Models and approaches for building knowledge translation capacity and capability in health services: a scoping review.

BACKGROUND: Building healthcare service and health professionals' capacity and capability to rapidly translate research evidence into health practice is critical to the effectiveness and sustainability of healthcare systems. This review scoped the literature describing programmes to build knowledge translation capacity and capability in health professionals and healthcare services, and the evidence supporting these. METHODS: This scoping review was undertaken using the Joanna Briggs Institute scoping review methodology. Four research databases (Ovid MEDLINE, CINAHL, Embase, and PsycInfo) were searched using a pre-determined strategy. Eligible studies described a programme implemented in healthcare settings to build health professional or healthcare service knowledge translation capacity and capability. Abstracts and full texts considered for inclusion were screened by two researchers. Data from included papers were extracted using a bespoke tool informed by the scoping review questions. RESULTS: Database searches yielded 10,509 unique citations, of which 136 full texts were reviewed. Thirty-four papers were included, with three additional papers identified on citation searching, resulting in 37 papers describing 34 knowledge translation capability building programmes. Programmes were often multifaceted, comprising a combination of two or more strategies including education, dedicated implementation support roles, strategic research-practice partnerships and collaborations, co-designed knowledge translation capability building programmes, and dedicated funding for knowledge translation. Many programmes utilised experiential and collaborative learning, and targeted either individual, team, organisational, or system levels of impact. Twenty-seven programmes were evaluated formally using one or more data collection methods. Outcomes measured varied significantly and included participant self-reported outcomes, perceived barriers and enablers of knowledge translation, milestone achievement and behaviour change. All papers reported that programme objectives were achieved to varying degrees. CONCLUSIONS: Knowledge translation capacity and capability building programmes in healthcare settings are multifaceted, often include education to facilitate experiential and collaborative learning, and target individual, team, organisational, or supra-organisational levels of impact. Although measured differently across the programmes, the outcomes were positive. The sustainability of programmes and outcomes may be undermined by the lack of long-term funding and inconsistent evaluation. Future research is required to develop evidence-informed frameworks to guide methods and outcome measures for short-, medium- and longer-term programme evaluation at the different structural levels.

Intratemporal facial nerve neurofibroma causing facial paralysis in an infant: Case report and review of the literature.

This article describes the first recorded case of intratemporal neurofibroma in an infant. A literature review of all other existing cases of intratemporal neurofibroma is performed, finding that the majority of cases involve multiple segments and can be found in the mastoid segment most often. Most common symptoms described included facial paralysis, otalgia, and conductive hearing loss, respectively.

Quality of life in south-eastern Australia: normative values for the WHOQOL-BREF in a population-based sample of adults.

OBJECTIVES: The abbreviated World Health Organisation Quality of Life tool (WHOQOL-BREF) is a short-form quality of life (QoL) assessment commonly used worldwide in both healthy and ill populations. Normative data for the Australian general population are limited. The objective of this study was to present normative data for the WHOQOL-BREF based on a general population sample. A secondary aim was to explore sociodemographic factors related to QoL. DESIGN: Population-based cross-sectional study. PARTICIPANTS: 929 men and 830 women aged 24-94 years participating in the Geelong Osteoporosis Study. OUTCOME MEASURES: The 26-item WHOQOL-BREF. RESULTS: Means and SD for each domain are presented by age group and sex. Percentile scores were also generated. Mean scores for WHOQOL-BREF domains were 74.52 (SD=16.22) for physical health, 72.07 (SD=15.35) for psychological, 72.87 (SD=18.78) for social relationships and 79.68 (SD=12.55) for environment. We identified significant associations between sociodemographic factors and WHOQOL-BREF domains. Notably, being married or in a relationship was associated with increased odds for high QoL across all four WHOQOL-BREF domains: physical health (women OR 2.46, 95% CI 1.36 to 4.44, p=0.003), psychological (men OR 2.07, 95% CI: 1.20 to 3.55, p=0.009; women OR 2.15, 95% CI 1.21 to 3.81, p=0.009), social relationships (men OR 2.28, 95% CI 1.29 to 4.04, p=0.005; women OR 2.77, 95% CI 1.42 to 5.41, p=0.003) and environment (women OR 2.07, 95% CI 1.13 to 3.80, p=0.019). CONCLUSIONS: This study provides population norms for the WHOQOL-BREF based on a representative sample of Australian adults. Our results will be useful to researchers and clinicians who can use these data as a reference point for interpreting WHOQOL-BREF scores.

Correction: The Tight Junction Associated Signalling Proteins ZO-1 and ZONAB Regulate Retinal Pigment Epithelium Homeostasis in Mice.

[This corrects the article DOI: 10.1371/journal.pone.0015730.].

Research translation mentoring for emerging clinician researchers in rural and regional health settings: a qualitative study.

BACKGROUND: Building clinician and organisation-level research translation capacity and capability is fundamental for increasing the implementation of research into health practice and policy and improving health outcomes. Research translation capacity and capability building is particularly crucial in rural and regional settings to address complex problems impacting these socially and economically disadvantaged communities. Programs to build clinicians' research translation capability typically involve training and mentoring. Little is known about the features of and influences on mentorships in the context of training for emerging clinician-researchers working in rural and regional healthcare settings. Research translation mentorships were established as part of the Supporting Translation Research in Rural and Regional settings (STaRR) program developed and delivered in Victoria, Australia from 2020 to 2021. The study sought to address the following research questions: 1) What context-specific types of support do research translation mentors provide to emerging researchers?. 2) How does the mentoring element of a rural research translational training program influence research translation capacity and capability development in rural emerging researchers and mentors, if at all?. 3) How does the mentoring element of the program influence translation capacity and capability at the organisational and regional level, if at all? METHODS: We conducted a qualitative descriptive study. Interviews with individuals involved in the STaRR program took place approximately 12 months after the program and explored participants' experiences of the mentored training. Interviews were undertaken via telephone, audio-recorded, and transcribed. Data were analysed using a team-based five-stage framework approach. RESULTS: Participants included emerging researchers (n = 9), mentors (n = 5), and managers (n = 4), from five health services and two universities. We identified four themes in the interview data: (1) Mentors play an educative role; (2) Mentoring enhanced by a collaborative environment; (3) Organisational challenges can influence mentorships, and (4) Mentorships help develop research networks and collective research and translation capacity. CONCLUSIONS: Mentorships contributed to the development of research translation capabilities. The capabilities were developed through mentors' deepened understanding of the rural and regional healthcare contexts in which their emerging researchers worked, the broadening and strengthening of rural and regional research networks, and building and sharing research translation knowledge and skills.

Obesity and sarcopenic obesity characterized by low-grade inflammation are associated with increased risk for major depression in women.

Background: We aimed to determine women's risk of major depressive disorder (MDD) in relation to obesity phenotypes characterized by levels of circulating high-sensitivity C-reactive protein (hsCRP). Methods: This population-based retrospective cohort study comprised 808 women (ages 20-84 y) recruited 1994-1997 and followed for a median 16.1 y (IQR 11.9-16.8). At baseline, body fat and lean tissue mass were measured by whole body dual-energy x-ray absorptiometry (DXA). Obesity was identified as high fat mass index (>12.9 kg/m2), body fat percentage (≥35%) and body mass index (≥30 kg/m2); sarcopenic obesity referred to a high ratio fat mass/fat-free mass (≥0.80). Systemic inflammation was operationalized as serum hsCRP concentration in the upper tertile (>2.99 mg/L). Obesity phenotypes were: non-obese + lowCRP, non-obese + highCRP, obese + lowCRP, and obese + highCRP. During follow-up, the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP) was used to identify lifetime history of MDD and age of onset. Poisson regression models were used to estimate the MDD rate for each obesity phenotype during follow-up. Demographic, health and lifestyle factors were tested as potential confounders. Results: During 11,869 p-y of follow-up, 161 (19.9%) women experienced an MDD episode. For obesity phenotypes based on fat mass index, models adjusted for baseline age and prior MDD, and non-obese + lowCRP as reference, RR for non-obese + highCRP was 1.21 (95% CI 0.80, 1.82), obese + lowCRP 1.46 (0.86, 2.47) and obese + highCRP 1.56 (1.03, 2.37). Patterns were similar for obesity by body fat percentage, body mass index and sarcopenic obesity. Conclusion: Consistently across different obesity definitions, this longitudinal study reports that women with both obesity and systemic inflammation are at increased risk of subsequent MDD. Future research should examine whether tackling this metabolically unhealthy obesity type - through, for example, lifestyle or medication approaches - can reduce depression risk.

Light-Seq: light-directed in situ barcoding of biomolecules in fixed cells and tissues for spatially indexed sequencing.

We present Light-Seq, an approach for multiplexed spatial indexing of intact biological samples using light-directed DNA barcoding in fixed cells and tissues followed by ex situ sequencing. Light-Seq combines spatially targeted, rapid photocrosslinking of DNA barcodes onto complementary DNAs in situ with a one-step DNA stitching reaction to create pooled, spatially indexed sequencing libraries. This light-directed barcoding enables in situ selection of multiple cell populations in intact fixed tissue samples for full-transcriptome sequencing based on location, morphology or protein stains, without cellular dissociation. Applying Light-Seq to mouse retinal sections, we recovered thousands of differentially enriched transcripts from three cellular layers and discovered biomarkers for a very rare neuronal subtype, dopaminergic amacrine cells, from only four to eight individual cells per section. Light-Seq provides an accessible workflow to combine in situ imaging and protein staining with next generation sequencing of the same cells, leaving the sample intact for further analysis post-sequencing.

Phase I trial of sargramostim/pelareorep therapy in pediatric patients with recurrent or refractory high-grade brain tumors.

Background: Brain tumors are the leading cause of cancer death for pediatric patients. Pelareorep, an immunomodulatory oncolytic reovirus, has intravenous efficacy in preclinical glioma models when preconditioned with GM-CSF (sargramostim). We report a phase I trial with the primary goal of evaluating the safety of sargramostim/pelareorep in pediatric patients with recurrent or refractory high-grade brain tumors and a secondary goal of characterizing immunologic responses. Methods: The trial was open to pediatric patients with recurrent or refractory high-grade brain tumors (3 + 3 cohort design). Each cycle included 3 days of subcutaneous sargramostim followed by 2 days of intravenous pelareorep. Laboratory studies and imaging were acquired upon recruitment and periodically thereafter. Results: Six patients participated, including three glioblastoma, two diffuse intrinsic pontine glioma, and one medulloblastoma. Two pelareorep dose levels of 3 × 108 and 5 × 108 tissue culture infectious dose 50 (TCID50) were assessed. One patient experienced a dose limiting toxicity of persistent hyponatremia. Common low-grade (1 or 2) adverse events included transient fatigue, hypocalcemia, fever, flu-like symptoms, thrombocytopenia, and leukopenia. High-grade (3 or 4) adverse events included neutropenia, lymphopenia, leukopenia, hypophosphatemia, depressed level of consciousness, and confusion. All patients progressed on therapy after a median of 32.5 days and died a median of 108 days after recruitment. Imaging at progression did not show evidence of pseudoprogression or inflammation. Correlative assays revealed transient but consistent changes in immune cells across patients. Conclusions: Sargramostim/pelareorep was administered to pediatric patients with recurrent or refractory high-grade brain tumors. Hyponatremia was the only dose limiting toxicity (DLT), though maximum tolerated dose (MTD) was not determined.

How Well Do Low Population-Specific Values for Muscle Parameters Associate with Indices of Poor Physical Health? Cross-Sectional Data from the Geelong Osteoporosis Study.

We aimed to examine associations between skeletal muscle deficits and indices of poor health. Cut-points for skeletal muscle deficits were derived using data from the Geelong Osteoporosis Study and definitions from the revised European Consensus on Definition and Diagnosis and the Foundation for the National Institutes of Health. Participants (n = 665; 323 women) aged 60-96 year had handgrip strength measured by dynamometry and appendicular lean mass by whole-body dual-energy X-ray absorptiometry. Physical performance was assessed using the Timed Up and Go test. Sex-specific cut-points were equivalent to two standard deviations below the mean young reference range from the Geelong Osteoporosis Study. Indices of poor health included fractures, falls, and hospitalisations. Low trauma fractures since age 50 year (excluding skull, face, digits) were self-reported and confirmed using radiological reports. Falls (≥1 in the past 12 months) and hospitalisations (past month) were self-reported. Logistic regression models (age- and sex-adjusted) were used to examine associations. Receiver Operating Characteristic curves were applied to determine optimal cut-points for handgrip strength, Timed Up and Go, appendicular lean mass/height2, and appendicular lean mass/body mass index that discriminated poor health outcomes. There were 48 participants (6.9%) with hospitalisations, 94 (13.4%) with fractures, and 177 (25.3%) with at least one fall (≥1). For all cut-points, low handgrip strength was consistently associated with falls. There was little evidence to support an association between low appendicular lean mass, using any cut-point, and indices of poor health. Optimal cut-offs for predicting falls (≥1) were: handgrip strength 17.5 kg for women and 33.5 kg for men; Timed Up and Go 8.6 s for women and 9.9 s for men; appendicular lean mass/height2 6.2 kg/m2 for women and 7.46 kg/m2 for men; and appendicular lean mass/body mass index 0.6 m2 for women and 0.9 m2 for men. In conclusion, muscle strength and function performed better than lean mass to indicate poor health. These findings add to the growing evidence base to inform decisions regarding the selection of skeletal muscle parameters and their optimal cut-points for identifying sarcopenia.

Intravenous Oncolytic Vaccinia Virus Therapy Results in a Differential Immune Response between Cancer Patients.

Pexa-Vec is an engineered Wyeth-strain vaccinia oncolytic virus (OV), which has been tested extensively in clinical trials, demonstrating enhanced cytotoxic T cell infiltration into tumours following treatment. Favourable immune consequences to Pexa-Vec include the induction of an interferon (IFN) response, followed by inflammatory cytokine/chemokine secretion. This promotes tumour immune infiltration, innate and adaptive immune cell activation and T cell priming, culminating in targeted tumour cell killing, i.e., an immunologically 'cold' tumour microenvironment is transformed into a 'hot' tumour. However, as with all immunotherapies, not all patients respond in a uniformly favourable manner. Our study herein, shows a differential immune response by patients to intravenous Pexa-Vec therapy, whereby some patients responded to the virus in a typical and expected manner, demonstrating a significant IFN induction and subsequent peripheral immune activation. However, other patients experienced a markedly subdued immune response and appeared to exhibit an exhausted phenotype at baseline, characterised by higher baseline immune checkpoint expression and regulatory T cell (Treg) levels. This differential baseline immunological profile accurately predicted the subsequent response to Pexa-Vec and may, therefore, enable the development of predictive biomarkers for Pexa-Vec and OV therapies more widely. If confirmed in larger clinical trials, these immunological biomarkers may enable a personalised approach, whereby patients with an exhausted baseline immune profile are treated with immune checkpoint blockade, with the aim of reversing immune exhaustion, prior to or alongside OV therapy.

The Relationship Between Adverse Childhood Experiences and Alzheimer's Disease: A Systematic Review.

Background: Alzheimer's disease is a global health concern, and with no present cure, prevention is critical. Exposure to adverse childhood experiences may increase the risk of developing Alzheimer's disease. This systematic review was conducted to synthesize the evidence on the associations between adverse childhood experiences (<18 years) and the risk of Alzheimer's disease in adulthood. Methods: A search strategy was developed and conducted to identify articles investigating the associations between exposure to adverse childhood experiences and the onset of Alzheimer's disease by searching key databases (CINAHL, MEDLINE and PsycInfo). Two reviewers independently determined the eligibility of studies according to pre-determined criteria, and assessed the methodological quality using the US National Heart, Lung and Blood Institute 14-item checklist for observational cohort and cross-sectional studies, respectively. Due to limited studies, a descriptive synthesis was performed. The protocol for this review is published in BMJ Open and registered with PROSPERO (CRD42020191439). Results: Our search yielded 781 articles, of which three (two separate analyses from the same cohort study and one cross-sectional study) met the predetermined eligibility criteria. The methodological quality assessment yielded an overall mean score of 78.9% (range 66.6 - 84.6%). All studies found adverse childhood experiences were associated with an increased risk of Alzheimer's disease. However, there was a limited number of available studies to inform the synthesis. Conclusions: Adverse childhood experiences appear to be associated with an increased risk of Alzheimer's disease, although, further research is needed. Registration and Protocol: The protocol for this review is registered with PROSPERO (CRD42020191439) and published with BMJ Open (Corney et al., 2021).

Research education and training for nurses and allied health professionals: a systematic scoping review.

BACKGROUND: Research capacity building (RCB) initiatives have gained steady momentum in health settings across the globe to reduce the gap between research evidence and health practice and policy. RCB strategies are typically multidimensional, comprising several initiatives targeted at different levels within health organisations. Research education and training is a mainstay strategy targeted at the individual level and yet, the evidence for research education in health settings is unclear. This review scopes the literature on research education programs for nurses and allied health professionals, delivered and evaluated in healthcare settings in high-income countries. METHODS: The review was conducted systematically in accordance with the Joanna Briggs Institute scoping review methodology. Eleven academic databases and numerous grey literature platforms were searched. Data were extracted from the included full texts in accordance with the aims of the scoping review. A narrative approach was used to synthesise findings. Program characteristics, approaches to program evaluation and the outcomes reported were extracted and summarised. RESULTS: Database searches for peer-reviewed and grey literature yielded 12,457 unique records. Following abstract and title screening, 207 full texts were reviewed. Of these, 60 records were included. Nine additional records were identified on forward and backward citation searching for the included records, resulting in a total of 69 papers describing 68 research education programs. Research education programs were implemented in fourteen different high-income countries over five decades. Programs were multifaceted, often encompassed experiential learning, with half including a mentoring component. Outcome measures largely reflected lower levels of Barr and colleagues' modified Kirkpatrick educational outcomes typology (e.g., satisfaction, improved research knowledge and confidence), with few evaluated objectively using traditional research milestones (e.g., protocol completion, manuscript preparation, poster, conference presentation). Few programs were evaluated using organisational and practice outcomes. Overall, evaluation methods were poorly described. CONCLUSION: Research education remains a key strategy to build research capacity for nurses and allied health professionals working in healthcare settings. Evaluation of research education programs needs to be rigorous and, although targeted at the individual, must consider longer-term and broader organisation-level outcomes and impacts. Examining this is critical to improving clinician-led health research and the translation of research into clinical practice.

Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anticancer Immunity in Patients.

Improving the chances of curing patients with cancer who have had surgery to remove metastatic sites of disease is a priority area for cancer research. Pexa-Vec (Pexastimogene Devacirepvec; JX-594, TG6006) is a principally immunotherapeutic oncolytic virus that has reached late-phase clinical trials. We report the results of a single-center, nonrandomized biological end point study (trial registration: EudraCT number 2012-000704-15), which builds on the success of the presurgical intravenous delivery of oncolytic viruses to tumors. Nine patients with either colorectal cancer liver metastases or metastatic melanoma were treated with a single intravenous infusion of Pexa-Vec ahead of planned surgical resection of the metastases. Grade 3 and 4 Pexa-Vec-associated side effects were lymphopaenia and neutropaenia. Pexa-Vec was peripherally carried in plasma and was not associated with peripheral blood mononuclear cells. Upon surgical resection, Pexa-Vec was found in the majority of analyzed tumors. Pexa-Vec therapy associated with IFNα secretion, chemokine induction, and resulted in transient innate and long-lived adaptive anticancer immunity. In the 2 patients with significant and complete tumor necrosis, a reduction in the peripheral T-cell receptor diversity was observed at the time of surgery. These results support the development of presurgical oncolytic vaccinia virus-based therapies to stimulate anticancer immunity and increase the chances to cure patients with cancer.

Antioxidant and lipid supplementation improve the development of photoreceptor outer segments in pluripotent stem cell-derived retinal organoids.

The generation of retinal organoids from human pluripotent stem cells (hPSC) is now a well-established process that in part recapitulates retinal development. However, hPSC-derived photoreceptors that exhibit well-organized outer segment structures have yet to be observed. To facilitate improved inherited retinal disease modeling, we determined conditions that would support outer segment development in maturing hPSC-derived photoreceptors. We established that the use of antioxidants and BSA-bound fatty acids promotes the formation of membranous outer segment-like structures. Using new protocols for hPSC-derived retinal organoid culture, we demonstrated improved outer segment formation for both rod and cone photoreceptors, including organized stacked discs. Using these enhanced conditions to generate iPSC-derived retinal organoids from patients with X-linked retinitis pigmentosa, we established robust cellular phenotypes that could be ameliorated following adeno-associated viral vector-mediated gene augmentation. These findings should aid both disease modeling and the development of therapeutic approaches for the treatment of photoreceptor disorders.

Fatty Liver Index and Skeletal Muscle Density.

Accumulation of fat in the liver and skeletal muscle is associated with obesity and poor health outcomes. Liver steatosis is a characteristic of non-alcoholic fatty liver disease (NAFLD) and myosteatosis, of poor muscle quality in sarcopenia. In this study of 403 men (33-96 years), we investigated associations between the fatty liver index (FLI) and muscle density, as markers of fat accumulation in these organs. We also investigated associations between the FLI and parameters of sarcopenia, including DXA-derived appendicular lean mass (ALM) and handgrip strength by dynamometry. Muscle density was measured using pQCT at the radius and tibia. FLI was calculated from BMI, waist circumference, and levels of triglycerides and gamma-glutamyltransferase. There was a pattern of decreasing muscle density across increasing quartiles of FLI. After adjusting for age and lifestyle, mean radial muscle density in Q4 was 2.1% lower than Q1 (p < 0.001) and mean tibial muscle density was 1.8% lower in Q3 and 3.0% lower in Q4, compared to Q1 (p = 0.022 and < 0.001, respectively). After adjusting for age and sedentary lifestyle, participants in the highest FLI quartile were sixfold more likely to have sarcopenia. In conclusion, our results suggest that fat accumulation in the liver co-exists with fat infiltration into skeletal muscle.

Spatiotemporal patterns of neuronal subtype genesis suggest hierarchical development of retinal diversity.

How do neuronal subtypes emerge during development? Recent molecular studies have profiled existing neuronal diversity, but neuronal subtype genesis remains elusive. The 15 types of mouse retinal bipolar interneurons are characterized by distinct functions, morphologies, and transcriptional profiles. Here, we develop a comprehensive spatiotemporal map of bipolar subtype genesis in the murine retina. Combining multiplexed detection of 16 RNA markers with timed delivery of 5-ethynyl uridine (EdU) and bromodeoxyuridine (BrdU), we analyze more than 30,000 single cells in full retinal sections to classify all bipolar subtypes and their birthdates. We find that bipolar subtype birthdates are ordered and follow a centrifugal developmental axis. Spatial analysis reveals a striking wave pattern of bipolar subtype birthdates, and lineage analyses suggest clonal restriction on homotypic subtype production. These results inspire a hierarchical developmental model, with ordered subtype genesis within lineages. Our results provide insight into neuronal subtype development and establish a framework for studying subtype diversification.

Development and diversification of bipolar interneurons in the mammalian retina.

The bipolar interneurons of the mammalian retina have evolved as a diverse set of cells with distinct subtype characteristics, which reflect specialized contributions to visual circuitry. Fifteen subtypes of bipolar interneurons have been identified in the mouse retina, each with characteristic gene expression, morphology, and light responses. This review provides an overview of the developmental events that underlie the generation of the diverse bipolar cell class, summarizing the current knowledge of genetic programs that establish and maintain bipolar subtype fates, as well as the events that shape the final distribution of bipolar subtypes. With much left to be discovered, bipolar interneurons present an ideal model system for studying the interplay between cell-autonomous and non-cell-autonomous mechanisms that influence neuronal subtype development within the central nervous system.

Is sarcopenia associated with anxiety symptoms and disorders? A systematic review and meta-analysis protocol.

INTRODUCTION: Sarcopenia is a skeletal muscle disorder characterised by a progressive decline in muscle mass and function (strength and performance). Sarcopenia is associated with numerous adverse health outcomes and has recently been linked to neurological and psychiatric disorders, including dementia and depression. Whether sarcopenia is related to other common psychiatric illnesses, such as anxiety, is unclear. We aim to systematically identify and review the extant literature regarding the association between sarcopenia and anxiety symptomatology and/or disorders (anxiety) in adults. METHODS AND ANALYSIS: We will conduct a systematic search across four online databases (CINAHL, Embase, MEDLINE Complete and PsycINFO) from inception to September 2021. Two reviewers will independently confirm study selection and assess methodological quality of included studies. If possible, a meta-analysis will be performed to determine pooled OR for the relationship between sarcopenia and anxiety. If meta-analysis is not possible due to methodological heterogeneity a 'best evidence synthesis' will be performed. ETHICS AND DISSEMINATION: This review will use published data only, thus, ethical approval will not be required. Findings will be published in a peer-reviewed journal and presented at conferences. PROSPERO REGISTRATION NUMBER: CRD42020209420.

Nanotube-like processes facilitate material transfer between photoreceptors.

Neuronal communication is typically mediated via synapses and gap junctions. New forms of intercellular communication, including nanotubes (NTs) and extracellular vesicles (EVs), have been described for non-neuronal cells, but their role in neuronal communication is not known. Recently, transfer of cytoplasmic material between donor and host neurons ("material transfer") was shown to occur after photoreceptor transplantation. The cellular mechanism(s) underlying this surprising finding are unknown. Here, using transplantation, primary neuronal cultures and the generation of chimeric retinae, we show for the first time that mammalian photoreceptor neurons can form open-end NT-like processes. These processes permit the transfer of cytoplasmic and membrane-bound molecules in culture and after transplantation and can mediate gain-of-function in the acceptor cells. Rarely, organelles were also observed to transfer. Strikingly, use of chimeric retinae revealed that material transfer can occur between photoreceptors in the intact adult retina. Conversely, while photoreceptors are capable of releasing EVs, at least in culture, these are taken up by glia and not by retinal neurons. Our findings provide the first evidence of functional NT-like processes forming between sensory neurons in culture and in vivo.