Innovations in diagnostic and treatment options for pediatric epilepsy and their anesthetic implications.

PURPOSE OF REVIEW: To provide an overview of anesthetic techniques for innovative diagnostic and therapeutic epilepsy procedures performed on pediatric patients. RECENT FINDINGS: Recent studies have been published on the anesthetic consideration for functional MRI, robotic-assisted stereoelectroencephalography, high-intensity focused ultrasound, and magnetoencephalography. These articles describe the anesthesia management, risks, and outcome for these procedures. SUMMARY: The number of diagnostic and treatment options being used for the management of pediatric epilepsy has increased significantly. In the past few years, a handful of articles have been published, which describe the anesthetic considerations for these procedures. These studies are helpful to anesthesiologists who are planning an upcoming anesthetic or who are developing a 'best practice' model for their institution. Because unlike other diagnostic studies, failure to understand what effects anesthetics have on the brain, may negate the utility of the study. Although these new findings can be used to provide some anesthesia practice recommendations for epilepsy procedures in which the best management is still unclear, additional high-quality studies are needed.

Racial and Ethnic Disparities in Physical and Mental Health Care and Clinical Trials.

Historically, in the United States, scientific racism has been used to justify differential treatment of Black, Indigenous, People of Color (BIPOC) populations compared with the White population. Discrimination toward BIPOC populations by the medical community has contributed to racial and ethnic disparities in health care that persist to this day. At the 2022 American Society of Clinical Psychopharmacology Annual Meeting, a panel of 5 experts from the areas of academia, advocacy, and clinical research discussed racial and ethnic disparities in mental health care. This Academic Highlights summarizes and expands on that discussion by tracing the history of scientific racism from the colonization of the US to present-day health inequities, illustrating the ongoing problem of low diversity in clinical trials, and outlining solutions through community engagement.

Perceptions of Use of Names, Recognition of Roles, and Teamwork After Labeling Surgical Caps.

Importance: Communication failures in perioperative areas are common and have negative outcomes for both patients and clinicians. Names and roles of teammates are difficult to remember or discern contributing to suboptimal communication, yet the utility of labeled surgical caps with names and roles for enhancing perceived teamwork and connection is not well studied. Objective: To evaluate the use of labeled surgical caps in name use and role recognition, as well as teamwork and connection, among interprofessional perioperative teammates. Design, Setting, and Participants: In this quality improvement study, caps labeled with names and roles were distributed to 967 interprofessional perioperative clinicians, along with preimplementation and 6-month postimplementation surveys. Conducted between July 8, 2021, and June 25, 2022, at a single large, academic, quaternary health care center in the US, the study comprised surgeons, anesthesiologists, trainees, and all interprofessional hospital staff who work in adult general surgery perioperative areas. Intervention: Labeled surgical caps were offered cost-free, although not mandatory, to each interested clinician. Main Outcome and Measure: Quantitative survey of self-reported frequency for name use and role recognition as well as postimplementation sense of teamwork and connection. The surveys also elicited free response comments. Results: Of the 1483 eligible perioperative clinicians, 967 (65%; 387 physicians and 580 nonphysician staff; 58% female) completed preimplementation surveys and received labeled caps, and 243 of these individuals (51% of physicians and 8% of staff) completed postimplementation surveys. Pre-post results were limited to physicians, due to the low postsurvey staff response rate. The odds of participants reporting that they were often called by their name increased after receiving a labeled cap (adjusted odds ratio [AOR], 13.37; 95% CI, 8.18-21.86). On postsurveys, participants reported that caps with names and roles substantially improved teamwork (80%) and connection (79%) with teammates. Participants who reported an increased frequency of being called by their name had higher odds for reporting improved teamwork (AOR, 3.46; 95% CI, 1.91-6.26) and connection with teammates (AOR, 3.21; 95% CI, 1.76-5.84). Free response comments supported the quantitative data that labeled caps facilitated knowing teammates' names and roles and fostered a climate of wellness, teamwork, inclusion, and patient safety. Conclusions and Relevance: The findings of this quality improvement study performed with interprofessional teammates suggest that organizationally sponsored labeled surgical caps was associated with improved teamwork, indicated by increased name use and role recognition in perioperative areas.

A Pilot Quality Improvement Project to Reduce Intraoperative MRI Hypothermia in Neurosurgical Patients.

Intraoperative hypothermia increases patient morbidity, including bleeding and infection risk. Neurosurgical intraoperative magnetic resonance imaging (iMRI) can lead to hypothermia from patient exposure and low ambient temperature in the MRI suite. This quality improvement project aimed to reduce the risk of hypothermia during pediatric neurosurgery laser ablation procedures with iMRI. The primary aim was to increase the mean lowest core temperature in pediatric patients with epilepsy during iMRI procedures by 1 °C from a baseline mean lowest core temperature of 34.2 ± 1.2 °C within 10 months and sustain for 10 months. Methods: This report is a single-institution quality improvement project from March 2019 to June 2021, with 21 patients treated at a pediatric hospital. After identifying key drivers, temperature-warming interventions were instituted to decrease hypothermia among patients undergoing iMRI during neurosurgery procedures. A multidisciplinary team of physicians, nurses, and MRI technologists convened for huddles before each case. Interventions included prewarmed operating rooms (ORs), blanket coverings, MRI table and room; forced-air blanket warming, temperature monitoring in the OR and iMRI environments; and the MRI fan turned off. Results: Data were analyzed for five patients before and nine patients after the institution of the temperature-warming elements. The sustainment period included 15 patients. The mean lowest intraoperative temperature rose from 34.2 ± 1.3 °C in the preintervention period to 35.5 ± 0.6 °C in sustainment (P = 0.004). Conclusion: Hybrid OR and MRI procedures increase hypothermia risk, which increases patient morbidity. Implementation of a multidisciplinary, multi-item strategy for patient warming mitigates the risk.

Order processing of number symbols is influenced by direction, but not format.

This study probed the cognitive mechanisms that underlie order processing for number symbols, specifically the extent to which the direction and format in which number symbols are presented influence the processing of numerical order, as well as the extent to which the relationship between numerical order processing and mathematical achievement is specific to Arabic numerals or generalisable to other notational formats. Seventy adults who were bilingual in English and Chinese completed a Numerical Ordinality Task, using number sequences of various directional conditions (i.e., ascending, descending, mixed) and notational formats (i.e., Arabic numerals, English number words, and Chinese number words). Order processing was found to occur for ascending and descending number sequences (i.e., ordered but not non-ordered trials), with the overall pattern of data supporting the theoretical perspective that the strength and closeness of associations between items in the number sequence could underlie numerical order processing. However, order processing was found to be independent of the notational format in which the numerical stimuli were presented, suggesting that the psychological representations and processes associated with numerical order are abstract across different formats of number symbols. In addition, a relationship between the processing speed for numerical order judgements and mathematical achievement was observed for Arabic numerals and Chinese number words, and to a weaker extent, English number words. Together, our findings have started to uncover the cognitive mechanisms that could underlie order processing for different formats of number symbols, and raise new questions about the generalisability of these findings to other notational formats.

Outcome in young adults who were diagnosed with complex regional pain syndrome in childhood and adolescence.

INTRODUCTION: Complex regional pain syndrome (CRPS) is a neuropathic pain condition of unknown etiology. Little is known of long-term outcomes of young adults who were diagnosed with CRPS as children. METHODS: In this study, surveys were mailed to adults who were treated for childhood CRPS at the Lucile Packard Children's Hospital between 1994 and 2018. Completed surveys were analyzed for pain symptoms. Health-related quality-of-life surveys, the Optum SF-8, were analyzed based on norm-based scoring. RESULTS: This study had a 50% response rate. Patients were treated with physical and occupational therapy, peripheral or sympathetic nerve blocks, medication for neuropathic pain, and psychotherapy. Sixty-eight percent of the subjects reported pain. Each 1-year increase in the patient's age at the time of CRPS diagnosis increased the odds of having at least mild pain as an adult by 61% (P = 0.005). Most patients had slightly lower quality-of-life scores than the US population average in both the mental component score (43.4, 95%, confidence interval 3.4) and the physical component score (44.4, 95%, confidence interval 3.3). CONCLUSIONS: Young adults in our sample had long-lasting pain symptoms. More than two-thirds of adult patients reported some degree of pain, and these patients had a lower quality of life. Encouraging was that the majority did not have CRPS spreading to other areas, and their pain did not warrant further treatment. Understanding long-term outcomes may lead to risk stratification earlier in the disease to improve future quality of life.

Early Assessment of Molecular Progression and Response by Whole-genome Circulating Tumor DNA in Advanced Solid Tumors.

Treatment response assessment for patients with advanced solid tumors is complex and existing methods require greater precision. Current guidelines rely on imaging, which has known limitations, including the time required to show a deterministic change in target lesions. Serial changes in whole-genome (WG) circulating tumor DNA (ctDNA) were used to assess response or resistance to treatment early in the treatment course. Ninety-six patients with advanced cancer were prospectively enrolled (91 analyzed and 5 excluded), and blood was collected before and after initiation of a new, systemic treatment. Plasma cell-free DNA libraries were prepared for either WG or WG bisulfite sequencing. Longitudinal changes in the fraction of ctDNA were quantified to retrospectively identify molecular progression (MP) or major molecular response (MMR). Study endpoints were concordance with first follow-up imaging (FFUI) and stratification of progression-free survival (PFS) and overall survival (OS). Patients with MP (n = 13) had significantly shorter PFS (median 62 days vs. 310 days) and OS (255 days vs. not reached). Sensitivity for MP to identify clinical progression was 54% and specificity was 100%. MP calls were from samples taken a median of 28 days into treatment and 39 days before FFUI. Patients with MMR (n = 27) had significantly longer PFS and OS compared with those with neither call (n = 51). These results demonstrated that ctDNA changes early after treatment initiation inform response to treatment and correlate with long-term clinical outcomes. Once validated, molecular response assessment can enable early treatment change minimizing side effects and costs associated with additional cycles of ineffective treatment.

Transition to Practice in Anesthesiology: Survey Results of Practicing Anesthesiologists on Their Experience.

STUDY OBJECTIVE: To assess the experiences and attitudes of practicing anesthesiologists on practice/business management training received during residency and transitioning to practice through an online survey. DESIGN: An online survey, consisting of 39 questions developed by the American Society of Anesthesiologists (ASA) Committee on Young Physicians, was emailed to 2 6551 practicing US anesthesiologists who were ASA members. MEASUREMENTS: Questions about individuals' demographic information, transition to practice (TTP) experiences, medical business training, and TTP curricula in residency were included. Results were reported as descriptive statistics. MAIN RESULTS: A total of 1199 responses were obtained (response rate 4.5%), and68% reported working in private practice over an average of 17 years. Those practicing ≤ 10 years were more likely to have a TTP curriculum in residency compared to those in practice ≥ 11 years. Common problems reported by many participants regarding TTP included: lack of effective mentorship, inadequate residency curricula/education, and an unfamiliarity with available resources. CONCLUSIONS: Although medical business practice education is now required by training programs, there is room for improvement in education. One potential solution is establishing TTP curricula in residency programs, which emphasize the business aspects of medicine and practice management, thus easing trainees from a training to practice environment.

Magnitude processing of written number words is influenced by task, rather than notation.

The extent to which task and notation influence the processing of numerical magnitude is under theoretical and empirical debate. To date, behavioural studies have yielded a mixed body of evidence. Using the case of written number words in English and Chinese, we re-examined this issue. Thirty-nine bilingual participants who showed a balanced profile of language dominance in English and Chinese completed three tasks of numerical processing (Magnitude Comparison, Numerical Matching, and Language Matching) with pure English, pure Chinese, and mixed notation number words. We conducted frequentist and Bayesian statistics on the data. Magnitude processing, as indexed by the numerical distance effect (NDE), was found to be dependent on task. Specifically, the NDE occurred in all notation conditions in the Magnitude Comparison Task and mixed notation trials in the Numerical Matching Task only. However, the data indicated that magnitude processing was independent of notation. Task and notation had an interactive influence on overall speed of processing, where participants responded to Chinese number words significantly faster than other notations for the Magnitude Comparison and Numerical Matching Tasks only. Finally, Bayesian analyses indicated that task and notation do not interact to affect magnitude processing. Specifically, the Bayes Factor and posterior model probabilities of the Bayesian ANOVA yielded strongest support for the model with three main effects (Task, Notation, Numerical Distance) and two two-way interactions (Task × Numerical Distance, Task × Notation). These findings highlight the critical role of task in numerical magnitude processing, provide support for a notation-independent account of magnitude processing, and suggest that linguistic/orthographic factors, combined with task, may interact to affect overall speed of processing.

Neurolinguistics: Structure, Function, and Connectivity in the Bilingual Brain.

Advances in neuroimaging techniques and analytic methods have led to a proliferation of studies investigating the impact of bilingualism on the cognitive and brain systems in humans. Lately, these findings have attracted much interest and debate in the field, leading to a number of recent commentaries and reviews. Here, we contribute to the ongoing discussion by compiling and interpreting the plethora of findings that relate to the structural, functional, and connective changes in the brain that ensue from bilingualism. In doing so, we integrate theoretical models and empirical findings from linguistics, cognitive/developmental psychology, and neuroscience to examine the following issues: (1) whether the language neural network is different for first (dominant) versus second (nondominant) language processing; (2) the effects of bilinguals' executive functioning on the structure and function of the "universal" language neural network; (3) the differential effects of bilingualism on phonological, lexical-semantic, and syntactic aspects of language processing on the brain; and (4) the effects of age of acquisition and proficiency of the user's second language in the bilingual brain, and how these have implications for future research in neurolinguistics.

Single-digit Arabic numbers do not automatically activate magnitude representations in adults or in children: evidence from the symbolic same-different task.

We investigated whether the mere presentation of single-digit Arabic numbers activates their magnitude representations using a visually-presented symbolic same-different task for 20 adults and 15 children. Participants saw two single-digit Arabic numbers on a screen and judged whether the numbers were the same or different. We examined whether reaction time in this task was primarily driven by (objective or subjective) perceptual similarity, or by the numerical difference between the two digits. We reasoned that, if Arabic numbers automatically activate magnitude representations, a numerical function would best predict reaction time; but if Arabic numbers do not automatically activate magnitude representations, a perceptual function would best predict reaction time. Linear regressions revealed that a perceptual function, specifically, subjective visual similarity, was the best and only significant predictor of reaction time in adults and in children. These data strongly suggest that, in this task, single-digit Arabic numbers do not necessarily automatically activate magnitude representations in adults or in children. As the first study to date to explicitly study the developmental importance of perceptual factors in the symbolic same-different task, we found no significant differences between adults and children in their reliance on perceptual information in this task. Based on our findings, we propose that visual properties may play a key role in symbolic number judgements.

Adolescent political activism and long-term happiness: a 21-year longitudinal study on the development of micro- and macrosocial worries.

Utilizing latent growth modeling, the long-term development of worries among peace movement supporters is examined. Data originate from a seven-wave German longitudinal study started in 1985 with on average 14-year-olds. Waves were interspersed 3 and a half years each. Activists are assumed to have lower (self-related) microworries (Hypothesis 1) and higher macroworries (concerned with larger entities; Hypothesis 2) than nonactivists at the onset of the study. Nonactivists who appraised the threat of nuclear war as high in 1985 are assumed to report worse mental health than their activist age-mates 21 years later (Hypothesis 3). Activists are assumed to express relatively more macroworries than nonactivists in midadulthood (Hypothesis 4). All four hypotheses were confirmed. Results are interpreted in a stress-coping (Lazarus) and resource (Elder) framework, suggesting that refraining from acting out against a perceived sociopolitical threat is a long-term risk for a positive mental health trajectory.

Association of hypoglycemia, hyperglycemia, and glucose variability with morbidity and death in the pediatric intensive care unit.

OBJECTIVE: We evaluated retrospectively plasma glucose levels and the degree of hypoglycemia, hyperglycemia, and glucose variability in a PICU and then assessed their association with hospital length of stay and mortality rates. METHODS: Electronic medical records at the Packard Children's Hospital at Stanford University were reviewed retrospectively for all PICU admissions between March 1, 2003, and March 31, 2004. Patients with a known diagnosis of diabetes mellitus were excluded. The prevalence of hyperglycemia was defined with cutoff values of 110, 150, and 200 mg/dL. Hypoglycemia was defined as < or = 65 mg/dL. Glucose variability was assessed with a calculated glucose variability index. RESULTS: In 13 months, 1094 eligible admissions generated 18865 glucose values (median: 107 mg/dL; range: 13-1839 mg/dL). Patients in the highest maximal glucose quintile had a significantly longer median PICU length of stay, compared with those in the lowest quintile (7.5 days vs 1 day). Mortality rates increased as patients' maximal glucose levels increased, reaching 15.2% among patients with the greatest degree of hyperglycemia. Hypoglycemia was also prevalent, with 18.6% of patients (182 of 980 patients) having minimal glucose levels of < or = 65 mg/dL. There was an increased median PICU length of stay (9.5 days vs 1 day) associated with glucose values in the lowest minimal quintile, compared with those in the highest quintile. Hypoglycemia was correlated with mortality rates; 16.5% of patients with glucose levels of < or = 65 mg/dL died. Glucose variability also was associated with increased length of stay and mortality rates. In multivariate logistic regression analyses, glucose variability, taken with hyperglycemia and hypoglycemia, showed the strongest association with mortality rates. CONCLUSIONS: Hyperglycemia and hypoglycemia were prevalent in the PICU. Hypoglycemia, hyperglycemia, and, in particular, increased glucose variability were associated with increased morbidity (length of stay) and mortality rates.

Sequence-resolved detection of pausing by single RNA polymerase molecules.

Transcriptional pausing by RNA polymerase (RNAP) plays an important role in the regulation of gene expression. Defined, sequence-specific pause sites have been identified biochemically. Single-molecule studies have also shown that bacterial RNAP pauses frequently during transcriptional elongation, but the relationship of these "ubiquitous" pauses to the underlying DNA sequence has been uncertain. We employed an ultrastable optical-trapping assay to follow the motion of individual molecules of RNAP transcribing templates engineered with repeated sequences carrying imbedded, sequence-specific pause sites of known regulatory function. Both the known and ubiquitous pauses appeared at reproducible locations, identified with base-pair accuracy. Ubiquitous pauses were associated with DNA sequences that show similarities to regulatory pause sequences. Data obtained for the lifetimes and efficiencies of pauses support a model where the transition to pausing branches off of the normal elongation pathway and is mediated by a common elemental state, which corresponds to the ubiquitous pause.

Analysis of the Arabidopsis MADS AFFECTING FLOWERING gene family: MAF2 prevents vernalization by short periods of cold.

The Arabidopsis FLOWERING LOCUS C (FLC) gene is a key floral repressor in the maintenance of a vernalization response. In vernalization-sensitive genetic backgrounds, FLC levels are high, and they decline after exposure to long cold periods. Four FLC paralogs (MAF2 [MADS AFFECTING FLOWERING2] to MAF5) are arranged in a tandem array on the bottom of Arabidopsis chromosome V. We used a reverse genetics approach to analyze their functions. Loss-of-function and gain-of-function studies indicate that MAF2 acts as a floral repressor. In particular, maf2 mutant plants display a pronounced vernalization response when subjected to relatively short cold periods, which are insufficient to elicit a strong flowering response in the wild type, despite producing a large reduction in FLC levels. MAF2 expression is less sensitive to vernalization than that of FLC, and its repressor activity is exerted independently or downstream of FLC transcription. Thus, MAF2 can prevent premature vernalization in response to brief cold spells. Overexpression of MAF3 or MAF4 produces alterations in flowering time that suggest that these genes also act as floral repressors and might contribute to the maintenance of a vernalization requirement. However, the final gene in the cluster, MAF5, is upregulated by vernalization. Therefore, MAF5 could play an opposite role to FLC in the vernalization response.