (OR) = 42.0, 95% CI 5.8–305), psychosis (OR = 15.0, 95% CI 2.0–113), anxiety disorders (OR = 6.0, 95% CI 2.3–15.5) and drug misuse (OR = 2.9, 95% CI 1.3–6.4). Lifetime psychiatric disorders associated with near-lethal attempts included recurrent depression and psychoses. Although cases were more likely than controls to meet criteria for antisocial personality disorder, the difference was not statistically significant. Comorbidity was also significantly more common among cases than controls for both current and lifetime disorders.

Conclusions

In male prisoners, psychiatric disorders, especially depression, psychosis, anxiety and drug misuse, are associated with near-lethal suicide attempts, and hence probably with suicide.
Nalmefene in the treatment of pathological gambling: multicentre, double-blind, placebo-controlled study
Authors: Grant Jon E. , Odlaug Brian L. , Potenza Marc N. , Hollander Eric , Kim Suck Won
Published: September 2010

Pathological gambling is a disabling disorder experienced by about 1% of adults. We randomised 233 participants (41.6% women) 1:1:1 to nalmefene (20 or 40 mg) or placebo. In analyses performed using an intention-to-treat (ITT) population, nalmefene failed to show statistically significant differences from placebo on primary and secondary outcomes. Post hoc analyses of only participants who received a full titration of the medication for at least 1 week demonstrated that nalmefene 40 mg/day resulted in significantly greater reductions on the primary outcome measure. These findings suggest that medication dosing may be an important consideration in achieving symptom control.
Evaluation of evidence for the psychotic subtyping of post-traumatic stress disorder
Authors: Gaudiano Brandon A. , Zimmerman Mark
Published: September 2010

Psychotic symptoms may occur in 15–64% of individuals with post-traumatic stress disorder, suggesting that the syndrome could be subtyped in a similar fashion to mood disorders. In our study of 1800 psychiatric out-patients who completed comprehensive diagnostic interviews, the lifetime prevalence of psychotic symptoms in people with PTSD was 17% (odds ratio (OR) = 3.48, 95% CI 2.32–5.21). However, after excluding people with comorbid conditions also known to be associated with psychotic symptoms this dropped to only 2.5% (OR) = 0.60, 95% CI 0.08–4.52). In contrast, rates of psychotic major depression did not change after excluding these same comorbidities. Our results do not support the official psychotic subtyping of PTSD.
Does cannabidiol protect against the negative effects of THC?
Authors: Henquet Cécile , Kuepper Rebecca
Published: September 2010

A recent study by Morgan and colleagues found that cannabidiol attenuates the acute cognitive effects of delta-9-tetrahydrocannabinol (THC). This is of interest as THC has been associated with the detrimental effects of cannabis on mental health in at-risk users, and the potency of cannabis is increasing across Europe.
Psychiatric training in Europe
Authors: Oakley Clare , Malik Amit
Published: September 2010

Aims and method

This study aimed to establish the variations in the pre-defined aspects of postgraduate psychiatric training within the member countries of the European Federation of Psychiatric Trainees and illustrate the diversity of training experiences within Europe. Participants were required to complete a structured questionnaire.

Results

There are wide variations in the length, content and structure of postgraduate psychiatric training across Europe. There are differing requirements for, and access to, psychotherapy training. Some countries have no examinations or formal assessments.

Clinical implications

An understanding of the postgraduate training systems across Europe is essential not only for making informed choices about the development of trainees recruited from the European Economic Area but also for enhancing postgraduate training and patient care in all European countries.
Irish Mental Health Act 2001: impact on involuntary admissions in a community mental health service in Dublin
Authors: Nwachukwu Izu , Crumlish Niall , Heron Elizabeth A. , Gill Michael
Published: September 2010

Aims and method

On 1 November 2006, Ireland's Mental Health Act 2001 was implemented, replacing the country's Mental Treatment Act 1945. We aimed to assess the impact of this change in legislation on the number and duration of involuntary admissions. We undertook a retrospective review of all admissions to a psychiatric admissions unit from January to October 2006 (pre-implementation) and January to October 2007 (post-implementation).

Results

There were 46 involuntary admissions in the 10-month period under study in 2006, or 33.8 per 100 000 population. There were 53 in 2007, or 39.3 per 100 000 population. This increase was not significant (z = – 0.7, P = 0.46), however involuntary admissions formed a larger proportion of all admissions under the Mental Health Act 2001 than under the Mental Treatment Act 1945 (χ2 = 4.2, P =0.04). There was no difference in the duration of involuntary admissions but under the 2001 Act, involuntary patients had longer periods of voluntary status as part of their admissions than under the 1945 Act.

Clinical implications

The introduction of more rigorous procedures for involuntary admission did not significantly change the rate or duration of involuntary admissions in our centre. The finding that involuntary admissions included longer periods of voluntary status suggests that more care is being taken to revoke involuntary admission orders under the Mental Health Act 2001 than under the Mental Treatment Act 1945.
Her Majesty's Government's pleasure: providing appropriate community intervention can improve care and save money
Authors: Harris Mike
Published: September 2010

In answer to Louis Appleby's editorial, I am proposing that the role of mental health services in offender healthcare is to improve people's mental health and it is the role of the courts and the government to reduce the prison population. I also argue that with a reinvestment of existing resources into prison mental health we can reduce admission to expensive medium secure and low secure placements, save money and further reinvest in better care.
A Thrombospondin-Mimetic Peptide, ABT-898, Suppresses Angiogenesis and Promotes Follicular Atresia in Pre- and Early-Antral Follicles in Vivo
Authors: Garside Samantha A. , Henkin Jack , Morris Keith D. , Norvell Suzanne M. , Thomas Fiona H. , Fraser Hamish M.
Published: September 2010

Using a novel in vitro angiogenesis assay, we previously showed that thrombospondin (TSP)-1 has antiangiogenic effects on rat follicles and induces apoptosis in granulosa cells in vitro. ABT-898 is an octapeptide mimetic of TSP-1 closely related to ABT-510. Here, we demonstrate the inhibitory effects of ABT-898 on follicular angiogenesis and its proapoptotic effect on granulosa cells. To investigate the potential of this peptide to inhibit follicular angiogenesis in vivo, marmoset monkeys were treated with 2.5 mg/kg ABT-898 twice daily throughout the follicular phase of the cycle. Although treatment did not block emergence of dominant follicles, angiogenesis was reduced in preantral and early-antral follicles. Furthermore, the incidence of atresia at these follicle stages was increased. To investigate whether treatment with ABT-898 would interfere with the timing or duration of the normal ovulatory rise in plasma progesterone, marmosets were treated with a depot formulation containing 25 mg ABT-898 at the start of the follicular phase, with a second injection after 2 wk. Despite active concentrations of peptide being maintained in the circulation, no apparent effects on the ovulatory cycle were observed. Taken together, these results indicate that ABT-898 is capable of having a dual effect by inhibiting follicular angiogenesis and promoting atresia of antral follicles in vivo but does not prevent ovulation or induce luteolysis, as has been observed with direct vascular endothelial growth factor inhibitors. These results suggest that ABT-898 could be a novel therapeutic to inhibit abnormal angiogenesis and induce atresia of accumulated follicles in polycystic ovary syndrome.
Aldosterone Enhances IGF-I-Mediated Signaling and Biological Function in Vascular Smooth Muscle Cells
Authors: Cascella Teresa , Radhakrishnan Yashwanth , Maile Laura A. , Busby Walker H. , Gollahon Katherine , Colao Annamaria , Clemmons David R.
Published: September 2010

The IGF-I pathway and renin-angiotensin-aldosterone axis are both involved in the pathogenesis of hypertension and atherosclerosis, but no information is available about IGF-I and aldosterone interaction or their potential synergistic effects in vascular smooth muscle cells (VSMCs). The aims of this study were to investigate whether aldosterone influences IGF-I signaling and to determine the mechanism(s) by which aldosterone affects IGF-I function. Aldosterone resulted in significant increases in the Akt (1.87 ± 0.24, P < 0.001), MAPK (1.78 ± 0.13, P < 0.001), p70S6kinase (1.92 ± 0.15, P < 0.001), IGF-I receptor (1.69 ± 0.05, P < 0.01), and insulin receptor substrate-1 (1.7 ± 0.04, P < 0.01) (fold increase, mean ± SEM, n = 3) phosphorylation responses to IGF-I compared with IGF-I treatment alone. There were also significant increases in VSMC proliferation, migration, and protein synthesis (1.63 ± 0.03-, 1.56 ± 0.08-, and 1.51 ± 0.04-fold increases compared with IGF-I alone, respectively, n = 3, P < 0.001). Aldosterone induced osteopontin (OPN) mRNA expression and activation of αVβ3-integrin as well as an increase in the synthesis of IGF-I receptor. The enhancing effects of aldosterone were inhibited by eplerenone (10 μmol/liter), actinomycin-D (20 nmol/liter), and an anti-αVβ3-integrin antibody that blocks OPN binding. The antioxidant N-acetylcysteine (2 mmol/liter) completely inhibited the ability of aldosterone to induce any of these changes. In conclusion, our results show that aldosterone enhances IGF-I signaling and biological actions in VSMCs through induction of OPN followed by its subsequent activation of the αVβ3-integrin and by increasing IGF-I receptor. These changes are mediated in part through increased oxidative stress. The findings suggest a new mechanism by which aldosterone could accelerate the development of atherosclerosis.
Interplay of the Inflammatory and Stress Systems in a Hepatic Cell Line: Interactions between Glucocorticoid Receptor Agonists and Interleukin-6
Authors: Visser Koch , Smith Carine , Louw Ann
Published: September 2010

The liver plays an important role in inflammation and stress by producing the acute phase proteins (APPs) required for resolution of inflammation as well as by delivering systemic glucose, through gluconeogenesis, required to fuel the stress response. Disruption of the interplay between interleukin 6 (IL-6) and glucocorticoids (GCs), the peripheral mediators of inflammation and stress, respectively, may lead to side-effects associated with the pharmacological use of GCs. The current study investigated the interplay between IL-6 and GCs in a hepatoma cell line (BWTG3) at protein (protein activity assays, Western blotting, and ELISA) and mRNA (qPCR) levels. Specifically, the action of dexamethasone (Dex), a known antiinflammatory drug and glucocorticoid receptor (GR) agonist, is compared to that of Compound A (CpdA), a selective glucocorticoid receptor agonist (SEGRA). CpdA, like IL-6, but unlike Dex, increases GR binding and decreases the metabolic enzymes, tyrosine aminotransferase, phosphoenolpyruvate carboxykinase, and gamma glutamyltransferase, at protein or mRNA level. Like Dex, both CpdA and IL-6 increase the positive APPs, serum amyloid A and C-reactive protein, and decrease the negative APP, corticosteroid binding globulin. The study shows that the GC, Dex, and IL-6 generally have divergent effects on the GR and metabolic enzymes, while their functions are convergent on the APPs. In contrast to Dex, CpdA has effects convergent to that of IL-6 on the GR, metabolic enzymes, and APPs. Thus these findings suggest that CpdA, like Dex, modulates APPs, leading to effective control of inflammation, while, in contrast to Dex, it is less likely to lead to GC-induced side-effects.
Role of UBC9 in the Regulation of the Adipogenic Program in 3T3-L1 Adipocytes
Authors: Cignarelli Angelo , Melchiorre Mariangela , Peschechera Alessandro , Conserva Antonella , Renna Lucia Adelaide , Miccoli Sara , Natalicchio Annalisa , Perrini Sebastio , Laviola Luigi , Giorgino Francesco
Published: September 2010

The small ubiquitin-like modifier-conjugating enzyme UBC9, involved in protein modification through covalent attachment of small ubiquitin-like modifier and other less defined mechanisms, has emerged as a key regulator of cell proliferation and differentiation. To explore the role of UBC9 in adipocyte differentiation, the UBC9 protein levels were examined in differentiating 3T3-L1 cells. UBC9 mRNA and protein levels were increased 2.5-fold at d 2 and then gradually declined to basal levels at d 8 of differentiation. In addition, UBC9 was expressed predominantly in the nucleus of preadipocytes but shifted to cytoplasmic compartments after d 4, after induction of differentiation. UBC9 knockdown was then achieved in differentiating 3T3-L1 preadipocytes using a specific small interfering RNA. Oil-Red-O staining demonstrated accumulation of large triglyceride droplets in approximately 90% of control cells, whereas lipid droplets were smaller and evident in only 30% of cells treated with the UBC9-specific small interfering RNA. CCAAT/enhancer-binding protein (C/EBP)-δ, peroxisome proliferator-activated receptor-γ, and C/EBPα mRNA levels were increased severalfold 2–6 d after induction of differentiation in control cells, whereas the expression of these transcription factors was significantly lower in the presence of UBC9 gene silencing. Adenovirus-mediated overexpression of a catalytically inactive mutant UBC9 protein in 3T3-L1 cells resulted in no changes in expression of adipogenic transcription factors and conversion to mature adipocytes as compared with control. In conclusion, UBC9 appears to play an important role in adipogenesis. The temporal profile of UBC9 induction and its ability to affect C/EBPδ mRNA induction support a role for this protein during early adipogenesis.
Androgens Suppress EZH2 Expression Via Retinoblastoma (RB) and p130-Dependent Pathways: A Potential Mechanism of Androgen-Refractory Progression of Prostate Cancer
Authors: Bohrer Laura R. , Chen Shuai , Hallstrom Timothy C. , Huang Haojie
Published: September 2010

Androgens and the androgen receptor are important for both normal prostate development and progression of prostate cancer (PCa). However, the underlying mechanisms are not fully understood. The Polycomb protein enhancer of zeste homolog 2 (EZH2) functions as an epigenetic gene silencer and plays a role in oncogenesis by promoting cell proliferation and invasion. EZH2 has been implicated in human PCa progression, because its expression is often elevated in hormone-refractory PCa. Here, we demonstrated that expression of EZH2 is lower in androgen-sensitive LNCaP PCa cells compared with Rf and C4-2 cells, two androgen-refractory sublines that are derived from LNCaP cells. Androgen ablation by castration increased the level of EZH2 proteins in LNCaP xenografts in mice. In contrast, treatment of LNCaP cells in culture with the synthetic androgen methyltrieolone (R1881) at doses of 1 nm or higher suppressed EZH2 expression. Moreover, our data suggest that androgen repression of EZH2 requires a functional androgen receptor and this effect is mediated through the retinoblastoma protein and its related protein p130. We further showed that androgen treatment not only increases expression of EZH2 target genes DAB2IP and E-cadherin but also affects LNCaP cell migration. Our results reveal that androgens function as an epigenetic regulator in prostatic cells by repression of EZH2 expression through the retinoblastoma protein and p130-dependent pathways. Our findings also suggest that blockade of EZH2 derepression during androgen deprivation therapy may represent an effective tactic for the treatment of androgen-refractory PCa.
Glucocorticoid-Induced Impairment of Mammary Gland Involution Is Associated with STAT5 and STAT3 Signaling Modulation
Authors: Bertucci Paola Y. , Quaglino Ana , Pozzi Andrea G. , Kordon Edith C. , Pecci Adali
Published: September 2010

The mammary epithelium undergoes cyclical periods of cellular proliferation, differentiation, and regression. During lactation, the signal transducer and activator of transcription factor (STAT)-5A and the glucocorticoid receptor (GR) synergize to induce milk protein expression and also act as survival factors. During involution, STAT3 activation mediates epithelial cell apoptosis and mammary gland remodeling. It has been shown that the administration of glucocorticoids at weaning prevents epithelial cell death, probably by extracellular matrix breakdown prevention. Our results show that the synthetic glucocorticoid dexamethasone (DEX) modulates STAT5A and STAT3 signaling and inhibits apoptosis induction in postlactating mouse mammary glands, only when administered within the first 48 h upon cessation of suckling. DEX administration right after weaning delayed STAT5A inactivation and degradation, preserving gene expression of target genes as β-casein (bcas) and prolactin induced protein (pip). Weaning-triggered GR down-regulation is also delayed by the hormone treatment. Moreover, DEX administration delayed STAT3 activation and translocation into epithelial cells nuclei. In particular, DEX treatment impaired the increment in gene expression of signal transducer subunit gp130, normally up-regulated from lactation to involution and responsible for STAT3 activation. Therefore, the data shown herein indicate that glucocorticoids are able to modulate early involution by controlling the strong cross talk that GR, STAT5, and STAT3 pathways maintains in the mammary epithelium.
Central Nervous System (CNS) Delivery of Glucocorticoids Is Fine-Tuned by Saturable Transporters at the Blood-CNS Barriers and Nonbarrier Regions
Authors: Mason Brittany L. , Pariante Carmine M. , Jamel Sara , Thomas Sarah A.
Published: September 2010

Proper functioning of the hypothalamic-pituitary-adrenal axis depends on the ability of glucocorticoids (GCs), mainly cortisol in humans and corticosterone in rodents, to access brain targets and regulate their own secretion. Being highly lipophilic, GCs have been assumed to passively diffuse through the cell membrane. However, the access of these GCs to the brain may be a more complicated process, because the free movement of molecules into the central nervous system (CNS) is restricted by the presence of the blood-brain and blood-cerebrospinal fluid barriers. GCs do interact with some transporter systems, including the efflux transporter, P-glycoprotein, and members of the organic anion transporter polypeptide (oatp) family, both of which have been found at the blood-CNS barriers. Using an in situ brain/choroid plexus perfusion, P-glycoprotein was shown to not majorly regulate the access of [3H]cortisol and [3H]corticosterone to the choroid plexus or pituitary gland. Interactions of [3H]cortisol and [3H]corticosterone with saturable influx transporters were detected at the hypothalamus, cerebellum, choroid plexus, and pituitary gland. Oatp2 seems to have some role in the influx of [3H]cortisol and [3H]corticosterone to the choroid plexus and the pituitary gland and other transporters, unlikely to be oatp2, may play a very minor role in the access of [3H]cortisol and [3H]corticosterone to the brain, as well as having a significant effect on [3H]glucocorticoid receptor accumulation in the pituitary gland. Overall, these data suggest that the majority of cortisol and corticosterone present in the plasma diffuse into the CNS and that transporters do not play a major role in the accumulation of these GCs in the brain.