Adeno-associated virus perfusion enhanced expression: A commercially scalable, high titer, high quality producer cell line process.

With safety and efficacy demonstrated over hundreds of clinical trials in the last 30 years, along with at least six recent global marketing authorizations achieved since 2017, recombinant adeno-associated viruses (rAAVs) have been established as the leading therapeutic gene transfer vector for rare, monogenic diseases. Significant advances in manufacturing technology have been made in the last few decades to address challenges with GMP production of rAAV products, although yield, cost, scalability, and quality remain a challenge. With transient transfection processes established as a manufacturing platform for multiple commercial AAV products, there remains significant yield, cost, robustness, and scalability constraints that need to be resolved to enable a reliable supply of rAAV products for global patient access. The development of stable producer cell lines for rAAV products has enabled scalability and, in some cases, improvements in productivity. Herein we describe a novel AAV perfusion-enhanced expression (APEX) process, resulting in higher maximum cell densities in the production bioreactor with a 3- to 6-fold increase in volumetric productivity. This process has been successfully demonstrated across multiple serotypes in large scale cell culture with titers approaching 1 × 1012 GC/mL. The APEX production platform marks a significant leap forward in the efficient and effective manufacturing of rAAV vector products.

Acetylcholine Engages Distinct Amygdala Microcircuits to Gate Internal Theta Rhythm.

Acetylcholine (ACh) is released from basal forebrain cholinergic neurons in response to salient stimuli and engages brain states supporting attention and memory. These high ACh states are associated with theta oscillations, which synchronize neuronal ensembles. Theta oscillations in the basolateral amygdala (BLA) in both humans and rodents have been shown to underlie emotional memory, yet their mechanism remains unclear. Here, using brain slice electrophysiology in male and female mice, we show large ACh stimuli evoke prolonged theta oscillations in BLA local field potentials that depend upon M3 muscarinic receptor activation of cholecystokinin (CCK) interneurons (INs) without the need for external glutamate signaling. Somatostatin (SOM) INs inhibit CCK INs and are themselves inhibited by ACh, providing a functional SOM→CCK IN circuit connection gating BLA theta. Parvalbumin (PV) INs, which can drive BLA oscillations in baseline states, are not involved in the generation of ACh-induced theta, highlighting that ACh induces a cellular switch in the control of BLA oscillatory activity and establishes an internally BLA-driven theta oscillation through CCK INs. Theta activity is more readily evoked in BLA over the cortex or hippocampus, suggesting preferential activation of the BLA during high ACh states. These data reveal a SOM→CCK IN circuit in the BLA that gates internal theta oscillations and suggest a mechanism by which salient stimuli acting through ACh switch the BLA into a network state enabling emotional memory.

Unplanned Return to Hospital After Same Day Oral Cavity Resection: A Dual Institution Study.

OBJECTIVES: Primary objective: describe rates of 30-days unplanned readmission following outpatient resection of oral cavity cancer. Secondary objective: evaluate for patient and treatment factors associated with readmission. METHODS: Retrospective, dual-institution cohort study of 2 tertiary care referral centers involving adult patients undergoing resection of oral cavity cancer with plans for same-day discharge. Consecutive sample of 77 patients included. Primary outcome was unplanned readmission to emergency room or inpatient stay in the 30 days following surgery. Comparison testing was used between return and non-return groups. RESULTS: Among 77 patients treated with outpatient surgery for oral cavity cancer, 19 (25%) returned to the hospital within 30 days. Among the reasons for return, 16 (80%) were directly related to surgery, and 4 (20%) were related to perioperative medical complications not directly related to a surgical site. Among the 25 patients also undergoing sentinel lymph node biopsy with their oral cavity resection, none returned to the hospital for neck-related complications. While most patients could be safely observed and discharged after return to the hospital, 8 patients (10%) required inpatient readmission. No significant differences between return and non-return groups were identified, although there was a trend toward shorter driving distance from hospital for the return group (47.6 miles vs. 69.5 miles, P = 0.097). CONCLUSION: Unplanned return to the hospital following outpatient oral cavity resection is prevalent and primarily driven by postoperative primary resection site concerns. Among patients selected for same day discharge, no definite population at highest risk of unplanned return was identified.

Tuning mobile phase properties to improve empty and full particle separation in adeno-associated virus productions by anion exchange chromatography.

In the past decade, recombinant adeno-associated virus (rAAV) has gained increased attention as a prominent gene therapy technology to treat monogenetic diseases. One of the challenges in rAAV production is the enrichment of full rAAV particles containing the gene of interest (GOI) payload. By adjusting the mobile phase properties of anion-exchange chromatography (AEX), it was demonstrated that empty and full separation of rAAV was improved in monolith based preparative AEX chromatography. When compared to the baseline method using NaCl, the use of tetraethylammonium acetate (TEA-Ac) in the AEX mobile phase resulted in enhanced resolution from 0.75 to 1.23 between "Empty" and "Full" peaks by salt linear gradient elution, as well as increased the percentage of full rAAV particles from 20% to 36% and genome recovery from 59% to 62%. Furthermore, a dual wash plus step elution AEX method was developed. Wherein, the first wash step harnesses TEA-Ac to separate empty and full capsids, which is followed by a second wash step that ensures no TEA-Ac salt is carried over into AEX eluate. The resulting optimized AEX purification method has the potential to be adapted for manufacturing and purification processes involving various rAAV production platforms that experience empty and full rAAV separation challenges.

Improved adeno-associated virus empty and full capsid separation using weak partitioning multi-column AEX chromatography.

Recombinant adeno-associated virus (rAAV) empty and full capsid separation has been a topic of interest in the rAAV gene therapy community for many years and the anion exchange chromatography (AEX) step has undergone various process optimizations to improve rAAV empty capsid separation, including AEX stationary phase, mobile phase, and process parameters. Here, we present a new AEX method that employs both weak partitioning chromatography (WPC) and multi-column chromatography (MCC) to achieve improved full rAAV percentage in the AEX pool. The WPC technology allows empty rAAV to be displaced by full rAAV during loading, while the MCC technology enables parallel column processing which further increases AEX step productivity. Our results show that, compared to baseline AEX batch chromatography, the AEX-WPC-MCC method demonstrated improvements in both AEX pool full rAAV percentage (∼ 20% increase) and rAAV genome recovery (∼ 20% increase). As a result, the productivity (full capsid generated per liter of AEX column per hour of processing time) of the AEX step increased by ∼34-fold from the baseline AEX batch run to the AEX-WPC-MCC run. It is foreseeable that this AEX-WPC-MCC method could find applications in large-scale rAAV manufacturing processes to improve AEX yield and reduce the cost of goods of rAAV manufacturing.

Guideline-compliant adjuvant chemotherapy for resected high risk oral cavity cancer: Homefield advantage.

PURPOSE: Factors that are associated with failure to receive guideline-compliant adjuvant chemotherapy after resection of high-risk oral cavity cancer are understudied. Here, we performed a retrospective cohort study of surgically treated patients with oral cavity squamous cell carcinoma to determine rates of guideline-compliant adjuvant chemotherapy and to examine patient factors associated with receiving guideline-compliant chemotherapy. STUDY DESIGN: Retrospective cohort. SETTING: Two tertiary care referral centers. METHODS: Patients with resected high-risk oral cavity squamous cell carcinoma and known adjuvant therapy details were included. Extranodal extension or positive margins were considered high-risk features for which adjuvant chemoradiation was indicated. Patient factors were examined to determine associations with receiving on-guidelines treatment. Univariable and multivariable logistic regression were used to determine significance of associations. RESULTS: 75 patients were included. 36 (48 %) patients received guideline-compliant cisplatin. In total, 39 (52 %) patients did not receive guideline-compliant chemotherapy. On multivariable analysis, meeting with a university medical oncologist was significantly associated with the receipt of guideline-compliant cisplatin (OR 6.38, 95 % CI 2.26-20.0, p < 0.001). CONCLUSION: Adherence to on-guidelines treatment can be difficult to achieve in patients with advanced stage head and neck cancer. Meeting with university medical oncology is associated with an increased chance of receiving guideline-compliant chemotherapy.

COVID-19 impact on facial trauma: Insights from Mississippi's only level 1 trauma center.

PURPOSE: Our primary aim was to understand and describe the impact of COVID-19 on the incidence and etiology of facial trauma in the state of Mississippi. METHODS: Retrospective review of facial trauma-related Emergency Department encounters in Mississippi from March 11, 2019 to March 10, 2021, divided into three time periods using the state of Mississippi's Governor's Office Executive Orders. Chi-square tests and segmented linear regressions were used for analysis. RESULTS: Patients presenting with facial trauma were typically male, 18-44 years old, and lived in urban zip codes. Insurance payors significantly differed across time periods. There were no significant differences in self-inflicted assault or accidental injury between the 3 time periods, with pre- and pandemic patients more likely to be self-pay while patients during recovery being more likely to have private insurance. During the pandemic, facial trauma from a family member, partner or spouse, or other person in the household significantly increased. CONCLUSION: Similar accidental facial trauma trends may reflect lower adherence to social distancing guidelines. The increase in facial trauma perpetrated by family members is consistent with reported increases in domestic violence during the pandemic. While overall facial trauma demographic patterns did not change significantly during the COVID-19 pandemic, there were notable changes in the etiology and insurance payor of facial trauma cases. LAY SUMMARY: The COVID-19 pandemic impacted healthcare systems worldwide, and our study seeks to understand how the pandemic affected incidence of facial trauma.

Enhancing effective healthcare communication in Australia and Aotearoa New Zealand: Considerations for research, teaching, policy, and practice.

Objective: In this article we present a conceptual framework for enhancing effective healthcare communication in Australia and Aotearoa New Zealand. Methods: Through an iterative, deliberative dialogue approach, we, as experts from a variety of health professions and academic disciplines, worked together to identify core values and considerations for healthcare communication across numerous health professions and disciplines and within research, teaching, policy, and practice contexts. Results: The framework developed includes five core values at its centre: equitable, inclusive, evidence-based, collaborative, reflective. Around this are concentric circles showing key elements of collaborators, modality, context, and purpose. Each of these is explored. Conclusion: This work may support benchmarking for healthcare providers, researchers, policymakers, and educators across a breadth of professions to help improve communication in clinical practice. The framework will also help to identify areas across disciplines that are shared and potentially idiosyncratic for various professions to promote interprofessional recognition, education, and collaboration. Innovation: This framework is designed to start conversations, to form the foundation of a dialogue about the priorities and key considerations for developing teaching curricula, professional development, and research programs related to healthcare communication, providing a set of values specifically for the unique contexts of Australia and Aotearoa New Zealand. It can also be used to guide interdisciplinary healthcare professionals in advancing research, teaching, policy, and practice related to healthcare communication.

Improving localization accuracy for non-invasive automated early left ventricular origin localization approach.

Background: We previously developed a non-invasive approach to localize the site of early left ventricular activation origin in real time using 12-lead ECG, and to project the predicted site onto a generic LV endocardial surface using the smallest angle between two vectors algorithm (SA). Objectives: To improve the localization accuracy of the non-invasive approach by utilizing the K-nearest neighbors algorithm (KNN) to reduce projection errors. Methods: Two datasets were used. Dataset #1 had 1012 LV endocardial pacing sites with known coordinates on the generic LV surface and corresponding ECGs, while dataset #2 included 25 clinically-identified VT exit sites and corresponding ECGs. The non-invasive approach used "population" regression coefficients to predict the target coordinates of a pacing site or VT exit site from the initial 120-m QRS integrals of the pacing site/VT ECG. The predicted site coordinates were then projected onto the generic LV surface using either the KNN or SA projection algorithm. Results: The non-invasive approach using the KNN had a significantly lower mean localization error than the SA in both dataset #1 (9.4 vs. 12.5 mm, p < 0.05) and dataset #2 (7.2 vs. 9.5 mm, p < 0.05). The bootstrap method with 1,000 trials confirmed that using KNN had significantly higher predictive accuracy than using the SA in the bootstrap assessment with the left-out sample (p < 0.05). Conclusion: The KNN significantly reduces the projection error and improves the localization accuracy of the non-invasive approach, which shows promise as a tool to identify the site of origin of ventricular arrhythmia in non-invasive clinical modalities.

Optimization of a 12-Lead Electrocardiography Subset for Automated Early Left Ventricular Activation Localization Approach Based on Pace-Mapping Technology.

BACKGROUND: We previously developed an automated approach based on pace mapping to localise early left ventricular (LV) activation origin. To avoid a singular system, we require pacing from at least 2 more known sites than the number of electrocardiography (ECG) leads used. Fewer leads used means fewer pacing sites required. We sought to identify an optimal minimal ECG lead set for the automated approach. METHODS: We used 1715 LV endocardial pacing sites to create derivation and testing data sets. The derivation data set, consisting of 1012 known pacing sites pooled from 38 patients, was used to identify an optimal 3-lead set by means of random forest regression (RFR), and a second 3-lead set by means of exhaustive search. The performance of these sets and the calculated Frank leads was compared within the testing data set with 703 pacing sites pooled from 25 patients. RESULTS: The RFR yielded III, V1, and V4, whereas the exhaustive search identified leads II, V2 and V6. Comparison of these sets and the calculated Frank leads demonstrated similar performance when using 5 or more known pacing sites. Accuracy improved with additional pacing sites, achieving mean accuracy of < 5 mm, after including up to 9 pacing sites when they were focused on a suspected area of ventricular activation origin (radius < 10 mm). CONCLUSIONS: The RFR identified the quasi-orthogonal leads set to localise the source of LV activation, minimizing the training set of pacing sites. Localization accuracy was high with the use of these leads and was not significantly different from using leads identified by exhaustive search or empiric use of Frank leads.

Controlling the Self-Assembly and Material Properties of ß-Sheet Peptide Hydrogels by Modulating Intermolecular Interactions.

Self-assembling peptides are a promising biomaterial with potential applications in medical devices and drug delivery. In the right combination of conditions, self-assembling peptides can form self-supporting hydrogels. Here, we describe how balancing attractive and repulsive intermolecular forces is critical for successful hydrogel formation. Electrostatic repulsion is tuned by altering the peptide's net charge, and intermolecular attractions are controlled through the degree of hydrogen bonding between specific amino acid residues. We find that an overall net peptide charge of +/-2 is optimal to facilitate the assembly of self-supporting hydrogels. If the net peptide charge is too low then dense aggregates form, while a high molecular charge inhibits the formation of larger structures. At a constant charge, altering the terminal amino acids from glutamine to serine decreases the degree of hydrogen bonding within the assembling network. This tunes the viscoelastic properties of the gel, reducing the elastic modulus by two to three orders of magnitude. Finally, hydrogels could be formed from glutamine-rich, highly charged peptides by mixing the peptides in combinations with a resultant net charge of +/-2. These results illustrate how understanding and controlling self-assembly mechanisms through modulating intermolecular interactions can be exploited to derive a range of structures with tuneable properties.

A systematic review on inequalities in accessing and using community-based social care in dementia.

OBJECTIVES: To evaluate and synthesize the evidence base on barriers and facilitators to accessing and using community-based social care in dementia. DESIGN: Mixed-methods systematic review. SETTING: Community-based social care (such as day care, respite care, paid home care, and peer support groups). PARTICIPANTS: People living with dementia and unpaid carers. MEASUREMENTS: Seven databases were searched in March 2022, including English and German evidence published from 2000 focusing on inequalities in community-based social care for dementia across the globe. Titles and abstracts were screened by two reviewers, with all full texts screened by two reviewers also. Study quality was assessed using QualSyst. RESULTS: From 3,904 screened records, 39 papers were included. The majority of studies were qualitative, with 23 countries represented. Barriers and facilitators could be categorized into the following five categories/themes: situational, psychological, interpersonal, structural, and cultural. Barriers were notably more prominent than facilitators and were multifaceted, with many factors hindering or facilitating access to social care linked together. CONCLUSIONS: People with dementia and carers experience significant barriers in accessing care in the community, and a varied approach on multiple levels is required to address systemic and individual-level barriers to enable more equitable access to care for all.

The Effectiveness of Online Mental Health First Aid Training in Community Rugby: A Mixed-Methods Approach.

Mental Health First Aid (MHFA) training exists to improve supportive behaviours towards peers, increase mental health literacy, and reduce stigma. Community sport clubs have potential to successfully deliver mental health programs. This study investigated the effectiveness of online MHFA training undertaken by members of the rugby community and evaluated the feasibility and usefulness of the online delivery mode and users' engagement with it. A mixed-methods approach was used to provide depth of understanding through qualitative analysis, combined with quantitative outcomes. Online surveys examining participants' knowledge and perceptions were administered pre- and post-MHFA training. Significant improvements (p < 0.05) across all assessed domains were observed post- compared to pre-MHFA training. A large effect size was identified in relation to advice giving and sign and symptom identification. A moderate effect size pre- to post-improvement was identified for users' perceptions of therapy's effectiveness, the ability of people with severe mental health conditions to recover, and benefit of a healthcare professional. Participants endorsed the MHFA program to improve mental health literacy, advance non-technical skills, and improve confidence. MHFA training can increase the awareness and knowledge of mental health issues in key individuals in community sport clubs and enable them to aid people with mental health concerns. Online MHFA training is associated with improved mental health literacy and may be a suitable and economically sustainable model for community sport.

Workplace sense of belonging and paramedic wellbeing using network analysis: A cross-sectional study.

BACKGROUND: Workplace sense of belonging is an important contributor to health and wellbeing. It may be even more important for paramedics to buffer against distress inherent in the workplace. To date, however, there has been no research on paramedic workplace sense of belonging and wellbeing. METHODS: Using network analysis, this study aimed to identify the dynamic relationships of workplace sense of belonging in paramedics with variables associated with wellbeing and ill-being-identity, coping self-efficacy and unhealthy coping. Participants were a convenience sample of 72 employed paramedics. RESULTS: The results showed workplace sense of belonging linked to other variables through distress, distinguishable by the relationship with unhealthy coping for wellbeing and ill-being. The relationships between identity (perfectionism and sense of self) as well as the relationship between perfectionism and unhealthy coping were stronger for those with ill-being than observed for those with wellbeing. CONCLUSIONS: These results identified the mechanisms by which the paramedicine workplace can contribute to distress and unhealthy coping strategies, which can lead to mental illnesses. They also highlight contributions of individual components of sense of belonging highlighting potential targets for interventions to reduce the risk of psychological distress and unhealthy coping amongst paramedics in the workplace.

Synchrotron radiation circular dichroism spectroscopy reveals that gold and silver nanoparticles modify the secondary structure of a lung surfactant protein B analogue.

Inhaled nanoparticles (NPs) depositing in the alveolar region of the lung interact initially with a surfactant layer and in vitro studies have demonstrated that NPs can adversely affect the biophysical function of model pulmonary surfactants (PS), of which surfactant protein B (SP-B) is a key component. Other studies have demonstrated the potential for NPs to modify the structure and function of proteins. It was therefore hypothesised that NPs may affect the biophysical function of PS by modifying the structure of SP-B. Synchrotron radiation circular dichroism (SRCD) spectroscopy was used to explore the effect of various concentrations of gold nanoparticles (AuNPs) (5, 10, 20 nm), silver nanoparticles (AgNPs) (10 nm) and silver citrate on the secondary structure of surfactant protein B analogue, SP-B1-25, in a TFE/PB dispersion. For Au and Ag NPs the SRCD spectra indicated a concentration dependent reduction in the α-helical structure of SP-B1-25 (5 nm AuNP ≈ 10 nm AgNP ≫ 10 nm AuNP > 20 nm AuNP). For AuNPs the effect was greater for the 5 nm size, which was not fully explained by consideration of surface area. The impact of the 10 nm AgNPs was greater than that of the 10 nm AuNPs and the effect of AgNPs was greater than that of silver citrate at equivalent Ag mass concentrations. For 10 nm AuNPs, SRCD spectra for dispersions in, the more physiologically relevant, DPPC showed a similar concentration dependent pattern. The results demonstrate the potential for inhaled NPs to modify SP-B1-25 structure and thus potentially adversely impact the physiological function of the lung, however, further studies are necessary to confirm this.

Interventions to address impostor phenomenon: a scoping review protocol.

OBJECTIVE: This scoping review will identify and map the literature on interventions to address impostor phenomenon. INTRODUCTION: Impostor phenomenon, also known as impostor syndrome, describes intense feelings of fraudulence and chronic self-doubt. The phenomenon has been associated with a range of psychological issues and has been linked to negative career outcomes. While research on the prevalence of impostor phenomenon and its associated comorbidities has been reported for over 40 years, there is a paucity of studies that describe interventions to address this phenomenon. INCLUSION CRITERIA: The review will consider any English-language study that describes or evaluates interventions to mitigate impostor phenomenon. Quantitative and qualitative studies will be sourced from published literature, gray literature, and the references of retrieved articles. Studies will not be limited by participant or setting. Authors of primary studies will be contacted to identify additional sources or for clarifications, where required. Conference abstracts, editorials, and opinion papers will be excluded. METHODS: Databases to be searched will include APA PsycNet, MEDLINE, Scopus, and Web of Science. All databases will be searched from inception till the present. Retrieved citations will be independently reviewed by the reviewers, and relevant studies will be extracted using a data extraction form developed for this review. The results will be presented in tabular format and accompanied by a narrative summary. The review will be conducted in accordance with the JBI guidelines for scoping reviews. DETAILS OF THIS REVIEW AVAILABLE AT: Open Science Framework osf.io/w7xg6.

Evaluation of the CARES Skills Framework as a Peer Support Model in the Paramedic Undergraduate Curriculum: Facilitating Challenging Discussions in a Safe Environment.

OBJECTIVE: Infant or child death is reported as being the most distressing type of case paramedics attend. Student paramedics also identify supporting bereaved families as an area associated with low confidence. This study evaluated the CARES skills framework (Connect to emotion, Attention training, Reflective listening, Empathy, Support help seeking) as a peer support model to encourage student paramedics to talk about grief and death related to infants and children. METHOD: A convenience sample of first-year paramedic students (target n = 154) was recruited from a single Australian regional university. A modified nominal group technique method was used following a student debriefing session designed to identify problems, generate solutions, and make decisions regarding the efficacy of the CARES skills framework. RESULTS: Of 154 eligible participants, 141 participated (92% response rate). Peer social support normalized students' emotions related to death and dying. Although naming emotions was challenging, students reported that the CARES model facilitated a safe environment to talk about death and dying. Students reported feeling heard and connected to their peers during the exercise and an enhanced sense of belonging after the exercise. CONCLUSIONS: Findings contribute to evidence that suggests the CARES model is a useful mechanism to enhance peer social support in paramedic students.

Differential Regulation of Prelimbic and Thalamic Transmission to the Basolateral Amygdala by Acetylcholine Receptors.

The amygdalar anterior basolateral nucleus (BLa) plays a vital role in emotional behaviors. This region receives dense cholinergic projections from basal forebrain which are critical in regulating neuronal activity in BLa. Cholinergic signaling in BLa has also been shown to modulate afferent glutamatergic inputs to this region. However, these studies, which have used cholinergic agonists or prolonged optogenetic stimulation of cholinergic fibers, may not reflect the effect of physiological acetylcholine release in the BLa. To better understand these effects of acetylcholine, we have used electrophysiology and optogenetics in male and female mouse brain slices to examine cholinergic regulation of afferent BLa input from cortex and midline thalamic nuclei. Phasic ACh release evoked by single pulse stimulation of cholinergic terminals had a biphasic effect on transmission at cortical input, producing rapid nicotinic receptor-mediated facilitation followed by slower mAChR-mediated depression. In contrast, at this same input, sustained ACh elevation through application of the cholinesterase inhibitor physostigmine suppressed glutamatergic transmission through mAChRs only. This suppression was not observed at midline thalamic nuclei inputs to BLa. In agreement with this pathway specificity, the mAChR agonist, muscarine more potently suppressed transmission at inputs from prelimbic cortex than thalamus. Muscarinic inhibition at prelimbic cortex input required presynaptic M4 mAChRs, while at thalamic input it depended on M3 mAChR-mediated stimulation of retrograde endocannabinoid signaling. Muscarinic inhibition at both pathways was frequency-dependent, allowing only high-frequency activity to pass. These findings demonstrate complex cholinergic regulation of afferent input to BLa that is pathway-specific and frequency-dependent.SIGNIFICANCE STATEMENT Cholinergic modulation of the basolateral amygdala regulates formation of emotional memories, but the underlying mechanisms are not well understood. Here, we show, using mouse brain slices, that ACh differentially regulates afferent transmission to the BLa from cortex and midline thalamic nuclei. Fast, phasic ACh release from a single optical stimulation biphasically regulates glutamatergic transmission at cortical inputs through nicotinic and muscarinic receptors, suggesting that cholinergic neuromodulation can serve precise, computational roles in the BLa. In contrast, sustained ACh elevation regulates cortical input through muscarinic receptors only. This muscarinic regulation is pathway-specific with cortical input inhibited more strongly than midline thalamic nuclei input. Specific targeting of these cholinergic receptors may thus provide a therapeutic strategy to bias amygdalar processing and regulate emotional memory.

Mental Health First Aid training for paramedic students: An evaluation study.

BACKGROUND: The combination of first-year placements, an increasing proportion of mental health callouts, and the high incidence of mental illness in health-professional tertiary students means standard curricula may not adequately prepare early-year paramedic students for mental health challenges. METHODS: A retrospective online survey was used to explore the experiences of paramedic students who have completed Mental Health First Aid (MHFA) training within their undergraduate studies. The content-validated survey explored the relevance, appropriateness, and novelty of MHFA training, and invited participants to reflect on the course strengths and weaknesses. RESULTS: The majority of 102 respondents, predominantly female first- and second-year paramedic students aged 18-24 years, agreed the content was relevant (86%) and appropriate (88%), with 73% agreeing they would recommend to other university students. Thematic analysis identified strengths of the course as perceived increases in mental health literacy and empowerment to act on mental health concerns. A weakness was students perceived the course did not prepare them adequately for clinical practice. CONCLUSION: The inclusion of MHFA early in paramedic curricula is appropriate and relevant, increasing mental health literacy and empowering students to recognise and act upon mental health concerns. Application of practical scenarios may further enhance student learning experiences.