Addressing Burnout and Enhancing Well-Being Among Academic Physicians: A Call for Future Research and Organizational Support.

Description Burnout among academic physicians, who navigate multiple roles beyond the clinical environment, is a pressing issue. However, the factors driving burnout among academic physicians are not fully understood. Prior research has revealed differences in burnout dimensions between clinical and basic science faculty, but the impact of balancing research, education, and clinical demands on academic physicians is still unclear. This knowledge gap negatively affects the clinical, translational science, research, and medical education workforces and has particular implications for minoritized and marginalized groups working in academic medical centers. Creating a culture of well-being has been vital in addressing burnout. Further research is needed to explore the unique experiences and demands of academic physicians- particularly those from minoritized and marginalized backgrounds-and to develop effective strategies to promote well-being as they balance diverse roles and contexts. This commentary highlights gaps in understanding burnout among academic physicians and proposes guidelines for future research as well as strategies to improve well-being at academic medical centers.

Neonatal intracranial haemorrhage secondary to vein of Galen aneurysmal dilatation.

Paediatric neurovascular anomalies associated with the vein of Galen (VG) comprise of a spectrum of rare, complex, and life-threatening conditions. In this group, the "vein of Galen aneurysmal dilatation" (VGAD) is a distinct entity that often presents with progressive neurological symptoms in older children. Acute haemorrhage in VGAD is uncommon. We present an unusual presentation of VGAD in a neonate and discuss the challenges faced in the management.

hTERT Peptide Fragment GV1001 Prevents the Development of Porphyromonas gingivalis-Induced Periodontal Disease and Systemic Disorders in ApoE-Deficient Mice.

GV1001, an anticancer vaccine, exhibits other biological functions, including anti-inflammatory and antioxidant activity. It also suppresses the development of ligature-induced periodontitis in mice. Porphyromonas gingivalis (Pg), a major human oral bacterium implicated in the development of periodontitis, is associated with various systemic disorders, such as atherosclerosis and Alzheimer's disease (AD). This study aimed to explore the protective effects of GV1001 against Pg-induced periodontal disease, atherosclerosis, and AD-like conditions in Apolipoprotein (ApoE)-deficient mice. GV1001 effectively mitigated the development of Pg-induced periodontal disease, atherosclerosis, and AD-like conditions by counteracting Pg-induced local and systemic inflammation, partly by inhibiting the accumulation of Pg DNA aggregates, Pg lipopolysaccharides (LPS), and gingipains in the gingival tissue, arterial wall, and brain. GV1001 attenuated the development of atherosclerosis by inhibiting vascular inflammation, lipid deposition in the arterial wall, endothelial to mesenchymal cell transition (EndMT), the expression of Cluster of Differentiation 47 (CD47) from arterial smooth muscle cells, and the formation of foam cells in mice with Pg-induced periodontal disease. GV1001 also suppressed the accumulation of AD biomarkers in the brains of mice with periodontal disease. Overall, these findings suggest that GV1001 holds promise as a preventive agent in the development of atherosclerosis and AD-like conditions associated with periodontal disease.

The KAT module of the SAGA complex maintains the oncogenic gene expression program in MYCN-amplified neuroblastoma.

Pediatric cancers are frequently driven by genomic alterations that result in aberrant transcription factor activity. Here, we used functional genomic screens to identify multiple genes within the transcriptional coactivator Spt-Ada-Gcn5-acetyltransferase (SAGA) complex as selective dependencies for MYCN-amplified neuroblastoma, a disease of dysregulated development driven by an aberrant oncogenic transcriptional program. We characterized the DNA recruitment sites of the SAGA complex in neuroblastoma and the consequences of loss of SAGA complex lysine acetyltransferase (KAT) activity on histone acetylation and gene expression. We demonstrate that loss of SAGA complex KAT activity is associated with reduced MYCN binding on chromatin, suppression of MYC/MYCN gene expression programs, and impaired cell cycle progression. Further, we showed that the SAGA complex is pharmacologically targetable in vitro and in vivo with a KAT2A/KAT2B proteolysis targeting chimeric. Our findings expand our understanding of the histone-modifying complexes that maintain the oncogenic transcriptional state in this disease and suggest therapeutic potential for inhibitors of SAGA KAT activity in MYCN-amplified neuroblastoma.

Differential impact of prenatal PTSD symptoms and preconception trauma exposure on placental NR3C1 and FKBP5 methylation.

Perinatal stress is associated with altered placental methylation, which plays a critical role in fetal development and infant outcomes. This proof-of-concept pilot study investigated the impact of lifetime trauma exposure and perinatal PTSD symptoms on epigenetic regulation of placenta glucocorticoid signaling genes (NR3C1 and FKBP5). Lifetime trauma exposure and PTSD symptoms during pregnancy were assessed in a racially/ethnically diverse sample of pregnant women (N = 198). Participants were categorized into three groups: (1) No Trauma (-T); (2) Trauma, No Symptoms (T - S); and (3) Trauma and Symptoms (T + S). Placental tissue was analyzed via bisulfite pyrosequencing for degree of methylation at the NR3C1 promoter and FKBP5 regulatory regions. Analyses of covariance were used to test group differences in percentages of NR3C1 and FKBP5 methylation overall and at each CpG site. We found a significant impact of PTSD symptoms on placental NR3C1 methylation. Compared to the -T group, the T + S group had greater NR3C1 methylation overall and at CpG6, CpG8, CpG9, and CpG13, but lower methylation at CpG5. The T + S group had significantly higher NR3C1 methylation overall and at CpG8 compared to the T - S group. There were no differences between the T - S group and - T group. Additionally, no group differences emerged for FKBP5 methylation. Pregnant trauma survivors with PTSD symptoms exhibited differential patterns of placental NR3C1 methylation compared to trauma survivors without PTSD symptoms and pregnant women unexposed to trauma. Results highlight the critical importance of interventions to address the mental health of pregnant trauma survivors.

A scoping review of the role of policy in mitigating childhood obesity in underserved populations using the RE-AIM framework.

BACKGROUND: Childhood obesity is an escalating crisis in the United States. Health policy may impact this epidemic which disproportionally affects underserved populations. AIM: The aim was to use the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework to assess health policy impact on preventing or treating school-aged children (5 > 18 years) with obesity in underserved populations. METHODS: A scoping review of 842 articles was conducted. Twenty-four articles met the inclusion criteria and underwent data extraction. RESULTS: Twelve studies included subgroup analysis, with four suggesting an impact of policy on at-risk groups. None of the 24 studies fully applied the RE-AIM framework. Policies positively impacted childhood obesity in 12 studies across the sample. LINKING EVIDENCE TO ACTION: Our review revealed inconsistent evidence for the effectiveness of policy on childhood obesity, perhaps due to the lack of focus on the social determinants of health. In addition, many studies did not evaluate the outcomes for underserved populations. Therefore, we propose more attention to social determinants in future legislation and evaluation of policy effectiveness on underserved populations. Findings identify an urgent need for the design, implementation, and evaluation of policies specifically directed to address the inequities of racism, social injustices, and social determinants of health that impact childhood obesity in the United States. Future work needs to identify who was reached by the policy, who benefitted from the policy, and how policies were implemented to address obesity-related health disparities. Nurses should advocate for the evaluation of childhood obesity policies, particularly in underserved populations, to determine effectiveness. Nurses, particularly those trained in population and community health and research, should advocate for policy research that considers inequities rather than controls for these variables. Multi-layered interventions can then be tailored to sub-populations and evaluated more effectively.

The SAGA acetyltransferase module is required for the maintenance of MAF and MYC oncogenic gene expression programs in multiple myeloma.

Despite recent advances in therapeutic treatments, multiple myeloma (MM) remains an incurable malignancy. Epigenetic factors contribute to the initiation, progression, relapse, and clonal heterogeneity in MM, but our knowledge on epigenetic mechanisms underlying MM development is far from complete. The SAGA complex serves as a coactivator in transcription and catalyzes acetylation and deubiquitylation. Analyses of datasets in the Cancer Dependency Map Project revealed many SAGA components are selective dependencies in MM. To define SAGA-specific functions, we focused on ADA2B, the only subunit in the lysine acetyltransferase (KAT) module that specifically functions in SAGA. Integration of RNA-seq, ATAC-seq, and CUT&RUN results identified pathways directly regulated by ADA2B include MTORC1 signaling, MYC, E2F, and MM-specific MAF oncogenic programs. We discovered that ADA2B is recruited to MAF and MYC gene targets, and that MAF shares a majority of its targets with MYC in MM cells. Furthermore, we found the SANT domain of ADA2B is required for interaction with both GCN5 and PCAF acetyltransferases, incorporation into SAGA, and ADA2B protein stability. Our findings uncover previously unknown SAGA KAT module-dependent mechanisms controlling MM cell growth, revealing a vulnerability that might be exploited for future development of MM therapy.

Evidence for Reductions in Physical and Chemical Plant Defense Traits in Island Flora.

Reduced defense against large herbivores has been suggested to be part of the "island syndrome" in plants. However, empirical evidence for this pattern is mixed. In this paper, we present two studies that compare putative physical and chemical defense traits from plants on the California Channel Islands and nearby mainland based on sampling of both field and common garden plants. In the first study, we focus on five pairs of woody shrubs from three island and three mainland locations and find evidence for increased leaf area, decreased marginal leaf spines, and decreased concentrations of cyanogenic glycosides in island plants. We observed similar increases in leaf area and decreases in defense traits when comparing island and mainland genotypes grown together in botanic gardens, suggesting that trait differences are not solely driven by abiotic differences between island and mainland sites. In the second study, we conducted a common garden experiment with a perennial herb-Stachys bullata (Lamiaceae)-collected from two island and four mainland locations. Compared to their mainland relatives, island genotypes show highly reduced glandular trichomes and a nearly 100-fold reduction in mono- and sesquiterpene compounds from leaf surfaces. Island genotypes also had significantly higher specific leaf area, somewhat lower rates of gas exchange, and greater aboveground biomass than mainland genotypes across two years of study, potentially reflecting a broader shift in growth habit. Together, our results provide evidence for reduced expression of putative defense traits in island plants, though these results may reflect adaptation to both biotic (i.e., the historical absence of large herbivores) and climatic conditions on islands.

Plant species within Streptanthoid Complex associate with distinct microbial communities that shift to be more similar under drought.

Prolonged water stress can shift rhizoplane microbial communities, yet whether plant phylogenetic relatedness or drought tolerance predicts microbial responses is poorly understood. To explore this question, eight members of the Streptanthus clade with varying affinity to serpentine soil were subjected to three watering regimes. Rhizoplane bacterial communities were characterized using 16S rRNA gene amplicon sequencing and we compared the impact of watering treatment, soil affinity, and plant species identity on bacterial alpha and diversity. We determined which taxa were enriched among drought treatments using DESeq2 and identified features of soil affinity using random forest analysis. We show that water stress has a greater impact on microbial community structure than soil affinity or plant identity, even within a genus. Drought reduced alpha diversity overall, but plant species did not strongly differentiate alpha diversity. Watering altered the relative abundance of bacterial genera within Proteobacteria, Firmicutes, Bacteroidetes, Planctomycetes, and Acidobacteria, which responded similarly in the rhizoplane of most plant species. In addition, bacterial communities were more similar when plants received less water. Pseudarthrobacter was identified as a feature of affinity to serpentine soil while Bradyrhizobium, Chitinophaga, Rhodanobacter, and Paenibacillus were features associated with affinity to nonserpentine soils among Streptanthus. The homogenizing effect of drought on microbial communities and the increasing prevalence of Gram-negative bacteria across all plant species suggest that effects of water stress on root-associated microbiome structure may be predictable among closely related plant species that inhabit very different soil environments. The functional implications of observed changes in microbiome composition remain to be studied.

Female adolescents' early life stress and body mass index: Differential effects of anger and anxiety in response to rejection.

INTRODUCTION: Early life stress is linked to childhood obesity. As children enter adolescence, early life stress may be associated with increased rejection sensitivity, resulting in activation of behavioral and physiological changes that contribute to higher body mass index (BMI). Understanding the potential influence of rejection sensitivity on the association between early life stress and BMI is important to examine in female adolescents. For this secondary data analysis, we hypothesized that female adolescents with greater early life stress and greater rejection sensitivity would exhibit higher BMI-for-age 12 months later. METHODS: Seventy-eight adolescents (Mage = 13.1 years; 100% female sex; MBMI = 23.2 kg/m2) in the United States completed study procedures from 2012 to 2016. Among these procedures, the Psychosocial Schedule was used to assess cumulative early life stress and the Children's Rejection Sensitivity Questionnaire was used to assess anger and anxiety in response to rejection. Twelve months later, height and weight were measured to derive BMI-for-age. RESULTS: Higher early life stress was associated with higher BMI-for-age among female adolescents with low rejection-provoked anger (1 SD below the mean). However, this association was not observed among female adolescents with high rejection-provoked anger (1 SD above the mean). Finally, there was no significant interaction between early life stress and rejection-provoked anxiety in predicting BMI-for-age. CONCLUSIONS: Experiencing early life stress may interact with rejection-provoked anger, but not anxiety, to predict BMI-for-age. Findings inform a developmental perspective of how rejection sensitivity may influence the association between early life stress and early cardiometabolic risk.

Predator selection on phenotypic variability of cryptic and aposematic moths.

Natural selection generally favours phenotypic variability in camouflaged organisms, whereas aposematic organisms are expected to evolve a more uniform warning coloration. However, no comprehensive analysis of the phenotypic consequences of predator selection in aposematic and cryptic species exists. Using state-of-the-art image analysis, we examine 2800 wing images of 82 moth species accessed via three online museum databases. We test whether anti-predator strategy (i.e., camouflage or aposematism) explains intraspecific variation in wing colour and pattern across northern hemisphere moths. In addition, we test two mutually non-exclusive, ecological hypotheses to explain variation in colour pattern: diel-activity or dietary-niche. In this work, taking into account phylogenetic relationships, moth phenotypic variability is best explained by anti-predator strategy with camouflaged moths being more variable in wing patterning than aposematic species.

Complex lumbosacral spinal cord lipomas: A longitudinal study on outcomes from a Singapore children's hospital.

BACKGROUND: Total/near-total resection (TR/NTR) of complex lumbosacral lipomas (CSL) is reported to be associated with better long-term functional outcomes and lower symptomatic re-tethering rates. We report our institutional experience for CSL resection in affected children. METHODS: This is a single-institution, retrospective study. Inclusion criteria consist of patients with CSL with dorsal, transitional and chaotic lipomas based on Pang et al's classification. The study population is divided into 2 groups: asymptomatic patients with a normal preoperative workup referred to as 'prophylactic intent' and 'therapeutic intent' for those with pre-existing neuro-urological symptoms. Primary aims are to review factors that affect post-operative clean intermittent catheterization (CIC), functional outcomes based on Necker functional score (NFS), and re-tethering rates. RESULTS: 122 patients were included from 2000 to 2021. There were 32 dorsal lipomas (26.2 %), 74 transitional lipomas (60.7 %), and 16 chaotic lipomas (13.1 %). 82 % patients achieved TR/NTR. Favourable NFS at 1-year was 48.2 %. The re-tethering rate was 6.6 %. After multivariable analysis, post-operative CIC was associated with median age at surgery (p = 0.026), lipoma type (p = 0.029), conus height (p = 0.048) and prophylactic intent (p < 0.001). Next, extent of lipoma resection (p = 0.012) and the post-operative CSF leak (p = 0.004) were associated with re-tethering. Favourable NFS was associated with lipoma type (p = 0.047) and prophylactic intent surgery (p < 0.001). CONCLUSIONS: Our experience shows that TR/NTR for CSL is a feasible option to prevent functional deterioration and re-tethering. Efforts are needed to work on factors associated with post-operative CIC.

Society of Critical Care Medicine Guidelines on Glycemic Control for Critically Ill Children and Adults 2024.

RATIONALE: Maintaining glycemic control of critically ill patients may impact outcomes such as survival, infection, and neuromuscular recovery, but there is equipoise on the target blood levels, monitoring frequency, and methods. OBJECTIVES: The purpose was to update the 2012 Society of Critical Care Medicine and American College of Critical Care Medicine (ACCM) guidelines with a new systematic review of the literature and provide actionable guidance for clinicians. PANEL DESIGN: The total multiprofessional task force of 22, consisting of clinicians and patient/family advocates, and a methodologist applied the processes described in the ACCM guidelines standard operating procedure manual to develop evidence-based recommendations in alignment with the Grading of Recommendations Assessment, Development, and Evaluation Approach (GRADE) methodology. Conflict of interest policies were strictly followed in all phases of the guidelines, including panel selection and voting. METHODS: We conducted a systematic review for each Population, Intervention, Comparator, and Outcomes question related to glycemic management in critically ill children (≥ 42 wk old adjusted gestational age to 18 yr old) and adults, including triggers for initiation of insulin therapy, route of administration, monitoring frequency, role of an explicit decision support tool for protocol maintenance, and methodology for glucose testing. We identified the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the GRADE approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak or as a good practice statement. In addition, "In our practice" statements were included when the available evidence was insufficient to support a recommendation, but the panel felt that describing their practice patterns may be appropriate. Additional topics were identified for future research. RESULTS: This guideline is an update of the guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients. It is intended for adult and pediatric practitioners to reassess current practices and direct research into areas with inadequate literature. The panel issued seven statements related to glycemic control in unselected adults (two good practice statements, four conditional recommendations, one research statement) and seven statements for pediatric patients (two good practice statements, one strong recommendation, one conditional recommendation, two "In our practice" statements, and one research statement), with additional detail on specific subset populations where available. CONCLUSIONS: The guidelines panel achieved consensus for adults and children regarding a preference for an insulin infusion for the acute management of hyperglycemia with titration guided by an explicit clinical decision support tool and frequent (≤ 1 hr) monitoring intervals during glycemic instability to minimize hypoglycemia and against targeting intensive glucose levels. These recommendations are intended for consideration within the framework of the patient's existing clinical status. Further research is required to evaluate the role of individualized glycemic targets, continuous glucose monitoring systems, explicit decision support tools, and standardized glycemic control metrics.

Selective dorsal rhizotomy using a 3D high definition exoscope.

Selective dorsal rhizotomy (SDR) is an established neurosurgical technique for children with spastic diplegia secondary to cerebral palsy. Meticulous intraoperative testing of individual nerve roots with electromyography in tandem with the on-site neurorehabilitation team is recommended for good clinical outcomes. The standard approach requires the neurosurgeons to spend extended time under the traditional operating microscope. In this video, the authors describe the use of a 3D exoscope system for SDR. Overall, the 3D exoscope improves ergonomics and reduces musculoskeletal fatigue for the operating neurosurgeons. Furthermore, it provides excellent visualization of important structures, allowing safe and efficient completion of the procedure. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23105.

USP22 overexpression fails to augment tumor formation in MMTV-ERBB2 mice but loss of function impacts MMTV promoter activity.

The Ubiquitin Specific Peptidase 22 (USP22), a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) histone modifying complex, is overexpressed in multiple human cancers, but how USP22 impacts tumorigenesis is not clear. We reported previously that Usp22 loss in mice impacts execution of several signaling pathways driven by growth factor receptors such as erythroblastic oncogene B b2 (ERBB2). To determine whether changes in USP22 expression affects ERBB2-driven tumorigenesis, we introduced conditional overexpression or deletion alleles of Usp22 into mice bearing the Mouse mammary tumor virus-Neu-Ires-Cre (MMTV-NIC) transgene, which drives both rat ERBB2/NEU expression and Cre recombinase activity from the MMTV promoter resulting in mammary tumor formation. We found that USP22 overexpression in mammary glands did not further enhance primary tumorigenesis in MMTV-NIC female mice, but increased lung metastases were observed. However, deletion of Usp22 significantly decreased tumor burden and increased survival of MMTV-NIC mice. These effects were associated with markedly decreased levels of both Erbb2 mRNA and protein, indicating Usp22 loss impacts MMTV promoter activity. Usp22 loss had no impact on ERBB2 expression in other settings, including MCF10A cells bearing a Cytomegalovirus (CMV)-driven ERBB2 transgene or in human epidermal growth factor receptor 2 (HER2)+ human SKBR3 and HCC1953 cells. Decreased activity of the MMTV promoter in MMTV-NIC mice correlated with decreased expression of known regulatory factors, including the glucocorticoid receptor (GR), the progesterone receptor (PR), and the chromatin remodeling factor Brahma-related gene-1 (BRG1). Together our findings indicate that increased expression of USP22 does not augment the activity of an activated ERBB2/NEU transgene but impacts of Usp22 loss on tumorigenesis cannot be assessed in this model due to unexpected effects on MMTV-driven Erbb2/Neu expression.

Predictors of the inability to achieve full oral feeding in postoperative infants with CHD.

OBJECTIVES: Poor oral feeding is a known contributor to growth challenges in neonates with complex CHD who require early surgery. Almost 60% of these infants do not achieve full oral feeding by hospital discharge. This study's objective was to identify predictors of the inability to achieve full oral feeding by discharge in neonates with complex CHD following surgical intervention with cardiopulmonary bypass. STUDY DESIGN: A retrospective analysis of a prospective study of 192 full-term neonates with complex CHD was performed. A stepwise selection logistic regression model was developed to predict oral feeding status at hospital discharge. Univariate subgroup analysis was performed with groups determined based on a CHD classification system. RESULTS: 58% of neonates (112/192) failed to achieve full oral feeding by hospital discharge. A logistic regression model identified duration of deep hypothermic circulatory arrest and reintubation as predictors of the inability to achieve full oral feeding. Among neonates who achieved full oral feeding by discharge (42%), only 7.5% did so after postoperative day 10. Brain maturation, brain injury, and preoperative oral feeding were not predictors of full postoperative oral feeding. CONCLUSIONS: Many infants with CHD fail to achieve full oral feeding by time of hospital discharge. Longer duration of deep hypothermic circulatory arrest and increased number of intubations were predictive of poor feeding after surgery. Prolonging hospitalisation solely to achieve full oral feeding after postoperative day ten is of limited utility; earlier discharge should be promoted to avoid negative impacts on neonatal neurodevelopment as unintended consequences of lengthy hospitalisations.