bluuebunny/crossref_metadata_2025 huggingface dataset:
Physician-assisted suicide: a survey of attitudes among Swedish physicians
Authors: Lindblad Anna , Löfmark Rurik , Lynöe Niels
Published: August 2008

Aims: To investigate the attitudes of Swedish physicians towards physician-assisted suicide. Design: A postal questionnaire on the respondent's opinion of physician-assisted suicide was sent to a randomly selected sample of physicians in Sweden. The respondents were given the opportunity of furnishing arguments of their own and of prioritizing arguments. They were also asked about possible influence on their own and patients' trust in the healthcare system if physician-assisted suicide was to be legally accepted. Participants: 1,200 physicians from six specialties, approximately 200 individuals each in: general practice, geriatrics, internal medicine, oncology, psychiatry and surgery. Setting: The study was commissioned by the Swedish Medical Society and its logo was printed on questionnaires and envelopes. Results: The total response rate was 74%, ranging between 63%—80% among the specialties. On average 34% were pro physician-assisted suicide, 39% against it and 25% were doubtful; 2% per cent did not respond to the question at all. Psychiatrists were significantly more accepting than oncologists, who were the most restrictive specialty. Older physicians (>50 years) provided a significantly more accepting attitude than younger ones (≤51 years). Conclusions: Despite the fact that the World Medical Association condemns physician-assisted suicide as unethical, the present survey indicates that there is no clear majority for or against physician-assisted suicide among Swedish physicians, and that significantly more elderly physicians have an accepting attitude towards physician-assisted suicide. There is a need for further research explaining the differences between the age groups as well as the variation between specialities.
European community health monitoring: the EUPHIX-model
Authors: Achterberg Peter W. , Kramers Pieter G.N. , van Oers Hans A.M.
Published: August 2008

Aims: On 20 June 2008, the EUPHIX website (www.euphix.org) was officially launched. EUPHIX aims to provide policy relevant health information, data and knowledge for policy makers, public health experts and educated lay people in the European Union (EU). The project was carried out by a partnership of European health reporting experts. Methods: The conceptual structure of EUPHIX resembles the one used for the ECHI-indicator framework, but adds health policies. EUPHIX includes texts (EUphacts) next to indicator data, as well as links to organizations, data and literature. Other contributions, called EUphocus, address broader agenda issues, such as mental health and health inequalities. Some EUphocus contributions contain summarized outcomes of EU projects. In this sense, EUPHIX has a European platform function as well. Behind the surface of the EUPHIX website lies a complex internet application, including databases, i.e. for indicator data, for internal and external web links and for references and definitions. This back-office contains a Content Management System that guides an editorial process allowing the differentiation of the roles of authors, reviewers and content editors. User oriented functionalities include different ways to interactively manipulate data for personal presentation needs. Some EUphacts are linked to the Health-EU Portal. Results: EUPHIX is drawing increasing numbers of visitors and has the potential to become the nucleus of a health monitoring system for the EU. However, current financing practice puts serious limits to its sustainability. Conclusions: The conclusion is that the EUPHIX model launched in June 2008 is integrating data, information and knowledge into a new type of Health Information System. The EUPHIX model is proposed to be the future model for EU health reporting.
Paediatric chest trauma (part 2) — Hidden Injuries
Authors: Kerr Maya , Maconochie Ian
Published: August 2008

Chest trauma is the second greatest cause of mortality from trauma, a leading cause of death in children over the age of one. Prompt diagnosis can be difficult as the underlying thoracic injuries are often disproportionately severe compared to the visible surface injury and symptoms may not appear for several hours. Diagnosis are easily underestimated, delayed or missed. This is the second of a 2 part article reviewing Paediatric chest trauma and its current management. The injuries are usefully classified into 6 lethal injuries that need excluding in the primary survey and 6 hidden injuries that must be considered in the secondary survey. The 6 lethal injuries are covered in the first part of this article along with biomechanics and mechanisms of injury. This article looks in depth at the 6 hidden injuries, along with a review of chest trauma in non-accidental injury.
Basal Cell Carcinoma Is Not Granulation Tissue in the Venous Leg Ulcer
Authors: Janković Aleksandar , Binić Ivana , Ljubenović Milanka
Published: August 2008

The authors present a case of a 76-year-old female with a 7-year history of a nonhealing leg ulcer. The wound surface had epithelial tissue present in a diffuse way with shiny granulations on parts of the edge of the ulcer. A biopsy of the ulcer edge was performed to study the reasons for the absence of response to treatment and the presence of abnormal granulation tissue. The result showed the presence of a basal cell carcinoma. The authors conclude that skin biopsy is very important in nonhealing chronic venous ulcers because carcinomas may mimic granulation tissue and complicate venous ulcers.
Hyperhomocysteinemia and Lower Extremity Wounds
Authors: Schwartzfarb Elissa M. , Romanelli Paolo
Published: August 2008

Chronic lower extremity wounds include ulceration of the leg and foot. The underlying pathology that causes these conditions includes venous insufficiency, arterial disease, diabetes, and other less common disorders. Since the introduction of the homocysteine theory more than 30 years ago, considerable evidence has demonstrated hyperhomocysteinemia to be an independent risk factor for venous and arterial thrombosis, atherosclerosis and cardiovascular disease. Although any cause—effect relationship remains to be determined, hyperhomocysteinemia as a risk factor for these events suggests that elevated levels of homocysteine may also be a marker of chronic lower limb ulceration. This review addresses the metabolism of homocysteine, mechanisms of vascular injury, a role for hyperhomocysteinemia in lower extremity wounds and possible means of treatment.
Sutureless Laparoscopic Heminephrectomy: Safety and Efficacy in Physiologic and Chronically Obstructed Porcine Kidney
Authors: Derweesh Ithaar H. , Malcolm John B. , Diblasio Christopher J. , Mehrazin Reza , Jackson Scott
Published: August 2008

We sought to develop and examine the feasibility and efficacy of a streamlined sutureless system of repairing parenchymal and collecting system defects using BioGlue (bovine albumin-glutaraldehyde adhesive) and ProPatch (bovine pericardial patch) in swine under physiological conditions and mechanical stress imposed by chronic ureteral obstruction caused by complete ureteral transaction. Five pigs (10 kidneys) underwent left-side transperitoneal laparoscopic heminephrectomy, followed 2 weeks later by right-sided heminephrectomy with complete ureteral transaction (between clips) to provide a mechanical stressor on the repair, followed 2 weeks later by euthanasia. In each case, after hilar clamping, the lower pole was removed with a bipolar dissector. Hemostasis was obtained with argon beam coagulator and FloSeal (thrombin-gelatin matrix), followed by sutureless repair (ProPatch-BioGlue “sandwich”). At euthanasia, harvested kidneys underwent ex vivo retrograde-pyelography and pathological examination to rule out urinoma/perinephric fluid collection and determine collecting system/parenchymal healing. Mean operative time was 77.8 minutes. Mean warm ischemia time was 12.3 ± 5.6 minutes. Estimated blood loss was 49.5 ± 39.0 mL. All animals demonstrated immediate hemostasis on hilar clamp release. Pyelography failed to demonstrate any collecting system leakage, and closure and healing was confirmed in all. Four of 5 pigs had intact renal function at euthanasia. Two pigs were euthanized for causes unrelated to procedures 4 days prior to study end. This study provides proof of principle that sutureless laparoscopic heminephrectomy is effective in physiological and chronic obstruction conditions in the porcine model. The procedure is reproducible, and resection/renorrhaphy was completed on average with approximately 12 minutes warm ischemia time.
Is Operative Conversion Necessary for Patients Diagnosed With Dense Adhesions During an Elective Laparoscopic Colectomy?
Authors: Blumberg David
Published: August 2008

Laparoscopic colectomy is often complicated by adhesions. Studies examining the morbidity of laparoscopic lysis of adhesions (LOA) combined with colectomy are sparse. Objectives. The goal of this study was to prospectively evaluate the results of using the harmonic scalpel to lyse adhesions in patients undergoing laparoscopic colectomy. Methods. Laparoscopic colectomy was performed in 83 patients between November 2003 and April 2007. A total of 20 patients underwent laparoscopic colectomy with LOA and 53 patients underwent laparoscopic colectomy alone. Patients were prospectively followed to determine operative time (OT), blood loss, operative conversion, length of stay (LOS), and 30-day morbidity. Results. Operative conversion was 2%, mean estimated blood loss (EBL) was 95 ± 84 mL, and mean OT was 220 ± 64 minutes. There were no anastomotic leaks or perioperative mortalities. There were 9 major complications (11%). Patients undergoing laparoscopic colectomy with LOA (n = 20) compared with patients undergoing laparoscopic colectomy alone (n = 63) had similar conversion rates (5% vs 2%), EBL (115 ± 108 vs 88 ± 74 mL), and major complications (15% vs 10%), but prolonged minor complications (25% vs 6%) and LOS (6.0 ± 3.0 vs 4.6 ± 1.5 days). Conclusions. Laparoscopic LOA combined with colectomy leads to similar conversion rates and major morbidity compared to laparoscopic colectomy alone.
The Role of the Assistant in Laparoscopic Surgery: Important Considerations for the Apprentice-in-Training
Authors: Chiu Anita , Bowne Wilbur B. , Sookraj Kelley A. , Zenilman Michael E. , Fingerhut Abe , Ferzli George S.
Published: August 2008

Laparoscopic surgery is a dynamic and integral component of surgical training. In many surgical programs, the surgeon-in-training gradually incorporates the knowledge and skill-sets through a variable spectrum of assistant/ apprentice instruction with different surgical mentors. As a result, this lack of formal and/or standardized instruction may be inconsistent with a structured educational process. In the year 2008, with widespread applications for minimally invasive techniques and technology, contributions from skilled assistants are now increasingly more important for effective and safe operative conduct. Incorporating these challenges into a balanced educational process remains no easy matter. The authors believe the assistant's role is vital to all aspects of laparoscopic surgery, no matter how routine or complex. Laparoscopic assistants should participate and contribute directly in the ( a) preoperative evaluation and preparation, ( b) patient positioning, ( c) operative suite arrangement, ( d) trocar placement, plus important ( e) intraoperative maneuvers contingent upon acquired mastery of laparoscopic skills. Understanding these principles plus effective administration of various duties allows for the apprentice in training to progress to more complex procedures and eventual primary surgeon responsibility. In this report, the role of the laparoscopic assistant/apprentice is reviewed, with particular attention focused on requisite fundamentals for evolving laparoscopic surgeons. To date, there are few publications within the world literature that directly address these observations. Important considerations delineating the expectations and goals for the assistant/apprentice, as well as the mentor, during laparoscopic training are provided.
Distribution of Verbal and Physical Violence for Same and Opposite Genders Among Adolescents
Authors: Winstok Zeev , Enosh Guy
Published: August 2008

The present study was set up to test the perceived distribution of verbal and physical violent behaviors among same- and opposite-genders. More specifically, those perceived violent behaviors are examined as the outcome of adolescents' cost-risk goals. The study assumes two conflicting social goals: Whereas the goal of risk reduction may motivate withdrawal from conflict, and decrease the prevalence of violent events, the goal of pursuing social status may motivate initiation and/or retaliation, thus increasing the prevalence of violence. The study is based on a sample of 155 high-school students that recorded the frequency of observing violent events in their peer group over a one-week period. Findings demonstrate that for males, opponent gender had a primary effect on violence distribution. Males exhibited violence against males more frequently than against females. This result is consistent with the assumption that males set a higher priority to pursuing social status. For females, verbal violence was more frequent than physical forms of aggression. This is consistent with the assumption that females set a higher priority on avoiding risk. These results are discussed from an evolutionary cost-risk perspective.
Intimate Partner Violence Perpetration, Risky Sexual Behavior, and STI/HIV Diagnosis Among Heterosexual African American Men
Authors: Raj Anita , Reed Elizabeth , Welles Seth L. , Santana Maria Christina , Silverman Jay G.
Published: August 2008

Evidence indicates that abusive male partners pose increased risk for sexually transmitted infection (STI)/HIV among females. However, research with males on this issue is limited. The objective of this study was to assess the associations between intimate partner violence (IPV) perpetration and recent STI/HIV diagnosis, unprotected sex, and sex trade involvement among heterosexual African American men. In this cross-sectional study, heterosexual African American males aged 18 to 65 years who reported two or more sex partners in the past year were recruited from urban health clinics to complete a computerized survey assessing sociodemographic characteristics, IPV perpetration history, risky sexual behaviors, and substance use. Multivariate logistic regression analyses assessed associations between IPV perpetration and STI/HIV risk. More than half of participants in this sample (61%) were unemployed; 28.2% had less than a high school education and 23.1% were homeless. One-fifth of the sample (21.2%) reported IPV perpetration in their current relationship. IPV perpetration was significantly associated with recent STI/HIV diagnosis, unprotected anal sex, and buying sex. IPV perpetration is pervasive among heterosexually at-risk African American men presenting for clinical care, and those perpetrating IPV are at heightened risk for STI/HIV.
How we diagnose the antiphospholipid syndrome
Authors: Giannakopoulos Bill , Passam Freda , Ioannou Yiannis , Krilis Steven A.
Published: August 2008

The antiphospholipid syndrome (APS) is an acquired thrombophilia, characterized by the occurrence of venous and arterial events. This article examines the laboratory and key clinical aspects of APS. Particular focus is given to anti–beta 2-glycoprotein I (β2GPI) antibodies in view of their recent inclusion in the APS classification criteria. The clinical utility of using the β2GPI enzyme-linked immunosorbent assay, in conjunction with the established lupus anticoagulant assays and cardiolipin enzyme-linked immunosorbent assay, for diagnosing and risk stratifying patients suspected of having APS is discussed. The relative importance of the various assays in diagnosing obstetric APS (early and late gestation miscarriages) is explored. The implications of recent epidemiologic findings for possibly understanding the underlying pathophysiologic mechanisms of obstetric APS are highlighted. Insights into which patients with obstetric APS may be at most risk of thrombotic complications are presented.
CD18-dependent activation of the neutrophil NADPH oxidase during phagocytosis of Escherichia coli or Staphylococcus aureus is regulated by class III but not class I or II PI3Ks
Authors: Anderson Karen E. , Boyle Keith B. , Davidson Keith , Chessa Tamara A. M. , Kulkarni Suhasini , Jarvis Gavin E. , Sindrilaru Anca , Scharffetter-Kochanek Karin , Rausch Oliver , Stephens Len R. , Hawkins Phillip T.
Published: August 2008

Phagocytosis and activation of the NADPH oxidase are important mechanisms by which neutrophils and macrophages engulf and kill microbial pathogens. We investigated the role of PI3K signaling pathways in the regulation of the oxidase during phagocytosis of Staphylococcus aureus and Escherichia coli by mouse and human neutrophils, a mouse macrophage-like cell line and a human myeloid-like cell line. Phagocytosis of these bacteria was promoted by serum, independent of serum-derived antibodies, and effectively abolished in mouse neutrophils lacking the β2-integrin common chain, CD18. A combination of PI3K isoform-selective inhibitors, mouse knock-outs, and RNA-interference indicated CD18-dependent activation of the oxidase was independent of class I and II PI3Ks, but substantially dependent on the single class III isoform (Vps34). Class III PI3K was responsible for the synthesis of PtdIns(3)P on phagosomes containing either bacteria. The use of mouse neutrophils carrying an appropriate knock-in mutation indicated that PtdIns(3)P binding to the PX domain of their p40phox oxidase subunit is important for oxidase activation in response to both S aureus and E coli. This interaction does not, however, account for all the PI3K sensitivity of these responses, particularly the oxidase response to E coli, suggesting that additional mechanisms for PtdIns(3)P-regulation of the oxidase must exist.
Current differences in referral patterns for pulmonary endarterectomy in the UK
Authors: Toshner M. , Suntharalingam J. , Goldsmith K. , Niggebrugge A. , Pepke-Zaba J. , Morrell N. W. , Tsui S. , Flowers J. , Jenkins D.
Published: August 2008

Pulmonary endarterectomy (PEA) surgery is the treatment of choice in surgically accessible chronic thromboembolic pulmonary hypertension and is potentially curative. The UK is served by seven specialist pulmonary hypertension centres and, consequently, there are regions which do not have a specialist unit. Since 2000, Papworth Hospital (Papworth Everard, UK) has been the sole PEA provider for the UK, offering the opportunity to study the national incidence of operable disease and give potential insight into factors that might affect geographical distribution within the UK.

All 262 UK residents who underwent PEA surgery between April 2000 and May 2006 were included in the present study. The age-adjusted cumulative referral rates were compared between regions to test for uniformity.

Overall, observed rates differed significantly from expected, with evidence of significant nonuniformity across the UK. The highest rates were observed in proximity to the nationally designated specialist centres and in particular in East Anglia and the West Midlands, nearest Papworth. These two regions differed by >2×sdfrom the national mean rate.

The present study demonstrates wide geographical variation in the number of patients referred for pulmonary endarterectomy surgery. This suggests that there may be patients who are not presently being offered this potentially curative option.
Severity of obstructive sleep apnoea/hypopnoea syndrome and subsequent waking EEG spectral power
Authors: Grenèche J. , Sarémi M. , Erhardt C. , Hoeft A. , Eschenlauer A. , Muzet A. , Tassi P.
Published: August 2008

It is well known that most patients with obstructive sleep apnoea/hypopnoea syndrome (OSAHS) suffer sleepiness, although the underlying mechanisms of this relationship remain unclear. The present study examined the relationship between nocturnal variables and the subsequent waking electroencephalogram (EEG), in order to determine if sleepiness was related to OSAHS severity and due to sleep fragmentation or to nocturnal hypoxaemia.

In total, 12 moderate-to-severe OSAHS patients underwent a total sleep night followed by a 24-h period of sustained wakefulness where the waking EEG was measured every hour.

The results showed that alpha (7.9–12.6 Hz) and beta (12.7–29.2 Hz) activities were strongly related to OSAHS severity, mainly reflected by the apnoea index. Moreover, spectral power in most of the waking EEG components was significantly correlated with nocturnal hypoxaemia indices, namely alpha and beta activity when hypoxaemia becomes severe. However, no correlation was found between the waking EEG and sleep fragmentation parameters.

In conclusion, the present results suggest that the difficulty in maintaining an optimal level of alertness, reflected by a higher activity in awake alpha and beta bands (7.9–29.2 Hz) in obstructive sleep apnoea/hypopnoea syndrome, was better explained by: 1) the apnoea as opposed to the hypopnoea index; and 2) nocturnal hypoxaemia as opposed to sleep fragmentation.
Inhibition of airway proteases in cystic fibrosis lung disease
Authors: Griese M. , Kappler M. , Gaggar A. , Hartl D.
Published: August 2008

Progressive lung disease determines the morbidity and mortality of cystic fibrosis (CF) patients.

CF lung disease is characterised by endobronchial inflammation sustained by bacterial infections and an ongoing accumulation of airway neutrophils. Activated or necrotic neutrophils liberate proteases that cause damage to structural, cellular and soluble components of the pulmonary microenvironment.

Among various proteases released by airway cells, elastase is considered to play the major role in CF lung disease. Based on this concept, several therapeutic approaches have been developed to inhibit free elastolytic activity, including small synthetic chemical compounds, semi-synthetic inhibitors and natural inhibitors of free elastase.

The present review summarises and discusses the pathophysiological rationales, methodological requirements and clinical implications of inhibition of airway proteases in cystic fibrosis lung disease.
Short- and long-term response to corticosteroid therapy in chronic beryllium disease
Authors: Marchand-Adam S. , El Khatib A. , Guillon F. , Brauner M. W. , Lamberto C. , Lepage V. , Naccache J-M. , Valeyre D.
Published: August 2008

Chronic beryllium disease (CBD) is a granulomatous disorder that affects the lung after exposure to beryllium. The present study reports short- and long-term evolution of granulomatous and fibrotic components in eight patients with severe CBD receiving corticosteroid therapy.

Eight patients with confirmed CBD were studied at baseline, after initial corticosteroid treatment (4–12 months), at relapse and at the final visit. Beryllium exposure, Glu69(HLA-DPB1 genes coding for glutamate at position β69) polymorphism, symptoms, pulmonary function tests (PFT), serum angiotensin-converting enzyme (SACE) and high-resolution computed tomography (HRCT) quantification of pulmonary lesions were analysed.

The CBD patients were observed for a median (range) of 69 (20–180) months. After stopping beryllium exposure, corticosteroids improved symptoms and PFT (vital capacity +26%, diffusing capacity of the lung for carbon monoxide +15%), and decreased SACE level and active lesion HRCT score. In total, 18 clinical relapses occurred after the treatment was tapered and these were associated with SACE and active lesion HRCT score impairment. At the final visit, corticosteroids had completely stabilised all parameters including both HRCT scores of active lesions and fibrotic lesions in six out of eight patients.

Corticosteroids were beneficial in chronic beryllium disease. They were effective in suppressing granulomatosis lesions in all cases and in stopping the evolution to pulmonary fibrosis in six out of eight patients.
Modulation of cholinergic contractions of airway smooth muscle by cathinone: potential beneficial effects in airway diseases
Authors: Freund-Michel V. C. , Birrell M. A. , Patel H. J. , Murray-Lyon I. M. , Belvisi M. G.
Published: August 2008

Infusion of khat leaves is an African traditional remedy used to treat airway diseases. The beneficial effects of khat are thought to be due to the activity of its main active component, cathinone.

Cathinone inhibited electric field stimulation-induced acetylcholine release and the contractions of smooth muscle, which could be responsible for the beneficial effects seen in airway disease. The mechanism of action of this natural product appears to beviathe activation of both pre-junctional α2adrenergic and 5-hydroxytryptamine 7 receptors.

The present novel study describes how cathinone modulates airway tone, and may go some way to explaining the traditional use of khat as a remedy for the alleviation of respiratory disease symptoms.

In conclusion, cathinone may have beneficial effects in airway diseases with heightened cholinergic tone. There is some rationale for follow-up of these observations, given previous experience of other traditional remedies being developed for therapeutic use.
Primer sets for cloning the human repertoire of T cell Receptor Variable regions
Authors: Boria Ilenia , Cotella Diego , Dianzani Irma , Santoro Claudio , Sblattero Daniele
Published: August 2008

Background

Amplification and cloning of naïve T cell Receptor (TR) repertoires or antigen-specific TR is crucial to shape immune response and to develop immuno-based therapies. TR variable (V) regions are encoded by several genes that recombine during T cell development. The cloning of expressed genes as large diverse libraries from natural sources relies upon the availability of primers able to amplify as many V genes as possible.

Results

Here, we present a list of primers computationally designed on all functional TR V and J genes listed in the IMGT®, the ImMunoGeneTics information system®. The list consists of unambiguous or degenerate primers suitable to theoretically amplify and clone the entire TR repertoire. We show that it is possible to selectively amplify and clone expressed TR V genes in one single RT-PCR step and from as little as 1000 cells.

Conclusion

This new primer set will facilitate the creation of more diverse TR libraries than has been possible using currently available primer sets.
Pedigree with frontotemporal lobar degeneration – motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9
Authors: Luty Agnes A , Kwok John BJ , Thompson Elizabeth M , Blumbergs Peter , Brooks William S , Loy Clement T , Dobson-Stone Carol , Panegyres Peter K , Hecker Jane , Nicholson Garth A , Halliday Glenda M , Schofield Peter R
Published: August 2008

Background

Frontotemporal lobar degeneration (FTLD) represents a clinically, pathologically and genetically heterogenous neurodegenerative disorder, often complicated by neurological signs such as motor neuron-related limb weakness, spasticity and paralysis, parkinsonism and gait disturbances. Linkage to chromosome 9p had been reported for pedigrees with the neurodegenerative disorder, frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND). The objective in this study is to identify the genetic locus in a multi-generational Australian family with FTLD-MND.

Methods

Clinical review and standard neuropathological analysis of brain sections from affected pedigree members. Genome-wide scan using microsatellite markers and single nucleotide polymorphism fine mapping. Examination of candidate genes by direct DNA sequencing.

Results

Neuropathological examination revealed cytoplasmic deposition of the TDP-43 protein in three affected individuals. Moreover, we identify a family member with clinical Alzheimer's disease, and FTLD-Ubiquitin neuropathology. Genetic linkage and haplotype analyses, defined a critical region between markers D9S169 and D9S1845 on chromosome 9p21. Screening of all candidate genes within this region did not reveal any novel genetic alterations that co-segregate with disease haplotype, suggesting that one individual carrying a meiotic recombination may represent a phenocopy. Re-analysis of linkage data using the new affection status revealed a maximal two-point LOD score of 3.24 and a multipoint LOD score of 3.41 at marker D9S1817. This provides the highest reported LOD scores from a single FTLD-MND pedigree.

Conclusion

Our reported increase in the minimal disease region should inform other researchers that the chromosome 9 locus may be more telomeric than predicted by published recombination boundaries. Moreover, the existence of a family member with clinical Alzheimer's disease, and who shares the disease haplotype, highlights the possibility that late-onset AD patients in the other linked pedigrees may be mis-classified as sporadic dementia cases.
Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation
Authors: Lee Jae Woong , Lee Yong Kyung , Yuk Dong Yeon , Choi Dong Young , Ban Sang Bae , Oh Ki Wan , Hong Jin Tae
Published: August 2008

Background

Alzheimer's disease (AD) is characterized by extensive loss of neurons in the brain of AD patients. Intracellular accumulation of beta-amyloid peptide (Aβ) has also shown to occur in AD. Neuro-inflammation has been known to play a role in the pathogenesis of AD.

Methods

In this study, we investigated neuro-inflammation and amyloidogenesis and memory impairment following the systemic inflammation generated by lipopolysaccharide (LPS) using immunohistochemistry, ELISA, behavioral tests and Western blotting.

Results

Intraperitoneal injection of LPS, (250 μg/kg) induced memory impairment determined by passive avoidance and water maze tests in mice. Repeated injection of LPS (250 μg/kg, 3 or 7 times) resulted in an accumulation of Aβ1–42 in the hippocampus and cerebralcortex of mice brains through increased β- and γ-secretase activities accompanied with the increased expression of amyloid precursor protein (APP), 99-residue carboxy-terminal fragment of APP (C99) and generation of Aβ1–42 as well as activation of astrocytes in vivo. 3 weeks of pretreatment of sulindac sulfide (3.75 and 7.5 mg/kg, orally), an anti-inflammatory agent, suppressed the LPS-induced amyloidogenesis, memory dysfunction as well as neuronal cell death in vivo. Sulindac sulfide (12.5–50 μM) also suppressed LPS (1 μg/ml)-induced amyloidogenesis in cultured neurons and astrocytes in vitro.

Conclusion

This study suggests that neuro-inflammatory reaction could contribute to AD pathology, and anti-inflammatory agent could be useful for the prevention of AD.
‘Public psychiatry’: a neglected professional role?
Authors: Smith Michael J.
Published: August 2008

The importance of mental health to our social, financial and physical well-being has gained better recognition in recent years. The work of psychiatry is to understand, prevent and treat mental illness, and should therefore be of compelling interest to the public. Yet few care about the profession or practice of psychiatry other than psychiatrists themselves. The public and the profession would both benefit from a ‘conversation’ about practical, moral and political aspects of contemporary mental health. This should be a dialogue of equals, distinct from didactic approaches to ‘public education’ or from a ‘media psychiatry’ that exists primarily to entertain. This discourse would help to improve care, diminish stigma, promote recovery and improve the status of the profession itself. This article proposes that this kind of ‘public psychiatry’ should take its place as one of four interdependent professional domains.
Self-determination theory: a framework for the recovery paradigm
Authors: Mancini Anthony D.
Published: August 2008

Recovery is an increasingly important concept in mental health services research and policy-making. However, despite burgeoning interest in the concept, no overarching theoretical or empirical framework has been offered to support its key ideas. Further, it is often unclear how recovery ideas translate into routine practices of mental health programmes and practitioners. In this article, a theoretical framework for recovery ideas is derived from self-determination theory, a widely researched and empirically validated theory of human need fulfilment. I discuss the conceptual overlap of self-determination theory and recovery ideas, and, using key motivational concepts, develop a typology of recovery-oriented practices for three hypothetical programme types (controlling, traditional/paternalistic and recovery oriented). I describe existing measures of recovery-oriented practice and consider the implications of self-determination theory for measurement of and research on recovery-oriented practice.
Keeping PACE: fitness to be interviewed by the police
Authors: Ventress Michael A. , Rix Keith J. B. , Kent John H.
Published: August 2008

The second half of the 20th century witnessed a number of serious miscarriages of justice that resulted from improper police interviewing of suspects and unreliable and false confessions. To prevent miscarriages of justice involving people with mental disorder or particular mental vulnerabilities, psychiatrists have a role in determining the fitness to be interviewed of persons suspected of criminal offences. In this article, the role of the psychiatrist in assessing fitness to be interviewed is set against the background of the latest revisions of the Codes of Practice of the Police and Criminal Evidence Act 1984 and relevant case law in England and Wales.
‘Public psychiatry’: a challenge for the profession?
Authors: Yeomans David , Drake Frances
Published: August 2008

Michael Smith's article considering the present and future of ‘public psychiatry’ assumes the continued existence of psychiatry following a conversation with the public. But what if the public does not want psychiatry?
Video self-observation: a means of improving insight in psychosis
Authors: Vikram Sitara , Yarger Nishi , Coxell Adrian , Maier Michael
Published: August 2008

Aims and Method

To improve the level of insight (measured using standardised instruments) using a video interview and self-observation. Changes in levels of insight were measured using the Schedule for Assessing Insight (SAI) at the time of admission, at the time of discharge (both prior to and following the viewing of the videotape) and at follow-up a few months later.

Results

The comparison of the SAI scores indicated a significant improvement in insight at the time of discharge (P < 0.005), with a further significant improvement after watching the video (P < 0.006). This appeared to be sustained at 3- to 6-month follow-up.

Clinical Implications

Video self-observation is a simple, inexpensive procedure that can be used to improve insight in psychosis. This study provides further support for the clinical utility of video self-observation in improving client's insight.
Community model in treating obsessive–compulsive and body dysmorphic disorders
Authors: Drummond L. M. , Pillay A. , Kolb P. J. , Benson S. , Fogg R. , Jones-Thomas E. , Rani S.
Published: August 2008

Aims and Method

In November 2005, the National Institute for Health and Clinical Excellence published guidelines for the treatment of obsessive–compulsive disorder (OCD) and body dysmorphic disorder. These guidelines incorporated a stepped care approach with different interventions advised throughout the patient pathway. South West London and St George's Mental Health NHS Trust devised a system of expert clinicians with special expertise in OCD/body dysmorphic disorder to help deliver this model of care. To aid the delivery of service it was decided to operationalise the definitions of severity of OCD/body dysmorphic disorder at each of the stepped-care levels. Examples are given as to how this has been applied in practice. Outcome is presented in terms of clinical hours in the first year of operation.

Results

In total, 108 patients were referred to the service in the first year. Many of these patients were treated by offering advice and support and joint working with the community mental health team and psychotherapy in primary care teams who had referred. Sixty-eight patients were treated by a member of the specialist service alone and 57 of these suffered from severe OCD. Outcome data from these 57 patients is presented using an intention-to-treat paradigm. They showed a clinically and statistically significant reduction in OCD symptoms after 24 weeks of cognitive–behavioural therapy comprising graded exposure and self-imposed response prevention. the mean Yale–Brown Obsessive Compulsive Scale score dropped from 28 (severe OCD) to 19 (considerable OCD). Depressive symptoms on the Beck Depression Inventory also decreased by an average 24% over the same period.

Clinical Implications

The feasibility of extending this model of service organisation to other areas and other diagnoses is discussed.
Part-time working in psychiatry in Northern Ireland
Authors: Donnelly Caroline , McGarry Philip , Mills Heather
Published: August 2008

Aims and Method

To establish the proportion of psychiatrists in Northern Ireland who currently work part-time and the proportion of those working fulltime who wish to work part-time. A postal questionnaire was forwarded to psychiatrists and repeated 30 months later.

Results

In 2004, only 18.3% of respondents were working part-time, and 26.8% in 2006. A great majority stated their intent was to always work part-time, the most frequent reason being to achieve work–life balance.

Clinical Implications

A significant number of staff working part-time will have implications for the staffing of the service. Policy makers must plan for the adequate provision of part-time working arrangements.
7-Oxysterols Modulate Glucocorticoid Activity in Adipocytes through Competition for 11β-Hydroxysteroid Dehydrogenase Type
Authors: Wamil Malgorzata , Andrew Ruth , Chapman Karen E. , Street Jonathan , Morton Nicholas M. , Seckl Jonathan R.
Published: August 2008

Obesity is associated with an increased risk of diabetes type 2, dyslipidemia, and atherosclerosis. These cardiovascular and metabolic abnormalities are exacerbated by excessive dietary fat, particularly cholesterol and its metabolites. High adipose tissue glucocorticoid levels, generated by the intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), are also implicated in the pathogenesis of obesity, metabolic syndrome, and atherosclerosis. 11β-HSD1 also interconverts the atherogenic oxysterols 7-ketocholesterol (7KC) and 7β-hydroxycholesterol (7β-HC). Here, we report that 11β-HSD1 catalyzes the reduction of 7KC to 7β-HC in mature 3T3-L1 and 3T3-F442A adipocytes, leading to cellular accumulation of 7β-HC. Approximately 73% of added 7KC was reduced to 7β-HC within 24 h; this conversion was prevented by selective inhibition of 11β-HSD1. Oxysterol and glucocorticoid conversion by 11β-HSD1 was competitive and occurred with a physiologically relevant IC50 range of 450 nm for 7KC inhibition of glucocorticoid metabolism. Working as an inhibitor of 11β-reductase activity, 7KC decreased the regeneration of active glucocorticoid and limited the process of differentiation of 3T3-L1 preadipocytes. 7KC and 7β-HC did not activate liver X receptor in a transactivation assay, nor did they display intrinsic activation of the glucocorticoid receptor. However, when coincubated with glucocorticoid (10 nm), 7KC repressed, and 7β-HC enhanced, glucocorticoid receptor transcriptional activity. The effect of 7-oxysterols resulted from the modulation of 11β-HSD1 reaction direction, and could be ameliorated by overexpression of hexose 6-phosphate dehydrogenase, which supplies reduced nicotinamide adenine dinucleotide phosphate to 11β-HSD1. Thus, the activity and reaction direction of adipose 11β-HSD1 is altered under conditions of oxysterol excess, and could impact upon the pathophysiology of obesity and its complications.
Cyclin-Dependent Kinase 5 Regulates Steroidogenic Acute Regulatory Protein and Androgen Production in Mouse Leydig Cells
Authors: Lin Ho , Chen Mei-Chih , Ku Chien-Te
Published: August 2008

The roles of cyclin-dependent kinase 5 (Cdk5) in central nervous system and neurodegenerative diseases have been intensely investigated in recent decades. Because protein expressions of Cdk5 and its regulator, p35, have been identified in Leydig cells, it is informative to further explore the novel function of Cdk5/p35 in male reproduction. Here we show that Cdk5/p35 protein expression and kinase activity in mouse Leydig cells are regulated by human chorionic gonadotrophin (hCG) in both dose- and time-dependent manners. Blocking of Cdk5 by molecular inhibitors or small interfering RNA resulted in reduction of testosterone production by Leydig cells. cAMP, a second messenger in LH signaling, was identified as a factor in hCG-dependent regulation of Cdk5/p35. Importantly, Cdk5 protein and kinase activity could support accumulation of steroidogenic acute regulatory (StAR) protein, a crucial component of steroidogenesis. We additionally addressed the protein interaction between Cdk5/p35 and StAR. The Cdk5-dependent serine phosphorylation of StAR indicated a possible mechanism by which Cdk5 induced accumulation of StAR protein. In conclusion, Cdk5 modulates hCG-induced androgen production in mouse Leydig cells, possibly through regulation of StAR protein levels. These results indicate that Cdk5 may play an important role in male reproductive endocrinology and is a potential therapeutic target in androgen-related diseases.

The physiological function of cyclin-dependent kinase 5 (Cdk5) in mouse Leydig cells is to regulate androgen production through stabilizing the steroiodogenic acute regulatory (StAR) protein.
Testis Development, Fertility, and Survival in Ethanolamine Kinase 2-Deficient Mice
Authors: Gustin Sonja E. , Western Patrick S. , McClive Peter J. , Harley Vincent R. , Koopman Peter A. , Sinclair Andrew H.
Published: August 2008

Ethanolamine kinase 2 (Eki2) was previously isolated from a differential expression screen designed to identify candidate genes involved in testis development and differentiation. In mouse, Eki2 is specifically up-regulated in Sertoli cells of the developing testis at the time of sex determination. Based on this expression profile, Eki2 was considered a good candidate testis-determining gene. To investigate a possible role of Eki2 in testis development, we have generated a mouse with targeted disruption of the Eki2 gene by using an EGFP replacement strategy. No abnormalities were detected in the Eki2-deficient mice with regard to embryonic and adult testis morphology, differentiation, function, or fertility. Furthermore, no significant differences were observed in litter sizes, pup mortality rates, or distribution of the sexes among the offspring. Ethanolamine kinases are involved in the biosynthesis of phosphatidylethanolamine, a major membrane phospholipid. Expression analysis indicates that the absence of an apparent phenotype in the Eki2-deficient mice may be due to compensation by Eki2-family members or the activation of an alternative pathway to generate phosphatidylethanolamine. Expression of EGFP in this mouse model enabled the isolation of gonad cell populations, providing a useful resource from which to obtain relatively pure early steroidogenic cells for further studies.
Evidence that a Protein Kinase A Substrate, Small Heat-Shock Protein 20, Modulates Myometrial Relaxation in Human Pregnancy
Authors: Tyson Elisa K. , MacIntyre David A. , Smith Roger , Chan Eng-Cheng , Read Mark
Published: August 2008

For a successful human pregnancy, the phasic smooth muscle of the myometrium must remain quiescent until labor. Activation of cAMP/cAMP-dependent protein kinase A (PKA) pathways contributes to this quiescence. The small heat-shock protein 20 (HSP20) is a target of PKA, and phosphorylated HSP20 (pHSP20) modulates relaxation of tonic vascular smooth muscle via interaction with actin, independent of myosin dephosphorylation. Our objective was to determine whether relaxation in human myometrium is associated with changes in phosphorylation of HSP20. Myometrium was obtained at elective cesarean. Elevating cAMP with forskolin or rolipram (a phosphodiesterase inhibitor) caused substantial relaxation of spontaneously contracting human myometrial strips, of 92 ± 4% (mean ± sem, n = 10) and 84 ± 7% (n = 6), respectively. Subsequent two-dimensional electrophoresis with immunoblotting of strip extracts showed a significant 2.6- and 2.1-fold increase in phosphorylated HSP20 (pHSP20) after forskolin (P < 0.01; n = 5) or rolipram treatment (P < 0.05; n = 4). Noncyclic-nucleotide-mediated relaxation, induced by the calcium channel blocker nifedipine, did not alter pHSP20. Inhibition of PKA with H89 significantly attenuated rolipram-induced relaxation (P < 0.01; n = 4), and partially reduced rolipram-stimulated pHSP20. Total and pHSP20 protein was unchanged in term laboring and nonlaboring myometria. Coimmunoprecipitation studies revealed a specific association of HSP20 with α-smooth muscle actin and HSP27, a key regulator of actin filament dynamics. Finally, coimmunofluorescence demonstrated moderate colocalization of HSP20 with α-smooth muscle actin in the cytoplasm of laboring myometria. Our data support a novel role for pHSP20 in the modulation of cyclic-nucleotide-mediated myometrial relaxation, through interaction with actin. pHSP20 represents an important new target for future tocolytic therapy.
Genes Associated with Membrane-Initiated Signaling of Estrogen and Energy Homeostasis
Authors: Roepke T. A. , Xue C. , Bosch M. A. , Scanlan T. S. , Kelly M. J. , Rønnekleiv O. K.
Published: August 2008

During the reproductive cycle, fluctuations in circulating estrogens affect multiple homeostatic systems controlled by hypothalamic neurons. Two of these neuronal populations are arcuate proopiomelanocortin and neuropeptide Y neurons, which control energy homeostasis and feeding. Estradiol modulates these neurons either through the classical estrogen receptors (ERs) to control gene transcription or through a G protein-coupled receptor (mER) activating multiple signaling pathways. To differentiate between these two divergent ER-mediated mechanisms and their effects on homeostasis, female guinea pigs were ovariectomized and treated systemically with vehicle, estradiol benzoate (EB) or STX, a selective mER agonist, for 4 wk, starting 7 d after ovariectomy. Individual body weights were measured after each injection day for 28 d, at which time the animals were euthanized, and the arcuate nucleus was microdissected. As predicted, the body weight gain was significantly lower for EB-treated females after d 5 and for STX-treated females after d 12 compared with vehicle-treated females. Total arcuate RNA was extracted from all groups, but only the vehicle and STX-treated samples were prepared for gene microarray analysis using a custom guinea pig gene microarray. In the arcuate nucleus, 241 identified genes were significantly regulated by STX, several of which were confirmed by quantitative real-time PCR and compared with EB-treated groups. The lower weight gain of EB-treated and STX-treated females suggests that estradiol controls energy homeostasis through both ERα and mER-mediated mechanisms. Genes regulated by STX indicate that not only does it control neuronal excitability but also alters gene transcription via signal transduction cascades initiated from mER activation.