Online medical student OSCE examinations during the first three years of the COVID-19 pandemic compared to three years pre-pandemic: An Australian experience in psychiatry and addiction medicine.

PURPOSE: We have evaluated the final-year Psychiatry and Addiction Medicine (PAM) summative Objective Structured Clinical Examination (OSCE) examinations in a four-year graduate medical degree program, for the previous three years as a baseline comparator, and during three years of the COVID-19 pandemic (2020-2022). METHODS: A de-identified analysis of medical student summative OSCE examination performance, and comparative review for the 3 years before, and for each year of the pandemic. RESULTS: Internal reliability in test scores as measured by R-squared remained the same or increased following the start of the pandemic. There was a significant increase in mean test scores after the start of the pandemic compared to pre-pandemic for combined OSCE scores for all final-year disciplines, as well as for the PAM role-play OSCEs, but not for the PAM mental state examination OSCEs. CONCLUSIONS: Changing to online OSCEs during the pandemic was related to an increase in scores for some but not all domains of the tests. This is in line with a nascent body of literature on medical teaching and examination following the start of the pandemic. Further research is needed to optimise teaching and examination in a post-pandemic medical school environment.

Peer-supported physical activity intervention for academic probation freshmen in a physiology-related major: a feasibility study.

To retain students on academic probation, physiology and physiology-related programs may offer a variety of academic support initiatives. This pilot research study examined the feasibility and perceptions of implementing a success coach-led physical activity (PA) program for freshmen on academic probation in a physiology-related program. Freshman on academic probation [grade point average (GPA) <2.0] worked with a success coach on academic success strategies and PA. Freshmen completed validated surveys (Academic Self-Efficacy, Self-Efficacy of Regulated Learning, Institutional Integration Scale) before and after intervention and semistructured interviews after intervention. Retention rate was determined at longitudinal follow-up in Fall 2022. Six freshmen participated. Average GPA did not improve between Fall 2021 (1.561 ± 0.285) and Spring 2022 (1.606 ± 0.832) (P = 0.89). All felt that the program improved their study skills, but fewer (40%) felt that their grades improved. Most had positive perceptions of the PA program, including self-reported improvements in health/fitness (60%), mood/mental well-being (100%), and stress management (80%). Although most improved attention when studying (80%), this did not translate to improved academic performance (40%). For the Institutional Integration Scales, only the scale for "Faculty Concern for Student Development and Teaching" improved by the end of the semester (pre: 37 ± 7.6, post: 19 ± 3.4, P < 0.001). Retention rate of participants (83%) was higher than the university's overall retention rate for students on academic probation (37%). By fostering social integration, improving mood and mental well-being, and increasing university retention rates this pilot project confirmed the feasibility of using upperclassmen as success coaches for a physical activity intervention for academic probation freshmen.NEW & NOTEWORTHY Using upperclassmen as success coaches for a physical activity intervention for academic probation freshmen fostered social integration, improved mood and mental well-being, and increased university retention rates.

Increasing Linker Chain Length and Intestinal Stability Enhances Lymphatic Transport and Lymph Node Exposure of Triglyceride Mimetic Prodrugs of a Model Immunomodulator Mycophenolic Acid.

Targeted delivery of immunomodulators to the lymphatic system has the potential to enhance therapeutic efficacy by increasing colocalization of drugs with immune targets such as lymphocytes. A triglyceride (TG)-mimetic prodrug strategy has been recently shown to enhance the lymphatic delivery of a model immunomodulator, mycophenolic acid (MPA), via incorporation into the intestinal TG deacylation-reacylation and lymph lipoprotein transport pathways. In the current study, a series of structurally related TG prodrugs of MPA were examined to optimize structure-lymphatic transport relationships for lymph-directing lipid-mimetic prodrugs. MPA was conjugated to the sn-2 position of the glyceride backbone of the prodrugs using linkers of different chain length (5-21 carbons) and the effect of methyl substitutions at the alpha and/or beta carbons to the glyceride end of the linker was examined. Lymphatic transport was assessed in mesenteric lymph duct cannulated rats, and drug exposure in lymph nodes was examined following oral administration to mice. Prodrug stability in simulated intestinal digestive fluid was also evaluated. Prodrugs with straight chain linkers were relatively unstable in simulated intestinal fluid; however, co-administration of lipase inhibitors (JZL184 and orlistat) was able to reduce instability and increase lymphatic transport (2-fold for a prodrug with a 6-carbon spacer, i.e., MPA-C6-TG). Methyl substitutions to the chain resulted in similar trends in improving intestinal stability and lymphatic transport. Medium- to long-chain spacers (C12, C15) between MPA and the glyceride backbone were most effective in promoting lymphatic transport, consistent with increases in lipophilicity. In contrast, short-chain (C6-C10) linkers appeared to be too unstable in the intestine and insufficiently lipophilic to associate with lymph lipid transport pathways, while very long-chain (C18, C21) linkers were also not preferred, likely as a result of increases in molecular weight reducing solubility or permeability. In addition to more effectively promoting drug transport into mesenteric lymph, TG-mimetic prodrugs based on a C12 linker resulted in marked increases (>40 fold) in the exposure of MPA in the mesenteric lymph nodes in mice when compared to administration of MPA alone, suggesting that optimizing prodrug design has the potential to provide benefit in targeting and modulating immune cells.

Commentary on alignment of medical student assessment and vocational training in psychiatry and addiction medicine.

OBJECTIVE: To comment upon the potential for alignment of medical student assessment and vocational specialist training through the RANZCP-CanMEDS model of Entrustable Professional Activities (EPAs) and Workplace-Based Assessments (WBAs). We discuss a specific post hoc example of such an alignment in an Australian graduate medical school in Psychiatry and Addiction Medicine. CONCLUSIONS: Vocational training models of assessment, such as the RANZCP specialist training program for psychiatrists, can potentially be mapped to medical student education in formative and summative assessment through CanMEDs-based EPAs and WBAs, to assist in transition to specialist training.

Final-year medical student Psychiatry and Addiction Medicine synchronous summative tele-assessments during a COVID-19 Delta-variant stay-at-home lockdown.

OBJECTIVE: We describe the planning, process and evaluation of final-year Psychiatry and Addiction Medicine summative assessments in a four-year graduate medical degree program, during a COVID-19 Delta-variant public health stay-at-home lockdown. CONCLUSIONS: We conducted separate written and clinical synchronous (real-time simultaneous) tele-assessments. We used online assessment technology with students, examiners and simulated patients, all in different physical locations. Medical students' examination performance showed a good range. This was comparable to other discipline stations, and performance in previous years. There was no differential performance of students through the day of the assessments.

Maslow's hammer: considering the perils of solutionism in mental healthcare and psychiatric practice.

OBJECTIVE: To discuss narrow pragmatism, manifest as digital and technical solutionism, in mental healthcare and psychiatric practice. Pragmatism is a view of the field of psychiatry as an instrument or tool for the purpose of providing psychiatric care for people with a mental illness. Solutionism, as proposed by Morozov, can be considered a special case of pragmatism that valorises an approach to solving real-world problems based on computation, algorithms and digital technology,1 which we extend to discuss other technical solutions such as medication, non-invasive brain stimulation and psychotherapy. CONCLUSIONS: Digital or technical solutionism may unnecessarily constrain approaches to mental healthcare and psychiatric practice. Psychiatrists can consider, and should advocate for, appropriate adaptation of technology and technical solutions toward collaborative and effective mental healthcare.

Conduct and evaluation of final-year medical student summative assessments in Psychiatry and Addiction Medicine during COVID-19: an Australian University Medical School experience.

OBJECTIVE: To describe and share with the medical education community, the conduct and evaluation of summative graduate medical student assessments in Psychiatry and Addiction Medicine during COVID-19 at an Australian university. METHODS: Summative assessments were redesigned as follows: written assessments were administered via an online platform (WATTLE), while the Objective Structured Clinical Examinations (OSCE) were conducted via a secure video-conferencing software (Zoom). RESULTS: Our preliminary analysis of the summative assessments indicated that both examiners and students adapted to the format, with overall performance of the students showing no variation due to timing of the assessment (earlier versus later in the day) and performances similar to face-to-face assessments in previous years. Examiners also expressed positive feedback on the assessment process. CONCLUSIONS: Our graduate fourth-year medical student summative assessments were effectively conducted using online and video-conferencing software in accordance with existing COVID-19 pandemic public health measures for physical distancing and hygiene.

Targeted delivery of mycophenolic acid to the mesenteric lymph node using a triglyceride mimetic prodrug approach enhances gut-specific immunomodulation in mice.

The mesenteric lymph nodes (MLN) are a key site for the generation of adaptive immune responses to gut-derived antigenic material and immune cells within the MLN contribute to the pathophysiology of a range of conditions including inflammatory and autoimmune diseases, viral infections, graft versus host disease and cancer. Targeting immunomodulating drugs to the MLN may thus be beneficial in a range of conditions. This paper investigates the potential benefit of targeting a model immunosuppressant drug, mycophenolic acid (MPA), to T cells in the MLN, using a triglyceride (TG) mimetic prodrug approach. We confirmed that administration of MPA in the TG prodrug form (MPA-TG), increased lymphatic transport of MPA-related species 83-fold and increased MLN concentrations of MPA >20 fold, when compared to MPA alone, for up to 4 h in mice. At the same time, the plasma exposure of MPA and MPA-TG was similar, limiting the opportunity for systemic side effects. Confocal microscopy and flow cytometry studies with a fluorescent model prodrug (Bodipy-TG) revealed that the prodrug accumulated in the MLN cortex and paracortex at 5 and 10 h following administration and was highly associated with B cells and T cells that are found in these regions of the MLN. Finally, we demonstrated that MPA-TG was significantly more effective than MPA at inhibiting CD4+ and CD8+ T cell proliferation in the MLN of mice in response to an oral ovalbumin antigen challenge. In contrast, MPA-TG was no more effective than MPA at inhibiting T cell proliferation in peripheral LN when mice were challenged via SC administration of ovalbumin. This paper provides the first evidence of an in vivo pharmacodynamic benefit of targeting the MLN using a TG mimetic prodrug approach. The TG mimetic prodrug technology has the potential to benefit the treatment of a range of conditions where aberrant immune responses are initiated in gut-associated lymphoid tissues.

Flattening the curve of COVID-19 for medical education in psychiatry and addiction medicine.

OBJECTIVE: To describe the context, challenges and responses to COVID-19 public health measures for medical education in psychiatry, with an emphasis on sharing strategies for ongoing COVID-19 challenges. CONCLUSION: The rapidity of COVID-19 public health measures instituted in Australia required swift action for medical education to address lockdowns of student clinical placements. The responses included a transition to interim online learning followed by a return to truncated clinical placements renegotiated to conform to public health measures. Adjustment of formative and summative assessment has been necessary. However, further contingencies may emerge depending upon the overall progress of the COVID-19 pandemic.

Student evaluations of teaching (SET): implications for medical education in psychiatry and an approach to evaluating SET and student performance.

OBJECTIVE: We present reflections on student evaluation of teaching (SET) in the context of recent higher educational research that assesses SET, as well as concurrent and/or subsequent student performance. CONCLUSIONS: In a sense, there is in-built cynicism in SET, with more favourable SET for easier assessment. There is emerging evidence that SET is inversely proportional to the performance of students in subsequent courses, i.e. the higher the ratings, the poorer the students perform in subsequent studies. It is proposed that SET should be combined with contemporaneous formative and summative assessments of student performance in medical school settings, especially in psychiatry education.

A new graduate medical school curriculum in Psychiatry and Addiction Medicine: reflections on a decade of development.

OBJECTIVES: The aim of this study is to reflect upon the rationale, design and development of the Psychiatry and Addiction Medicine curriculum at the Australian National University Medical School, Canberra, Australian Capital Territory, Australia. CONCLUSIONS: We conclude that the development of the fourth-year curriculum of a four-year graduate medical degree was a complex evolutionary process.

Salt in the soul, steel in the eye and caution towards the winds: a mariner's guide for navigating a new academic psychiatry department.

OBJECTIVES: This paper describes principles and advice regarding the development of a new academic psychiatry department within a medical school for aspiring academic psychiatrists. We describe general principles based on the experience of the foundation of the Academic Unit of Psychiatry and Addiction Medicine at the Australian National University Medical School. CONCLUSIONS: Perspicacious leadership and organisation are the foundation for an academic psychiatry department which delivers teaching, research and broader intellectual engagement with the medical and broader community.

Resveratrol Enhances Exercise-Induced Cellular and Functional Adaptations of Skeletal Muscle in Older Men and Women.

Older men (n = 12) and women (n = 18) 65-80 years of age completed 12 weeks of exercise and took either a placebo or resveratrol (RSV) (500 mg/d) to test the hypothesis that RSV treatment combined with exercise would increase mitochondrial density, muscle fatigue resistance, and cardiovascular function more than exercise alone. Contrary to our hypothesis, aerobic and resistance exercise coupled with RSV treatment did not reduce cardiovascular risk further than exercise alone. However, exercise added to RSV treatment improved the indices of mitochondrial density, and muscle fatigue resistance more than placebo and exercise treatments. In addition, subjects that were treated with RSV had an increase in knee extensor muscle peak torque (8%), average peak torque (14%), and power (14%) after training, whereas exercise did not increase these parameters in the placebo-treated older subjects. Furthermore, exercise combined with RSV significantly improved mean fiber area and total myonuclei by 45.3% and 20%, respectively, in muscle fibers from the vastus lateralis of older subjects. Together, these data indicate a novel anabolic role of RSV in exercise-induced adaptations of older persons and this suggests that RSV combined with exercise might provide a better approach for reversing sarcopenia than exercise alone.

Vaccine nanocarriers: Coupling intracellular pathways and cellular biodistribution to control CD4 vs CD8 T cell responses.

Nanoparticle delivery systems are known to enhance the immune response to soluble antigens (Ags) and are thus a promising tool for the development of new vaccines. Our laboratory has engineered two different nanoparticulate systems in which Ag is either encapsulated within the core of polymersomes (PSs) or decorated onto the surface of nanoparticles (NPs). Previous studies showed that PSs are better at enhancing CD4 T cells and antibody titers, while NPs preferentially augment cytotoxic CD8 T cells. Herein, we demonstrate that the differential activation of T cell immunity reflects differences in the modes of intracellular trafficking and distinct biodistribution of the Ag in lymphoid organs, which are both driven by the properties of each nanocarrier. Furthermore, we found that Ags within PSs promoted better CD4 T cell activation and induced a higher frequency of CD4 T follicular helper (Tfh) cells. These differences correlated with changes in the frequency of germinal center B cells and plasma cell formation, which reflects the previously observed antibody titers. Our results show that PSs are a promising vector for the delivery of Ags for B cell vaccine development. This study demonstrates that nanocarrier design has a large impact on the quality of the induced adaptive immune response.

Toll-like receptor 8 agonist nanoparticles mimic immunomodulating effects of the live BCG vaccine and enhance neonatal innate and adaptive immune responses.

BACKGROUND: Newborns display distinct immune responses, leaving them vulnerable to infections and impairing immunization. Targeting newborn dendritic cells (DCs), which integrate vaccine signals into adaptive immune responses, might enable development of age-specific vaccine formulations to overcome suboptimal immunization. OBJECTIVE: Small-molecule imidazoquinoline Toll-like receptor (TLR) 8 agonists robustly activate newborn DCs but can result in reactogenicity when delivered in soluble form. We used rational engineering and age- and species-specific modeling to construct and characterize polymer nanocarriers encapsulating a TLR8 agonist, allowing direct intracellular release after selective uptake by DCs. METHODS: Chemically similar but morphologically distinct nanocarriers comprised of amphiphilic block copolymers were engineered for targeted uptake by murine DCs in vivo, and a range of TLR8 agonist-encapsulating polymersome formulations were then synthesized. Novel 96-well in vitro assays using neonatal human monocyte-derived DCs and humanized TLR8 mouse bone marrow-derived DCs enabled benchmarking of the TLR8 agonist-encapsulating polymersome formulations against conventional adjuvants and licensed vaccines, including live attenuated BCG vaccine. Immunogenicity of the TLR8 agonist adjuvanted antigen 85B (Ag85B)/peptide 25-loaded BCG-mimicking nanoparticle formulation was evaluated in vivo by using humanized TLR8 neonatal mice. RESULTS: Although alum-adjuvanted vaccines induced modest costimulatory molecule expression, limited TH-polarizing cytokine production, and significant cell death, BCG induced a robust adult-like maturation profile of neonatal DCs. Remarkably, TLR8 agonist polymersomes induced not only newborn DC maturation profiles similar to those induced by BCG but also stronger IL-12p70 production. On subcutaneous injection to neonatal mice, the TLR8 agonist-adjuvanted Ag85B peptide 25 formulation was comparable with BCG in inducing Ag85B-specific CD4+ T-cell numbers. CONCLUSION: TLR8 agonist-encapsulating polymersomes hold substantial potential for early-life immunization against intracellular pathogens. Overall, our study represents a novel approach for rational design of early-life vaccines.

A Cationic Micelle Complex Improves CD8+ T Cell Responses in Vaccination Against Unmodified Protein Antigen.

Nanoscale carrier platforms promote immune responses to vaccination by facilitating delivery of vaccine components to immunologically relevant sites. The technique is particularly valuable for subunit vaccination, in which coadministration of immunostimulatory adjuvant is known to enhance immune responses to protein antigen. The fabrication of polymer-based nanoparticle vaccines commonly requires covalent attachment of vaccine components to the carrier surface. In contrast, we here describe a cationic micelle vaccination platform in which antigen and adjuvant loading is mediated by noncovalent molecular encapsulation and electrostatic complexation. Cationic micelles were generated through self-assembly of a polyarginine-conjugated poly(ethylene glycol)-b-poly(propylene sulfide) (PEG-PPS) diblock copolymer amphiphile, with or without encapsulation of monophosphoryl lipid A (MPLA), an amphiphilic experimental vaccine adjuvant. Micelle complexes were subsequently formed by complexation of ovalbumin (OVA) and CpG-B oligodeoxynucleotide (a second experimental adjuvant) to the cationic micelles. In a 35-day study in mouse, micelle-mediated codelivery of OVA antigen and CpG-B enhanced cellular and humoral responses to vaccination. These outcomes were highlighted in spleen and lymph node CD8+ T cells, with significantly increased populations of IFNγ+, TNFα+, and polyfunctional IFNγ+ TNFα+ cells. Elevated cytokine production is a hallmark of robust cytotoxic T lymphocyte (CTL) responses sought in next-generation vaccine technologies. Increased production of OVA-specific IgG1, IgG2c, and IgG3 also confirmed micelle enhancement of humoral responses. In a subsequent 35-day study, we explored micelle-mediated vaccination against OVA antigen coadministered with MPLA and CpG-B adjuvants. A synergistic effect of adjuvant coadministration was observed in micelle-free vaccination but not in groups immunized with micelle complexes. This outcome underlines the advantage of the micelle carrier: we achieved optimal cellular and humoral responses to vaccination by use of this nanoparticle platform with a single adjuvant. In particular, enhanced CTL responses support future development of the cationic micelle platform in experimental cancer vaccines and for vaccination against reticent viral pathogens.

A plug-and-play ratiometric pH-sensing nanoprobe for high-throughput investigation of endosomal escape.

An important aspect in the design of nanomaterials for delivery is an understanding of its uptake and ultimate release to the cytosol of target cells. Real-time chemical sensing using a nanoparticle-based platform affords exquisite insight into the trafficking of materials and their cargo into cells. This versatile and tunable technology provides a powerful tool to probe the mechanism of cellular entry and cytosolic delivery of a variety of materials, allowing for a simple and convenient means to screen materials towards efficient delivery of therapeutics such as nucleic acids.

Exercise and dietary advice intervention for survivors of triple-negative breast cancer: effects on body fat, physical function, quality of life, and adipokine profile.

PURPOSE: Regular exercise and healthy eating are routinely recommended for breast cancer survivors, and past studies show benefits in quality of life and decreased inflammation. However, this has not been tested specifically in triple-negative breast cancer survivors. Increasing physical activity and losing body fat are thought to positively affect inflammatory biomarkers that have been associated with breast cancer. Therefore, the primary purpose of this study was to determine if participation in an exercise and dietary counseling program can improve body fat, physical function, and quality of life in survivors of this aggressive breast cancer. Secondarily, we sought to determine if participation in the program had beneficial effects on obesity-related markers of the adipokine profile. METHODS: Sixty-six survivors of triple-negative breast cancer with BMI >25 were invited to participate. Twenty-eight enrolled and 23 completed the randomized, controlled trial (13 intervention, 10 control). Moderate-intensity aerobic exercise (150 min per week, for 12 weeks) and diet counseling were compared to usual care, education only. The primary outcome of interest was weight loss (body mass, BMI, % fat), and secondary outcomes included physical function (exercise capacity), quality of life (Function After Cancer Therapy-Breast (FACT-B)), cytokines (C-reactive protein (CRP), TNF-α, IL-6), and adipokine profile (leptin, adiponectin, insulin). RESULTS: Participants in the program lost more body fat (2.4 % loss vs. 0.4 % gain, p < 0.05) than the control group. The intervention group also improved quality of life (FACT-B total score +14 pts) and decreased sedentary time but did not improve peak exercise capacity. The intervention had no effect on serum cytokines and adipokines after 12 weeks in the program. However, serum leptin and adiponectin and their ratio were significantly correlated with BMI in the intervention group (p < 0.05). CONCLUSIONS: Exercise and dietary counseling led to loss of body fat and improved quality of life in survivors of triple-negative breast cancer. BMI was associated with favorable changes in leptin and adiponectin which may reflect a change in adiposity with intervention. Exercise and healthy eating may be equally effective in this high-risk population as in other breast cancer survivors and should be encouraged as a part of a cancer survivorship program.

Improved arterial-ventricular coupling in metabolic syndrome after exercise training: a pilot study.

PURPOSE: The metabolic syndrome (MetS) is associated with threefold increased risk of cardiovascular (CV) morbidity and mortality, which is partly due to a blunted CV reserve capacity, reflected by a reduced peak exercise left ventricular (LV) contractility and aerobic capacity and a blunted peak arterial-ventricular coupling. To date, no study has examined whether aerobic exercise training in MetS can reverse peak exercise CV dysfunction. Furthermore, examining how exercise training alters CV function in a group of individuals with MetS before the development of diabetes and/or overt CV disease can provide insights into whether some of the pathophysiological CV changes can be delayed/reversed, lowering their CV risk. The objective of this study was to examine the effects of 8 wk of aerobic exercise training in individuals with MetS on resting and peak exercise CV function. METHODS: Twenty participants with MetS underwent either 8 wk of aerobic exercise training (MetS-ExT, n = 10) or remained sedentary (MetS-NonT, n = 10) during this period. Resting and peak exercise CV function was characterized using Doppler echocardiography and gas exchange. RESULTS: Exercise training did not alter resting LV diastolic or systolic function and arterial-ventricular coupling in MetS. In contrast, at peak exercise, an increase in LV contractility (40%, P < 0.01), cardiac output (28%, P < 0.05), and aerobic capacity (20%, P < 0.01), but a reduction in vascular resistance (30%, P < 0.05) and arterial-ventricular coupling (27%, P < 0.01), were noted in the MetS-ExT but not in the MetS-NonT group. Furthermore, an improvement in lifetime risk score was also noted in the MetS-ExT group. CONCLUSIONS: These findings have clinical importance because they provide insight that some of the pathophysiological changes associated with MetS can be improved and can lower the risk of CV disease.