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1.
Cell Death Dis ; 14(11): 714, 2023 11 02.
Article in English | MEDLINE | ID: mdl-37919300

ABSTRACT

Bruton's tyrosine kinase inhibitors (BTKi) and CAR T-cell therapy have demonstrated tremendous clinical benefits in mantle cell lymphoma (MCL) patients, but intrinsic or acquired resistance inevitably develops. In this study, we assessed the efficacy of the highly potent and selective MCL-1 inhibitor AZD5991 in various therapy-resistant MCL cell models. AZD5991 markedly induced apoptosis in these cells. In addition to liberating BAK from the antiapoptotic MCL-1/BAK complex for the subsequent apoptosis cascade, AZD5991 downregulated inhibitor of apoptosis proteins (IAPs) through a BAK-dependent mechanism to amplify the apoptotic signal. The combination of AZD5991 with venetoclax enhanced apoptosis and reduced mitochondrial oxygen consumption capacity in MCL cell lines irrespective of their BTKi or venetoclax sensitivity. This combination also dramatically inhibited tumor growth and prolonged mouse survival in two aggressive MCL patient-derived xenograft models. Mechanistically, the augmented cell lethality was accompanied by the synergistic suppression of IAPs. Supporting this notion, the IAP antagonist BV6 induced dramatic apoptosis in resistant MCL cells and sensitized the resistant MCL cells to venetoclax. Our study uncovered another unique route for MCL-1 inhibitor to trigger apoptosis, implying that the pro-apoptotic combination of IAP antagonists and apoptosis inducers could be further exploited for MCL patients with multiple therapeutic resistance.


Subject(s)
Lymphoma, Mantle-Cell , Humans , Mice , Animals , Adult , Lymphoma, Mantle-Cell/drug therapy , Lymphoma, Mantle-Cell/metabolism , Myeloid Cell Leukemia Sequence 1 Protein/metabolism , Inhibitor of Apoptosis Proteins/metabolism , Down-Regulation , Cell Proliferation , Cell Line, Tumor , Apoptosis , Proto-Oncogene Proteins c-bcl-2/metabolism
2.
Front Med (Lausanne) ; 10: 1146832, 2023.
Article in English | MEDLINE | ID: mdl-37849488

ABSTRACT

Introduction/background: Course evaluation in health education is a common practice yet few comprehensive evaluations of health education exist that measure the impact and outcomes these programs have on developing health graduate capabilities. Aim/objectives: To explore how curricula contribute to health graduate capabilities and what factors contribute to the development of these capabilities. Methods: Using contribution analysis evaluation, a six-step iterative process, key stakeholders in the six selected courses were engaged in an iterative theory-driven evaluation. The researchers collectively developed a postulated theory-of-change. Then evidence from existing relevant documents were extracted using documentary analysis. Collated findings were presented to academic staff, industry representatives and graduates, where additional data was sought through focus group discussions - one for each discipline. The focus group data were used to validate the theory-of-change. Data analysis was conducted iteratively, refining the theory of change from one course to the next. Results: The complexity in teaching and learning, contributed by human, organizational and curriculum factors was highlighted. Advances in knowledge, skills, attitudes and graduate capabilities are non-linear and integrated into curriculum. Work integrated learning significantly contributes to knowledge consolidation and forming professional identities for health professional courses. Workplace culture and educators' passion impact on the quality of teaching and learning yet are rarely considered as evidence of impact. Discussion: Capturing the episodic and contextual learning moments is important to describe success and for reflection for improvement. Evidence of impact of elements of courses on future graduate capabilities was limited with the focus of evaluation data on satisfaction. Conclusion: Contribution analysis has been a useful evaluation method to explore the complexity of the factors in learning and teaching that influence graduate capabilities in health-related courses.

3.
Aust J Gen Pract ; 51(9): 696-702, 2022 09.
Article in English | MEDLINE | ID: mdl-36045627

ABSTRACT

BACKGROUND AND OBJECTIVES: There is growing evidence regarding the effectiveness of registrar training through video cameras, which has relevance for quality supervision during times of crises such as the global COVID-19 pandemic. METHOD: Interviews were conducted in 2012 with supervisors, registrars and patients evaluating video camera use for tele-supervision across six rural sites in Gippsland, Australia. Thematic analysis was employed in 2013 - and re-examined in 2021 in light of the global COVID-19 pandemic - to explore user experience with video technology. RESULTS: Participants identified advantages of video supervision addressing distance and temporal issues, also emphasising quality supervision and education. Challenges included patient confidentiality, internet stability and loss of serendipitous 'corridor conversations'. DISCUSSION: Remote supervision is no longer simply an issue for rural and remote training. During crises such as a global pandemic, tele-supervision becomes the purview of all. There are distinct merits and limitations in adopting video technology, warranting consideration of individual training contexts. These findings can help inform remote supervision via video in varied milieu.


Subject(s)
COVID-19 , General Practice , Rural Health Services , Family Practice , General Practice/education , Humans , Pandemics/prevention & control
4.
PLoS One ; 16(5): e0251710, 2021.
Article in English | MEDLINE | ID: mdl-34003873

ABSTRACT

BACKGROUND: Writing and digital storage have largely replaced organic memory for encoding and retrieval of information in the modern era, with a corresponding decrease in emphasis on memorization in Western education. In health professional training, however, there remains a large corpus of information for which memorization is the most efficient means of ensuring: A) that the trainee has the required information readily available; and B) that a foundation of knowledge is laid, upon which the medical trainee builds multiple, complex layers of detailed information during advanced training. The carefully staged progression in early- to late- years' medical training from broad concepts (e.g. gross anatomy and pharmacology) to in-depth, specialised disciplinary knowledge (e.g. surgical interventions and follow-on care post-operatively) has clear parallels to the progression of training and knowledge exposure that Australian Aboriginal youths undergo in their progression from childhood to adulthood to Tribal Elders. METHODS: As part of the Rural Health curriculum and the undergraduate Nutrition and Dietetics program in the Monash University Faculty of Medicine, Nursing, and Health Sciences, we tested Australian Aboriginal techniques of memorization for acquisition and recall of novel word lists by first-year medical students (N = 76). We also examined undergraduate student evaluations (N = 49) of the use of the Australian Aboriginal memory technique for classroom study of foundational biomedical knowledge (the tricarboxylic acid cycle) using qualitative and quantitative analytic methods drawing from Bloom's taxonomy for orders of thinking and learning. Acquisition and recall of word lists were assessed without memory training, or after training in either the memory palace technique or the Australian Aboriginal narrative technique. RESULTS: Both types of memory training improved the number of correctly recalled items and reduced the frequency of specific error types relative to untrained performance. The Australian Aboriginal method resulted in approximately a 3-fold greater probability of improvement to accurate recall of the entire word list (odds ratio = 2.82; 95% c.i. = 1.15-6.90), vs. the memory palace technique (odds ratio = 2.03; 95% c.i. = 0.81-5.06) or no training (odds ratio = 1.5; 95% c.i. = 0.54-4.59) among students who did not correctly recall all list items at baseline. Student responses to learning the Australian Aboriginal memory technique in the context of biomedical science education were overwhelmingly favourable, and students found both the training and the technique enjoyable, interesting, and more useful than rote memorization. Our data indicate that this method has genuine utility and efficacy for study of biomedical sciences and in the foundation years of medical training.


Subject(s)
Curriculum , Education, Medical, Undergraduate , Learning , Memory , Adult , Australia , Female , Humans , Male , Native Hawaiian or Other Pacific Islander , Universities
5.
Med Teach ; 43(3): 325-333, 2021 03.
Article in English | MEDLINE | ID: mdl-33181038

ABSTRACT

BACKGROUND: Steering planetary and human health towards a more sustainable future demands educated and prepared health professionals. AIM: This research aimed: to explore health professions educators' sustainable healthcare education (SHE) knowledge, attitudes, self-efficacy and teaching practices across 13 health professions courses in one Australian university. METHODS: Utilising a sequential mixed-methods design: Phase one (understanding) involved an online survey to ascertain educators' SHE knowledge, attitudes, self-efficacy and teaching practices to inform phase two (solution generation), 'Teach Green' Hackathon. Survey data was descriptively analysed and a gap analysis performed to promote generation of solutions during phase two. Results from the hackathon were thematically analysed to produce five recommendations. RESULTS: Regarding SHE, survey data across 13 health professions disciplines (n = 163) identified strong content knowledge (90.8%); however, only (36.9%) reported confidence to 'explain' and (44.2%) to 'inspire' students. Two thirds of participants (67.5%) reported not knowing how best to teach SHE. Hackathon data revealed three main influencing factors: regulatory, policy and socio-cultural drivers. CONCLUSIONS: The five actionable recommendations to strengthen interdisciplinary capacity to integrate SHE include: inspire multi-level leadership and collaboration; privilege student voice; develop a SHE curriculum and resources repository; and integrate SHE into course accreditation standards.


Subject(s)
Curriculum , Health Occupations , Australia , Delivery of Health Care , Health Personnel/education , Humans
6.
Explore (NY) ; 16(4): 214-224, 2020.
Article in English | MEDLINE | ID: mdl-32335005

ABSTRACT

OBJECTIVE: This article explores chronic disease patients' personal symbolic meanings of their diseases, as emergent from their experience of Emotional Freedom Techniques (EFT) therapy. The present study is part of a larger study that explored chronic disease patients' and EFT practitioners' experiences of using EFT to support chronic disease healthcare. DESIGN: Eight chronic disease patients who had received EFT were interviewed for this study. Semi-structured interviews were conducted face to face, or via telephone, or the online videoconferencing platform, Zoom. Interviews were transcribed verbatim and data was analysed using Interpretative Phenomenological Analysis methodology. RESULTS: Three themes emerged, namely 'illness as an embodiment of unresolved emotional issues', 'illness as body's call for time-out and attention', and 'illness as a boundary from other people'. CONCLUSION: EFT offers promise as a suitable therapeutic approach to help chronic disease patients make sense of their life stories and lived experiences, and consequently, symbolic meanings of diseases. The exploration of illness symbology and meaning-making may offer therapeutic value to patients, from both an existential and a health behaviors perspective.


Subject(s)
Chronic Disease/psychology , Cognitive Behavioral Therapy , Emotions , Adult , Existentialism , Female , Humans , Middle Aged , Qualitative Research
7.
Disabil Rehabil ; 40(14): 1654-1662, 2018 Jul.
Article in English | MEDLINE | ID: mdl-28345427

ABSTRACT

PURPOSE: The objective of the present study was to explore Emotional Freedom Techniques (EFT) practitioners' experiences of using EFT to support chronic disease patients. This was part of a larger study exploring chronic disease patients' and EFT practitioners' experiences of using EFT to support chronic disease healthcare. METHODS: A qualitative approach was deemed suitable for this study. Eight practitioners were interviewed using semi-structured interviews via telephone or Zoom (an online video-conferencing platform). Interviews were transcribed verbatim and data was analyzed using Interpretative Phenomenological Analysis methodology. RESULTS AND CONCLUSION: This article presents two super-ordinate themes which explore application of EFT for addressing emotional issues faced by chronic disease patients, and for management of physical symptoms, respectively. Chronic disease patients may benefit from a holistic biopsychosocial, patient-centered healthcare approach. EFT offers potential as a technique that may be used by health practitioners to support the psychosocial aspect of chronic disease healthcare. Implications for Rehabilitation Rehabilitation professionals should incorporate suitable psychological interventions (e.g., EFT) to improve coping and acceptance in physical chronic disease patients and alleviate their fears about the future. Rehabilitation professionals are also recommended to address in chronic disease patients, long-standing or unresolved emotional issues, including past traumas from early life, using EFT or another suitable intervention. Rehabilitation professionals should help improve patients' emotional states using EFT to enhance physical symptom management.


Subject(s)
Acupuncture Therapy , Chronic Disease/psychology , Chronic Disease/therapy , Emotions , Psychotherapy/methods , Adaptation, Psychological , Adult , Female , Humans , Male , Middle Aged
8.
Adv Med Educ Pract ; 5: 407-13, 2014.
Article in English | MEDLINE | ID: mdl-25404864

ABSTRACT

BACKGROUND: This paper explores local community perceptions of a relatively new rural medical school. For the purposes of this paper, community engagement is conceptualized as involvement in planning, delivering, and evaluating the medical program. Although there are several reviews of patient involvement in medical curricula development, this study was designed to pilot an approach to exploring the perspectives of well members of the community in the transition of institutional policy on community engagement to one medical school. METHODS: An advertisement in the local newspaper invited volunteers to participate in a telephone interview about the new medical school. An independent researcher external to the medical school conducted the interviews using a topic guide. Audio recordings were not made, but detailed notes including verbatim statements were recorded. At least two research team members analyzed interview records for emergent themes. Human research ethics approval was obtained. RESULTS: Twelve interviews were conducted. Participants offered rich imaginings on the role of the school and expectations and opportunities for students. Most participants expressed strong and positive views, especially in addressing long-term health workforce issues. It was considered important that students live, mix, and study in the community. Some participants had very clear ideas about the need of the school to address specified needs, such as indigenous health, obesity, aging, drug and alcohol problems, teenage pregnancy, ethnic diversity, and working with people of low socioeconomic status. CONCLUSION: This study has initiated a dialogue with potential partners in the community, which can be built upon to shape the medical school's mission and contribution to the society it serves. The telephone interview approach and thematic analysis yielded valuable insights and is recommended for further studies. Our study was limited by its small study size and the single recruitment source. The community is a rich resource for medical education, but there is a dearth of literature on the perspectives of the community and its role in medical education.

10.
Nurs Times ; 99(11): 50-2, 2003.
Article in English | MEDLINE | ID: mdl-12683051

ABSTRACT

Rugby Children's Hospital at Home is an innovative community-based service for acutely ill children (Box 1). It enables children to be cared for at home during their illness by offering a plan of care in partnership with the child's parents. The child is visited as frequently as needed to ensure his or her safety and according to the child's condition (Samwell, 2000).


Subject(s)
Asthma/therapy , Home Care Services , Child, Preschool , Critical Pathways , Health Services Accessibility , Humans , Male , United Kingdom
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