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Aims The aims of this study were (i) to extend a psychosocial taxonomy of patients with diabetes to a primary care setting, and (ii) to validate the taxonomy using more sophisticated clustering methods across an array of psychological dimensions independent of demographic and medical variables. Methods In a cross-sectional study, 111 adults with Type 2 diabetes seen in a primary care setting completed the Multidimensional Diabetes Questionnaire and the Brief Symptom Inventory (BSI). They also provided diabetes-specific self-report measures along with HbA1c. Results Four psychosocial patient profiles were identified using model-based cluster analysis in a US primary care setting. The four profiles represent a replication of two and refinement of a third profile found previously in French-speaking patients at diabetes education centres. Validation of the profiles using the BSI was replicated for depression and extended to other psychological dimensions. The validity and distinctiveness of the four psychosocial profiles were independent of demographic and diabetes-specific medical variables. Conclusion Replication and extended validation of the psychosocial taxonomy into primary care may allow healthcare workers to supplement medical treatments with psychosocial interventions that can improve outcomes for patients with diabetes that are practical, individually tailored, and cost-effective. [ABSTRACT FROM AUTHOR]

Proteins from the PEBP (phosphatidylethanolamine-binding protein) family have been identified in a wide variety of species and are thought to regulate a range of intracellular signalling cascades. The rat homologue (known as RKIP; Raf-1 kinase inhibitor protein) has been shown to negatively regulate the MAP kinase pathway through formation of inhibitory complexes with Raf-1 and MEK. The crystal structure of a new, murine member of the PEBP family, termed mPEBP-2, has been determined. On the basis of amino-acid homology, mPEBP-2 belongs to a distinct subset of the mammalian PEBP proteins. Nonetheless, mPEBP-2 is seen to be very similar in structure to other PEBP proteins from human, bovine and plant sources. Regions of distinctive sequence associated with the PEBP-2 subset are discussed with reference to this structure. [ABSTRACT FROM AUTHOR]

Introduction. Radiotherapy is one of the mainstays of treatment for squamous cell carcinoma. Identifying tumour markers able to predict tumour sensitivity to radiotherapy could enable patient/tumour specific treatment targeting and/or dose modification. In a recent study we demonstrated that high levels of EGFR and cyclin D1 were associated with disease recurrence after radiotherapy for patients with T2 laryngeal cancer.1 The aim of this study was to investigate this relationship in a panel of cell lines derived from laryngeal squamous cell carcinomas (LSCC). Methods. Six LSCC cell lines were exposed to 2Gy of gamma irradiation from a 147Caesium source. Following irradiation, a clonogenic assay was used to define the relative radiosensitivity (SF2) of each cell line. Western blot analysis, followed by densitometry measurement, was used to determine the relative expression of EGFR and cyclin D1 in each cell line. Results. Levels of EGFR and cyclin D1 were individually not strongly predictive for radiosensitivity. However, cell lines with a combination of high expression of EGFR and low expression of cyclin D1 were found to correlate strongly with a radioresistant phenotype ( P = 0.95). Conclusions. This study accords with previous evidence that the cyclin D1/ EGFR axis is important in determining radiation susceptibility. However, in contrast to previous work we found that low, as opposed to high levels of cyclin D1, were associated with radioresistance. Our studies provide an opportunity for functional investigation of the roles of EGFR and cyclin D1 in determining radioresistance in LSCC cells. [ABSTRACT FROM AUTHOR]

Objectives. Radiotherapy is one of the mainstays of treatment for squamous cell carcinoma of the larynx but is often associated with severe morbidity. Providing patients with targeted treatment according to tumour type is a major goal of clinicians treating the disease. It has previously been shown that p53 is a critical mediator of radiation response and thus we investigated its influence on radiosensitivity and also whether Nutlin-3 (the small molecule inhibitor of p53/MDM2 interaction) could radiosensitise tumours. Methods. Seven cell lines derived exclusively from patients with laryngeal carcinoma and with defined p53 status (determined by direct sequencing of exons 2–11 and intron/exon boundaries) were examined. Radiosensitivity was determined by clonogenic assays following treatment with gamma irradiation in the presence and absence of Nutlin-3. Flow cytometry was used to determine cell cycle characteristics and the levels of apoptosis and senescence were also measured. Results. Cells with p53 homozygous mutations were relatively radiosensitive (SF2 < 20%). Cell lines with wild-type p53, heterozygous and homozygous non-sense mutations were relatively radioresistant (SF2 > 60%). Wild-type p53 cells were made significantly more radiosensitive after treatment with Nutlin-3. Neither apoptosis nor cell cycle responses corresponded with radiosensitivity. Interestingly, cells that displayed senescence were radioresistant whereas those that did not were radiosensitive suggesting a possible role for senescence in determining radiosensitivity. Conclusions. This is the first study to demonstrate that Nutlin-3 may be an effective radiosensitiser in laryngeal cancer cell lines with wild-type p53. The clinical application of Nutlin-3 might improve survival rates or reduce therapeutic doses in these patients. [ABSTRACT FROM AUTHOR]

Background: Outcome monitoring can support the delivery of quality service that meets the needs of clients, clinicians and services. However, few studies have examined client or staff perspectives on the design and implementation of outcomes monitoring within a service. Implementation of outcomes monitoring requires understanding the preferences and expectations of relevant stakeholders., Objective: Informed by the Consolidated Framework for Implementation Research, this study aimed to investigate the preferences and priorities of relevant staff, clients and family members to inform the design and implementation of an effective outcomes monitoring system in the context of a mental health service for military veterans and their families., Method: Twenty-nine staff participated across five online focus groups, including clinical staff, peer workers, policy staff and supervisors. Ten clients participated in online or telephone semi-structured interviews. Thematic analysis was used to develop themes from the data., Results: Clients and staff agreed that outcomes monitoring should cover more than symptoms, particularly by incorporating functional outcomes. Assessing mental health over time was considered a valuable tool for supporting treatment processes and providing actionable information. Challenges identified by clients and staff included the need for efficient processes, ensuring measures are relevant and acceptable, and maintaining client privacy. The ability to personalise data collection and have a streamlined, responsive system were key attributes of a quality outcomes monitoring framework., Conclusions: Findings suggest that an effective outcome monitoring framework should be client-led, tailored to the individual's needs, and provide feedback on progress. Outcomes monitoring should also be efficient, accessible and allow for safe information sharing., (© 2024 The Author(s). Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Objective: To test the effectiveness of a male-targeted upstream public health intervention in increasing help-seeking intentions for mental disorders and suicide in an adolescent population., Method: A two-arm controlled trial was conducted with 10 schools in the Australian Capital Territory. A total of 594 male adolescents aged between 16 and 18 years participated in the study. Participants in the intervention condition received the single session Silence is Deadly program, while participants in the control condition completed usual classes. All participants completed a pre-intervention, post-intervention, and a 6- to 12-week follow-up survey assessing help-seeking intentions, attitudes, and behaviors., Results: At follow-up, the Silence is Deadly program was found to significantly increase help-seeking intentions from friends, which was in line with the program's messaging to seek help from and provide support to friends in times of distress or suicide risk. The program did not have an effect on help-seeking intentions for other sources of help or on help-seeking attitudes and behavior., Conclusions: The present study provides preliminary support for male-targeted public health interventions for suicide that use male-focused norming and role modeling to improve help-seeking in this population., (© 2020 American Association of Suicidology.)

Objective: Few measures have been developed to assess the efficacy of community-based suicide prevention and recovery services. The current study aimed to develop a scale to provide accurate assessment and monitoring of functional recovery for people following a recent suicide attempt at The Way Back Support Service in Australia., Method: The study was conducted in multiple iterative stages: (1) literature review to identify existing scales; (2) structured informant interview with people with lived experience of a suicide attempt; (3) expert survey of researchers, clinicians, and people with lived experience on relevance and acceptability of candidate items; and (4) quantitative survey of the pilot scale to assess psychometric properties., Results: An 11-item scale assessing recovery in people who have recently attempted suicide was demonstrated to be a unidimensional measure with sound psychometric properties (α = 0.94). The scale was highly acceptable to researchers, clinicians, and people with lived experience. A short-form 6-item scale was also developed., Conclusions: The Functioning and Recovery Scale is likely to be useful for evaluating suicide prevention programs. No existing scale captures the broad construct of psychosocial functioning with sound psychometric rigor and the involvement of people with lived experience of suicide attempt., (© 2020 The American Association of Suicidology.)

HisF (imidazole glycerol phosphate synthase) is an important branch-point enzyme in the histidine biosynthetic pathway of microorganisms. Because of its potential relevance for structure-based drug design, the crystal structure of HisF from the hyperthermophilic archaeon Pyrobaculum aerophilum has been determined. The structure was determined by molecular replacement and refined at 2.0 A resolution to a crystallographic R factor of 20.6% and a free R of 22.7%. The structure adopts a classic (beta/alpha)(8) barrel fold and has networks of surface salt bridges that may contribute to thermostability. The active site is marked out by the presence of two bound phosphate ions and two glycerol molecules that delineate a long groove at one end of the (beta/alpha)(8) barrel. The two phosphate ions, 17 A apart, are bound to sequence-conserved structural motifs that seem likely to provide much of the specificity for the two phosphate groups of the HisF substrate. The two glycerol molecules bind in the vicinity of other sequence-conserved residues that are likely to be involved in binding and/or catalysis. Comparisons with the homologous HisF from Thermatoga maritima reveal a displaced loop that may serve as a lid over the active site.