Grandma Layton: A Cinderella Story

Students and their professor created a method of arts-informed research (AIR) in the practice of community-based art education to bring community members together, separated by age and distance. Essential features of this method included analyzing how local artist Elizabeth “Grandma” Layton addressed issues of ageing and mental health in her art and the direct engagement of participants in coloring her line designs. This postcard coloring project was designed during a time where extreme social distancing was in place and adapted for fifth-grade art classes and residents of a retirement community. In AIR the choice of artist, activity, medium of expression, presentation and participants are all important and related to the project’s success. The analysis of these practices is through the lens of place-based education and intergenerational (IG) learning. Understanding of place, age and ability of participants and the quality of the art activity are all significant and should be thoughtfully considered in IG learning

Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task

Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500kHz, 200–400 kPa, 4–5μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4–20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of’ visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4–5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used

Recognition without identification, erroneous familiarity, and déjà vu

Déjà vu is characterized by the recognition of a situation concurrent with the awareness that this recognition is inappropriate. Although forms of déjà vu resolve in favor of the inappropriate recognition and therefore have behavioral consequences, typical déjà vu experiences resolve in favor of the awareness that the sensation of recognition is inappropriate. The resultant lack of behavioral modification associated with typical déjà vu means that clinicians and experimenters rely heavily on self-report when observing the experience. In this review, we focus on recent déjà vu research. We consider issues facing neuropsychological, neuroscientific, and cognitive experimental frameworks attempting to explore and experimentally generate the experience. In doing this, we suggest the need for more experimentation and amore cautious interpretation of research findings, particularly as many techniques being used to explore déjà vu are in the early stages of development.PostprintPeer reviewe

Pulsed thulium:YAG laser-ready to dust all urinary stone composition types? Results from a PEARLS analysis.

PURPOSE To evaluate whether stone dust can be obtained from all prevailing stone composition types using the novel pulsed thulium:YAG (p-Tm:YAG), including analysis of stone particle size after lithotripsy. METHODS Human urinary stones of 7 different compositions were subjected to in vitro lithotripsy using a p-Tm:YAG laser with 270 µm silica core fibers (Thulio$^{®}$, Dornier MedTech GmbH$^{®}$, Wessling, Germany). A cumulative energy of 1000 J was applied to each stone using one of three laser settings: 0.1 J × 100 Hz, 0.4 J × 25 Hz and 2.0 J × 5 Hz (average power 10 W). After lithotripsy, larger remnant fragments were separated from stone dust using a previously described method depending on the floating ability of dust particles. Fragments and dust samples were then passed through laboratory sieves to evaluate stone particle count according to a semiquantitative analysis relying on a previous definition of stone dust (i.e., stone particles ≤ 250 µm). RESULTS The p-Tm:YAG laser was able to produce stone dust from lithotripsy up to measured smallest mesh size of 63 µm in all seven stone composition types. Notably, all dust samples from all seven stone types and with all three laser settings had high counts of particles in the size range agreeing with the definition stone dust, i.e., ≤ 250 µm. CONCLUSION This is the first study in the literature proving the p-Tm:YAG laser capable of dusting all prevailing human urinary stone compositions, with production of dust particles ≤ 250 µm. These findings are pivotal for the broader future implementation of the p-Tm:YAG in clinical routine

Linoleic acid improves PIEZO2 dysfunction in a mouse model of Angelman Syndrome

Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability and atypical behaviors. AS results from loss of expression of the E3 ubiquitin-protein ligase UBE3A from the maternal allele in neurons. Individuals with AS display impaired coordination, poor balance, and gait ataxia. PIEZO2 is a mechanosensitive ion channel essential for coordination and balance. Here, we report that PIEZO2 activity is reduced in Ube3a deficient male and female mouse sensory neurons, a human Merkel cell carcinoma cell line and female human iPSC-derived sensory neurons with UBE3A knock-down, and de-identified stem cell-derived neurons from individuals with AS. We find that loss of UBE3A decreases actin filaments and reduces PIEZO2 expression and function. A linoleic acid (LA)-enriched diet increases PIEZO2 activity, mechano-excitability, and improves gait in male AS mice. Finally, LA supplementation increases PIEZO2 function in stem cell-derived neurons from individuals with AS. We propose a mechanism whereby loss of UBE3A expression reduces PIEZO2 function and identified a fatty acid that enhances channel activity and ameliorates AS-associated mechano-sensory deficits.This work was supported by the Neuroscience Institute at UTHSC (Research Associate Matching Salary Support to J.L.), the Federico Baur endowed chair in Nanotechnology (to F.J.S.-V., 0020206BA1), a pilot research award from the Foundation for Prader-Willi Research (to L.T.R.), the Neuroscience Institute Research Supports Grant 2020 program (to V.V., and J.F.C.-M.), and the National Institutes of Health (R01GM133845 to V.V. and R01GM125629 to J.F.C.-M.)

Laser Ablation Efficiency, Laser Ablation Speed, and Laser Energy Consumption During Lithotripsy: What Are They and How Are They Defined? A Systematic Review and Proposal for a Standardized Terminology

Context Laser performance for lithotripsy is currently reported using units of measurement such as J/mm3, mm3/J, mm3/s, s/mm3, and mm3/min. However, there are no current standardized definitions or terminology for these metrics. This may lead to confusion when assessing and comparing different laser systems. Objective The primary objective was to summarize outcome values and corresponding terminology from studies on laser lithotripsy performance using stone volume in relation to time or energy. The secondary objective was to propose a standardized terminology for reporting laser performance metrics. Evidence acquisition A systematic review of the literature was conducted using the search string (“j*/mm3” OR “mm3/j*” OR “mm3/s*” OR “s*/mm3” OR “mm3/min*” OR “min*/mm3” AND “lithotripsy”) on Scopus, Web of Science, Embase, and PubMed databases. Study selection, data extraction, and quality assessment were performed independently by two authors. Evidence synthesis A total of 28 studies were included, covering holmium:yttrium-aluminum-garnet (Ho:YAG), MOSES, and thulium fiber laser (TFL) technologies. Laser energy consumption values reported for the studies ranged from 2.0 – 43.5 J/mm3 in vitro and from 2.7 – 47.8 J/mm3 in vivo, translating to laser ablation efficiency of 0.023 – 0.500 mm3/J and 0.021 – 0.370 mm3/J, respectively. Laser ablation speeds ranged from 0.3 – 8.5 mm3/s in vivo, translating to lasing time consumption of 0.12 – 3.33 s/mm3. Laser efficacy ranged from 4.35 – 51.7 mm3/min in vivo. There was high heterogeneity for the terminology used to describe laser performance for the same metrics. Conclusions The range of laser performance metric values relating stone volume to energy or time is wide, with corresponding differing terminology. We propose a standardized terminology for future studies on laser lithotripsy, including laser ablation efficiency (mm3/J), laser ablation speed (mm3/s), and laser energy consumption (J/mm3). Laser efficacy (mm3/min) is proposed as a broader term that is based on the total operative time, encompassing the whole technique using the laser. Patient summary We reviewed studies to identify the units and terms used for laser performance when treating urinary stones. The review revealed a wide range of differing units, outcomes, and terms. Therefore, we propose a standardized terminology for future studies on laser stone treatment. Keywords UreteroscopyPercutaneous nephrolithotomyLaserStone diseaseLithotripsyPerformanceUrolithiasi

Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task

Abstract Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500kHz, 200-400 kPa, 4-5μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemicallyadministered MB over 4-20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of' visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4-5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used

Characterizing Focused-Ultrasound Mediated Drug Delivery to the Heterogeneous Primate Brain In Vivo with Acoustic Monitoring

Focused ultrasound with microbubbles has been used to noninvasively and selectively deliver pharmacological agents across the blood-brain barrier (BBB) for treating brain diseases. Acoustic cavitation monitoring could serve as an on-line tool to assess and control the treatment. While it demonstrated a strong correlation in small animals, its translation to primates remains in question due to the anatomically different and highly heterogeneous brain structures with gray and white matteras well as dense vasculature. In addition, the drug delivery efficiency and the BBB opening volume have never been shown to be predictable through cavitation monitoring in primates. This study aimed at determining how cavitation activity is correlated with the amount and concentration of gadolinium delivered through the BBB and its associated delivery efficiency as well as the BBB opening volume in non-human primates. Another important finding entails the effect of heterogeneous brain anatomy and vasculature of a primate brain, i.e., presence of large cerebral vessels, gray and white matter that will also affect the cavitation activity associated with variation of BBB opening in different tissue types, which is not typically observed in small animals. Both these new findings are critical in the primate brain and provide essential information for clinical applications

Community engagement: The ‘last mile’ challenge for European research e-infrastructures

Europe is building its Open Science Cloud; a set of robust and interoperable e-infrastructures with the capacity to provide data and computational solutions through cloud-based services. The development and sustainable operation of such e-infrastructures are at the forefront of European funding priorities. The research community, however, is still reluctant to engage at the scale required to signal a Europe-wide change in the mode of operation of scientific practices. The striking differences in uptake rates between researchers from different scientific domains indicate that communities do not equally share the benefits of the above European investments. We highlight the need to support research communities in organically engaging with the European Open Science Cloud through the development of trustworthy and interoperable Virtual Research Environments. These domain-specific solutions can support communities in gradually bridging technical and socio-cultural gaps between traditional and open digital science practice, better diffusing the benefits of European e-infrastructures