Macrophage Reprogramming with Anti-miR223-Loaded Artificial Protocells Enhances In Vivo Cancer Therapeutic Potential

Several immune cell‐expressed miRNAs (miRs) are associated with altered prognostic outcome in cancer patients, suggesting that they may be potential targets for development of cancer therapies. Here, translucent zebrafish (Danio rerio) is utilized to demonstrate that genetic knockout or knockdown of one such miR, microRNA‐223 (miR223), globally or specifically in leukocytes, does indeed lead to reduced cancer progression. As a first step toward potential translation to a clinical therapy, a novel strategy is described for reprogramming neutrophils and macrophages utilizing miniature artificial protocells (PCs) to deliver anti‐miRs against the anti‐inflammatory miR223. Using genetic and live imaging approaches, it is shown that phagocytic uptake of anti‐miR223‐loaded PCs by leukocytes in zebrafish (and by human macrophages in vitro) effectively prolongs their pro‐inflammatory state by blocking the suppression of pro‐inflammatory cytokines, which, in turn, drives altered immune cell‐cancer cell interactions and ultimately leads to a reduced cancer burden by driving reduced proliferation and increased cell death of tumor cells. This PC cargo delivery strategy for reprogramming leukocytes toward beneficial phenotypes has implications also for treating other systemic or local immune‐mediated pathologies

\u3cem\u3eThe Bench to Community Initiative\u3c/em\u3e: Community-based Participatory Research Model for Translating Research Discoveries into Community Solutions

Methods: Community-based participatory research (CBPR) is an effective methodology for translating research findings from academia to community interventions. The Bench to Community Initiative (BCI), a CBPR program, builds on prior research to engage stakeholders across multiple disciplines with the goal of disseminating interventions to reduce breast cancer disparities and improve quality of life of Black communities. The BCI program was established to understand sociocultural determinants of personal care product use, evaluate the biological impact of endocrine disrupting chemicals, and develop community interventions. The three pillars of the program include research, outreach and engagement as well as advocacy activities. The research pillar of the BCI includes development of multidisciplinary partnerships to understand the sociocultural and biological determinants of harmful chemical (e.g., endocrine disrupting chemicals) exposures from personal care products and to implement community interventions. The outreach and engagement pillar includes education and translation of research into behavioral practice. The research conducted through the initiative provides the foundation for advocacy engagement with applicable community-based organizations. Essential to the mission of the BCI is the participation of community members and trainees from underrepresented backgrounds who are affected by breast cancer disparities. Results: Two behavioral interventions will be developed building on prior research on environmental exposures with the focus on personal care products including findings from the BCI. In person and virtual education activities include tabling at community events with do-it-yourself product demonstrations, Salon Conversations—a virtual platform used to bring awareness, education, and pilot behavior change interventions, biennial symposiums, and social media engagement. BCI’s community advisory board members support activities across the three pillars, while trainees participate in personal and professional activities that enhance their skills in research translation. Discussion: This paper highlights the three pillars of the BCI, lessons learned, testimonies from community advisory board members and trainees on the impact of the initiative, as well as BCI’s mission driven approaches to achieving health equity

The effects of laryngeal mask airway passage simulation training on the acquisition of undergraduate clinical skills: a randomised controlled trial

Background\ud Effective use of the laryngeal mask airway (LMA) requires learning proper insertion technique in normal patients undergoing routine surgical procedures. However, there is a move towards simulation training for learning practical clinical skills, such as LMA placement. The evidence linking different amounts of mannequin simulation training to the undergraduate clinical skill of LMA placement in real patients is limited. The purpose of this study was to compare the effectiveness in vivo of two LMA placement simulation courses of different durations. \ud \ud Methods\ud Medical students (n = 126) enrolled in a randomised controlled trial. Seventy-eight of these students completed the trial. The control group (n = 38) received brief mannequin training while the intervention group (n = 40) received additional more intensive mannequin training as part of which they repeated LMA insertion until they were proficient. The anaesthetists supervising LMA placements in real patients rated the participants' performance on assessment forms. Participants completed a self-assessment questionnaire. \ud \ud Results\ud Additional mannequin training was not associated with improved performance (37% of intervention participants received an overall placement rating of > 3/5 on their first patient compared to 48% of the control group, $X^2$ = 0.81, p = 0.37). The agreement between the participants and their instructors in terms of LMA placement success rates was poor to fair. Participants reported that mannequins were poor at mimicking reality. \ud \ud Conclusions\ud The results suggest that the value of extended mannequin simulation training in the case of LMA placement is limited. Educators considering simulation for the training of practical skills should reflect on the extent to which the in vitro simulation mimics the skill required and the degree of difficulty of the procedure. \ud \u

Validation of “Care of the Dying Evaluation” in emergency medicine (CODEEM): pilot phase of End-of-life Management Protocol Offered Within Emergency Room (EMPOWER) study

Background: An increasing number of patients who present to emergency departments are at their endof-life phase and have significant palliative care needs such as in symptom control for pain and dyspnoea. Evaluating quality of care provided is imperative, yet there is no suitable tool validated in the emergency and Asian settings. We aim to examine the face and construct validity, and reliability of a newly developed questionnaire, Care of the Dying Evaluation - Emergency Medicine, for measuring the quality of end-of-life care in an Asian emergency context. Methods: A mixed methods pilot study was conducted. Participants composed of the next-of-kin to thirty dying patients who presented to the emergency departments of three public hospitals in Singapore. Qualitative evaluation, using cognitive "think-aloud" interviews, and quantitative analysis were employed. Percentage agreement and κ statistic were measured to evaluate temporal stability of the questionnaire. Cronbach's α and item-total correlations were used to assess internal consistency within the constructs. Confirmatory factor analysis was performed for construct validity. Results: All participants reported clear understanding of the questionnaire with no ambiguity; a minority felt the questions caused emotional distress (7/30, 23.3%). The questions showed moderate to good testretest reliability. Internal consistencies within the constructs were good for "ENVIRONMENT" and "CARE", and moderate for "COMMUNICATION". Factor loadings range from 0.40 to 0.99. Conclusions: The Care of the Dying Evaluation - Emergency Medicine questionnaire may be valid and reliable for use in an Asian emergency setting. Our prospective multicentre study using this evaluation tool may provide more insight on the quality of care rendered to dying patients and identify areas for improvement. Trial registration: ClinicalTrials.gov (NCT03906747)

Circadian rhythm in cardiac arrest: The Singapore experience

Singapore Medical Journal499719-723SIMJ

Corrigendum to “Antibiotic expectation, behaviour, and receipt among patients presenting to emergency departments with uncomplicated upper respiratory tract infection during the COVID-19 pandemic” [Journal of Global Antimicrobial Resistance 33 (2023) 89–96, (S2213716523000401), (10.1016/j.jgar.2023.02.025)]

10.1016/j.jgar.2023.04.001Journal of Global Antimicrobial Resistance33376