bluuebunny/crossref_metadata_2025 huggingface dataset:
Lessons Learnt in Conducting a Clinical Drug Trial in Children with Asperger Syndrome
Authors: Mathai John , Bourne Angela , Cranswick Noel
Published: December 2009

Objective: To describe the authors' experience of conducting a clinical drug trial in children with Asperger Syndrome, including the pitfalls encountered and lessons learnt.

Conclusions: The main barrier encountered was in the recruitment of children: it was not possible to recruit the target of 60 patients. The recruitment of children is often the major barrier to the progress of a successful clinical trial. Conducting the clinical drug trial was greatly facilitated by the appropriate setting and experienced clinical pharmacology staff.
General Practitioners and Mental Health Staff Sharing Patient Care: Working Model
Authors: Horner Deborah , Asher Kim
Published: December 2009

Objective: The paper describes a shared care programme developed by mental health services and general practitioners for shifting patients with chronic psychiatric disorders to the care of a general practitioner. The programme is characterized by: (i) a dedicated mental health service general practitioner liaison position to manage the programme and provide support to both patients and doctors; (ii) a multidisciplinary care planning meeting that includes mental health staff, the patient, the general practitioner and a carer; and (iii) a jointly developed individual management plan that specifies patient issues, strategies to deal with these issues, persons responsible for monitoring and a review date.

Methods: The shared care protocol, the results of a review of patient mental health indicators and general practitioner satisfaction with the programme are described.

Results: Outcomes to date suggest that patients' mental health is not compromised and may be enhanced by transfer to general practitioners within the shared care model. Indicators of mental health outcomes (Health of the Nation Outcome Scale and Life Skills Profile scores) show improved patient symptomatology and functioning in most cases.

Conclusions: The programme fits the model of recovery-based mental health services and complies with current local, state and Commonwealth policies that encourage integrated and collaborative approaches by mental health services and general practitioners in delivering mental health care to persons with chronic mental illness.
Survey of Depot Antipsychotic Prescribing in Southern Adelaide
Authors: Herriot Peter , Kheirani Kamran
Published: December 2009

Objective: Depot antipsychotic medication (DAP) is widely used in the treatment of schizophrenia and related disorders. The objectives of this study were to (i) determine whether DAP was being prescribed in accordance with established guidelines in terms of dose, interval of administration and indications; and (ii) assess the quality of the assessment and documentation of tardive dyskinesia (TD) as well as blood glucose and lipid abnormalities.

Methods: The survey was carried out between April and June 2003 at all three public hospital affiliated community mental health centres located in the southern region of Adelaide. Data were extracted from three sources: depot prescription charts, community mental health service case notes and hospital case notes.

Results: Two hundred and sixty-one patients were receiving DAP. The majority (89%) had a diagnosis of schizophrenia or schizoaffective disorder. The DAP prescribed most frequently was zuclopenthixol decanoate (57%) at a modal dose of 200 mg and a modal administration interval of 2weeks. Fifty-three per cent of patients had at least one dose reduction during the course of treatment. Four per cent of patients had a case note documented diagnosis of TD. Fifty-seven per cent of patients had at least one blood glucose test in the past year, with nearly half showing high results. Forty-seven per cent of patients had at least one lipid study in the past year, with more than half having high total cholesterol and 22% having high triglycerides.

Conclusion: The results of this study indicate that DAP is being used mostly for the treatment of schizophrenia and related disorders, which is in agreement with established evidence-based guidelines. The finding of at least one documented attempt at DAP dose reduction or extension of interval of administration in approximately half of the patients receiving DAP is encouraging and may have an impact on reducing the likelihood of TD. A formal TD surveillance programme using a screening tool such as the Abnormal Involuntary Movement Scale is recommended. In addition, more frequent evaluation of blood glucose and lipid levels is needed.
Models and Patterns of Service in Child and Youth Consultation–Liaison Services
Authors: Wagner Ingrid , Stathis Stephen , Harden Scott , Crimmins Jennifer
Published: December 2009

Objective: The aim was to examine referral pathways to child and youth consultation–liaison (C-L) services to identify patterns associated with demographic characteristics of patients, referral sources, the presenting problem and models of service.

Method: A case record review with a cross-sectional design. Data were extracted from the records of all patients referred to the C-L service for a 3month period.

Results: Adolescents were more likely to accessmental health services through informal liaison services. Medical specialty areas that were inclusive of nursing and allied health, in both the request for service and initial response to the request, had higher frequencies of referral. There was no difference between the disciplines of medicine and social work in the frequency of referrals. However, medicine, social work and nursing differed in the number of staff who initiated the request for consultation, and the types of problems that were presented as reasons for referral.

Conclusions: Inclusive multidisciplinary models may facilitate the development of service relationships in paediatric hospital settings, due to the stability of staffing arrangements. The wider participation of allied health and nursing staff within paediatric hospitals may extend opportunities for the identification of mental health problems and enhance timely management of referrals.
Providing Integrated Mental Health Services: A Policy and Management Perspective
Authors: Callaly Tom , Fletcher Anna
Published: December 2009

Objective: To review the challenge of providing integrated mental health services from a policy and health management perspective.

Conclusions: The provision of integrated mental health services involving specialist mental health services, general practitioners, psychiatric disability and rehabilitation services and public community health services is a major challenge in the Australian health care context and is increasingly an expectation of the community. Government, Divisions of General Practice and public community health policy and many Government, State and local initiatives have attempted to address this challenge. However, much remains to be done, including culture change within services and professions and the development of technology to support integrated service provision.
Mrs Hitler and her doctor
Authors: Macleod Sandy
Published: December 2009

Objective: The doctor who attended the mother of Adolf Hitler in her terminal illness has been blamed as a cause of the Holocaust. The medical details recorded of this professional relationship are presented and discussed.

Conclusions: Dr Bloch's medical care of Mrs Hitler was consistent with the prevailing medical practice of the management of fungating breast carcinoma. Indeed, the general practitioner's care and attention of the family appear to have been astute and supportive. There is nothing to suggest that Dr Bloch's medical care was other than competent. Doctors who have the (mis)fortune to professionally attend major figures of history may be unfairly viewed, despite their appropriate and adequate care.
Contribution of ‘School-Link’ to an Area Mental Health Service
Authors: Maloney Danielle , Walter Garry
Published: December 2009

Objective: To evaluate the contribution of the ‘School-Link’ initiative to an Area Mental Health Service.

Method: Surveys and focus groups of school and health service personnel were conducted to examine the three foci of the School-Link initiative, namely prevention, early intervention and service access.

Results: Improvements witnessed since the commencement of School-Link include an increasein the number of evidence-based mental health promotion programmes in schools, improvements in the communication between health and education departments, improvements in referral patterns and better practices, such as improved feedback, in both health and education sectors. School counsellors feel more supported in their role by health services and better able to manage certain patients.

Conclusions: The actual and potential benefits of School-Link for young persons appear considerable. School-Link has provided opportunities for communication, upgrading of skills and collaborative work on mental health issues, in both education and health settings.
Data Collection in Consultation– Liaison Psychiatry: An Evaluation of Casemix
Authors: Ellen Steven , Lacey Cameron , Kouzma Nadya , Sauvey Nick , Carroll Rhonda
Published: December 2009

Objective: To evaluate the usefulness of Casemix as a data collection system for consultation–liaison psychiatry services.

Method: Health information staff were requested to code psychiatric assessments and diagnosis prospectively for admissions to the Alfred Hospital, Melbourne, between July 2002 and June 2004 using Casemix.

Results: Psychiatric assessments were requested on 2.5% of all hospital admissions (n = 2575). Casemix provided extensive demographic and hospital unit data for referred patients, is easy to set up, and is cost-free for the psychiatry service.

Conclusions: Casemix can provide extensive meaningful data for consultation–liaison psychiatry services that could assist in the argument for greater funding of these services.
Psychiatrists in New Zealand: Are They Burning Out, Satisfied at Work and, in any Case, who Cares??
Authors: Kumar Shailesh , Nath Bhagat Ravindra , Lau Trevor , Ng Bradley
Published: December 2009

Objective: To explore possible contributing or mitigating factors for burn out in New Zealand psychiatrists as well as future research directions in this area.

Method: A selective review of the literature pertaining to burnout and reports regarding New Zealand's medical workforce.

Results: Possible factors contributing to burnout in New Zealand psychiatrists include rapid changes in the country's health system, the challenge of recruiting and retaining psychiatrists, poor distribution of staff and funds and difficulties in psychiatric training. Potential protective factors against burnout include lifestyle factors, long experience in psychiatry, proposed long lengths of career in New Zealand and potentially positive changes in the health system. Research challenges include subject recruitment, the lack of exploration of personal protective factors and completing longitudinal studies.

Conclusions: Given the current state of knowledge, it would be difficult to accurately know whether New Zealand psychiatrists were burnt out or satisfied with their work. Carefully designed studies would help to clarify this issue.
Is Real Reform of the Medicare Benefits Schedule for Psychiatrists in Australia Economically, Socially or Professionally Desirable?
Authors: Hickie Ian , Davenport Tracey , Luscombe Georgina , Scott Elizabeth , Mackenzie Elizabeth , Morgan Hugh , Wilson Andrew , Barton David , Barrett Elaine
Published: December 2009

Objective: To propose alternative Medicare Benefits Schedule-based funding models for outpatient psychiatric services in Australia.

Method: Development of alternative funding schedules for a variety of under-serviced populations.

Conclusions: Consideration of alternative systems is necessary to address the restrictive work practices, inequity and poor distribution of the psychiatric workforce.
On being a Supervisor: The Importance of Feedback and how to give it
Authors: Chur-Hansen Anna , Mclean Steven
Published: December 2009

Objective: We outline some of the dominant opinions regarding the provision of formative feedback, as expressed by both trainees and their supervisors.

Methods: Trainee psychiatrists and their supervisors were interviewed and asked to identify ‘good’ as opposed to ‘poor’ supervision.

Results: A recurrent theme in interview data was that of formative feedback. Trainees expressed a desire to receive it, but some supervisors discussed misgivings and a lack of skill in providing such feedback.

Conclusions: Formative feedback is an essential part of the supervisor's role. We describe the principles of how to best deliver feedback, in order to increase supervisors' confidence and ability in utilizing this learning and teaching skill.
A Report on Economic Studies of Australian Mental Health Issues
Authors: Williams Ruth , Doessel Darrel
Published: December 2009

Objective: To report on economic studies of Australian mental health issues.

Conclusion: Although the international literature on the economics of mental health issues is increasing, and although many Australian studies exist on one comorbid condition of mental illness, namely substance abuse, there are very few empirical studies by economists of Australia's mental health issues.
An Interdisciplinary Course for Trainee Psychiatrists: Feedback and Implications
Authors: Chur-Hansen Anna , Koopowitz Leslie , Jureidini Jon , Abhary Sotoodeh , Mclean Steve
Published: December 2009

Objective: To describe a course for trainee psychiatrists, designed to encourage critical thinking within an interdisciplinary framework. Trainees’ responses to the course, and the implications of these for teaching, learning and clinical practice, are considered.

Method: Trainees were interviewed, and their responses subjected to content analysis.

Results: To some extent, the course appears to have met its objectives. However, some trainees found parts of the course content threatening, and reported negative perceptions of teaching staff and the process of critical appraisal.

Conclusions: Challenging taken for granted beliefs in psychiatry is a fundamental skill, which should be fostered in trainee psychiatrists if the profession is to move forwards as an intellectual and clinical discipline. The lessons learned from the course we describe may be useful to others who wish to pursue integrated, interdisciplinary teaching methods.
Why do Health Professionals Work in a Community Mental Health Service?
Authors: Spear Jonathan
Published: December 2009

Objective: The aim of this pilot study was to determine the reasons why mental health professionals work in a community mental health service.

Methods: A survey of psychiatrists and trainees (n = 13) and other mental health professionals (n = 67) was conducted in an Australian community mental health service with a socioeconomically deprived catchment population. Respondents were asked to list their main reasons for working and to complete measures of job design, well-being, social support, role clarity, teamwork and job satisfaction. The qualitative results were validated using focus groups.

Results: The response rate was 53.7% (43/80). Income (31/43), belonging (21/43), self-esteem (30/43) and self-actualization (9/43) were the main reasons given for working. Mental health professionals, who reported self-actualization as a reason for work, had significantly higher well-being and job satisfaction than other subjects. Mental health professionals who cited self-actualization as a reason for work perceived that their work was more significant and had higher task identity compared with other subjects.

Conclusions: This study is limited by a small sample size and the inability to exclude confounding variables. Maslow's hierarchy of needs was a useful framework for categorizing reasons for work. Some practical approaches to meet the needs of the mental health workforce are discussed.
Trends in Antipsychotic Prescribing in Schizophrenia in Auckland
Authors: Wheeler Amanda , Humberstone Verity , Robinson Gail
Published: December 2009

Objective: This study describes antipsychotic prescribing practices for outpatients with schizophrenia over a 3 year period in two large mental health catchment areas of Auckland.

Methods: All community files were reviewed at three time points. Patient characteristics, diagnosis and antipsychotic treatment information were recorded and analysed.

Results: Over the three time periods, the number of outpatients with a diagnosis of schizophrenia or schizoaffective disorder was stable. There was a marked change in the type of antipsychotic prescribed, with an 18.6% increase in atypical antipsychotics and a decrease in both intramuscular and oral typical antipsychotics. Clozapine was the most commonly prescribed antipsychotic in 2003 (35%). Despite the fact that polypharmacy was relatively low (14.6% in 2003), those receiving more than one antipsychotic had a greater likelihood of being prescribed a higher total daily dose.

Conclusions: This study describes a change in antipsychotic prescribing towards recommended practice guidelines for the treatment of schizophrenia over a 3 year period.
The Need for the Development and Evaluation of Preventive Psychosocial Forensic Interventions in Mainstream Adult Community Mental Health Services
Authors: Gleeson John , Nathan Pamela , Bradley Gail
Published: December 2009

Objective: This paper provides a selective review of forensic research with the aim of making recommendations for the development and evaluation of psychosocial interventions for the mainstream community mental health setting to address the needs of patients with a history of offending.

Conclusion: Mainstream community mental health services can be guided by existing findings in the design of psychosocial intervention and prevention programmes. There is growing need to develop and evaluate such interventions.
Remote Area Indigenous Psychiatry: Not your usual Day at the Office
Authors: Cord-Udy Nigel
Published: December 2009

Objective: To describe the development since 2001 of visiting psychiatric services for the very remotely located indigenous communities in South Australia.

Conclusions: The South Australian experience indicates that visiting psychiatric services can be provided in a sustainable and culturally appropriate manner for the benefit of Aboriginal people who live in the remotest places in Australia. These services are an important part of the broader response by the health sector to the mental and physical health needs of indigenous Australians. The work is professionally rewarding for clinicians.
Mood Stabilizer Prescribing in a Christchurch Adolescent Sample: Does it Comply with Guidelines?
Authors: Craig Brian , Olsen Annalise , Swadi Harith , Bobier Candace
Published: December 2009

Objective: To determine the level of compliance with official guidelines for prescribing mood stabilizers among adolescents in Christchurch, New Zealand.

Methods: A retrospective audit of clinical files of patients aged 13–19 years attending inpatient and outpatient services in the Child, Adolescent and Family Service in the Canterbury District catchment area was carried out against set criteria derived from the Ministry of Health Guidelines regarding the use of mood stabilizers (lithium and sodium valproate). A guideline compliance index was also created to measure overall compliance.

Results: Over a period of 3 years beginning from January 2000, we identified 68 episodes of initiation among 58 adolescents. Of those, 91.2% were for indications set in the guidelines. More than half appeared to have been given no information about the medication, and only 61.8% had documented consent. Two-thirds had a full laboratory work-up before initiation. More than one-third had no evidence of communication with general practitioners about being initiated on a mood stabilizer. Overall, only 13.2% were 100% compliant and only 50% were 80% compliant.

Conclusion: In general, mood stabilizers were prescribed as indicated, but adherence to the guidelines beyond that appears to fall short of standards set by the guidelines.
Books Reconsidered: Emile Durkheim, Le Suicide
Authors: Robertson Michael
Published: December 2009

Objective: To reappraise Emile Durkheim's taxonomy of suicide in Le Suicide in the light of recent experience.

Conclusions: While Durkheim's scientific method and argument are fundamentally fiawed, some of his concepts have instrumental value in attempting to understand the complex origins of suicidal behaviour. Durkheim's baseless dismissal of mental illness as a key determinant of suicidal behaviour weakens his thesis significantly. However, his conceptualization of anomic, egoistic and altruistic suicide provides a means of comprehending recent trends in suicidal behaviour in the former Soviet states and a possible window into the psyche of the suicides of religious and political extremists.
Hepatitis C in People With Mental Illness: How Big is the Problem and How Do We Respond?
Authors: Seccull Alison , Richmond Jacqui , Thomas Ben , Herrman Helen
Published: December 2009

Objective: To review the evidence available on best practice care of people with both hepatitis C and mental illness and its application in a mental health service.

Methods: A literature search was conducted for publications dealing with screening, referral for specialist review and antiviral treatment for this population group.

Results: A small number of studies was identified that specifically dealt with screening and treatment for hepatitis C in people with mental illness.

Conclusions: Screening, referral and treatment for hepatitis C in people with mental illness is worthwhile and achievable.
Mother–Infant Psychotherapy and Perinatal Psychiatry: Current Clinical Practice and Future Directions
Authors: Galbally Megan , Lewis Andrew , Snellen Martien , Paul Campbell , Szego Klara , Trauer Tom
Published: December 2009

Objective: To explore trends in the practice of mother–infant psychotherapy among perinatal psychiatry clinicians based in Melbourne.

Methods: A cross-sectional survey with a purpose designed self-report questionnaire was used to assess the attitudes and practices of 47 perinatal and infant psychiatry clinicians in their use and understanding of mother–infant psychotherapy.

Results: Seventy per cent of clinicians in this field of psychotherapy who responded to the questionnaire subscribe to a psychodynamic model, although cognitive behavioural models are also used. The interventions were mostly used in conjunction with other interventions, would be more accurately described as ‘parent–infant psychotherapy’, and non-psychiatrists in the area tended to be more likely to be formally trained in psychotherapy, but only 4% were formally trained in specific mother–infant psychotherapy. There was a unanimous request for further clinical training in this area.

Conclusions: The emerging field of perinatal psychiatry needs to develop coherent therapeutic models and conduct outcome trials on specific interventions. Specific trainings in these models, in assessment and in diagnostic frameworks are required to enhance clinical efficacy, for research and service development purposes.
Psychiatric Emergencies in Children and Adolescents: An Emergency Department Audit
Authors: Jean Starling , Kim Bridgland , Donna Rose
Published: December 2009

Objective: To describe a cohort of children presenting to a paediatric emergency department with mental health problems.

Methods: An Emergency Department (ED) computerized record system and hospital records were used to obtain data on children who presented to a paediatric ED with mental health problems.

Results: There were 291 presentations of 231 children in a 10-month period, about one per day. They were a small (0.8%) but complicated part of the ED workload. Most were first presentations and came voluntarily to ED. There were a wide variety of presenting symptoms including self-harm, suicide attempts, behavioural disorders and medical disorders with associated psychological problems. Acute psychosis was rare.

Conclusions: Many children with mental health problems were seen for the first time in ED. With the growing awareness of mental health problems in this age group, it is likely that such presentations will increase. Paediatric and psychiatry services have an opportunity to work together to provide early intervention services for what is potentially a very accessible population.
Overall Cdk activity modulates the DNA damage response in mammalian cells
Authors: Cerqueira Antonio , Santamaría David , Martínez-Pastor Bárbara , Cuadrado Miriam , Fernández-Capetillo Oscar , Barbacid Mariano
Published: December 2009

In response to DNA damage, cells activate a phosphorylation-based signaling cascade known as the DNA damage response (DDR). One of the main outcomes of DDR activation is inhibition of cyclin-dependent kinase (Cdk) activity to restrain cell cycle progression until lesions are healed. Recent studies have revealed a reverse connection by which Cdk activity modulates processing of DNA break ends and DDR activation. However, the specific contribution of individual Cdks to this process remains poorly understood. To address this issue, we have examined the DDR in murine cells carrying a defined set of Cdks. Our results reveal that genome maintenance programs of postreplicative cells, including DDR, are regulated by the overall level of Cdk activity and not by specific Cdks.
Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78
Authors: Conrad Melanie L. , Ferstl Ruth , Teich René , Brand Stephanie , Blümer Nicole , Yildirim Ali Ö. , Patrascan Cecilia C. , Hanuszkiewicz Anna , Akira Shizuo , Wagner Hermann , Holst Otto , von Mutius Erika , Pfefferle Petra I. , Kirschning Carsten J. , Garn Holger , Renz Harald
Published: December 2009

The pre- and postnatal environment may represent a window of opportunity for allergy and asthma prevention, and the hygiene hypothesis implies that microbial agents may play an important role in this regard. Using the cowshed-derived bacterium Acinetobacter lwoffii F78 together with a mouse model of experimental allergic airway inflammation, this study investigated the hygiene hypothesis, maternal (prenatal) microbial exposure, and the involvement of Toll-like receptor (TLR) signaling in prenatal protection from asthma. Maternal intranasal exposure to A. lwoffii F78 protected against the development of experimental asthma in the progeny. Maternally, A. lwoffii F78 exposure resulted in a transient increase in lung and serum proinflammatory cytokine production and up-regulation of lung TLR messenger RNA. Conversely, suppression of TLRs was observed in placental tissue. To investigate further, the functional relevance of maternal TLR signaling was tested in TLR2/3/4/7/9−/− knockout mice. The asthma-preventive effect was completely abolished in heterozygous offspring from A. lwoffii F78–treated TLR2/3/4/7/9−/− homozygous mother mice. Furthermore, the mild local and systemic inflammatory response was also absent in these A. lwoffii F78–exposed mothers. These data establish a direct relationship between maternal bacterial exposures, functional maternal TLR signaling, and asthma protection in the progeny.
Interleukin (IL)-23 mediates Toxoplasma gondii–induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17
Authors: Muñoz Melba , Heimesaat Markus M. , Danker Kerstin , Struck Daniela , Lohmann Uwe , Plickert Rita , Bereswill Stefan , Fischer André , Dunay Ildikò Rita , Wolk Kerstin , Loddenkemper Christoph , Krell Hans-Willi , Libert Claude , Lund Leif R. , Frey Oliver , Hölscher Christoph , Iwakura Yoichiro , Ghilardi Nico , Ouyang Wenjun , Kamradt Thomas , Sabat Robert , Liesenfeld Oliver
Published: December 2009

Peroral infection with Toxoplasma gondii leads to the development of small intestinal inflammation dependent on Th1 cytokines. The role of Th17 cells in ileitis is unknown. We report interleukin (IL)-23–mediated gelatinase A (matrixmetalloproteinase [MMP]-2) up-regulation in the ileum of infected mice. MMP-2 deficiency as well as therapeutic or prophylactic selective gelatinase blockage protected mice from the development of T. gondii–induced immunopathology. Moreover, IL-23–dependent up-regulation of IL-22 was essential for the development of ileitis, whereas IL-17 was down-regulated and dispensable. CD4+ T cells were the main source of IL-22 in the small intestinal lamina propria. Thus, IL-23 regulates small intestinal inflammation via IL-22 but independent of IL-17. Gelatinases may be useful targets for treatment of intestinal inflammation.
Intestinal epithelial cell secretion of RELM-β protects against gastrointestinal worm infection
Authors: Herbert De'Broski R. , Yang Jun-Qi , Hogan Simon P. , Groschwitz Kathryn , Khodoun Marat , Munitz Ariel , Orekov Tatyana , Perkins Charles , Wang Quan , Brombacher Frank , Urban Joseph F. , Rothenberg Marc E. , Finkelman Fred D.
Published: December 2009

Th2 cells drive protective immunity against most parasitic helminths, but few mechanisms have been demonstrated that facilitate pathogen clearance. We show that IL-4 and IL-13 protect against intestinal lumen-dwelling worms primarily by inducing intestinal epithelial cells (IECs) to differentiate into goblet cells that secrete resistin-like molecule (RELM) β. RELM-β is essential for normal spontaneous expulsion and IL-4–induced expulsion of Nippostrongylus brasiliensis and Heligmosomoides polygyrus, which both live in the intestinal lumen, but it does not contribute to immunity against Trichinella spiralis, which lives within IEC. RELM-β is nontoxic for H. polygyrus in vitro but directly inhibits the ability of worms to feed on host tissues during infection. This decreases H. polygyrus adenosine triphosphate content and fecundity. Importantly, RELM-β–driven immunity does not require T or B cells, alternative macrophage activation, or increased gut permeability. Thus, we demonstrate a novel mechanism for host protection at the mucosal interface that explains how stimulation of epithelial cells by IL-4 and IL-13 contributes to protection against parasitic helminthes that dwell in the intestinal lumen.
External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers
Authors: Kubo Akiharu , Nagao Keisuke , Yokouchi Mariko , Sasaki Hiroyuki , Amagai Masayuki
Published: December 2009

Outermost barriers are critical for terrestrial animals to avoid desiccation and to protect their bodies from foreign insults. Mammalian skin consists of two sets of barriers: stratum corneum (SC) and tight junctions (TJs). How acquisition of external antigens (Ags) by epidermal Langerhans cells (LCs) occur despite these barriers has remained unknown. We show that activation-induced LCs elongate their dendrites to penetrate keratinocyte (KC) TJs and survey the extra-TJ environment located outside of the TJ barrier, just beneath the SC. Penetrated dendrites uptake Ags from the tip where Ags colocalize with langerin/Birbeck granules. TJs at KC–KC contacts allow penetration of LC dendrites by dynamically forming new claudin-dependent bicellular- and tricellulin-dependent tricellular TJs at LC–KC contacts, thereby maintaining TJ integrity during Ag uptake. Thus, covertly under keratinized SC barriers, LCs and KCs demonstrate remarkable cooperation that enables LCs to gain access to external Ags that have violated the SC barrier while concomitantly retaining TJ barriers to protect intra-TJ environment.
Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network
Authors: Chorro Laurent , Sarde Aurélien , Li Mei , Woollard Kevin J. , Chambon Pierre , Malissen Bernard , Kissenpfennig Adrien , Barbaroux Jean-Baptiste , Groves Richard , Geissmann Frédéric
Published: December 2009

Most tissues develop from stem cells and precursors that undergo differentiation as their proliferative potential decreases. Mature differentiated cells rarely proliferate and are replaced at the end of their life by new cells derived from precursors. Langerhans cells (LCs) of the epidermis, although of myeloid origin, were shown to renew in tissues independently from the bone marrow, suggesting the existence of a dermal or epidermal progenitor. We investigated the mechanisms involved in LC development and homeostasis. We observed that a single wave of LC precursors was recruited in the epidermis of mice around embryonic day 18 and acquired a dendritic morphology, major histocompatibility complex II, CD11c, and langerin expression immediately after birth. Langerin+ cells then undergo a massive burst of proliferation between postnatal day 2 (P2) and P7, expanding their numbers by 10–20-fold. After the first week of life, we observed low-level proliferation of langerin+ cells within the epidermis. However, in a mouse model of atopic dermatitis (AD), a keratinocyte signal triggered increased epidermal LC proliferation. Similar findings were observed in epidermis from human patients with AD. Therefore, proliferation of differentiated resident cells represents an alternative pathway for development in the newborn, homeostasis, and expansion in adults of selected myeloid cell populations such as LCs. This mechanism may be relevant in locations where leukocyte trafficking is limited.
Drosophila ORC localizes to open chromatin and marks sites of cohesin complex loading
Authors: MacAlpine Heather K. , Gordân Raluca , Powell Sara K. , Hartemink Alexander J. , MacAlpine David M.
Published: December 2009

The origin recognition complex (ORC) is an essential DNA replication initiation factor conserved in all eukaryotes. In Saccharomyces cerevisiae, ORC binds to specific DNA elements; however, in higher eukaryotes, ORC exhibits little sequence specificity in vitro or in vivo. We investigated the genome-wide distribution of ORC in Drosophila and found that ORC localizes to specific chromosomal locations in the absence of any discernible simple motif. Although no clear sequence motif emerged, we were able to use machine learning approaches to accurately discriminate between ORC-associated sequences and ORC-free sequences based solely on primary sequence. The complex sequence features that define ORC binding sites are highly correlated with nucleosome positioning signals and likely represent a preferred nucleosomal landscape for ORC association. Open chromatin appears to be the underlying feature that is deterministic for ORC binding. ORC-associated sequences are enriched for the histone variant, H3.3, often at transcription start sites, and depleted for bulk nucleosomes. The density of ORC binding along the chromosome is reflected in the time at which a sequence replicates, with early replicating sequences having a high density of ORC binding. Finally, we found a high concordance between sites of ORC binding and cohesin loading, suggesting that, in addition to DNA replication, ORC may be required for the loading of cohesin on DNA in Drosophila.
Misorientations in rolled and recrystallized zirconium compared with random distribution. A new scheme of misorientation analysis
Authors: Bacroix Brigitte , Tarasiuk Jacek , Wierzbanowski Krzysztof , Zhu Kangying
Published: December 2009

The noncorrelated misorientation distributions found in a zirconium alloy after deformation, complete recrystallization and subsequent grain growth are first compared with those found in a quasi-isotropic hexagonal material (i.e.associated with a random orientation distribution). They are then recalculated with respect to the specific misorientation axes 〈0001〉, 〈10{\overline 1}0〉 and 〈11{\overline 2}0〉. The results are discussed with reference to the specific misorientations that are often assumed to play a role during the recrystallization process.
SSMBS: a web server to locate sequentially separated motifs in biological sequences
Authors: Kumar Chetan , Sekar K.
Published: December 2009

The identification of sequence (amino acids or nucleotides) motifs in a particular order in biological sequences has proved to be of interest. This paper describes a computing server,SSMBS, which can locate and display the occurrences of user-defined biologically important sequence motifs (a maximum of five) present in a specific order in protein and nucleotide sequences. While the server can efficiently locate motifs specified using regular expressions, it can also find occurrences of long and complex motifs. The computation is carried out by an algorithm developed using the concepts of quantifiers in regular expressions. The web server is available to users around the clock at http://dicsoft1.physics.iisc.ernet.in/ssmbs/.
Linearly graded GeSi beam-expanding/compressing X-ray monochromator
Authors: Korytár D. , Ferrari C. , Mikulík P. , Vagovič P. , Dobročka E. , Áč V. , Konopka P. , Erko A. , Abrosimov N.
Published: December 2009

In standard single-crystal V-channel germanium (220) X-ray beam-expanding/compressing monochromators for Cu Kα1radiation, a total beam expansion/compression of 5 and 10 corresponding to the asymmetry angles of 9 and 12° is achieved, respectively. Higher one-dimensional beam expansion/compression is achievable using larger angles of asymmetry at the expense of a decrease in the total intensity. To increase the intensity, a linearly graded Ge-rich GexSi1−xsingle crystal was used to prepare a monochromator with 15° asymmetry angles (total expansion/compression factor of 21) for Cu Kα1radiation. The X-ray diffraction measurements show more than three times higher peak intensity at the output compared with that of a pure Ge monochromator.
Multiphase approximation for small-angle scattering
Authors: Tatchev Dragomir
Published: December 2009

The two-phase approximation in small-angle scattering is well known and is still the dominant approach to data analysis. The intensity scattered at small angles is proportional to the second power of the difference between the scattering densities of the two phases. Nevertheless, scattering contrast variation techniques are widely used, and they are obviously suitable for multiphase systems or systems with gradually varying scattering density, since if no parasitic scattering contributions are present the scattering contrast variation would only change a proportionality coefficient. It is shown here that the scattered intensity at small angles of a multiphase system can be represented as a sum of the scattering of two-phase systems and terms describing interference between all pairs of phases. Extracting two-phase scattering patterns from multiphase samples by contrast variation is possible. These two-phase patterns can be treated with the usual small-angle scattering formalism. The case of gradually varying scattering density is also discussed.
Histone acetylation and steroid receptor coactivator expression during clofibrate‐induced rat hepatocarcinogenesis
Authors: Asano Jumpei , Kudo Toshihiro , Shimizu Takeshi , Fan Yang , Nanashima Naoki , Yamana Daisuke , Miura Takuya , Yamada Toshiyuki , Tsuchida Shigeki
Published: December 2009

Peroxisome proliferators (PPs), non‐genotoxic rodent carcinogens, cause the induction of the peroxisomal fatty acid β‐oxidation system, including bifunctional enzyme (BE) and 3‐ketoacyl‐CoA thiolase (TH), in the liver. GST M1 gene is polymorphic in Sprague–Dawley rats, NC‐ and KS‐type. The KS‐type rats showed enhanced susceptibility to ethyl‐α‐chlorophenoxyisobutyrate (clofibrate, CF), one of the PPs. The degree of BE induction was higher in the KS‐type and preneoplastic foci developed after 6–8 weeks of treatment, whereas no foci developed in the NC‐type. In the preset study, factors involved in different BE inducibility were investigated. There were no differences in hepatic peroxisome proliferator‐activated receptor (PPAR) α levels between them. Among various coactivators for PPARα, only steroid receptor coactivator (SRC)‐3 level was higher in the KS‐type. To investigate the association between PPARα and SRC‐3 or other proteins, nuclear extracts from CF‐treated livers were applied to a PPARα column. In the KS‐type, 110, 72, and 42 kDa proteins were bound and these were identified as SRC‐3, BE, and TH, respectively. EMSA supported the binding of these proteins to PPARα associated to the BE enhancer in CF‐treated KS‐type, but not in the NC‐type. Histone H3 acetylation was increased 11‐fold in the KS‐type by CF treatment but not in the NC‐type. As BE and TH are responsible for acetyl‐CoA production and SRC‐3 possesses a histone acetyltransferase activity, these results suggest that enhanced BE induction in the KS‐type livers is due to acetylation‐mediated transcriptional activation and epigenetic mechanisms might be involved in CF‐induced rat hepatocarcinogenesis.

(Cancer Sci 2010; 101: 876–875)
Establishment of six new human biliary tract carcinoma cell lines and identification of MAGEH1 as a candidate biomarker for predicting the efficacy of gemcitabine treatment
Authors: Ojima Hidenori , Yoshikawa Daitaro , Ino Yoshihiro , Shimizu Hiroko , Miyamoto Masashi , Kokubu Akiko , Hiraoka Nobuyoshi , Morofuji Noriaki , Kondo Tadashi , Onaya Hiroaki , Okusaka Takuji , Shimada Kazuaki , Sakamoto Yoshihiro , Esaki Minoru , Nara Satoshi , Kosuge Tomoo , Hirohashi Setsuo , Kanai Yae , Shibata Tatsuhiro
Published: December 2009

The aim of this study was to establish new biliary tract carcinoma (BTC) cell lines and identify predictive biomarkers for the potential effectiveness of gemcitabine therapy. Surgical specimens of BTC were transplanted directly into immunodeficient mice to establish xenografts, then subjected to in vitro cell culture. The gemcitabine sensitivity of each cell line was determined and compared with the genome‐wide gene expression profile. A new predictive biomarker candidate was validated using an additional cohort of gemcitabine‐treated BTC cases. From 55 BTC cases, we established 19 xenografts and six new cell lines. Based on their gemcitabine sensitivity, 10 BTC cell lines (including six new and four publicly available ones) were clearly categorized into two groups, and MAGEH1 mRNA expression in the tumor cells showed a significant negative correlation with their sensitivity to gemcitabine. Immunohistochemically, MAGEH1 protein was detected in three (50%) out of six sensitive cell lines, and four (100%) out of four resistant cell lines. In the validation cohort of gemcitabine‐treated recurrence cases, patients were categorized into “effective” and “non‐effective” groups according to the RECIST guidelines for assessment of chemotherapeutic effects. MAGEH1 protein expression was detected in two (40%) out of five “effective” cases and all four (100%) “non‐effective” cases. We have established a new BTC bioresource that covers a wide range of biological features, including drug sensitivity, and is linked with clinical information. Negative expression of MAGEH1 protein serves as a potential predictive marker for the effectiveness of gemcitabine therapy in BTC.

(Cancer Sci 2010; 101: 882–888)
Associations of polymorphisms in the promoter I of bovine acetyl‐CoA carboxylase‐α gene with beef fatty acid composition
Authors: Zhang S. , Knight T. J. , Reecy J. M. , Wheeler T. L. , Shackelford S. D. , Cundiff L. V. , Beitz D. C.
Published: December 2009

The objectives of this study were to identify single nucleotide polymorphisms (SNPs) in the promoter I (PI) region of the bovine acetyl‐CoA carboxylase‐α (ACACA) gene and to evaluate the extent to which they were associated with lipid‐related traits. Eight novel SNPs were identified, which were AJ276223:g.2064T>A (SNP1), g.2155C>T (SNP2), g.2203G>T (SNP3), g.2268T>C (SNP4), g.2274G>A (SNP5), g.2340A>G (SNP6), g.2350T>C (SNP7) and g.2370A>G (SNP8). Complete linkage disequilibrium was observed among SNP1, 2, 4, 5, 6 and 8. Phenotypic data were collected from 573 cross‐bred steers with six sire breeds, including Hereford, Angus, Brangus, Beefmaster, Bonsmara and Romosinuano. The genotypes of SNP1/2/4/5/6/8 were significantly associated with adjusted backfat thickness. The genotypes of SNP3 were significantly associated with triacylglycerol (TAG) content and fatty acid composition of longissimus dorsi muscle (LM) in Brangus‐, Romosinuano‐ and Bonsmara‐sired cattle. Cattle with g.2203GG genotype had greater concentrations of TAG, total lipid, total saturated fatty acid and total monounsaturated fatty acid than did cattle with g.2203GT genotype. The genotypes of SNP7 were significantly associated with fatty acid composition of LM. Cattle with genotype g.2350TC had greater amounts of several fatty acids in LM than did cattle with genotype g.2350CC. Our results suggested that the SNPs in the PI region of ACACA gene are associated with variations in the fatty acid contents in LM.
Closing and continentalization of the South Pyrenean foreland basin (NE Spain): magnetochronological constraints
Authors: Costa Elisenda , Garcés Miguel , López‐Blanco Miguel , Beamud Elisabet , Gómez‐Paccard Miriam , Larrasoaña Juan Cruz
Published: December 2009

This paper presents new magnetostratigraphic results from a 1100‐m‐thick composite section across the marine to continental sediments of the central part of the SE margin of the Ebro basin (NE Spain). Integration with existing marine and continental biochronological data allows a robust correlation with the geomagnetic polarity time scale. The resulting absolute chronology ranges from 36.3 to 31.1 Ma (Priabonian to Rupelian), and yields an interpolated age of ∼36.0 Ma (within chron C16n.2n) for the youngest marine sediments of the eastern Ebro basin. This age is in concordance with a reinterpretation of earlier magnetostratigraphic data from the western South Pyrenean foreland basin, and indicates that continentalization of the basin occurred as a rapid and isochronous event. The basin continentalization, determined by the seaway closure that resulted from the uplift of the western Pyrenees, was probably coincident with a mid‐amplitude eustatic sea level low with a maximum at 36.2 Ma. The base level drop that followed the basin closure and desiccation does not appear associated to a significant sedimentary hiatus along the margins, suggesting a late Eocene shallow marine basin that rapidly refilled and raised its base level after the seaway closing. Rapid basin filling following continentalization predates the phase of rapid exhumation of the Central Pyrenean Axial Zone from 35.0 to 32.0 Ma, determined from the thermochronology data. It is possible then that sediment aggradation at the front of the fold‐and‐thrust belt could have contributed to a decrease in the taper angle, triggering growth of the inner orogenic wedge through break‐back thrusting and underplating. Contrasting sedimentation trends between the western and eastern sectors of the South Pyrenean foreland indicate that basin closing preferentially affected those areas subjected to sediment bypass towards the ocean domain. As a result, sediment ponding after basin closure is responsible for a two‐fold increase of sedimentation rates in the western sector, while changes of sedimentation rates are undetected in the more restricted scenario of the eastern Ebro basin.
Haemostasis and thrombosis in liver disease
Authors: Roberts Lara N. , Patel Raj K. , Arya Roopen
Published: December 2009

Liver disease impacts on both primary and secondary haemostatic mechanisms and historically these changes were thought to underpin the bleeding diathesis. However, bleeding complications in patients with liver disease are unpredictable, with the majority of haemorrhagic episodes occurring as a result of porto‐systemic varices. Thrombosis is an increasingly recognised complication and systemic hypercoagulability may contribute to the development of parenchymal extinction and accelerated hepatic fibrosis. Routine laboratory tests do not reliably predict the risk of haemorrhage and the optimal management strategy to avert potential bleeding complications is yet to be established. There may be a future role for global coagulation assays, such as thrombelastograpy and thrombin generation, in both stratifying the risk of bleeding and guiding management of these patients.