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Immunotherapy has emerged as a therapeutic option for many cancers. For some tumors, immune checkpoint inhibitors show great efficacy in promoting anti-tumor immunity. However, not all tumors respond to immunotherapies. These tumors often exhibit reduced inflammation and are resistant to checkpoint inhibitors. Therapies that turn these 'cold' tumors 'hot' could improve the efficacy and applicability of checkpoint inhibitors, and in some cases may be sufficient on their own to promote anti-tumor immunity. One strategy to accomplish this goal is to activate innate immunity pathways within the tumor. Here we describe how this can be accomplished by activating doublestranded RNA (dsRNA) sensors. These sensors evolved to detect and respond to dsRNAs arising from viral infection but can also be activated by endogenous dsRNAs. A set of proteins, referred to as suppressors of dsRNA sensing, are responsible for preventing sensing 'self' dsRNA and activating innate immunity pathways. The mechanism of action of these suppressors falls into three categories: (1) Suppressors that affect mature RNAs through editing, degradation, restructuring, or binding. (2) Suppressors that affect RNA processing. (3) Suppressors that affect RNA expression. In this review we highlight suppressors that function through each mechanism, provide examples of the effects of disrupting those suppressors in cancer cell lines and tumors, and discuss the therapeutic potential of targeting these proteins and pathways. [ABSTRACT FROM AUTHOR]

Abstract Background The NAD+-dependent histone deacetylases, known as "sirtuins", participate in a variety of processes critical for single- and multi-cellular life. Recent studies have elucidated the importance of sirtuin activity in development, aging, and disease; yet, underlying mechanistic pathways are not well understood. Specific sirtuins influence chromatin structure and gene expression, but differences in their pathways as they relate to distinct chromatin functions are just beginning to emerge. To further define the range of global chromatin changes dependent on sirtuins, unique biological features of the ciliated protozoan Tetrahymena thermophila can be exploited. This system offers clear spatial and temporal separation of multiple whole genome restructuring events critical for the life cycle. Results Inhibition with nicotinamide revealed that sirtuin deacetylase activity in Tetrahymena cells promotes chromatin condensation during meiotic prophase, differentiation of heterochromatin from euchromatin during development, and chromatin condensation/degradation during programmed nuclear death. We identified a class I sirtuin, called Thd14, that resides in mitochondria and nucleoli during vegetative growth, and forms a large sub-nuclear aggregate in response to prolonged cell starvation that may be peripherally associated with nucleoli. During sexual conjugation and development Thd14 selectively concentrates in the parental nucleus prior to its apoptotic-like degradation. Conclusions Sirtuin activity is important for several functionally distinct events requiring global chromatin condensation. Our findings suggest a novel role for sirtuins in promoting programmed pycnosis by acting on chromatin destined for degradation. The sirtuin Thd14, which displays physiological-dependent differential localization within the nucleus, is a candidate for a chromatin condensation enzyme that is coupled to nuclear degradation.

There has been a strong policy emphasis over the past decade on optimising patient‐centred care and reducing general practitioners' (GPs') workload by extending community pharmacy services and collaboration between pharmacists and GPs. Our aim was to review current evidence of pharmacists' and GPs' views of extended community pharmacy services and pharmacists' roles in the United Kingdom (UK). A systematic review was undertaken looking at UK studies investigating pharmacists' and/or GPs' views of community pharmacy services or roles from 2005 to 2017. A range of databases were searched including EMBASE, PubMed, Scopus, Web of Science, International Pharmaceutical Abstracts (IPA), PsycINFO, Science Direct and The Cumulative Index to Nursing and Allied Health Literature (CINAHL). In addition, reference lists of included studies were screened and grey literature was searched. Following the application of inclusion/exclusion criteria, the quality of papers was critically analysed, findings were extracted into a grid and subjected to narrative synthesis following thematic analysis. The search strategy yielded a total of 4,066 unique papers from which 60 were included. Forty‐seven papers covered pharmacists' views, nine combined both pharmacists' and GPs' views and four covered GPs' views. Study designs included interviews (n = 31, 52%), questionnaire surveys (n = 17, 28%) and focus groups (n = 7, 12%). Three main themes emerged from the data: "attitudes towards services/roles", "community pharmacy organisations" and "external influences". Pharmacists and GPs perceived a number of barriers to successful implementation and integration of pharmacy services. Moreover, collaboration between pharmacists and GPs remains poor despite the introduction of extended services. Overall, extending community pharmacy services require quality‐driven incentives and joint working between community pharmacists and GPs to achieve better integration within the patient's primary care pathway. [ABSTRACT FROM AUTHOR]

Abstract: The introduction of Universal Healthcare Coverage (JKN) in 2014 has changed the landscape of the Indonesian healthcare and affected the community pharmacy sector. This paper investigates perceptions of healthcare and pharmacy stakeholders about the impact of JKN on the practice of pharmacists and pharmacy in both public (Puskesmas) and private (Community or Retail pharmacy) settings. In‐depth, semi‐structured interviews were conducted from February to August 2016 involving 29 participants representing key stakeholders from different provinces in Indonesia. While JKN was actually designed with good policy objectives for pharmacy integration within primary care network, it has created some unintended and unanticipated distortion in the healthcare system which may be detrimental to the community pharmacy sector. In fact, community pharmacy practice is still limited to dispensing and continued to be hampered by ongoing challenges mainly pharmacists' absence, lack of clinical competence and limited support from regulation changes. It is a missed opportunity for pharmacists to play a greater role in primary care services indicating the need for an overhaul to pharmacy education and policy system. [ABSTRACT FROM AUTHOR]

Researchers in a variety of disciplines pursue creative ways to explore complex areas of inquiry. This literature review examines the use of concept maps as a unique tool for conducting research. This study embraces an inclusive definition of concept mapping. Three main approaches for conducting research using concept maps as a tool emerged: relational, cluster, and word frequency. These approaches are included in the different phases of research process such as data collection, analysis, and presentation. Each approach revealed strengths and limitations that researchers need to take into account. This discussion broadens the lens of the meaning of concept mapping as a tool for innovative research approaches. [ABSTRACT FROM AUTHOR]

In 2011, the US Department of Veterans Affairs established five Centers of Excellence to study training in the patient-centered medical home clinical microsystem. Early on, our center began a discourse analysis in order to better understand each profession’s assumptions about roles, responsibilities, and the basis for “truth” in clinical care. We discovered that these different discourses were pervasive and led to unhelpful stereotypes of each other. This article describes the evidence we identified that led us to hypothesize these conflicting discourses and stereotypes. Specifically, we report on our attempts to identify the traditional discourses of four post-graduate professions—medicine, nurse practitioner, psychology, and pharmacy. We also share lessons from our efforts to defuse participants from their identified discursive assumptions, and develop appreciation and value for the discursive contributions of other professions—a process we call professional equipoise. We conclude that we can change these discourses and the professional identity formation of novices if we provide sustained, integrated interprofessional education curriculum. This implies that we need: embedded, longitudinal training; faculty role modeling of inquisitiveness, respectful relationships, and risk taking; and safe and honest discussion about our differences. [ABSTRACT FROM PUBLISHER]