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Hepatocytes and liver-resident macrophages known as Kupffer cells (KCs) are key cell types involved in liver fibrosis. The transcription factor c-Jun plays a fundamental role in regulating hepatocyte and macrophage functions. We have examined c-Jun’s role in the functional interaction of these cells during liver fibrosis induced by carbon tetrachloride. While hepatocyte-specific c-jun deletion led to increased fibrosis, the opposite outcome was observed when c-jun was deleted in both hepatocytes and KCs. Molecular analyses revealed compromised cytokine gene expression as the apical event related to the phenotype. Yet, purified hepatocytes from both mouse cohorts showed similar defects in cytokine gene expression. However, we noted increased macrophage infiltration in the absence of c-Jun in hepatocytes, which when chemically depleted, reversed the phenotype. Consistently, c-jun deletion in KCs alone also led to reduced fibrosis and cytokine gene expression. By contrast, c-jun deletion in hepatocytes and KCs did not affect the resolution phase after fibrotic injury. These data together demonstrate a pro-fibrogenic role for c-Jun in hepatocytes and KCs that functionally interact to regulate liver fibrosis.Concern has been raised about whether HPV vaccines might cause serious neurological disorders including postural orthostatic tachycardia syndrome (POTS) and chronic regional pain syndrome (CRPS). The European Medicines Agency (EMA) investigated the issue and declared in 2015 that there is no link between HPV vaccines and serious neurological adverse events. However, the certainty conveyed in EMA’s official report is undermined by a leaked, confidential document that reveals important disagreements among the experts. Furthermore, in its assessments, EMA relied on the data the drug companies had provided to them even though it had been demonstrated that the companies had underreported possible neurological harms. Even though active comparators were used (aluminium adjuvants and other vaccines), our research group found significantly more serious neurological harms in the HPV vaccine groups than in the comparator groups in a systematic review based on clinical study reports in EMA’s possession. Brequinar clinical trial We outline areas where we believe the basis for EMA’s decision was flawed; highlight that the relationship between HPV vaccines and POTS remains uncertain; and suggest ways forward to resolve the uncertainty and debate.In response to the government’s drive to expand Electronic Palliative Care Co-ordination Systems (EPaCCS) across England by 2020, further evidence for this intervention needs to be established quickly. With palliative and end-of-life care research being an underfunded area, the availability and lower costs of routine databases make it an attractive resource to integrate into studies evaluating EPaCCS without jeopardising research quality. This article describes how routine databases can be used to address the current paucity of high-quality evidence; they can be used in a range of study designs, including randomised controlled trials and quasi-experimental designs, and may also be able to contribute quality of life or patient-reported outcome measures.

This study aimed to gather and synthesise educational strategies that can improve teaching and learning of evidence-based medicine (EBM) in the workplace, and make them concrete by listing ideas for implementing these strategies. Insight into current workplace-based EBM teaching and learning in general practice was the starting point to generate these strategies and ideas.

Exploratory, qualitative focus group study, applying the consensus method of the nominal group technique.

Postgraduate medical education; general practitioner (GP) specialty training at University Medical Centre Utrecht, the Netherlands PARTICIPANTS 33 GPs and 17 GP trainees, divided in four focus groups. Using opportunistic sampling, participants were selected from the GP workplace because of their role as supervisor or trainee.

An overview of educational strategies and ideas on how to implement these strategies in the workplace, followed by the participants’ global ranking of the most useful ideas.

The supervisors and trainees gractice. As a great deal of GP training takes place in clinical practice, supervisors and trainees could apply the suggested ideas to enhance EBM teaching and learning in the workplace.

In light of the current national mental health crisis, we use Google Trends, Twitter and data obtained from the National Suicide Prevention Lifeline to evaluate the effect of ‘1-800-273-8255’ on public awareness for the National Suicide Prevention Lifeline.

Cross-sectional analysis.

We extracted data from Google Trends and Twitter for terms related to suicide following the release of Logic’s song, ‘1-800-273-8255’. We then used a forecasting autoregressive integrated moving algorithm model to determine the greater than expected search interest.

Google searches for ‘Suicide Hotline’ increased 49% more than expected the day after Logic’s song was released and sustained increase of queries resulted in an average relative search volume of 59.5%-9.1% higher than the mean forecasted value of 50.4% for the 28 days following the release. Tweets that engaged with the account ‘@800 273talk’ on Twitter increased by 10 450% more than expected the day after the song was released and increased by a mean of 1497% greater than expected the week after the songs released.

Findings from our study suggest that the entertainment industry can play an important role in increasing awareness of hotline numbers. Logic’s song provides an example of a positive influence on public health and provides support for further development and standards for proper awareness of suicide in the public view.

Findings from our study suggest that the entertainment industry can play an important role in increasing awareness of hotline numbers. Logic’s song provides an example of a positive influence on public health and provides support for further development and standards for proper awareness of suicide in the public view.

To examine whether early β-amyloid (Aβ) accumulation and metabolic risk factors are associated with neuroinflammation in elderly individuals without dementia.

We examined 54 volunteers (mean age 70.0 years, 56% women, 51%

ɛ4 carriers) with the translocator protein (TSPO) tracer [

C]PBR28 to assess neuroinflammation and with [

C] Pittsburgh compound B (PiB) to assess cerebral Aβ accumulation. [

C]PBR28 and [

C]PiB standardized uptake value ratios (SUVRs) were quantified in 6 regions of interests by using the cerebellar cortex as a pseudo-reference and reference region, respectively. Fasting venous glucose, insulin, and high-sensitivity C-reactive protein (hs-CRP) values were determined. Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. A subset of individuals (n = 11) underwent CSF sampling, and Aβ

, Aβ

, total tau, phospho-tau, soluble TREM2, and YKL-40 levels were measured.

Among the whole study group, no significant association was found between [

C]PiB and [

C]PBR28 SUVR composite scores (slope 0.