The many faces of the megakaryocytes and their biological implications.

PURPOSE OF REVIEW: Single-cell RNA sequencing studies have revealed transcriptional heterogeneity within the megakaryocytic lineage and the identified unique subsets. In this review, we discuss the functional and phenotypic plasticity of these subpopulations as well as the impacts on health and disease. RECENT FINDINGS: Megakaryocytes (MKs) can be transcriptionally categorized into platelet generating, niche supporting, immune, and cycling cells, which are distinguished by their unique gene expression patterns and cellular markers. Additionally, a significant population of these cells has been established to reside in the nonhematopoietic tissues and they display enhanced immune-related characteristics. Combined with the location in which the megakaryocytes exist, these cells can play unique roles dictated by their current environment and biological needs, including responding to changes in pathogen exposure. SUMMARY: Advances in megakaryocyte research has elucidated the existence of multiple subpopulations of MKs that serve different functions. These subpopulations implicate a greater potential for MKs to be regulators of health and suggest new avenues for treatments and therapies in related diseases.

A randomised controlled trial examining the efficacy of smoking-related response inhibition training in smokers: a study protocol.

BACKGROUND: Smoking is one of the leading preventable causes of illness and premature death worldwide. Despite a variety of effective treatments, relapse rates remain high, and novel, innovative interventions are needed in order to reduce the global prevalence of smoking. Research has indicated that deficits in the ability to inhibit a response (referred to as response inhibition) is a predictor of relapse and subsequently, targeting this potentially modifiable risk factor may lead to improvements in smoking outcomes. Indeed, in recent years, stimulus-specific response inhibition training has emerged as a potentially efficacious intervention to reduce unwanted/unhealthy behaviours such as alcohol and unhealthy food consumption. As such, the present trial is the first to evaluate the real-world efficacy of response inhibition smoking training (INST) in a sample of adult heavy smokers. METHODS/DESIGN: This randomised controlled trial will recruit nicotine dependent smokers aged between 18 and 60 using social media and advertisements in Victoria, Australia. The sample target was 150 to account for drop out and non-adherence. Once informed consent has been obtained, participants complete a range of baseline measures during a face to face interview. Participants are randomly allocated to one of two online training conditions: an intervention training group (INST), which requires participants to exercise response inhibition towards smoking-related stimuli; or an active control group, which requires participants to exercise response inhibition towards household items and does not include any smoking-related stimuli. They complete the first training session during the interview to ensure the training protocol is clear. Both groups are instructed to complete a further 13 training sessions (1 per day) at home on their computer and follow-up phone calls will be conducted at three time points: post-intervention, one-month and three months. The primary outcomes are: a) rates of smoking cessation and; b) reduction in the quantity of average daily smoking at post-intervention, one and three months follow-up. DISCUSSION: There is a pressing need to develop novel and innovative smoking interventions. If proven to be effective, INST could make a highly cost-effective contribution to improvements in smoking intervention outcomes. TRIAL REGISTRATION: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry 17th February 2017. Trial ID: ACTRN12617000252314 .

IMMIGRANT CHILDREN IN THE CONTEXT OF MULTICULTURAL EARLY CHILDHOOD EDUCATION.

In a multicultural country, such as New Zealand, multicultural education has become the subject of early childhood polices and research. Increased national and international attention towards minority rights has resulted in the development and implementation of multicultural practice for realizing quality early childhood education for children and families of diverse cultural backgrounds. The study addressed in this paper set out to examine the multicultural education of early childhood set- tings in New Zealand from the experiences and perspectives of Chinese immigrant young children, their teachers and parents. It analyses data in the conceptualization of children as active agents, with the emphasis on the influence of their homes and the early childhood centres, giving rise to a tension between the children's needs to fit in the centres and the children's and their parents' right to inclusion and be different.

Impact of Implementing Serious Illness Conversations Across a Comprehensive Cancer Center Using an Interdisciplinary Approach.

BACKGROUND: Gaps in communication of end-of-life care preferences increase risk of patient harm. Adoption of oncology practice guidelines advocating serious illness communication for patients with advanced cancer is limited. OBJECTIVES: (1) Increase Serious Illness Conversation (SIC) use across oncology teams via an interdisciplinary quality improvement (QI) approach and (2) assess patient reported shared decision making (SDM) experiences with clinicians engaged in SIC implementation. DESIGN: QI methodology was applied to spread the implementation of SIC across 4 oncology teams. CollaboRATE scores were used to evaluate patient reported outcomes of SDM for patients with advanced cancer. SETTINGS/SUBJECTS: The SIC QI initiative was a component of the Promise Partnership Learning Health System (PPLHS) piloted in the Dartmouth Cancer Center, Lebanon, NH, USA. MEASUREMENTS: (1) The percentage of eligible patients with documented SIC and (2) a comparison of a patient reported measure of SDM (CollaboRATE) among SIC eligible patients in encounters with providers who took part in the implementation versus those who did not. RESULTS: Oncology teams screened a total of 538 patients, identified 278 eligible patients, and completed 144 SIC conversations. The teams improved the proportion of documented SIC among eligible patients from near 0% to a collective frequency of 52%. For clinicians' top-box CollaboRATE scores, a chi-squared test demonstrated a statistically significant association between providers implementing SIC into practice and patient reported shared decision making (.16, p = .031). CONCLUSIONS: This approach allows for tailoring of iterative improvement cycles to mitigate barriers and improve the practice of SIC among oncology teams.

Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36.

Lipids contribute to hematopoiesis and membrane properties and dynamics, however, little is known about the role of lipids in megakaryopoiesis. Here, a lipidomic analysis of megakaryocyte progenitors, megakaryocytes, and platelets revealed a unique lipidome progressively enriched in polyunsaturated fatty acid (PUFA)-containing phospholipids. In vitro, inhibition of both exogenous fatty acid functionalization and uptake and de novo lipogenesis impaired megakaryocyte differentiation and proplatelet production. In vivo, mice on a high saturated fatty acid diet had significantly lower platelet counts, which was prevented by eating a PUFA-enriched diet. Fatty acid uptake was largely dependent on CD36, and its deletion in mice resulted in thrombocytopenia. Moreover, patients with a CD36 loss-of-function mutation exhibited thrombocytopenia and increased bleeding. Our results suggest that fatty acid uptake and regulation is essential for megakaryocyte maturation and platelet production, and that changes in dietary fatty acids may be a novel and viable target to modulate platelet counts.

A psychometric validation study of the Impulsive-Compulsive Behaviours Checklist: A transdiagnostic tool for addictive and compulsive behaviours.

The occurrence of repetitive behaviours that are often harmful has been attributed to traits traditionally described as "impulsive" or "compulsive" e.g. substance dependence, excessive gambling, and hoarding. These behaviours are common and often co-occur in both the general population and psychiatric populations. The lack of measures to concurrently index a range of such behaviours led to the development of the Impulsive-Compulsive Behaviours (ICB) Checklist. This study aims to validate the ICB Checklist in a general community sample. Factor analyses revealed a two-factor structure, demonstrating good model fit in two independent samples. These were labelled Impulsive-Compulsions and Compulsive-Impulsions, comprising of classically compulsive and impulsive behaviours respectively. Reliability and construct validity were further confirmed using correlations with existing measures of impulsivity and compulsivity. Results suggest that the ICB Checklist is a valid and practical assessment that can be used to monitor behavioural clusters characterised by deficits in inhibition.