Continuing Competence Trends of Occupational Therapy Practitioners

The purpose of this pilot study was to examine the perceptions and practices of occupational therapists regarding the types of professional development activities they seek to ensure competency. A self-report survey was used to investigate the therapists’ selection of and engagement in professional learning activities. The results from 43 occupational therapists were analyzed. Descriptive results identified the value of a professional development plan and collaboration with colleagues. Self-assessment and searching for and analyzing journal articles emerged as frequently used continuing competence learning practices. The results showed that therapists actively plan and select formal and informal professional activities to promote meaningful learning for continuing competence practices. Productivity standards were considered the main challenge that impeded the participants’ professional development plans and continued competence

Assessment of CAR-T cell-mediated cytotoxicity in 3D microfluidic cancer co-culture models for combination therapy

Chimeric antigen receptor (CAR)-T cell therapy is efficacious against many haematological malignancies, but challenges remain when using this cellular immunotherapy for treating solid tumours. Classical 2D in vitro models fail to recapitulate the complexity of the tumour microenvironment, whilst in vivo models, such as patient-derived xenografts, are costly and labour intensive. Microfluidic technologies can provide miniaturized solutions to assess CAR-T therapies in 3D complex preclinical models of solid tumours. Here, we present a novel microfluidic immunoassay for the evaluation of CAR-T cell cytotoxicity and targeting specificity on 3D spheroids containing cancer cells and stromal cells. Monitoring the interaction between CAR-T cells and spheroid co-cultures, we show that CAR-T cells home towards target-expressing cancer cells and elicit a cytotoxic effect. Testing CAR-T cells in combination therapies, we show that CAR-T cell cytotoxicity is enhanced with anti-PD-L1 therapy and carboplatin chemotherapy. We propose this proof-of-concept microfluidic immunoassay as a material-saving, pre-clinical screening tool for quantification of cell therapy efficacy

Microfluidic technologies for immunotherapy studies on solid tumours

Immunotherapy is a powerful and targeted cancer treatment that exploits the body's immune system to attack and eliminate cancerous cells. This form of therapy presents the possibility of long-term control and prevention of recurrence due to the memory capabilities of the immune system. Various immunotherapies are successful in treating haematological malignancies and have dramatically improved outcomes in melanoma. However, tackling other solid tumours is more challenging, mostly because of the immunosuppressive tumour microenvironment (TME). Current in vitro models based on traditional 2D cell monolayers and animal models, such as patient-derived xenografts, have limitations in their ability to mimic the complexity of the human TME. As a result, they have inadequate translational value and can be poorly predictive of clinical outcome. Thus, there is a need for robust in vitro preclinical tools that more faithfully recapitulate human solid tumours to test novel immunotherapies. Microfluidics and lab-on-a-chip technologies offer opportunities, especially when performing mechanistic studies, to understand the role of the TME in immunotherapy, and to expand the experimental throughput when using patient-derived tissue through its miniaturization capabilities. This review first introduces the basic concepts of immunotherapy, presents the current preclinical approaches used in immuno-oncology for solid tumours and then discusses the underlying challenges. We provide a rationale for using microfluidic-based approaches, highlighting the most recent microfluidic technologies and methodologies that have been used for studying cancer–immune cell interactions and testing the efficacy of immunotherapies in solid tumours. Ultimately, we discuss achievements and limitations of the technology, commenting on potential directions for incorporating microfluidic technologies in future immunotherapy studies

Sources of Sex Information Used by Young British Women Who Have Sex with Women (WSW) and Women Who Have Sex Exclusively with Men (WSEM): Evidence from the National Survey of Sexual Attitudes and Lifestyles

There is little consideration about the provision of information about sex to women who have sex with women (WSW). This study drew on data from the third National Survey of Sexual Attitudes and Lifestyle, a nationally representative survey of people in Great Britain. Logistic regression was undertaken to examine firstly the relationships between WSW and women who have sex exclusively with men (WSEM) and their main source of information about sex, and secondly between WSW/WSEM and unmet need for information about sex. Each source was included as the binary outcome indicating yes this was the main source, or no this was not the main source of information about sex. The results found that WSW had significantly lower odds of reporting lessons at schools as their main source of information, and significantly higher odds of reporting sources defined as ‘other’ (predominantly first girlfriend/boyfriend or sexual partner) as their main source of information. Reported levels of unmet need for information was also higher amongst young WSW compared with WSEM. This study provides new insights into the sex educational needs of young women and highlights the need for sex education in schools in Great Britain to include information on a full-range of sexual practices, including same-sex sexual relationships

Attractiveness of a Four-component Pheromone Blend to Male Navel Orangeworm Moths

The attractiveness to male navel orangeworm moth, Amyelois transitella, of various combinations of a four-component pheromone blend was measured in wind-tunnel bioassays. Upwind flight along the pheromone plume and landing on the odor source required the simultaneous presence of two components, (11Z,13Z)-hexadecadienal and (3Z,6Z,9Z,12Z,15Z)-tricosapentaene, and the addition of either (11Z,13Z)-hexadecadien-1-ol or (11Z,13E)-hexadecadien-1-ol. A mixture of all four components produced the highest levels of rapid source location and source contact. In wind-tunnel assays, males did not seem to distinguish among a wide range of ratios of any of the three components added to (11Z,13Z)-hexadecadienal. Dosages of 10 and 100 ng of the 4-component blend produced higher levels of source location than dosages of 1 and 1,000 ng

The complex TIE between macrophages and angiogenesis

Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

Identification of the cathelicidin peptide LL-37 as agonist for the type I insulin-like growth factor receptor

The human cathelicidin antimicrobial protein-18 and its C terminal peptide, LL-37, displays broad antimicrobial activity that is mediated through direct contact with the microbial cell membrane. In addition, recent studies reveal that LL-37 is involved in diverse biological processes such as immunomodulation, apoptosis, angiogenesis and wound healing. An intriguing role for LL-37 in carcinogenesis is also beginning to emerge and the aim of this paper was to explore if and how LL-37 contributes to the signaling involved in tumor development. To this end, we investigated the putative interaction between LL-37 and growth factor receptors known to be involved in tumor growth and progression. Among several receptors tested, LL-37 bound with the highest affinity to insulin-like growth factor 1 receptor (IGF-1R), a receptor that is strongly linked to malignant cellular transformation. Furthermore, this interaction resulted in a dose-dependent phosphorylation and ubiquitination of IGF-1R, with downstream signaling confined to the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK)-pathway but not affecting phosphatidylinositol 3 kinase/Akt signaling. We found that signaling induced by LL-37 was dependent on the recruitment of β-arrestin to the fully functional IGF-1R and by using mutant receptors we demonstrated that LL-37 signaling is dependent on β-arrestin-1 binding to the C-terminus of IGF-1R. When analyzing the biological consequences of increased ERK activation induced by LL-37, we found that it resulted in enhanced migration and invasion of malignant cells in an IGF-1R/β-arrestin manner, but did not affect cell proliferation. These results indicate that LL-37 may act as a partial agonist for IGF-1R, with subsequent intra-cellular signaling activation driven by the binding of β-arrestin-1 to the IGF-1R. Functional experiments show that LL-37-dependent activation of the IGF-1R signaling resulted in increased migratory and invasive potential of malignant cells

Author correction: CRISPR/Cas9-derived models of ovarian high grade serous carcinoma targeting Brca1, Pten and Nf1, and correlation with platinum sensitivity

Transplantable murine models of ovarian high grade serous carcinoma (HGSC) remain an important research tool. We previously showed that ID8, a widely-used syngeneic model of ovarian cancer, lacked any of the frequent mutations in HGSC, and used CRISPR/Cas9 gene editing to generate derivatives with deletions in Trp53 and Brca2. Here we have used one ID8 Trp53−/− clone to generate further mutants, with additional mutations in Brca1, Pten and Nf1, all of which are frequently mutated or deleted in HGSC. We have also generated clones with triple deletions in Trp53, Brca2 and Pten. We show that ID8 Trp53−/−;Brca1−/− and Trp53−/−;Brca2−/− cells have defective homologous recombination and increased sensitivity to both platinum and PARP inhibitor chemotherapy compared to Trp53−/−. By contrast, loss of Pten or Nf1 increases growth rate in vivo, and reduces survival following cisplatin chemotherapy in vivo. Finally, we have also targeted Trp53 in cells isolated from a previous transgenic murine fallopian tube carcinoma model, and confirmed that loss of p53 expression in this second model accelerates intraperitoneal growth. Together, these CRISPR-generated models represent a new and simple tool to investigate the biology of HGSC, and the ID8 cell lines are freely available to researchers