Sphingosine-1-phosphate receptor 2 restrains egress of γδ T cells from the skin.

Maintenance of a population of IL-17-committed γδ T cells in the dermis is important in promoting tissue immunity. However, the signals facilitating γδ T cell retention within the dermis remain poorly understood. Here, we find that sphingosine-1-phosphate receptor 2 (S1PR2) acts in a cell-intrinsic manner to oppose γδ T cell migration from the dermis to the skin draining lymph node (dLN). Migration of dermal γδ T cells to the dLN under steady-state conditions occurs in an S1PR1-dependent manner. S1PR1 and CD69 are reciprocally expressed on dermal γδ T cells, with loss of CD69 associated with increased S1PR1 expression and enhanced migration to the dLN. γδ T cells lacking both S1PR2 and CD69 are impaired in their maintenance within the dermis. These findings provide a mechanism for how IL-17+ γδ T cells establish residence within the dermis and identify a role for S1PR2 in restraining the egress of tissue-resident lymphocytes

Direct observation of weight-related communication in primary care : a systematic review

Funding: Review was carried out as part of a PhD funded by the University of St Andrews 600th Anniversary Scholarship.Background. Primary care is ideally placed to play an effective role in patient weight management however patient weight is seldom discussed in this context. A synthesis of studies that directly observe weight discussion in primary care is required to more comprehensively understand and improve primary care weight-related communication. Objective. To systematically identify and examine primary care observational research that investigates weight-related communication and its relationship to patient weight outcomes. Methods. A systematic review of literature published up to August 2015, using seven electronic databases (including MEDLINE, Scopus, and PsycINFO), was conducted using search terms such as overweight, obese, doctor patient communication. Results. Twenty papers were included in the final review. Communication analysis focused predominantly on practitioner use of specific patient-centred communication. Practitioner use of motivational interviewing was associated with improved patient weight-related outcomes, including patient weight loss and increased patient readiness to lose weight; however few studies measured patient weight-related outcomes. Conclusion. Studies directly observing weight-related communication in primary care are scarce and limited by a lack of focus on patient communication and patient weight-related outcomes. Future research should measure practitioner and patient communications during weight discussion, and their impact on patient weight-related outcomes. This knowledge may inform the development of a communication intervention to assist practitioners to more effectively discuss weight with their overweight and/or obese patients.PostprintPeer reviewe

Predictors of weight discussion in primary care consultations : a multilevel modelling approach

This research was funded by a University of St Andrews 600th Anniversary Doctoral Scholarship.Objective To understand how primary care weight-related communication processes are influenced by individual differences in primary care practitioner (PCP) and patient characteristics and communication use. Methods Two multilevel logistic regression models were calculated to predict the occurrence of 1) weight-related discussion and 2) weight-related consultation outcomes. Coded communication data (Roter Interaction Analysis System) from 218 video-recorded consultations between PCPs and patients with overweight and obesity in Scottish primary care practices were combined with their demographic data to develop the multilevel models. Results Weight-related discussions were more likely to occur when a greater proportion of PCP’s total communication was partnership building and activating communication. More discrete weight discussions during a consultation predicted weight-related consultation outcomes. Patient BMI positively predicted both weight-related discussion and consultation outcomes. Conclusion This work demonstrates that multilevel modelling is a viable approach to investigating coded primary care weight-related communication data and that it can provide insight into the impact that various patient and PCP factors have on these communication processes. Practice Implications Through the increased use of partnership building and activating communications, and by engaging in shorter, but more frequent, discussions about patient weight, PCPs may better facilitate weight-related discussion and weight-related consultation outcomes for their patients.PostprintPeer reviewe

Barriers to Pregnancy Spacing in Women Living with HIV: A Series of Informational Interviews

For reproductive-age women living with HIV, birth spacing allows for optimization of maternal health and viral suppression to prevent mother-to-child transmission of HIV. We conducted semi-structured informational interviews to explore use of contraception for birth spacing. Interviews were transcribed and analyzed. Audio files were reviewed to capture non-explicit data. We interviewed 18 multiparous HIV positive women. All described experiences with at least one contraceptive method. Six themes emerged: Burden of contraception, Failure of birth control, Impact of youth and lack of life experience, Community beliefs about birth control, Lack of partner cooperation, and Altruism. Women viewed birth spacing favorably. Young age at first delivery, contraceptive side effects, non-adherence to short-acting methods, lack of partner cooperation, and prior contraceptive failure were identified as barriers to ideal birth spacing. Additional outreach is needed in women living with HIV to overcome barriers to planned pregnancy and birth spacing

To develop evidence-based interventions to support doctors’ wellbeing and promote resilience during COVID-19 (and beyond)

Publisher PD

Effect of a farnesyl transferase inhibitor (R115777) on ductal carcinoma in situ of the breast in a human xenograft model and on breast and ovarian cancer cell growth in vitro and in vivo

INTRODUCTION: The ras pathway is essential for cell growth and proliferation. The effects of R115777, a farnesyl transferase inhibitor, were investigated in cancer cell lines expressing varying levels of growth factor receptors and with differing ras status. Effects on tumour xenografts and human ductal carcinoma in situ (DCIS) of the breast in a xenograft mouse model were also tested. METHOD: In vitro, the concentrations required to reduce cell numbers by 50% (50% inhibitory concentration) were established (MDA-MB231, MCF-7, MCF-7/HER2-18, BT-474, SK-BR3 and SKOV3). Human DCIS was implanted in nude mice or, in separate experiments, cultured cells were injected (MDA-MB231, MCF-7/HER2-18, SKOV3) and allowed to form tumours. Proliferation and apoptosis were determined by immunohistochemistry in xenografts and cell tumours. RESULTS: The 50% inhibitory concentrations varied a hundred-fold, from 39 nmol/l (± 26 nmol/l) for SKBR3 to 5.9 μmol/l(± 0.8 μmol/l) for MDA-MB231. In MCF-7/HER2-18 and SKOV3 cells the levels of tumour growth inhibition were approximately 85% and 40%, respectively. There was a significant decrease in the cell turnover index (CTI; proliferation/apoptosis). In MDA-MB 231 with activated k-ras no inhibition was observed. In treated DCIS xenografts proliferation decreased and apoptosis increased. The CTI ratio between the start and 1 and 2 weeks of treatment were 1.99 and 1.50, respectively, for controls and 0.85 (P = 0.005) and 0.75 (P = 0.08) for treated xenografts. CONCLUSION: Treatment with the farnesyl transferase inhibitor reduced cell growth in vitro and cell tumour growth in vivo. In DCIS treatment resulted in a reduced CTI. R115777 is a promising treatment for breast cancer but the relation between effect and growth factor receptor and ras status has to be established

A rapid systematic review of public responses to health messages encouraging vaccination against infectious diseases in a pandemic or epidemic

Public health teams need to understand how the public responds to vaccination messages in a pandemic or epidemic to inform successful campaigns encouraging the uptake of new vaccines as they become available. A rapid systematic review was performed by searching PsycINFO, MED-LINE, healthevidence.org, OSF Preprints and PsyArXiv Preprints in May 2020 for studies including at least one health message promoting vaccine uptake of airborne-, droplet-and fomite-spread vi-ruses. Included studies were assessed for quality using the Mixed Methods Appraisal Tool (MMAT) or the Assessment of Multiple Systematic Reviews (AMSTAR), and for patient and public involvement (PPI) in the research. Thirty-five articles were included. Most reported messages for seasonal influenza (n = 11; 31%) or H1N1 (n = 11; 31%). Evidence from moderate to high quality studies for improving vaccine uptake included providing information about virus risks and vaccination safety, as well as addressing vaccine misunderstandings, offering vaccination reminders, including vaccination clinic details, and delivering mixed media campaigns across hospitals or communities. Behavioural influences (beliefs and intentions) were improved when: shorter, risk-reducing or relative risk framing messages were used; the benefits of vaccination to society were emphasised; and beliefs about capability and concerns among target populations (e.g., vaccine safety) were addressed. Clear, credible, messages in a language target groups can understand were associated with higher accept-ability. Two studies (6%) described PPI in the research process. Future campaigns should consider the beliefs and information needs of target populations in their design, including ensuring that vaccine eligibility and availability is clear, and messages are accessible. More high quality research is needed to demonstrate the effects of messaging interventions on actual vaccine uptake

SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection