Mindfulness supports emotional resilience in children during the COVID-19 pandemic.

An important aspect of mental health in children is emotional resilience: the capacity to adapt to, and recover from, stressors and emotional challenges. Variation in trait mindfulness, one's disposition to attend to experiences with an open and nonjudgmental attitude, may be an important individual difference in children that supports emotional resilience. In this study, we investigated whether trait mindfulness was related to emotional resilience in response to stressful changes in education and home-life during the COVID-19 pandemic in the United States. We conducted a correlational study examining self-report data from July 2020 to February 2021, from 163 eight-to ten-year-old children living in the US. Higher trait mindfulness scores correlated with less stress, anxiety, depression, and negative affect in children, and lower ratings of COVID-19 impact on their lives. Mindfulness moderated the relationship between COVID-19 child impact and negative affect. Children scoring high on mindfulness showed no correlation between rated COVID-19 impact and negative affect, whereas those who scored low on mindfulness showed a positive correlation between child COVID-19 impact and negative affect. Higher levels of trait mindfulness may have helped children to better cope with a wide range of COVID-19 stressors. Future studies should investigate the mechanisms by which trait mindfulness supports emotional resilience in children.

The LazyBox Educational Intervention Trial: Can Longitudinal Practice on a Low-Fidelity Microsurgery Simulator Improve Microsurgical Skills?

Introduction Every surgical trainee must acquire microsurgical skills within a limited timeframe. Therefore, identifying effective educational strategies to help learners attain these skills is crucial. Objective Establish the effectiveness of a low-fidelity microsurgery simulator to improve the execution and one's perception of the difficulty of basic surgical techniques. Methods From 2021 to 2022, 24 medical students were randomized to either (1) a treatment group (n=12) that engaged in longitudinal practice on a low-fidelity microsurgery simulator (the LazyBox) or (2) a control group (n=12) that did not practice. Students performed vessel loop ligation, catheter macroanastomosis, and synthetic vessel microanastomosis prior to and six weeks after intervention. Both objective metrics and subjective metrics (Swedish Occupational Fatigue Inventory (SOFI) and Surgery Task Load Index (SURG-TLX)) were obtained. Results The treatment and control arms had 1.2 (SD = 2.6) and 2.1 (SD = 2.4) points increase in the vessel loop ligation, respectively (p = 0.39). The treatment and control arms had a 3.4 (SD = 4.1) and 2.9 (SD = 3.6) points increase in the macroanastomosis task, respectively (p = 0.74). In the synthetic vessel microanastomosis task training, the experimental and control arms showed a 5.4 (SD = 8.3) and a 2.9 (SD = 5.6) points increase, respectively (p = 0.30). No differences were found between the groups regarding survey metrics of mental (p = 0.82), temporal (p = 0.23), and physical demands (p = 0.48). Conclusion In our randomized educational intervention, we found no significant difference in objective and subjective metrics of microsurgical task performance between learners who did and did not use the LazyBox simulator.

At-home use of app-based mindfulness for children: A randomized active-controlled trial.

Objectives: School-based mindfulness interventions in children have shown benefits to child well-being. Here, we investigated the effectiveness of a remote, app-based mindfulness intervention for promoting well-being in children. Methods: We conducted a randomized controlled trial (RCT) with two control groups to examine the effects of an 8-week mindfulness intervention in U.S. children ages 8-10. We compared pre-post effects between a mindfulness intervention using the Inner Explorer app, and two audiobook control interventions. The 279 children who participated in the interventions were assessed on self-report measures of anxiety and depression symptoms, perceived stress and trait mindfulness and we also collected parental reports. Results: Over 80% of children completed the intervention in each condition. There was evidence for reduced self-perceived stress in children and reduced negative affect in children by parental reports using the mindfulness app, but no significant reduction for anxiety or depression symptoms. In general, between-group effect sizes were small (ds < 0.45). Regular use, defined as at least 30 days of mindfulness practice within the study period, was associated with reduced child negative affect by parental reports, as well as reduced parental stress and child self-perceived stress. Conclusions: These findings suggest that home use of a mindfulness app in young children can have a positive impact on children's emotional well-being if the app is used regularly, specifically for at least 30 days in the 8-week study period. Strategies aimed at promoting regular use of the mindfulness app at home could lead to even better outcomes for children. Preregistration: Preregistered on OSF at https://osf.io/23vax.

Mindfulness supports emotional resilience in children during the COVID-19 Pandemic.

An important aspect of mental health in children is emotional resilience, the capacity to adapt to, and recover from, stressors and emotional challenges. Variation in trait mindfulness, one’s disposition to attend to experiences with an open and nonjudgmental attitude, may be an important individual difference in children that supports emotional resilience. In this study, we investigated whether trait mindfulness was related to emotional resilience in response to stressful changes in education and home-life during the COVID-19 pandemic in the United States. We conducted a correlational study examining self-report data from July 2020 to February 2021, from 163 eight-to-ten-year-old children living in the US. Higher trait mindfulness scores correlated with less stress, anxiety, depression, and negative affect in children, and lower ratings of COVID-19 impact on their lives. Mindfulness moderated the relationship between COVID-19 child impact and negative affect. Children scoring high on mindfulness showed no correlation between rated COVID-19 impact and negative affect, whereas those who scored low on mindfulness showed a positive correlation between child COVID-19 impact and negative affect. Higher levels of trait mindfulness may have helped children to better cope with a wide range of COVID-19 stressors. Future studies should investigate the mechanisms by which trait mindfulness supports emotional resilience in children.

The Early Bird Gets the Worm: Introducing Medical Students to Microsurgical Technique via a Low-Cost, User-Friendly, Reusable Simulation System.

BACKGROUND: Mastery of microsurgical technique requires thousands of hours of deliberate practice, often with equipment that is not accessible to medical students. This study aimed to develop, test, and report a novel simulation system for providing medical students with early access to microsurgical technique. METHODS: Low-cost, user-friendly, reusable microsurgery kits were iteratively developed using excess surgical supplies, such as catheter tubing and vessel loops. Students were tested on 2 separate tasks, with grading via a standardized performance scale incorporating aspects of alignment, leak, and anastomotic patency. RESULTS: Twelve medical students were tested on standardized microsurgery kits at 2 different time points 6 weeks apart with no additional training received in between. Median change in total score on the vessel loop suturing task after 6 weeks was +2.6 points (range, -1.7 to +5 points); median change in completion time was -1.9 minutes (range, -3.5 to +2.7 minutes). Median change in total score on the red rubber anastomosis task was +5.8 points (range, -2.6 to +9.6 points) with a median improvement of -4.3 minutes (range, -9.6 to +2.6 minutes). CONCLUSIONS: Reusable microsurgery kits designed with excess surgical supplies are educationally impactful tools that introduce medical students to microsurgical techniques early in their training, while also providing objective measures for skills acquisition over time.

A step toward equal representation? A cross-sectional analysis of the gender composition of neurosurgical editorial boards from 2000 to 2020.

OBJECTIVE: At present, females constitute less than 10% of neurosurgeons in the US, despite representing approximately half of all medical students. Multiple barriers have been described for females entering the neurosurgical field, particularly academic neurosurgery. Understanding the environment that female neurosurgeons face and any potential barriers preventing career advancement is needed to recruit, promote, and retain females in neurosurgery. METHODS: The gender composition of editorial boards for 5 high-impact neurosurgery journals was analyzed from 2000 to 2020. The names of editorial board members were obtained directly from the journal administration, physical copies of the published journal, or publicly available data through each journal's website. The gender, degrees, academic titles, H-index, and country were determined for each individual and statistical tests were performed to identify significant differences. RESULTS: Of the 466 identified individuals that served on at least one editorial board between 2000 and 2020, there were 36 females (7.7%) and 430 males (92.3%). There were no significant differences between males and females serving on multiple editorial boards. Most females possessed an additional graduate degree (58.3%), while only one-third of males (33.5%) obtained such a degree (p = 0.002). In addition, males had significantly higher average H-indices than females (p = 0.002). These trends were also observed when analyzing only US-based editorial board members. Although females were more likely overall to be identified as associate professors, males were more likely to be appointed as full professors (p = 0.001); this trend did not remain true in the US-based cohort. When analyzing the editorial boards for individual journals, all 5 journals experienced an increase of female representation since 2000 or since their inception after 2000. The highest proportion of females for a single journal was 27.3% in 2020. All other journals ranged from 11.0% to 13.5% in 2020. CONCLUSIONS: When entering the field of neurosurgery, females continue to face significant social and academic barriers. While the proportion of females on editorial boards for neurosurgery journals in 2020 is consistent with the proportion of practicing female neurosurgeons, there is a statistically significantly higher likelihood that females possess additional graduate degrees and lower H-indices compared to their male counterparts. The authors encourage neurosurgical journals to continue expanding female representation on editorial boards.

ATRX loss promotes immunosuppressive mechanisms in IDH1 mutant glioma.

BACKGROUND: ATRX inactivation occurs with IDH1R132H and p53 mutations in over 80% of Grades II/III astrocytomas. It is believed that ATRX loss contributes to oncogenesis by dysregulating epigenetic and telomere mechanisms but effects on anti-glioma immunity have not been explored. This paper examines how ATRX loss contributes to the malignant and immunosuppressive phenotypes of IDH1R132H/p53mut glioma cells and xenografts. METHODS: Isogenic astrocytoma cells (+/-IDH1R132H/+/-ATRXloss) were established in p53mut astrocytoma cell lines using lentivirus encoding doxycycline-inducible IDH1R132H, ATRX shRNA, or Lenti-CRISPR/Cas9 ATRX. Effects of IDH1R132H+/-ATRXloss on cell migration, growth, DNA repair, and tumorigenicity were evaluated by clonal growth, transwell and scratch assays, MTT, immunofluorence and immunoblotting assays, and xenograft growth. Effects on the expression and function of modulators of the immune microenvironment were quantified by qRT-PCR, immunoblot, T-cell function, macrophage polarization, and flow cytometry assays. Pharmacologic inhibitors were used to examine epigenetic drivers of the immunosuppressive transcriptome of IDH1R132H/p53mut/ATRXloss cells. RESULTS: Adding ATRX loss to the IDH1R132H/p53mut background promoted astrocytoma cell aggressiveness, induced expression of BET proteins BRD3/4 and an immune-suppressive transcriptome consisting of up-regulated immune checkpoints (e.g., PD-L1, PD-L2) and altered cytokine/chemokine profiles (e.g., IL33, CXCL8, CSF2, IL6, CXCL9). ATRX loss enhanced the capacity of IDH1R132H/p53mut cells to induce T-cell apoptosis, tumorigenic/anti-inflammatory macrophage polarization and Treg infiltration. The transcriptional and biological immune-suppressive responses to ATRX loss were enhanced by temozolomide and radiation and abrogated by pharmacologic BET inhibition. CONCLUSIONS: ATRX loss activates a BRD-dependent immune-suppressive transcriptome and immune escape mechanism in IDH1R132H/p53mut astrocytoma cells.

International trends in grant and fellowship funding awarded to women in neurosurgery.

OBJECTIVE: Metric tracking of grant funding over time for academic neurosurgeons sorted by gender informs the current climate of career development internationally for women in neurosurgery. METHODS: Multivariate linear trend analysis of grant funding awarded to neurosurgeons in the NIH and World Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) was performed. Traveling fellowships for international neurosurgery residents sponsored by the AANS and Congress of Neurological Surgeons (CNS) were also analyzed. RESULTS: Within the US, funding awarded to female neurosurgeons has remained static from 2009 to 2019 after adjusting for inflation and overall trends in NIH funding (ß = -$0.3 million per year, p = 0.16). Internationally, female neurosurgeons represented 21.7% (n = 5) of project leads for World RePORTER grants. Traveling fellowships are also an important building block for young international female neurosurgeons, of which 7.4% (n = 2) of AANS international traveling fellowships and 19.4% (n = 7) of AANS/CNS pediatrics international traveling fellowships are women. CONCLUSIONS: Over the past decade, funding has increased in neurosurgery without a concordant increase in funding awarded to women. Recognition of this trend is essential to focus efforts on research and career development opportunities for women in neurosurgery. Worldwide, female neurosurgeons head one-fifth of the funded project leads and constitute a minority of international traveling fellowships awarded by organized neurosurgery.

Implementing Remote Developmental Research: A Case Study of a Randomized Controlled Trial Language Intervention During COVID-19.

Intervention studies with developmental samples are difficult to implement, in particular when targeting demographically diverse communities. Online studies have the potential to examine the efficacy of highly scalable interventions aimed at enhancing development, and to address some of the barriers faced by underrepresented communities for participating in developmental research. During the COVID-19 pandemic, we executed a fully remote randomized controlled trial (RCT) language intervention with third and fourth grade students (N = 255; age range 8.19-10.72 years, mean = 9.41, SD = 0.52) from diverse backgrounds across the United States. Using this as a case study, we discuss both challenges and solutions to conducting an intensive online intervention through the various phases of the study, including recruitment, data collection, and fidelity of intervention implementation. We provide comprehensive suggestions and takeaways, and conclude by summarizing some important tradeoffs for researchers interested in carrying out such studies.

Acute social isolation evokes midbrain craving responses similar to hunger.

When people are forced to be isolated from each other, do they crave social interactions? To address this question, we used functional magnetic resonance imaging to measure neural responses evoked by food and social cues after participants (n = 40) experienced 10 h of mandated fasting or total social isolation. After isolation, people felt lonely and craved social interaction. Midbrain regions showed selective activation to food cues after fasting and to social cues after isolation; these responses were correlated with self-reported craving. By contrast, striatal and cortical regions differentiated between craving food and craving social interaction. Across deprivation sessions, we found that deprivation narrows and focuses the brain's motivational responses to the deprived target. Our results support the intuitive idea that acute isolation causes social craving, similar to the way fasting causes hunger.

Modular and Distinct Plexin-A4/FARP2/Rac1 Signaling Controls Dendrite Morphogenesis.

Diverse neuronal populations with distinct cellular morphologies coordinate the complex function of the nervous system. Establishment of distinct neuronal morphologies critically depends on signaling pathways that control axonal and dendritic development. The Sema3A-Nrp1/PlxnA4 signaling pathway promotes cortical neuron basal dendrite arborization but also repels axons. However, the downstream signaling components underlying these disparate functions of Sema3A signaling are unclear. Using the novel PlxnA4KRK-AAA knock-in male and female mice, generated by CRISPR/cas9, we show here that the KRK motif in the PlxnA4 cytoplasmic domain is required for Sema3A-mediated cortical neuron dendritic elaboration but is dispensable for inhibitory axon guidance. The RhoGEF FARP2, which binds to the KRK motif, shows identical functional specificity as the KRK motif in the PlxnA4 receptor. We find that Sema3A activates the small GTPase Rac1, and that Rac1 activity is required for dendrite elaboration but not axon growth cone collapse. This work identifies a novel Sema3A-Nrp1/PlxnA4/FARP2/Rac1 signaling pathway that specifically controls dendritic morphogenesis but is dispensable for repulsive guidance events. Overall, our results demonstrate that the divergent signaling output from multifunctional receptor complexes critically depends on distinct signaling motifs, highlighting the modular nature of guidance cue receptors and its potential to regulate diverse cellular responses.SIGNIFICANCE STATEMENT The proper formation of axonal and dendritic morphologies is crucial for the precise wiring of the nervous system that ultimately leads to the generation of complex functions in an organism. The Semaphorin3A-Neuropilin1/Plexin-A4 signaling pathway has been shown to have multiple key roles in neurodevelopment, from axon repulsion to dendrite elaboration. This study demonstrates that three specific amino acids, the KRK motif within the Plexin-A4 receptor cytoplasmic domain, are required to coordinate the downstream signaling molecules to promote Sema3A-mediated cortical neuron dendritic elaboration, but not inhibitory axon guidance. Our results unravel a novel Semaphorin3A-Plexin-A4 downstream signaling pathway and shed light on how the disparate functions of axon guidance and dendritic morphogenesis are accomplished by the same extracellular ligand in vivo.

ShRNA-based POLD2 expression knockdown sensitizes glioblastoma to DNA-Damaging therapeutics.

Glioblastoma (GBM) has limited therapeutic options. DNA repair mechanisms contribute GBM cells to escape therapies and re-establish tumor growth. Multiple studies have shown that POLD2 plays a critical role in DNA replication, DNA repair and genomic stability. We demonstrate for the first time that POLD2 is highly expressed in human glioma specimens and that expression correlates with poor patient survival. siRNA or shRNA POLD2 inhibited GBM cell proliferation, cell cycle progression, invasiveness, sensitized GBM cells to chemo/radiation-induced cell death and reversed the cytoprotective effects of EGFR signaling. Conversely, forced POLD2 expression was found to induce GBM cell proliferation, colony formation, invasiveness and chemo/radiation resistance. POLD2 expression associated with stem-like cell subsets (CD133+ and SSEA-1+ cells) and positively correlated with Sox2 expression in clinical specimens. Its expression was induced by Sox2 and inhibited by the forced differentiation of GBM neurospheres. shRNA-POLD2 modestly inhibited GBM neurosphere-derived orthotopic xenografts growth, when combined with radiation, dramatically inhibited xenograft growth in a cooperative fashion. These novel findings identify POLD2 as a new potential therapeutic target for enhancing GBM response to current standard of care therapeutics.

Oncogenic MicroRNA-20a is downregulated by the HIF-1α/c-MYC pathway in IDH1 R132H-mutant glioma.

Mutations in the isocitrate dehydrogenase 1 (IDH1) gene have been identified as one of the earliest events in gliomagenesis, occurring in over 70% of low grade gliomas and are present in the vast majority of secondary glioblastoma (GBM) that develop from these low-grade lesions. The aim of this study was to investigate whether the IDH1 R132H mutation influences the expression of oncogenic miR-20a and shed light on the underlying molecular mechanisms. The findings of the current study demonstrate presence of the IDH1 R132H mutation in primary human glioblastoma cell lines with upregulated HIF-1α expression, downregulating c-MYC activity and resulting in a consequential decrease in miR-20a, which is responsible for cell proliferation and resistance to standard temozolomide treatment. Elucidating the mechanism of oncogenic miR-20a activity introduces its role among well-established signaling pathways (i.e. HIF/c-MYC) and may be a meaningful prognostic biomarker or target for novel therapies among patients with IDH1-mutant glioma.