Human cell surface-AAV interactomes identify LRP6 as blood-brain barrier transcytosis receptor and immune cytokine IL3 as AAV9 binder.

Adeno-associated viruses (AAVs) are foundational gene delivery tools for basic science and clinical therapeutics. However, lack of mechanistic insight, especially for engineered vectors created by directed evolution, can hamper their application. Here, we adapt an unbiased human cell microarray platform to determine the extracellular and cell surface interactomes of natural and engineered AAVs. We identify a naturally-evolved and serotype-specific interaction between the AAV9 capsid and human interleukin 3 (IL3), with possible roles in host immune modulation, as well as lab-evolved low-density lipoprotein receptor-related protein 6 (LRP6) interactions specific to engineered capsids with enhanced blood-brain barrier crossing in non-human primates after intravenous administration. The unbiased cell microarray screening approach also allows us to identify off-target tissue binding interactions of engineered brain-enriched AAV capsids that may inform vectors' peripheral organ tropism and side effects. Our cryo-electron tomography and AlphaFold modeling of capsid-interactor complexes reveal LRP6 and IL3 binding sites. These results allow confident application of engineered AAVs in diverse organisms and unlock future target-informed engineering of improved viral and non-viral vectors for non-invasive therapeutic delivery to the brain.

Financial investment of United States pharmacy schools on international activities.

INTRODUCTION: The primary objective of this study was to determine the financial resources that United States (US) pharmacy schools spend and receive for international activities, as well as the future direction of expenditures and revenue. METHODS: An online survey was sent in April 2019 to the chief financial or administrative officer at each accredited pharmacy school (N = 141) to ask about average annual budget for international activities and areas of expenditure (student travel, partnership development, faculty salary, staff salary, training programs) and revenue (dean's office, university, student tuition and fees, alumni, grants and contracts, other) associated with their budget. Participants were asked whether they anticipated spending or receiving more, the same, or less on the aforementioned expenditure and revenue areas. RESULTS: Sixty-three programs (45%) responded, with 61 (43%) complete responses used for data analysis. Thirty-eight schools (62%) had an annual budget for international activities with an average of $77,327, a median of $18,750, and a range from $2000 to $615,000. Public schools averaged $102,129 compared to $43,225 for private schools. The largest expenditure source was split evenly between student travel and faculty salaries while the largest revenue source was student tuition and fees. The most common response for future trends was to spend or receive the same amount of support. CONCLUSIONS: There is wide variance regarding the amount each US pharmacy school spends on international activities, with most programs anticipating spending or receiving the same amount in the future.

Becoming 'ward smart' medical students.

BACKGROUND: A small number of medical students elect to work as health care assistants (HCAs) during or prior to their undergraduate training. There is a significant body of evidence in the literature regarding the impact of HCA experience on student nurses; however, little research has examined the effects of such experience on medical students. METHODS: All fourth-year medical students with self-declared experience as HCAs from a single UK medical school were invited to participate in focus groups to explore their experiences and perceptions. Ten students from the year group took part. RESULTS: Participants felt that their experience as HCAs enhanced their learning in the workplace through becoming 'ward smart', helping them to become socialised into the world of health care, providing early meaningful and humanised patient interaction, and increasing their understanding of multidisciplinary team (MDT) members' roles. Little research has examined the effects of [HCA] experience on medical students DISCUSSION: Becoming 'ward smart' and developing a sense of belonging are central to maximising learning in, from and through work on the ward. Experience as a HCA provides a range of learning and social opportunities for medical students, and legitimises their participation within clinical communities. HCA experience also seems to benefit in the 'hard to reach' dimensions of medical training: empathy; humanisation of patient care; professional socialisation; and providing a sense of belonging within health care environments.

Consultation via telemedicine and access to operative care for patients with head and neck cancer in a Veterans Health Administration population.

BACKGROUND: The purpose of this study was to evaluate a telemedicine model that utilizes an audiovisual teleconference as a preoperative visit. METHODS: Veterans Health Administration (VHA) patients with head and neck cancer at 2 remote locations were provided access to the Palo Alto Veterans Affairs (PAVA) Health Care System otolaryngology department via the telemedicine protocol: tissue diagnosis and imaging at the patient site; data review at PAVA; and a preoperative teleconference connecting the patient to PAVA. Operative care occurred at PAVA. Follow-up care was provided remotely via teleconference. RESULTS: Fifteen patients were evaluated. Eleven underwent surgery, 4 with high-grade neoplasms (carcinoma). Average time from referral to operation was 28 days (range, 17-36 days) and 72 (range, 31-108 days), respectively, for high-grade and low-grade groups. The average patient was spared 28 hours traveling time and $900/patient was saved on travel-related costs. CONCLUSION: A telemedicine model enables timely access to surgical care and permits considerable savings among select VHA patients with head and neck cancer. © 2016 Wiley Periodicals, Inc. Head Neck 38: 925-929, 2016.

The Acceptance and Use of Virtual Gaming as an Intervention Strategy for Older Adults in Occupational Therapy.

OBJECTIVE: With the advent of occupational therapists' use of virtual gaming as an intervention strategy to enhance the occupational performance of many populations, there is a need to better understand the factors influencing occupational therapists' acceptance and use of this strategy as it pertains to specific groups. This study investigated the appropriateness of using the Unified Theory of Acceptance and Use of Technology (UTAUT) to predict what drives occupational therapists' use of this ad hoc, intuitive, and idiosyncratic intervention strategy with their older adult clients. MATERIALS AND METHODS: A cross-sectional Web-based survey of occupational therapists who primarily work with older adults was designed to measure constructs based from the validated UTAUT. Evidence was elicited from 516 occupational therapists. Analyses included descriptive analyses, Cronbach's alpha reliability analysis, confirmatory factor analysis, and examination of goodness of fit criteria and factor loading indicators. RESULTS: The results confirmed that performance expectancy, attitude, and social influence significantly contribute to occupational therapists' behavioral intention to use off-the-shelf virtual gaming as an intervention strategy with older adults in occupational therapy. Contrary to technology acceptance research, performance expectancy had a negative impact on behavioral intention in this study. The research model explained 83 percent of the variance in behavioral intention and 30 percent of the variance in use behavior. CONCLUSIONS: The study demonstrates that the UTAUT model provides an effective means to understand occupational therapists' acceptance and use of off-the-shelf virtual gaming as an intervention strategy with their older adult clients.