Virtual Reality as Anxiolysis During Laceration Repair in the Pediatric Emergency Department.

BACKGROUND: Although procedural pain is effectively treated with analgesics, managing anxiety during laceration repair is more challenging. OBJECTIVES: We examined the feasibility of using immersive virtual reality (VR) as anxiolysis during laceration repair in the pediatric emergency department (ED). METHODS: We conducted a non-blinded, observational, pilot study in an urban pediatric ED that enrolled a convenience sample of children aged 5-13 years undergoing sutured repair of non-facial lacerations. Subjects played an immersive VR game while undergoing laceration repair. Parents assessed their child's anxiety on a 100-mm visual analogue scale at enrollment and during laceration repair. The primary outcome measure was the percentage of children whose anxiety score did not increase by ≥ 20 mm from enrollment to the first stitch. RESULTS: Forty patients completed the study. Mean initial anxiety score was 54 mm (standard deviation 33 mm). Thirty-seven of forty patients (93%; 95% confidence interval [CI] 83-99%) had anxiety scores that did not increase by 20 mm or more from enrollment to the first stitch. Eighty percent (95% CI 64-91%) of patients' anxiety scores decreased between enrollment and first stitch. The mean change in anxiety score at first stitch was -39 mm (95% CI -51 mm to -27 mm; p < 0.001). Similar downward trends in anxiety scores were noted throughout the procedure. All laceration repairs were successfully completed without sedation or restraints. There were no adverse events noted, and the main barriers identified with VR use involved easily correctable technical difficulties with the equipment. CONCLUSION: Immersive VR is a safe and effective distractive technique to reduce procedural anxiety during laceration repair in the pediatric ED.

Clotting events among hospitalized patients infected with COVID-19 in a large multisite cohort in the United States.

INTRODUCTION: COVID-19 infection has been hypothesized to precipitate venous and arterial clotting events more frequently than other illnesses. MATERIALS AND METHODS: We demonstrate this increased risk of blood clots by comparing rates of venous and arterial clotting events in 4400 hospitalized COVID-19 patients in a large multisite clinical network in the United States examined from April through June of 2020, to patients hospitalized for non-COVID illness and influenza during the same time period and in 2019. RESULTS: We demonstrate that COVID-19 increases the risk of venous thrombosis by two-fold compared to the general inpatient population and compared to people with influenza infection. Arterial and venous thrombosis were both common occurrences among patients with COVID-19 infection. Risk factors for thrombosis included male gender, older age, and diabetes. Patients with venous or arterial thrombosis had high rates of admission to the ICU, re-admission to the hospital, and death. CONCLUSION: Given the ongoing scientific discussion about the impact of clotting on COVID-19 disease progression, these results highlight the need to further elucidate the role of anticoagulation in COVID-19 patients, particularly outside the intensive care unit setting. Additionally, concerns regarding clotting and COVID-19 vaccines highlight the importance of addressing the alarmingly high rate of clotting events during actual COVID-19 infection when weighing the risks and benefits of vaccination.

Private High School Reopened-COVID Mitigation and Clinical Surveillance Using an Internet Application.

CONTEXT: Recommendations for COVID-safe, in-person, high school education have included masks and distancing between students but do not describe a scalable surveillance solution to rapidly identify and mitigate disease prevalence or exposure. METHODS: Through an Internet application, all school participants reported symptoms, illness, or exposure daily. Physician-supervised follow-up interviews were reviewed and recorded in daily rounds. Students and faculty were allowed or prohibited to enter school based on the results. RESULTS: From August 30, 2020, until April 13, 2021, a high school in Bergen County, New Jersey (an epicenter of high COVID prevalence), with 889 students and 214 faculty members, staff, and volunteers, generated 1497 assessments. Reasons for initial evaluation included 48 (3%) participants with positive COVID tests, 520 (34%) COVID-exposed, 178 (12%) exposed to someone with symptoms and unknown COVID status, 208 (14%) subjects with symptoms themselves, 525 (35%) exposed to a high-risk geography or air travel, and 12 (1%) contacts of a contact. Of the 61 subjects ultimately diagnosed with COVID, the sources of infection were 36 (57%) home exposure, 16 (27%) confirmed nonschool sources, 8 (13%) unknown, 1 (2%) travel to a high-risk area, and only one potential case of in-school transmission. CONCLUSIONS: Masks, distance, and aggressive contact tracing supported by an Internet application with consistent application of quarantine protocols successfully permitted in-school education without COVID spread in a high prevalence environment. This finding remains important to guide safety measures should vaccine-resistant strains-or new pandemics-challenge us in the future.

Inhibition by stabilization: targeting the Plasmodium falciparum aldolase-TRAP complex.

BACKGROUND: Emerging resistance of the malaria parasite Plasmodium to current therapies underscores the critical importance of exploring novel strategies for disease eradication. Plasmodium species are obligate intracellular protozoan parasites. They rely on an unusual form of substrate-dependent motility for their migration on and across host-cell membranes and for host cell invasion. This peculiar motility mechanism is driven by the 'glideosome', an actin-myosin associated, macromolecular complex anchored to the inner membrane complex of the parasite. Myosin A, actin, aldolase, and thrombospondin-related anonymous protein (TRAP) constitute the molecular core of the glideosome in the sporozoite, the mosquito stage that brings the infection into mammals. METHODS: Virtual library screening of a large compound library against the PfAldolase-TRAP complex was used to identify candidate compounds that stabilize and prevent the disassembly of the glideosome. The mechanism of these compounds was confirmed by biochemical, biophysical and parasitological methods. RESULTS: A novel inhibitory effect on the parasite was achieved by stabilizing a protein-protein interaction within the glideosome components. Compound 24 disrupts the gliding and invasive capabilities of Plasmodium parasites in in vitro parasite assays. A high-resolution, ternary X-ray crystal structure of PfAldolase-TRAP in complex with compound 24 confirms the mode of interaction and serves as a platform for future ligand optimization. CONCLUSION: This proof-of-concept study presents a novel approach to anti-malarial drug discovery and design. By strengthening a protein-protein interaction within the parasite, an avenue towards inhibiting a previously "undruggable" target is revealed and the motility motor responsible for successful invasion of host cells is rendered inactive. This study provides new insights into the malaria parasite cell invasion machinery and convincingly demonstrates that liver cell invasion is dramatically reduced by 95 % in the presence of the small molecule stabilizer compound 24.

Tagetitoxin inhibits RNA polymerase through trapping of the trigger loop.

Tagetitoxin (Tgt) inhibits multisubunit chloroplast, bacterial, and some eukaryotic RNA polymerases (RNAPs). A crystallographic structure of Tgt bound to bacterial RNAP apoenzyme shows that Tgt binds near the active site but does not explain why Tgt acts only at certain sites. To understand the Tgt mechanism, we constructed a structural model of Tgt bound to the transcription elongation complex. In this model, Tgt interacts with the ß' subunit trigger loop (TL), stabilizing it in an inactive conformation. We show that (i) substitutions of the Arg residue of TL contacted by Tgt confer resistance to inhibitor; (ii) Tgt inhibits RNAP translocation, which requires TL movements; and (iii) paused complexes and a "slow" enzyme, in which the TL likely folds into an altered conformation, are resistant to Tgt. Our studies highlight the role of TL as a target through which accessory proteins and antibiotics can alter the elongation complex dynamics.

Social approach-avoidance behavior of inbred mouse strains towards DBA/2 mice.

Little is known about the genetics of social approach-avoidance behaviors. We measured social approach-avoidance of prepubescent female C57BL/6J, DBA/2J, FVB/NJ, AKR/J, A/J, and BALB/cJ mice towards prepubescent DBA/2J female mice. C57BL/6J mice showed the greatest predominance of approach, while BALB/cJ mice showed the greatest predominance of avoidance. Thus, this phenotype is affected by spontaneous genetic variation in mice and can be measured in an assay useful for future neurogenetic studies.