A Prospective Randomized Controlled Trial Using Virtual Reality in Pediatric Pre-intervention Echocardiograms to Decrease Child Anxiety and Fear.

Virtual reality (VR) as a distraction tool decreases anxiety and fear in children undergoing procedures, but its use has not been studied during transthoracic echocardiograms (TTEs). We hypothesized that VR in children undergoing pre-intervention TTEs decreases anxiety and fear and increases TTE study comprehensiveness and diagnostic accuracy when compared with standard distractors (television, mobile devices). Patients (6-18 years old) scheduled for pre-intervention TTEs at Lucile Packard Children's Hospital in 2021 and 2022 were prospectively enrolled and randomized to VR and non-VR groups. Patients completed pre- and post-TTE surveys using the Children's Anxiety Meter-State (CAM-S) and Children's Fear Scale (CFS). Patients, parents, and sonographers completed post-TTE experience surveys. TTEs were reviewed by pediatric cardiologists for study comprehensiveness and compared with electronic medical records for diagnostic accuracy. Among 67 enrolled patients, 6 declined VR, 31 randomized to the VR group, and 30 to the non-VR group. Anxiety (average CAM-S difference 0.78 ± 1.80, p = 0.0012) and fear (average CFS difference 0.36 ± 0.74, p = 0.0005) decreased in both groups. There was no difference between groups in the change in anxiety and fear pre- and post-TTE (p = 0.96-1.00). TTE study comprehensiveness and diagnostic accuracy were high in both groups. Procedure time (time in the echocardiography room) was less for the VR group (48.4 ± 18.1 min) than the non-VR group (58.8 ± 24.4 min), but without a statistically significant difference (p = 0.075). VR is similar to standard distractors and may decrease procedure time. Patients, parents, and sonographers rated the VR experience highly and encouraged its use with future procedures.

Pediatric Central Nervous System Cancers in the Democratic People's Republic of Korea.

PURPOSE: Central nervous system (CNS) cancers rank as the most frequent solid tumors and the leading cause of cancer-related deaths in children and adolescents. There is less information available about pediatric brain and CNS tumors in low-income and middle-income countries, suggesting a lack of surgical accessibility or limited capacity to treat these conditions. In this study, we chose to study the epidemiology of CNS cancers in the Democratic People's Republic of Korea (DPRK). METHODS: We extracted the prevalence, incidence, deaths, and disability-adjusted life years (DALYs) associated with CNS cancers in individuals under the age of 20 from the 2017 Global Burden of Disease study from the Institute for Health Metrics and Evaluation. DALYs, which signify the number of healthy life years lost due to ill health, disability, or early death. Economic impact was calculated from DALYs. CONCLUSIONS: Given the large burden of brain and CNS cancers among all pediatric cancers in the DPRK, scaling up and strengthening surgical services for children is an essential component to improving care of pediatric CNS cancers in the DPRK. Childhood cancers are time sensitive, and early diagnosis and treatment are vital in ensuring improved survival for the vulnerable pediatric cancer patient population. As surgical treatment can often prolong lives and even prevent premature deaths from these cancers, further analysis of current surgical capacity can inform the path to meeting these critical pediatric surgical needs.

3-[(5-Chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl ]-1,3,4-oxadiazol-2(3H)-one, BMS-191011: opener of large-conductance Ca(2+)-activated potassium (maxi-K) channels, identification, solubility, and SAR.

Compound 8a (BMS-191011), an opener of the cloned large-conductance, Ca2+-activated potassium (maxi-K) channel, demonstrated efficacy in in vivo stroke models, which led to its nomination as a candidate for clinical evaluation. Its maxi-K channel opening properties were consistent with its structural topology, being derived by combining elements from other known maxi-K openers. However, 8a suffered from poor aqueous solubility, which complicated elucidation of SAR during in vitro evaluation. The activity of 8a in in vivo stroke models and studies directed toward improving its solubility are reported herein. Enhanced solubility was achieved by appending heterocycles to the 8a scaffold, and a notable observation was made that inclusion of a simple amino group (anilines 8k and 8l) yielded excellent in vitro maxi-K ion channel opening activity and enhanced brain-to-plasma partitioning compared to the appended heterocycles.

Synthesis and structure-activity relationships of 3-aryloxindoles: a new class of calcium-dependent, large conductance potassium (maxi-K) channel openers with neuroprotective properties.

A series of 3-aryloxindole derivatives were synthesized and evaluated as activators of the cloned maxi-K channel mSlo expressed in Xenopus laevis oocytes using electrophysiological methods. The most promising maxi-K openers to emerge from this study were (+/-)-3-(5-chloro-2-hydroxyphenyl)-1,3-dihydro-3-hydroxy-6-(trifluoromethyl)-2H-indol-2-one ((+/-)-8c) and its 3-des-hydroxy analogue (+/-)-11b. The individual enantiomers of (+/-)-8c were synthesized, and the maxi-K channel-opening properties were shown to depend on the absolute configuration of the single stereogenic center with the efficacy of (-)-8c superior to that of both (+)-8c and the racemic mixture when evaluated at a concentration of 20 microM. Racemic 11b exhibited greater efficacy than either the racemic 8c or the more active enantiomer in the electrophysiological evaluation. In vitro metabolic stability studies conducted with (+/-)-8c and (+/-)-11b in rat liver S9 microsomal fractions revealed significant oxidative degradation with two hydroxylated metabolites observed by liquid chromatography/mass spectrometry for each compound in addition to the production of 8c from 11b. The pharmacokinetic properties of (+/-)-8c and (+/-)-11b were determined in rats as a prelude to evaluation in a rat model of stroke that involved permanent occlusion of the middle cerebral artery (MCAO model). In the MCAO model, conducted in the spontaneously hypertensive rat, the more polar 3-hydroxy derivative (+/-)-8c did not demonstrate a significant reduction in cortical infarct volume when administered intravenously at doses ranging from 0.1 to 10 mg/kg as a single bolus 2 h after middle cerebral artery occlusion when compared to vehicle-treated controls. In contrast, intravenous administration of (+/-)-11b at a dose of 0.03 mg/kg was found to reduce the measured cortical infarct volume by approximately 18% when compared to vehicle-treated control animals. Intraperitoneal administration of (+/-)-11b at a dose of 10 mg/kg 2 h following artery occlusion was shown to reduce infarct volume by 26% when compared to vehicle-treated controls. To further probe the effects of compounds (+/-)-8c and (+/-)-11b on neurotransmitter release in vitro, both compounds were examined for their ability to reduce electrically stimulated [3H]-glutamate release from rat hippocampal slices that had been preloaded with [3H]-glutamate. Only (+/-)-11b was able to demonstrate a significant inhibition [3H]-glutamate release in this assay at a concentration of 20 microM, providing concordance with the profile of these compounds in the MCAO model. Although (+/-)-11b showed some promise as a potential developmental candidate for the treatment of the sequelae of stroke based on its efficacy in the rat MCAO model, the pharmacokinetic profile of this compound was considered to be less than optimal and was not pursued in favor of derivatives with enhanced metabolic stability.

The synthesis and structure-activity relationships of 4-aryl-3-aminoquinolin-2-ones: a new class of calcium-dependent, large conductance, potassium (maxi-K) channel openers targeted for post-stroke neuroprotection.

A series of 4-aryl-3-aminoquinoline-2-one derivatives was synthesized and evaluated as activators of the cloned maxi-K channel mSlo (hSlo) expressed in Xenopus laevis oocytes using electrophysiological methods. A brain penetrable activator of maxi-K channels was identified and shown to be significantly active in the MCAO model of stroke.