Racial Categories in Medical Practice: How Useful Are They?

Is it good medical practice for physicians to "eyeball" a patient's race when assessing their medical status or even to ask them to identify their race

Loss of signalling via Gα13 in germinal center B-cell-derived lymphoma

Germinal centre B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) is a common malignancy, yet the signalling pathways that are deregulated and the factors leading to its systemic dissemination are poorly defined1,2. Work in mice showed that sphingosine-1-phosphate receptor-2 (S1PR2), a Gα12 and Gα13 coupled receptor, promotes growth regulation and local confinement of germinal centre B cells3,4. Recent deep sequencing studies of GCB-DLBCL have revealed mutations in many genes in this cancer, including in GNA13 (encoding Gα13) and S1PR2 (refs 5,6, 7). Here we show, using in vitro and in vivo assays, that GCB-DLBCL-associated mutations occurring in S1PR2 frequently disrupt the receptor's Akt and migration inhibitory functions. Gα13-deficient mouse germinal centre B cells and human GCB-DLBCL cells were unable to suppress pAkt and migration in response to S1P, and Gα13-deficient mice developed germinal centre B-cell-derived lymphoma. Germinal centre B cells, unlike most lymphocytes, are tightly confined in lymphoid organs and do not recirculate. Remarkably, deficiency in Gα13, but not S1PR2, led to germinal centre B-cell dissemination into lymph and blood. GCB-DLBCL cell lines frequently carried mutations in the Gα13 effector ARHGEF1, and Arhgef1 deficiency also led to germinal centre B-cell dissemination. The incomplete phenocopy of Gα13- and S1PR2 deficiency led us to discover that P2RY8, an orphan receptor that is mutated in GCB-DLBCL and another germinal centre B-cell-derived malignancy, Burkitt's lymphoma, also represses germinal centre B-cell growth and promotes confinement via Gα13. These findings identify a Gα13-dependent pathway that exerts dual actions in suppressing growth and blocking dissemination of germinal centre B cells that is frequently disrupted in germinal centre B-cell-derived lymphoma

Characterization of a Human Cell Line Stably Over-Expressing the Candidate Oncogene, Dual Specificity Phosphatase 12

Analysis of chromosomal rearrangements within primary tumors has been influential in the identification of novel oncogenes. Identification of the "driver" gene(s) within cancer-derived amplicons is, however, hampered by the fact that most amplicons contain many gene products. Amplification of 1q21-1q23 is strongly associated with liposarcomas and microarray-based comparative genomic hybridization narrowed down the likely candidate oncogenes to two: the activating transcription factor 6 (atf6) and the dual specificity phosphatase 12 (dusp12). While atf6 is an established transcriptional regulator of the unfolded protein response, the potential role of dusp12 in cancer remains uncharacterized.To evaluate the oncogenic potential of dusp12, we established stable cell lines that ectopically over-express dusp12 in isolation and determined whether this cell line acquired properties frequently associated with transformed cells. Here, we demonstrate that cells over-expressing dusp12 display increased cell motility and resistance to apoptosis. Additionally, over-expression of dusp12 promoted increased expression of the c-met proto-oncogene and the collagen and laminin receptor intergrin alpha 1 (itga1) which is implicated in metastasis.Collectively, these results suggest that dusp12 is oncologically relevant and exposes a potential association between dusp12 and established oncogenes that could be therapeutically targeted

Service Users’ Perceptions of an Outreach Wellbeing Service:A Social Enterprise for Promoting Mental Health

Inadequate provision and limited access to mental healthcare has been highlighted with the need to offer more contemporary ways to provide clinically effective interventions. This study aimed to present an insight into service users’ perceptions of an outreach Wellbeing Service (WBS), providing psychological therapy in social settings. Descriptive and thematic analysis was undertaken of 50 returned surveys. Comparison of initial and final mental health measures demonstrated a significant improvement in all outcomes with 96% of participants reporting being helped by attending. Participants were assisted to rebuild social connections in a safe and supportive environment and were facilitated to become more self-determining as their resourcefulness to self-manage was cultivated. Situated within different settings within the community, the WBS offers a workable example of a novel approach to supporting and promoting citizens to become more resilient and lead a more fulfilling and independent life in the community

The experience of foot problems and decisions to access foot care in patients with rheumatoid arthritis: A qualitative study

© 2017 The Author(s). Background: Although foot problems are common in rheumatoid arthritis (RA), the consequences of foot problems from the patient perspective have not been fully explored. The aims of this study were to explore the experience of foot problems and decisions to access foot care services or not in patients with RA. Methods: Semi structured, one-to-one interviews with patients recruited from 2 UK rheumatology units, purposively sampled for self-reported foot problems and a range of personal/disease characteristics. Inductive thematic analysis was used, with rigour provided by multiple independent analysers. Emerging themes were discussed and agreed by all authors. Results: Twelve patients participated: 7 female mean age 56 years (29-72); mean disease duration 12 years (2-27), 5 had accessed foot care services. The 'Impact' of foot problems was substantial and formed the underpinning theme, comprising three organising themes: 'Foot symptoms'; 'Consequences'; and 'Cost'. Foot symptoms such as pain and numbness required self-management, and affected daily life (walking, working) leading to social and emotional costs. The global theme, 'Decision to access foot care or not', also comprised three organising themes: 'Access perceived unnecessary' (no problem, can cope); 'Access hindered by patients' perception'; and 'Access supported by patient and clinician'. Decisions to access foot care or not were complex and influenced by patient beliefs regarding possible treatments and how to access these, and hindered by patient perceptions that their feet were ignored by rheumatology clinicians. Positive experience of foot care encouraged continued utilisation but negative experiences contributed to patients' decisions to discontinue foot care services. Conclusions: Foot problems are important issues for patients and impact on many aspects of their physical, social and emotional lives. Patients who had accessed foot care services prioritised their foot problems as an important health care need. However, for others who would like foot care services, personal knowledge and values, and perceived barriers in clinical practice, appear to interact to inhibit foot care access. The extent which these interactions affect overall access to foot care in RA patients in general now needs to be quantified to help to inform and improve the effectiveness of the organisation and delivery of foot care

Racial categories in medicine: a failure of evidence-based practice?

Race and ethnicity are imprecise markers of the genotypic and sociocultural determinants of health, argue the authors