Measuring Urease and Phospholipase Secretion in Cryptococcus neoformans.

Urease and phospholipase are enzymes that are important virulence factors for Cryptococcus neoformans. These are two of the most studied enzymes involved in how C. neoformans breaches the blood-brain barrier. Additionally, phospholipase secretion also supports dissemination from the lungs. This chapter describes the methods used to measure the secretion of these enzymes, which may be used to characterize strain invasiveness and virulence.

Effects of a Virtual Reality Game on Children's Anxiety During Dental Procedures (VR-TOOTH): Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Dental fear and anxiety (DFA) is a condition that affects approximately one-quarter of children and adolescents. It is a significant cause for pediatric patients to avoid dental care later in adulthood. Lack of patient cooperation due to DFA can create an environment of stress, often obligating dentists to end appointments prematurely and consider alternative pharmacological treatment options. Virtual reality (VR) use during dental care, providing an immersive experience through sensory stimuli, is potentially an additional nonpharmacologic tool to better manage DFA in children with special health care needs (SHCN) undergoing dental procedures. OBJECTIVE: This pilot study aims to assess the feasibility and acceptability of VR immersion as a tool to reduce DFA in pediatric special needs patients undergoing dental procedures. The study also aims to gain insight on parent and health care provider perspectives on the use of VR during dental appointments. METHODS: This pilot randomized controlled trial study will follow a parallel design including 2 groups: a control group (clinic's standard care using a wall TV) and an experimental group (using a VR game). We will randomize 20 participants to either group. Recruitment will be carried out at the dental clinic of the Centre Hospitalier Universitaire Sainte-Justine, a tertiary-quaternary care center that mostly serves pediatric patients with SHCN. The primary outcome will be patient recruitment rates and completion rates of planned procedures. DFA in children will be assessed using both an observation-based proxy assessment with the Venham Anxiety and Behavior Rating Scale and physiological assessments using parameters such as change in heart rate and levels of salivary alpha-amylase as a stress biomarker before and 10 minutes after the procedure. Sociodemographic characteristics, measures of the levels of parent and health care professional satisfaction, occurrence of side effects, and any deviation from normal procedure length will also be collected. Descriptive statistics, nonparametric tests, and effect sizes will be used for demographic and clinical variables and to present parent and health care professional satisfaction levels as well as procedural time. RESULTS: This study will be conducted from May 2023 to May 2024, with results expected to be available in December 2024. CONCLUSIONS: The pilot study will provide insight on the feasibility and acceptability of VR use in clinical dentistry to reduce DFA for pediatric patients with SHCN. This study will guide future research on VR use in pediatric dentistry and can serve as a framework for a larger randomized clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05898100; https://classic.clinicaltrials.gov/ct2/show/NCT05898100. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49956.

Using Immersive Virtual Reality Distraction to Reduce Fear and Anxiety before Surgery.

Presurgical anxiety is very common and is often treated with sedatives. Minimizing or avoiding sedation reduces the risk of sedation-related adverse events. Reducing sedation can increase early cognitive recovery and reduce time to discharge after surgery. The current case study is the first to explore the use of interactive eye-tracked VR as a nonpharmacologic anxiolytic customized for physically immobilized presurgery patients. Method: A 44-year-old female patient presenting for gallbladder surgery participated. Using a within-subject repeated measures design (treatment order randomized), the participant received no VR during one portion of her preoperative wait and interactive eye-tracked virtual reality during an equivalent portion of time in the presurgery room. After each condition (no VR vs. VR), the participant provided subjective 0-10 ratings and state-trait short form Y anxiety measures of the amount of anxiety and fear she experienced during that condition. Results: As predicted, compared to treatment as usual (no VR), the patient reported having 67% lower presurgical anxiety during VR. She also experienced "strong fear" (8 out of 10) during no VR vs. "no fear" (0 out of 10) during VR. She reported a strong sense of presence during VR and zero nausea. She liked VR, she had fun during VR, and she recommended VR to future patients during pre-op. Interactive VR distraction with eye tracking was an effective nonpharmacologic technique for reducing anticipatory fear and anxiety prior to surgery. The results add to existing evidence that supports the use of VR in perioperative settings. VR technology has recently become affordable and more user friendly, increasing the potential for widespread dissemination into medical practice. Although case studies are scientifically inconclusive by nature, they help identify new directions for future larger, carefully controlled studies. VR sedation is a promising non-drug fear and anxiety management technique meriting further investigation.

Desktop Virtual Reality Offers a Novel Approach to Minimize Pain and Anxiety during Burn Wound Cleaning/Debridement in Infants and Young Children: A Randomized Crossover Pilot Study.

Although most scald burn injuries involve children under six, because of the challenges of using head mounted displays with young children there is very little research exploring the use of VR in children under six. The current clinical pilot study measured the analgesic effectiveness of our new desktop VR system (with no VR helmet) in children under six during burn wound care (a within-subjects design with randomized treatment order). Between December 2021-April 2022, nine children with burn injuries (10 months to 5 years age, mean = 18 months) participated. The mean burn size was 10% Total Body Surface Area, range 2-22%. Using nurse's ratings, VR significantly reduced children's pain during burn wound care by 40% on the observational Faces, Legs, Activity, Crying, and Consolability (FLACC) pain scale. Specifically, non-parametric within-subject sign tests compared nurse's ratings of the young patients' pain during burn wound care using usual pain medications with no VR = 6.67, (SD = 2.45) vs. adjunctive Animal Rescue World VR (VR = 4.00, SD = 2.24, p < 0.01). The observational Procedure-Behavior Checklist (PBCL) nurse's scale measured a 34% reduction in anxiety with VR as compared to pharmacologic treatment alone (p < 0.005). Similarly, when using single graphic rating scales the patients' parents reported a significant 36% decrease in their child's pain during VR (p < 0.05), a 38% (p < 0.005) decrease in their child's anxiety during VR, and a significant increase in patients' joy during VR. It can be concluded that during burn wound care with no distraction (traditional pain medications), children under 6 years old experienced severe pain during a 10 min burn wound cleaning session. During burn wound care combining desktop virtual reality and traditional pain medications, the same pediatric patients experienced only mild pain during burn wound cleaning/debridement. VR significantly reduced the children's pain and anxiety during burn wound care.

Adding tactile feedback increases avatar ownership and makes virtual reality more effective at reducing pain in a randomized crossover study.

Severe pain is a widespread health problem in need of novel treatment approaches. In the current study we used real water to give virtual objects (i.e., animated virtual water) more realistic physical properties (wet liquid qualities). Healthy volunteers aged 18-34 participated in a within-subject randomized study comparing participants' worst pain during brief thermal stimuli with (1) No Immersive Virtual Reality (VR), versus (2) during VR + no tactile feedback versus (3) VR + real water (with tactile feedback from co-located real objects). Tactile feedback significantly decreased pain intensity (VR analgesia, p < 0.01), compared to VR with no tactile feedback, and compared to No VR (baseline). Tactile feedback made the virtual water feel significantly more real, increased participant's sense of presence, and both VR conditions were distracting (significantly reduced accuracy on an attention demanding task). As a non-pharmacologic analgesic, mixed reality reduced pain by 35% in the current study, comparable to the analgesia from a moderate dose of hydromorphone in previous published experimental studies. Tactile feedback also significantly increased avatar embodiment, the participants illusion of ownership of the virtual hands, which has potential to improve the effectiveness of avatar therapy for chronic pain in future studies. Mixed reality should be tested as treatment in pain patients.

The Emerging Role of Virtual Reality as an Adjunct to Procedural Sedation and Anesthesia: A Narrative Review.

Over the past 20 years, there has been a significant reduction in the incidence of adverse events associated with sedation outside of the operating room. Non-pharmacologic techniques are increasingly being used as peri-operative adjuncts to facilitate and promote anxiolysis, analgesia and sedation, and to reduce adverse events. This narrative review will briefly explore the emerging role of immersive reality in the peri-procedural care of surgical patients. Immersive virtual reality (VR) is intended to distract patients with the illusion of "being present" inside the computer-generated world, drawing attention away from their anxiety, pain, and discomfort. VR has been described for a variety of procedures that include colonoscopies, venipuncture, dental procedures, and burn wound care. As VR technology develops and the production costs decrease, the role and application of VR in clinical practice will expand. It is important for medical professionals to understand that VR is now available for prime-time use and to be aware of the growing body in the literature that supports VR.

A comparison of interactive immersive virtual reality and still nature pictures as distraction-based analgesia in burn wound care.

PURPOSE: Non-pharmacologic adjuncts to opioid analgesics for burn wound debridement enhance safety and cost effectiveness in care. The current study explored the feasibility of using a custom portable water-friendly immersive VR hardware during burn debridement in adults, and tested whether interactive VR would reduce pain more effectively than nature stimuli viewed in the same VR goggles. METHODS: Forty-eight patients with severe burn injuries (44 adults and 4 children) had their burn injuries debrided and dressed in a wet wound care environment on Study Day 1, and 13 also participated in Study Day 2. INTERVENTION: The study used a within-subject design to test two hypotheses (one hypothesis per study day) with the condition order randomized. On Study Day 1, each individual (n = 44 participants) spent 5 min of wound care in an interactive immersive VR environment designed for burn care, and 5 min looking at still nature photos and sounds of nature in the same VR goggles. On Study Day 2 (n = 12 adult participants and one adolescent from Day 1), each participant spent 5 min of burn wound care with no distraction and 5 min of wound care in VR, using a new water-friendly VR system. On both days, during a post-wound care assessment, participants rated and compared the pain they had experienced in each condition. OUTCOME MEASURES ON STUDY DAYS 1 AND 2: Worst pain during burn wound care was the primary dependent variable. Secondary measures were ratings of time spent thinking about pain during wound care, pain unpleasantness, and positive affect during wound care. RESULTS: On Study Day 1, no significant differences in worst pain ratings during wound care were found between the computer-generated world (Mean = 71.06, SD = 26.86) vs. Nature pictures conditions (Mean = 68.19, SD = 29.26; t < 1, NS). On secondary measures, positive affect (fun) was higher, and realism was lower during computer-generated VR. No significant differences in pain unpleasantness or "presence in VR" between the two conditions were found, however. VR VS. NO VR. (STUDY DAY 2): Participants reported significantly less worst pain when distracted with adjunctive computer generated VR than during standard wound care without distraction (Mean = 54.23, SD = 26.13 vs 63.85, SD = 31.50, t(11) = 1.91, p < .05, SD = 17.38). In addition, on Study Day 2, "time spent thinking about pain during wound care" was significantly less during the VR condition, and positive affect was significantly greater during VR, compared to the No VR condition. CONCLUSION: The current study is innovative in that it is the first to show the feasibility of using a custom portable water-friendly immersive VR hardware during burn debridement in adults. However, contrary to predictions, interactive VR did not reduce pain more effectively than nature stimuli viewed in the same VR goggles.

Virtual Reality Animal Rescue World: Pediatric virtual reality analgesia during just noticeable pressure pain in children aged 2-10 years old (crossover design).

Background and aims: Excessive pain during medical procedures is a worldwide medical problem. Most scald burns occur in children under 6, who are often undermedicated. Adjunctive Virtual Reality (VR) distraction has been shown to reduce pain in children aged 6-17, but little is known about VR analgesia in young children. This study tests whether desktop VR (VR Animal Rescue World) can reduce the just noticeable pressure pain of children aged 2-10. Methods: A within-subject repeated measures design was used. With treatment order randomized, each healthy volunteer pediatric participant underwent brief cutaneous pressure stimuli under three conditions: (1) no distraction, (2) a verbal color naming task (no VR), and (3) a large TV-based desktop VR distraction. A hand-held Wagner pressure pain stimulation device was used to generate just noticeable pain sensations. Participants indicated when a steadily increasing non-painful pressure stimulus first turned into a painful pressure sensation (just noticeable pain). Results: A total of 40 healthy children participated (43% aged 2-5 years; and 57% aged 6-10 years). Compared to the no distraction condition, the 40 children showed significant VR analgesia (i.e., a significant reduction in pain sensitivity during the VR Animal Rescue World condition), t(39) = 9.83, p < 0.001, SD = 6.24. VR was also significantly more effective at reducing pain sensitivity vs. an auditory color naming task, t(39) = 5.42, p < 0.001, SD = 5.94. The subset of children aged 2-5 showed significant reductions in pain during VR. Children under 6 showed greater sensitivity to pain during no distraction than children aged 6-10. Conclusion: During no distraction, children under 6 years old were significantly more sensitive to pain than children aged 6-10. Virtual reality (VR) significantly reduced the "just noticeable" pressure pain sensitivity of children in both age groups.

Altered microbial biogeography in an innate model of colitis.

Changes in the spatial organization, or biogeography, of colonic microbes have been observed in human inflammatory bowel disease (IBD) and mouse models of IBD. We have developed a mouse model of IBD that occurs spontaneously and consistently in the absence of adaptive immunity. Mice expressing tumor necrosis factor-induced protein 3 (TNFAIP3) in intestinal epithelial cells (villin-TNFAIP3) develop colitis when interbred with Recombination Activating 1-deficient mice (RAG1^-/-). The colitis in villin-TNFAIP3 × RAG1^-/- (TRAG) mice is prevented by antibiotics, indicating a role for microbes in this innate colitis. We therefore explored the biogeography of microbes and responses to antibiotics in TRAG colitis. Laser capture microdissection and 16S rRNA sequencing revealed altered microbial populations across the transverse axis of the colon as the inner mucus layer of TRAG, but not RAG1^-/-, mice was infiltrated by microbes, which included increased abundance of the classes Gammaproteobacteria and Actinobacteria. Along the longitudinal axis differences in the efficacy of antibiotics to prevent colitis were evident. Neomycin was most effective for prevention of inflammation in the cecum, while ampicillin was most effective in the proximal and distal colon. RAG1^-/-, but not TRAG, mice exhibited a structured pattern of bacterial abundance with decreased Firmicutes and Proteobacteria but increased Bacteroidetes along the proximal to distal axis of the gut. TRAG mice exhibited increased relative abundance of potential pathobionts including <i>Bifidobacterium animalis</i> along the longitudinal axis of the gut whereas others, like <i>Helicobacter hepaticus</i> were increased only in the cecum. Potential beneficial organisms including <i>Roseburia</i> were decreased in the proximal regions of the TRAG colon, while <i>Bifidobacterium pseudolongulum</i> was decreased in the TRAG distal colon. Thus, the innate immune system maintains a structured, spatially organized, gut microbiome along the transverse and longitudinal axis of the gut, and disruption of this biogeography is a feature of innate immune colitis.

An Exploratory Study on the Effectiveness of Virtual Reality Analgesia for Children and Adolescents with Kidney Diseases Undergoing Venipuncture.

The current study evaluated the effectiveness of VR analgesia among pediatric and adolescent patients with kidney disease undergoing venipuncture. Patients at an Italian Children's hospital (N = 82, age range 7-17 years) undergoing venipuncture were randomly assigned to a No VR group (non-medical conversation) vs. a Yes VR group (VR analgesia). After the procedure, patients gave 0-10 Verbal Numeric Pain Scale ratings. Compared with patients in the No VR Group, patients in the Yes VR group reported significantly lower "Pain intensity"(No VR mean = 2.74, SD = 2.76 vs. Yes VR mean = 1.56, SD = 1.83) and the VR group also rated "Pain unpleasantness" significantly lower than the No VR group (No VR mean = 2.41, SD = 0.94 vs. Yes VR mean = 1.17, SD = 1.80). Patients distracted with VR also reported having significantly more fun during the venipuncture procedure. No side effects emerged. In addition to reducing pain intensity, VR has the potential to make venipuncture a more fun and less unpleasant experience for children with CKD, as measured in the present study for the first time. Finally, in exploratory analyses, children aged 7-11 in the VR group reported 55% lower worst pain than control subjects in the same age range, whereas children aged 12 to 17 in the VR group only reported 35% lower worst pain than control subjects. Additional research and development using more immersive VR is recommended.

Utility of SPECT Functional Neuroimaging of Pain.

Functional neuroimaging modalities vary in spatial and temporal resolution. One major limitation of most functional neuroimaging modalities is that only neural activation taking place inside the scanner can be imaged. This limitation makes functional neuroimaging in many clinical scenarios extremely difficult or impossible. The most commonly used radiopharmaceutical in Single Photon Emission Tomography (SPECT) functional brain imaging is Technetium 99 m-labeled Ethyl Cysteinate Dimer (ECD). ECD is a lipophilic compound with unique pharmacodynamics. It crosses the blood brain barrier and has high first pass extraction by the neurons proportional to regional brain perfusion at the time of injection. It reaches peak activity in the brain 1 min after injection and is then slowly cleared from the brain following a biexponential mode. This allows for a practical imaging window of 1 or 2 h after injection. In other words, it freezes a snapshot of brain perfusion at the time of injection that is kept and can be imaged later. This unique feature allows for designing functional brain imaging studies that do not require the patient to be inside the scanner at the time of brain activation. Functional brain imaging during severe burn wound care is an example that has been extensively studied using this technique. Not only does SPECT allow for imaging of brain activity under extreme pain conditions in clinical settings, but it also allows for imaging of brain activity modulation in response to analgesic maneuvers whether pharmacologic or non-traditional such as using virtual reality analgesia. Together with its utility in extreme situations, SPECTS is also helpful in investigating brain activation under typical pain conditions such as experimental controlled pain and chronic pain syndromes.

Spanish-Speaking Therapists Increasingly Switch to Telepsychology During COVID-19: Networked Virtual Reality May Be Next.

Background: Social distancing restrictions imposed due to the Novel Coronavirus 2019 (COVID-19) pandemic resulted in a rapid shift in the delivery of psychological interventions from in-person to telehealth. Much of the research on this transition has been conducted with English-speaking mental health providers, leaving a gap in understanding related to how this shift has impacted Spanish-speaking treatment providers. Methods: Fifty non-U.S. Spanish-speaking therapists completed a survey related to their use of telecommunication modalities; client population characteristics; professional, ethical, and legal/regulatory issues; and telehealth training and practice. Participants completed the survey at one time point and retrospectively described their use of telehealth both pre-pandemic and during the pandemic. Results: Most of the 50 Spanish-speaking therapists surveyed reported using telepsychology 58% before COVID-19 versus 84% during the COVID-19 pandemic (χ2 = 5.76, p < 0.05). Compared with pre-pandemic, the number of hours therapists spent using telepsychology per week increased significantly for early adopter therapists (those who began using telehealth before the pandemic began) (Z = -3.18, p = 0.001) and also for late adopter therapists who only began using telehealth during the pandemic (Z = -3.74, p < 0.001). Many therapists reported equity issues. Most participants also reported ethical and regulatory concerns regarding security/confidentiality or Health Insurance Porability and Accountability Act. Conclusions: The rapid adoption of technology to deliver therapy during COVID-19 has spurred growing pains for Spanish-speaking therapists and their underserved clients, and more research is needed to better understand and improve the therapists' adoption of these technologies with diverse patient populations.

Interacting with virtual objects via embodied avatar hands reduces pain intensity and diverts attention.

The current study introduces a new paradigm for exploring cognitive factors in pain. Interacting with virtual objects via embodied avatar hands increased the illusion of "being there" in the virtual world, increased VR analgesia for acute pain, and reduced accuracy on an attention demanding task. Twenty-four healthy volunteer college students participated in this within-subject randomized crossover design study. During Phase 1, each participant received brief thermal pain stimuli during interactive embodied avatar VR vs. passive VR (no avatar and no interactivity), VR treatment order randomized. After each pain stimulus, participants provided subjective 0-10 ratings of pain. Compared to the passive VR condition, during the interactive avatar VR, participants reported significant reductions in (1) worst pain, (2) pain unpleasantness, (3) time thinking about pain and (4). they had significantly more fun during the pain stimulus (p = .000 for each). During Phase 2, participants performed a divided attention task in each of the two VR conditions. Participants made significantly more errors on the divided attention task during the interactive avatar VR condition, compared to passive VR, implicating an attention mechanism for how virtual reality reduces pain and helping understand how VR influences pain perception.Trial registration: NCT04245475. Date of registration: 29/01/2020.

Prenatal methadone exposure disrupts behavioral development and alters motor neuron intrinsic properties and local circuitry.

Despite the rising prevalence of methadone treatment in pregnant women with opioid use disorder, the effects of methadone on neurobehavioral development remain unclear. We developed a translational mouse model of prenatal methadone exposure (PME) that resembles the typical pattern of opioid use by pregnant women who first use oxycodone then switch to methadone maintenance pharmacotherapy, and subsequently become pregnant while maintained on methadone. We investigated the effects of PME on physical development, sensorimotor behavior, and motor neuron properties using a multidisciplinary approach of physical, biochemical, and behavioral assessments along with brain slice electrophysiology and in vivo magnetic resonance imaging. Methadone accumulated in the placenta and fetal brain, but methadone levels in offspring dropped rapidly at birth which was associated with symptoms and behaviors consistent with neonatal opioid withdrawal. PME produced substantial impairments in offspring physical growth, activity in an open field, and sensorimotor milestone acquisition. Furthermore, these behavioral alterations were associated with reduced neuronal density in the motor cortex and a disruption in motor neuron intrinsic properties and local circuit connectivity. The present study adds to the limited body of work examining PME by providing a comprehensive, translationally relevant characterization of how PME disrupts offspring physical and neurobehavioral development.

The far-reaching opioid crisis extends to babies born to mothers who take prescription or illicit opioids during pregnancy. Opioids such as oxycodone and methadone can freely cross the placenta from mother to baby. With the rising misuse of and addiction to opioids, the number of babies born physically dependent on opioids has risen sharply over the last decade. Although these infants are only passively exposed to opioids in the womb, they can still experience withdrawal symptoms at birth. This withdrawal is characterized by irritability, excessive crying, body shakes, problems with feeding, fevers and diarrhea. While considerable attention has been given to treating opioid withdrawal in newborn babies, little is known about how these children develop in their first years of life. This is, in part, because it is difficult for researchers to separate drug-related effects from other factors in a child's home environment that can also disrupt their development. In addition, the biological mechanisms underpinning opioid-related impairments to infant development also remain unclear. Animal models have been used to study the effects of opioid exposure during pregnancy (termed prenatal exposure) on infants. These models, however, could be improved to better replicate the typical pattern of opioid use among pregnant women. Recognizing this gap, Grecco et al. have developed a mouse model of prenatal methadone exposure where female mice that were previously dependent on oxycodone were treated with methadone throughout their pregnancy. Methadone is an opioid drug commonly prescribed for treating opioid use disorder in pregnant women and was found to accumulate at high levels in the fetal brain of mice, which fell quickly after birth. The offspring also experienced withdrawal symptoms. Grecco et al. then examined the physical, behavioral and brain development of mice born to opioid-treated mothers. These included assessments of the animals' motor skills, sensory reflexes and behavior in their first four weeks of life. Additional experiments tested the properties of nerve cells in the brain to examine cell-level changes. The assessments showed that methadone exposure in the womb impaired the physical growth of offspring and this persisted into 'adolescence'. Prenatal methadone exposure also delayed progress towards key developmental milestones and led to hyperactivity in three-week-old mice. Moreover, Grecco et al. found that these mice had reduced neuron density and cell-to-cell connectivity in the part of the brain which controls movement. These findings shed light on the potential consequences of prenatal methadone exposure on physical, behavioral and brain development in infants. This model could also be used to study new potential treatments or intervention strategies for offspring exposed to opioids during pregnancy.

Hypnotic Enhancement of Virtual Reality Distraction Analgesia during Thermal Pain: A Randomized Trial.

Excessive pain during medical procedures is a pervasive health challenge. This study tested the (additive) analgesic efficacy of combining hypnotic analgesia and virtual reality (VR) pain distraction. A single blind, randomized, and controlled trial was used to study 205 undergraduate volunteers aged 18 to 20. The individual and combined effects of hypnotic analgesia (H) and VR distraction on experimentally induced acute thermal pain were examined using a 2 X 2, between-groups parallel design (4 groups total). Participants in groups that received hypnosis remained hypnotized during the test phase pain stimulus. The main outcome measure was "worst pain" ratings. Hypnosis reduced acute pain even for people who scored low on hypnotizability. As predicted, H+ VR was significantly more effective than VR distraction alone. However, H+ VR was not significantly more effective than hypnotic analgesia alone. Being hypnotized during thermal pain enhanced VR distraction analgesia.

Therapists Make the Switch to Telepsychology to Safely Continue Treating Their Patients During the COVID-19 Pandemic. Virtual Reality Telepsychology May Be Next.

Before COVID-19, most therapists had concerns about telepsychology, and only treated patients in person. During the COVID-19 lockdown, patients still needed therapy, but in-person therapy sessions became unsafe. The current study measured how many therapists are using online therapy before vs. during COVID-19, how much training they have received, and their knowledge about legal restrictions on using telepsychology. A sample of 768 U.S.A. mental health professionals completed a 29-item online survey. Results show that before COVID-19, most therapists only saw their patients in person (e.g., at the therapists office), but during the COVID-19 pandemic, nearly all therapists used a wide range of telecommunication technologies to communicate with their quarantined patients, including texting, telephones, video conferences, and even virtual reality. According to within-subject related samples comparisons, 39% of survey respondents used telepsychology before COVID-19, vs. 98% during COVID-19 (χ2 = 450.02, p< 0.001). Therapists reported high treatment effectiveness using telepsychology (7.45 on 0-10 scale). However, overall, on a 0-10 scale, therapists reported a significant increase in feeling burned out during the COVID-19 pandemic, Mean = 3.93 (SD = 1.93) before vs. 6.22 (SD = 2.27) during the pandemic (Z = -18.57, p < 0.001). Although the APA ethics guidelines encourage therapists to use telepsychology with their patients during the crisis, gaps in respondents' knowledge identify a need for increased specialized training and education. Although the current study showed that virtual reality is rarely used by the therapists surveyed, virtual reality is a promising new telepsychology technology. Billions of dollars are currently being invested in mass producing immersive virtual reality systems. In the future, as networked immersive Virtual Reality becomes more widely available, therapists and patients in physically different locations will be able to "meet" in a shared computer-generated world designed for therapy sessions, potentially including group sessions. Telepsychology and virtual reality have the potential to be increasingly valuable tools to help therapists mitigate the consequences of COVID-19. Research, development and training is recommended.

Decreasing Pain and Fear in Medical Procedures with a Pediatric Population (DREAM): A Pilot Randomized Within-Subject Trial.

BACKGROUND: Many children with injuries, including burns and fractures, experience moderate to severe pain during medical procedures. Recent studies claim that nonpharmacologic pain management using virtual reality (VR) could distract children from procedural pain by engaging multiple senses. AIMS: The aims of this pilot randomized clinical trial were to assess the acceptability and feasibility of VR distraction in children with burns or fractures undergoing painful medical procedures, as well as the staff nurses, and assess the preliminary efficacy of VR distraction on pain intensity, pain-related fear, and subsequent recall of both. MATERIALS AND METHOD: A within-subject study design, in which participants served as their own control, was used. A total of 20 children from 7 to 17 years old with an injury were recruited at the surgical-trauma outpatient clinics of the Centre hospitalier universitaire Sainte-Justine (CHU Sainte-Justine). Each participant received both standard and experimental treatments through randomized order. Pain (numerical rating scale) and pain-related fear (Children's Fear Scale) measures were taken before the procedure and after each sequence, followed by a measure of children's (graphic rating scale) and nurses' acceptability of the intervention through their satisfaction level. Recall of pain intensity and pain-related fear were assessed 24 hours after the procedure. Wilcoxon signed-rank tests were used, with a significance level at 0.05. RESULTS: Results showed that VR distraction was an acceptable and feasible intervention for children and nurses of these outpatient clinics. Preliminary effects showed that, compared to standard of care, children participants reported a significant decrease in pain intensity (p = .023) and pain-related fear (p = .011) during VR as well as less recalled pain-related fear (p = .012) at 24 hours after the procedure. No side effects were reported. CONCLUSION: VR is a promising intervention with children undergoing painful procedures because it is immersive and engages multiple senses. It is a low-cost intervention well accepted by children and nursing staff at this clinical site and is easy to implement in daily practice for procedural pain management.

Mu opioid receptors on vGluT2-expressing glutamatergic neurons modulate opioid reward.

The role of Mu opioid receptor (MOR)-mediated regulation of GABA transmission in opioid reward is well established. Much less is known about MOR-mediated regulation of glutamate transmission in the brain and how this relates to drug reward. We previously found that MORs inhibit glutamate transmission at synapses that express the Type 2 vesicular glutamate transporter (vGluT2). We created a transgenic mouse that lacks MORs in vGluT2-expressing neurons (MORflox-vGluT2cre) to demonstrate that MORs on the vGluT2 neurons themselves mediate this synaptic inhibition. We then explored the role of MORs in vGluT2-expressing neurons in opioid-related behaviors. In tests of conditioned place preference, MORflox-vGluT2cre mice did not acquire place preference for a low dose of the opioid, oxycodone, but displayed conditioned place aversion at a higher dose, whereas control mice displayed preference for both doses. In an oral consumption assessment, these mice consumed less oxycodone and had reduced preference for oxycodone compared with controls. MORflox-vGluT2cre mice also failed to show oxycodone-induced locomotor stimulation. These mice displayed baseline withdrawal-like responses following the development of oxycodone dependence that were not seen in littermate controls. In addition, withdrawal-like responses in these mice did not increase following treatment with the opioid antagonist, naloxone. However, other MOR-mediated behaviors were unaffected, including oxycodone-induced analgesia. These data reveal that MOR-mediated regulation of glutamate transmission is a critical component of opioid reward.

A multi-omic analysis of the dorsal striatum in an animal model of divergent genetic risk for alcohol use disorder.

The development of selectively bred high and low alcohol-preferring mice (HAP and LAP, respectively) has allowed for an assessment of the polygenetic risk for pathological alcohol consumption and phenotypes associated with alcohol use disorder (AUD). Accumulating evidence indicates that the dorsal striatum (DS) is a central node in the neurocircuitry underlying addictive processes. Therefore, knowledge of differential gene, protein, and phosphorylated protein expression in the DS of HAP and LAP mice may foster new insights into how aberrant DS functioning may contribute to AUD-related phenotypes. To begin to elucidate these basal differences, a complementary and integrated analysis of DS tissue from alcohol-naïve male and female HAP and LAP mice was performed using RNA sequencing, quantitative proteomics, and phosphoproteomics. These datasets were subjected to a thorough analysis of gene ontology, pathway enrichment, and hub gene assessment. Analyses identified 2,108, 390, and 521 significant differentially expressed genes, proteins, and phosphopeptides, respectively between the two lines. Network analyses revealed an enrichment in the differential expression of genes, proteins, and phosphorylated proteins connected to cellular organization, cytoskeletal protein binding, and pathways involved in synaptic transmission and functioning. These findings suggest that the selective breeding to generate HAP and LAP mice may lead to a rearrangement of synaptic architecture which could alter DS neurotransmission and plasticity differentially between mouse lines. These rich datasets will serve as an excellent resource to inform future studies on how inherited differences in gene, protein, and phosphorylated protein expression contribute to AUD-related phenotypes.