Experiences of Living With the Nonmotor Symptoms of Parkinson's Disease: A Photovoice Study.

BACKGROUND: Nonmotor symptoms (NMSs) are frequently experienced by people with Parkinson's disease (PD) and are often perceived as their most bothersome symptoms. However, these remain poorly understood with suboptimal clinical management. These unmet needs are an important determinant of health-related quality of life (QoL) in PD. OBJECTIVE: The aim of this study was to gain insights into the experience of living with the NMS of PD in real-time using participatory action methodology. METHOD: Using the photovoice method, 14 people with PD took photographs to document their experiences of living with the NMS of PD. They composed corresponding written narratives to capture the impact of NMS on their daily activities and QoL. In total, 152 photographs and corresponding narratives were analysed using thematic analysis with an inductive approach. RESULTS: Four interrelated themes were identified. Emotional well-being and sense of self encompassed a process of adjustment to living with PD. Engaging in valued activities, adopting a positive mindset and utilising coping strategies were thought to enhance confidence and self-esteem. Social support and societal awareness highlighted the importance of supportive relationships and socialising to aid participation and avoid isolation. Barriers to social engagement included the unpredictability of NMS and nonvisible NMS being neglected or misunderstood. CONCLUSION: Findings demonstrated the far-reaching impact of nonmotor aspects of PD on emotional, occupational and social dimensions. These needs could be addressed through person-centred and comprehensive approaches to care. PATIENT OR PUBLIC CONTRIBUTION: This study utilised a participatory research approach allowing participants to choose the subjects that mattered to them and how to present their results. Additionally, a group workshop was held with people with PD, their family members and healthcare professionals to guide theme development.

A systematic review of vestibular stimulation in post-stroke visual neglect.

Unilateral visual neglect is a condition that negatively impacts the lives of many stroke survivors. Studies have investigated different forms of vestibular stimulation as a potential therapy, but evidence is yet to be systematically reviewed. We therefore reviewed the effects of vestibular stimulation on outcomes of neglect and activities of daily living (ADL) for people with visual neglect. We searched relevant databases up until September 2022. Eligible articles included any form of vestibular stimulation, study design, or control condition. Included participants were 18 years or older, presenting with neglect following a haemorrhagic or ischaemic stroke. Relevant outcomes were clinically validated measures of neglect and ADL. Cochrane risk of bias tools were used to assess study quality. Meta-analyses and narrative methods were used to synthesize the data. Our search returned 17 relevant studies comprising 180 participants. Meta-analyses showed no difference between galvanic vestibular stimulation and sham conditions on outcomes, whereas caloric vestibular stimulation led to improvement compared to pre-stimulation scores. Narrative syntheses showed mixed results. Clinical and methodological heterogeneity was found both within and between studies. Overall, results were inconsistent regarding the effects of vestibular stimulation as a treatment for neglect. Further trials are warranted but require more careful methodological planning.

Framework for an interprofessional experience addressing health and disability for health professional students.

BACKGROUND AND PURPOSE: A Health and Disabilities Interprofessional Education (IPE) course was implemented to join three healthcare disciplines together to collaboratively plan, implement, and reflect on professional roles and responsibilities. The goal and purpose of this course was to create an advancement of interprofessional education and practice within health science professions early in their students' programs utilizing innovative teaching methods working directly with individuals with disabilities. EDUCATIONAL ACTIVITY AND SETTING: 72 students were assigned to interprofessional teams of 10-11 people. Through asynchronous and synchronous learning activities, student teams worked together to plan and conduct community-based client interviews. FINDINGS: Quantitative and qualitative evaluation methods were used to explore the impact of interprofessional experiential learning experiences. Qualitative data showed a greater awareness and understanding of the different roles and responsibilities in interprofessional teams as well as a greater appreciation for the value of interacting with persons with disabilities (PWD) during their training. Quantitative data showed a significant change in students' understanding of their roles and responsibilities as a member of an interprofessional team, their confidence with working with PWD in a future healthcare capacity, as well as their understanding of how the social determinants of health may influence the healthcare experience of a PWD. SUMMARY: Interprofessional education and experiential learning opportunities are good ways to facilitate "real" patient care experiences and team roles and responsibilities. This enables healthcare students to practice communication, build relationships, and understand the lived experience of their patients.

Cognition in vestibular disorders: state of the field, challenges, and priorities for the future.

Vestibular disorders are prevalent and debilitating conditions of the inner ear and brain which affect balance, coordination, and the integration of multisensory inputs. A growing body of research has linked vestibular disorders to cognitive problems, most notably attention, visuospatial perception, spatial memory, and executive function. However, the mechanistic bases of these cognitive sequelae remain poorly defined, and there is a gap between our theoretical understanding of vestibular cognitive dysfunction, and how best to identify and manage this within clinical practice. This article takes stock of these shortcomings and provides recommendations and priorities for healthcare professionals who assess and treat vestibular disorders, and for researchers developing cognitive models and rehabilitation interventions. We highlight the importance of multidisciplinary collaboration for developing and evaluating clinically relevant theoretical models of vestibular cognition, to advance research and treatment.

Engineered In Vitro Tumor Model Recapitulates Molecular Signatures of Invasion in Glioblastoma.

Glioblastoma stem cells (GSCs) play an important role in the invasive nature of glioblastoma (GBM); yet, the mechanisms driving this behavior are poorly understood. To recapitulate tumor invasion in vitro, we developed a GBM tumor-mimetic hydrogel using extracellular matrix components upregulated in patients. We show that our hydrogel facilitates the infiltration of a subset of patient-derived GSCs, differentiating samples based on phenotypic invasion. Invasive GSCs are enriched for injury-responsive pathways while noninvasive GSCs are enriched for developmental pathways, reflecting established GSC stratifications. Using small molecule inhibitors, we demonstrate that the suppression of matrix metalloprotease and rho-associated protein kinase processes results in a significant reduction of cell invasion into the hydrogel, reflecting mesenchymal- and amoeboid-dependent mechanisms. Similar reduction in cell invasion was observed by siRNA knockdown of ITGB1 and FAK focal adhesion pathways. We elucidate the transcriptomic profile of cells invading in the hydrogel by performing bulk RNA sequencing of cells cultured in the hydrogel and compare these to cells cultured in conventional tissue culture polystyrene (TCP). In our 3D hydrogel cultures, invasion-related molecular signatures along with proliferation and injury response pathways are upregulated while development processes are downregulated compared to culture on 2D TCP. With this validated in vitro model, we establish a valuable tool to find therapeutic intervention strategies against cellular invasion in glioblastoma.

Impact and experiences of vestibular disorders and psychological distress: Qualitative findings from patients, family members and healthcare professionals.

INTRODUCTION: People with vestibular disorders frequently experience reduced quality of life and challenges with activities of daily living. Anxiety, depression and cognitive problems often co-present with vestibular disorders and can aggravate symptoms and prolong clinical recovery. We aimed to gain in-depth insights into the impact of vestibular disorders and the contribution of psychological factors by exploring multistakeholder perspectives. METHODS: Semistructured interviews were conducted between October 2021 and March 2022 with 47 participants in the United Kingdom including: 20 patients (age M = 50.45 ± 13.75; 15 females), nine family members (age M = 61.0 ± 14.10; four females), and 18 healthcare professionals. Data were analysed using framework analysis. RESULTS: Vestibular disorders impact diverse aspects of patients' lives including work, household chores, socialising, and relationships with family and friends. Being unable to engage in valued activities or fulfil social roles contributes to feelings of grief and frustration, affecting identity, confidence, and autonomy. Anxiety and low mood contribute to negative thought processes, avoidance, and social withdrawal, which can impede clinical recovery through reduced activity levels, and end engagement with treatment. Coping strategies were thought to help empower patients to self-manage their symptoms and regain a sense of control, but these require oversight from healthcare providers. CONCLUSIONS: Daily activity limitations, social participation restrictions, and psychological distress can interact to impact quality of life, sense of self, and clinical recovery amongst people with vestibular disorders. Information and resources could aid societal awareness of the impact of vestibular disorders and help patients and families feel understood. An individualised and comprehensive approach that concurrently addresses mental, physical, social, and occupational needs is likely to be beneficial. PATIENT OR PUBLIC CONTRIBUTION: Two group meetings were held at the beginning and end of the study with a patient and public involvement network formed of people with vestibular disorders and family members. These individuals commented on the study aims, interview schedule, participant recruitment practices, and interpretation of the themes identified. Two core patient members were involved at all stages of the research. These individuals contributed to the formulation of the interview schedule, development and application of the coding scheme, development and interpretation of themes, and preparation of the final manuscript.

Experiential Interprofessional Education Rooted in the Social Determinants of Health and Ecological Model Fosters Interprofessional Socialization.

OBJECTIVE: Experiential interprofessional education (IPE) fostering socialization to interprofessional teams is essential to clinical practice. Inclusion of authentic patient voices cultivates an understanding of social factors that patients face. We qualitatively assessed how experiential IPE framed around social determinants of health (SDH) and socioecological model (SEM) influenced early health profession students' development of interprofessional socialization while working with patients. Secondarily, we explored how students shifted their mindsets for future interactions. METHODS: Fifty-one health profession students participated in the Longitudinal Interprofessional Family-based Experience (LIFE), a virtual, 13-week experiential IPE opportunity during which students interacted with patients living with chronic illnesses through two interviews. Prompts representing aspects of working on an interprofessional team while interacting with a patient framed around social factors affecting healthcare were coded using the constant comparative method of analysis. Themes were derived and tallied for frequencies. RESULTS: Themes from prompt related to working with an interprofessional team included: 1) perspectives, 2) informative, and 3) collaboration. Themes related to patients as a team member included: 1) active listening, 2) patients of similar/dissimilar back¬grounds, 3) person-centered care, and 4) awareness. Themes derived from prompt about future collaborations included: 1) collaboration, 2) awareness, and 3) person-centered care. CONCLUSIONS: This SDH-focused experiential IPE advanced the understanding among early learners of how social factors that patients experience are barriers to how care is delivered and interprofessional teams must collaborate to consider factors to support patients.

Tissue-Engineered Disease Modeling of Lymphangioleiomyomatosis Exposes a Therapeutic Vulnerability to HDAC Inhibition.

Lymphangioleiomyomatosis (LAM) is a rare disease involving cystic lung destruction by invasive LAM cells. These cells harbor loss-of-function mutations in TSC2, conferring hyperactive mTORC1 signaling. Here, tissue engineering tools are employed to model LAM and identify new therapeutic candidates. Biomimetic hydrogel culture of LAM cells is found to recapitulate the molecular and phenotypic characteristics of human disease more faithfully than culture on plastic. A 3D drug screen is conducted, identifying histone deacetylase (HDAC) inhibitors as anti-invasive agents that are also selectively cytotoxic toward TSC2-/- cells. The anti-invasive effects of HDAC inhibitors are independent of genotype, while selective cell death is mTORC1-dependent and mediated by apoptosis. Genotype-selective cytotoxicity is seen exclusively in hydrogel culture due to potentiated differential mTORC1 signaling, a feature that is abrogated in cell culture on plastic. Importantly, HDAC inhibitors block invasion and selectively eradicate LAM cells in vivo in zebrafish xenografts. These findings demonstrate that tissue-engineered disease modeling exposes a physiologically relevant therapeutic vulnerability that would be otherwise missed by conventional culture on plastic. This work substantiates HDAC inhibitors as possible therapeutic candidates for the treatment of patients with LAM and requires further study.

The GBA variant E326K is associated with alpha-synuclein aggregation and lipid droplet accumulation in human cell lines.

Sequence variants or mutations in the GBA gene are numerically the most important risk factor for Parkinson disease (PD). The GBA gene encodes for the lysosomal hydrolase enzyme, glucocerebrosidase (GCase). GBA mutations often reduce GCase activity and lead to the impairment of the autophagy-lysosomal pathway, which is important in the turnover of alpha-synuclein, accumulation of which is a key pathological hallmark of PD. Although the E326K variant is one of the most common GBA variants associated with PD, there is limited understanding of its biochemical effects. We have characterized homozygous and heterozygous E326K variants in human fibroblasts. We found that E326K variants did not cause a significant loss of GCase protein or activity, endoplasmic reticulum (ER) retention or ER stress, in contrast to the L444P GBA mutation. This was confirmed in human dopaminergic SH-SY5Y neuroblastoma cell lines overexpressing GCase with either E326K or L444P protein. Despite no loss of the GCase activity, a significant increase in insoluble alpha-synuclein aggregates in E326K and L444P mutants was observed. Notably, SH-SY5Y overexpressing E326K demonstrated a significant increase in the lipid droplet number under basal conditions, which was exacerbated following treatment with the fatty acid oleic acid. Similarly, a significant increase in lipid droplet formation following lipid loading was observed in heterozygous and homozygous E326K fibroblasts. In conclusion, the work presented here demonstrates that the E326K mutation behaves differently to the common loss of function GBA mutations; however, lipid dyshomeostasis and alpha-synuclein pathology are still evident.

Working Memory Impairment in Transient Ischaemic Attack: N-back as a Sensitive Measure for Detection.

BACKGROUND: Transient ischaemic attack (TIA) can lead to lasting changes in brain structure and function resulting in cognitive impairment. Cognitive screening tools may lack sensitivity for detecting cognitive impairments, particularly executive function, which tends to be the earliest affected domain in vascular cognitive impairment. AIM: In this preliminary study, we examine a working memory (WMem) task as a sensitive measure of cognitive impairment in TIA. METHOD: Patients referred to a TIA clinic for transient neurological symptoms completed a general cognitive screening tool (Montreal Cognitive Assessment; MoCA), and a WMem task (2-N-back) in a cross-sectional design. RESULTS: TIA patients (n = 12) showed significantly reduced WMem performance on the N-back compared to patients diagnosed with mimic clinical conditions with overlapping symptoms (n = 16). No group differences were observed on the MoCA. CONCLUSIONS: Assessing WMem may provide a sensitive measure of cognitive impairment after TIA, with implications for cognitive screening in TIA services to triage patients for further neuropsychological support, or for interventions to prevent vascular dementia.

Genetic variations in GBA1 and LRRK2 genes: Biochemical and clinical consequences in Parkinson disease.

Variants in the GBA1 and LRRK2 genes are the most common genetic risk factors associated with Parkinson disease (PD). Both genes are associated with lysosomal and autophagic pathways, with the GBA1 gene encoding for the lysosomal enzyme, glucocerebrosidase (GCase) and the LRRK2 gene encoding for the leucine-rich repeat kinase 2 enzyme. GBA1-associated PD is characterized by earlier age at onset and more severe non-motor symptoms compared to sporadic PD. Mutations in the GBA1 gene can be stratified into severe, mild and risk variants depending on the clinical presentation of disease. Both a loss- and gain- of function hypothesis has been proposed for GBA1 variants and the functional consequences associated with each variant is often linked to mutation severity. On the other hand, LRRK2-associated PD is similar to sporadic PD, but with a more benign disease course. Mutations in the LRRK2 gene occur in several structural domains and affect phosphorylation of GTPases. Biochemical studies suggest a possible convergence of GBA1 and LRRK2 pathways, with double mutant carriers showing a milder phenotype compared to GBA1-associated PD. This review compares GBA1 and LRRK2-associated PD, and highlights possible genotype-phenotype associations for GBA1 and LRRK2 separately, based on biochemical consequences of single variants.

Natural variations in AAVHSC16 significantly reduce liver tropism and maintain broad distribution to periphery and CNS.

Adeno-associated viruses derived from human hematopoietic stem cells (AAVHSCs) are naturally occurring AAVs. Fifteen AAVHSCs have demonstrated broad biodistribution while displaying differences in transduction. We examine the structure-function relationships of these natural amino acid variations on cellular binding. We demonstrate that AAVHSC16 is the only AAVHSC that does not preferentially bind to terminal galactose. AAVHSC16 contains two unique amino acids, 501I and 706C, compared with other AAVHSCs. Through mutagenesis, we determined that residue 501 contributes to the lack of galactose binding. Structural analysis revealed that residue 501 is in proximity to the galactose binding pocket, hence confirming its functional role in galactose binding. Biodistribution analysis of AAVHSC16 indicated significantly less liver tropism in mice and non-human primates compared with other clade F members, likely associated with overall binding differences observed in vitro. AAVHSC16 maintained robust tropism to other key tissues in the peripheral and central nervous systems after intravenous injection, including to the brain, heart, and gastrocnemius. Importantly, AAVHSC16 did not induce elevated liver enzyme levels in non-human primates after intravenous injection at high doses. The unique glycan binding and tropism of AAVHSC16 makes this naturally occurring capsid an attractive candidate for therapies requiring less liver tropism while maintaining broad biodistribution.

Priming with biocides: A pathway to antibiotic resistance?

AIMS: To investigate the priming effects of sub-inhibitory concentrations of biocides on antibiotic resistance in bacteria. METHODS AND RESULTS: Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus were exposed to sub-inhibitory concentrations of biocides via a gradient plate method. Minimum inhibitory concentration (MIC) and antibiotic susceptibility were determined, and efflux pump inhibitors (thioridazine and chlorpromazine) were used to investigate antibiotic resistance mechanism(s). Escherichia coli displayed a twofold increase in MIC (32-64 mg l-1 ) to H2 O2 which was stable after 15 passages, but lost after 6 weeks, and P. aeruginosa displayed a twofold increase in MIC (64-128 mg l-1 ) to BZK which was also stable for 15 passages. There were no other tolerances observed to biocides in E. coli, P. aeruginosa or S. aureus; however, stable cross-resistance to antibiotics was observed in the absence of a stable increased tolerance to biocides. Sixfold increases in MIC to cephalothin and fourfold to ceftriaxone and ampicillin were observed in hydrogen peroxide primed E. coli. Chlorhexidine primed S. aureus showed a fourfold increase in MIC to oxacillin, and glutaraldehyde-primed P. aeruginosa showed fourfold (sulphatriad) and eightfold (ciprofloxacin) increases in MIC. Thioridazine increased the susceptibility of E. coli to cephalothin and cefoxitin by fourfold and twofold, respectively, and both thioridazine and chlorpromazine increased the susceptibility S. aureus to oxacillin by eightfold and fourfold, respectively. CONCLUSIONS: These findings demonstrate that sub-inhibitory concentrations of biocides can prime bacteria to become resistant to antibiotics even in the absence of stable biocide tolerance and suggests activation of efflux mechanisms may be a contributory factor. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the effects of low-level exposure of biocides (priming) on antibiotic resistance even in the absence of obvious increased biocidal tolerance.

A passive and objective measure of recognition memory in Alzheimer's disease using Fastball memory assessment.

Earlier diagnosis of Alzheimer's disease requires biomarkers sensitive to associated structural and functional changes. While considerable progress has been made in the development of structural biomarkers, functional biomarkers of early cognitive change, unconfounded by effort, practice and level of education, are still needed. We present Fastball, a new EEG method for the passive and objective measurement of recognition memory, that requires no behavioural memory response or comprehension of the task . Younger adults, older adults and Alzheimer's disease patients (n = 20 per group) completed the Fastball task, lasting just under 3 min. Participants passively viewed rapidly presented images and EEG assessed their automatic ability to differentiate between images based on previous exposure, i.e. old/new. Participants were not instructed to attend to previously seen images and provided no behavioural response. Following the Fastball task, participants completed a two-alternative forced choice (2AFC) task to measure their explicit behavioural recognition of previously seen stimuli. Fastball EEG detected significantly impaired recognition memory in Alzheimer's disease compared to healthy older adults (P < 0.001, Cohen's d = 1.52), whereas behavioural recognition was not significantly different between Alzheimer's disease and healthy older adults. Alzheimer's disease patients could be discriminated with high accuracy from healthy older adult controls using the Fastball measure of recognition memory (AUC = 0.86, P < 0.001), whereas discrimination performance was poor using behavioural 2AFC accuracy (AUC = 0.63, P = 0.148). There were no significant effects of healthy ageing, with older and younger adult controls performing equivalently in both the Fastball task and behavioural 2AFC task. Early diagnosis of Alzheimer's disease offers potential for early treatment when quality of life and independence can be retained through disease modification and cognitive enhancement. Fastball provides an alternative way of testing recognition responses that holds promise as a functional marker of disease pathology in stages where behavioural performance deficits are not yet evident. It is passive, non-invasive, quick to administer and uses cheap, scalable EEG technology. Fastball provides a new powerful method for the assessment of cognition in dementia and opens a new door in the development of early diagnosis tools.

A Framework and Recommendations to Recruit and Engage Faculty Facilitators for Large-Scale IPE Events.

AIMS: As integration of interprofessional education (IPE) events gains traction in health sciences, there is an increased need to recruit and train faculty to facilitate student groups from multiple health care disciplines. This report describes a framework used to effectively recruit and prepare faculty as facilitators for a large-scale, one-time IPE event. We detail recruitment strategies, training tools, facilitators' perceptions about the training, and recommendations for future training. PROCEDURES: Faculty were recruited via email to facilitate an IPE student group of 8-10 learners for an in-person, one-time event. Before the event, faculty facilitators received a Welcome Video and Guidebook providing a description of their role, best practices of facilitation, and scripts. On the event day, facilitators engaged in a face-to-face session to familiarize themselves with the Guidebook and best practices. After the event, facilitators received an email to thank them and invite their participation in a survey regarding perceptions of the training. Data were collected on 2018 and 2019 facilitators. Descriptive statistics were calculated for Likert scales or agreement survey items, and thematic analysis was completed for open-ended questions. RESULTS: Over two offerings of the event, 235 faculty facilitators across 10 academic units participated in 2018 and 2019. Most facilitators felt prepared (92.5% average across 2018 and 2019), the Guidebook was helpful (91%), and an increased interest in IPE (78.5%). Written responses indicated engaging diverse students as the main challenge. Fifty-three percent of facilitators in 2019 were newly recruited. CONCLUSIONS: This work demonstrates an effective training program with a hybrid self-directed and in-person approach that adequately prepares faculty to facilitate IPE discussions. Inclusion of academic unit leaders for recruiting and acknowledging faculty facilitation may add value to the IPE event.

Single-cell chromatin accessibility profiling of glioblastoma identifies an invasive cancer stem cell population associated with lower survival.

Chromatin accessibility discriminates stem from mature cell populations, enabling the identification of primitive stem-like cells in primary tumors, such as glioblastoma (GBM) where self-renewing cells driving cancer progression and recurrence are prime targets for therapeutic intervention. We show, using single-cell chromatin accessibility, that primary human GBMs harbor a heterogeneous self-renewing population whose diversity is captured in patient-derived glioblastoma stem cells (GSCs). In-depth characterization of chromatin accessibility in GSCs identifies three GSC states: Reactive, Constructive, and Invasive, each governed by uniquely essential transcription factors and present within GBMs in varying proportions. Orthotopic xenografts reveal that GSC states associate with survival, and identify an invasive GSC signature predictive of low patient survival, in line with the higher invasive properties of Invasive state GSCs compared to Reactive and Constructive GSCs as shown by in vitro and in vivo assays. Our chromatin-driven characterization of GSC states improves prognostic precision and identifies dependencies to guide combination therapies.

Attenuated diphtheria toxin mediates siRNA delivery.

Toxins efficiently deliver cargo to cells by binding to cell surface ligands, initiating endocytosis, and escaping the endolysosomal pathway into the cytoplasm. We took advantage of this delivery pathway by conjugating an attenuated diphtheria toxin to siRNA, thereby achieving gene downregulation in patient-derived glioblastoma cells. We delivered siRNA against integrin-ß1 (ITGB1)-a gene that promotes invasion and metastasis-and siRNA against eukaryotic translation initiation factor 3 subunit b (eIF-3b)-a survival gene. We demonstrated mRNA downregulation of both genes and the corresponding functional outcomes: knockdown of ITGB1 led to a significant inhibition of invasion, shown with an innovative 3D hydrogel model; and knockdown of eIF-3b resulted in significant cell death. This is the first example of diphtheria toxin being used to deliver siRNAs, and the first time a toxin-based siRNA delivery strategy has been shown to induce relevant genotypic and phenotypic effects in cancer cells.

From formulation to in vivo model: A comprehensive study of a synergistic relationship between vancomycin, carvacrol, and cuminaldehyde against Enterococcus faecium.

Vancomycin-resistant Enterococcus faecium (VRE) has become endemic in healthcare settings, reducing treatment options for enterococcal infections. New antimicrobials for VRE infections are a high priority, but the development of novel antibiotics is time-consuming and expensive. Essential oils (EOs) synergistically enhance the activity of some existing antibiotics, suggesting that EO-antibiotic combinations could resensitise resistant bacteria and maintain the antibiotic repertoire. The mechanism of resensitisation of bacteria to antibiotics by EOs is relatively understudied. Here, the synergistic interactions between carvacrol (1.98 mM) and cuminaldehyde (4.20 mM) were shown to reestablish susceptibility to vancomycin (0.031 mg/L) in VRE, resulting in bactericidal activity (4.73 log10 CFU/ml reduction). Gene expression profiling, coupled with ß-galactosidase leakage and salt tolerance assays, suggested that cell envelope damage contributes to the synergistic bactericidal effect against VRE. The EO-vancomycin combination was also shown to kill clinical isolates of VRE (2.33-5.25 log10 CFU/ml reduction), and stable resistance did not appear to develop even after multiple passages. The in vivo efficacy of the EO-vancomycin combination was tested in a Galleria mellonella larvae assay; however, no antimicrobial action was observed, indicating that further drug development is required for the EO-vancomycin combination to be clinically useful for treatment of VRE infections.

A rapid, neural measure of implicit recognition memory using fast periodic visual stimulation.

Fast periodic visual stimulation (FPVS) has recently emerged as a powerful new tool in cognitive neuroscience. Capable of measuring a range of cognitive functions in single subjects in just minutes of recording time, it has been adapted to measure visual, semantic and linguistic processing. We present a new adaptation of the FPVS approach to measure recognition memory via old/new contrasts. Twenty one subjects (23 (±6) yrs, 7 males) completed an FPVS-oddball paradigm that assessed their spontaneous ability to differentiate between rapidly presented images on the basis of a pre-FPVS encoding task, i.e. oddball stimuli were only defined by the subject's experimentally induced memory of them. A clear oddball detection response reflecting recognition memory was observed within one minute of EEG recording time, simply through the passive viewing of stimuli, i.e. subjects received no task instructions and provided no behavioural response. Performance on a subsequent behavioural recognition task showed high levels of recognition of the oddball stimuli. As such, the FPVS approach returned an objective, non-verbal measure of recognition memory in just one minute of recording time, free from the confounds of behavioural recognition tasks. This finding reinforces the adaptability of the FPVS approach for the examination of higher-level cognition and provides a new method for the neural measurement of recognition memory.

Large-Scale Asynchronous Online Interprofessional Learning Experience.

AIMS: As interprofessional education (IPE) grows, more health professions programs have begun promoting it in their accreditation standards. A frequent challenge of large universities is how to include the large set of diverse students in their foundational offerings. A potential way would be to implement an online IPE asynchronous experience with an optional synchronous discussion. The purpose of this study was to: 1) describe implementation of that approach at a large multi-campus university; 2) explore the associations between IPE activities and students' reported level of usefulness; and 3) provide recommendations for online IPE experiences. METHODS: An IPE Module was developed that had 4 sequential online learning activities. After finishing the module, participants completed a self-administered questionnaire that included questions about demographics, retrospective pre and post assessment of key IPE concepts, and rating of the usefulness of the learning based on the module activities. RESULTS: 1,017 participants, representing 8 different health professional programs, completed the survey. The numbers of students were evenly distributed, with dentistry representing the highest number (21%), and most participants were first-year students (71.9%). The learning activities "reading posts/messages of colleagues from other professions" and "watching the video" were reported useful or very useful by 77.4% and 71.4% of participants, respectively. The self-reflection writing activity (67.1%) and the "6-word message" (59.4%) were rated as useful or very useful by over half of participants. DISCUSSION: Most participants reported that the learning activities in the online asynchronous IPE module were useful or very useful in achieving the learning objectives. Thus, an introductory experience based on an online program combining both asynchronous and decentralized optional synchronous instruction might be a viable method of delivering foundational IPE information.