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The COMPASS protein family catalyzes histone H3 Lys 4 (H3K4) methylation and its members are essential for regulating gene expression. MLL2/COMPASS methylates H3K4 on many developmental genes and bivalent clusters. To understand MLL2-dependent transcriptional regulation, we performed a CRISPR-based screen with an MLL2-dependent gene as a reporter in mouse embryonic stem cells. We found that MLL2 functions in gene expression by protecting developmental genes from repression via repelling PRC2 and DNA methylation machineries. Accordingly, repression in the absence of MLL2 is relieved by inhibition of PRC2 and DNA methyltransferases. Furthermore, DNA demethylation on such loci leads to reactivation of MLL2-dependent genes not only by removing DNA methylation but also by opening up previously CpG methylated regions for PRC2 recruitment, diluting PRC2 at Polycomb-repressed genes. These findings reveal how the context and function of these three epigenetic modifiers of chromatin can orchestrate transcriptional decisions and demonstrate that prevention of active repression by the context of the enzyme and not H3K4 trimethylation underlies transcriptional regulation on MLL2/COMPASS targets. A CRISPR screen for MLL2-dependent transcription identifies a compensatory repressive mechanism involving PRC2 and DNA methylation. PRC2 inactivation or DNA demethylation activates gene expression in the absence of H3K4me3.

Background/AimThe physician–administrator dyads are a strategic method of collaboration in healthcare organisations. Dyad leaders are part of a multidisciplinary team that integrates their expertise to generate better patient, physician, and organisational outcomes. An assumption of team science is that diverse experts, while knowledgeable, struggle to work together to resolve problems because of their vastly different decision-making and implementation strategies. Similarly, conflicting priorities, competing pressures, and lack of clear understanding of the other member’s role will result in ineffective teamwork between the dyad.MethodsWe conducted a literature review of dyad leadership in healthcare and connected these insights to the teamwork literature.ResultsWe connect the challenges of dyad leadership with practical solutions that help physicians and administrators integrate their diverse expertise. To overcome these challenges, healthcare employees, teams, and organisations must implement an effective structure for diverse dyads to work together effectively. We develop a framework based on a review of the literature on dyads and describe what is needed for an effective partnership between the physician and administrator.ConclusionsWe describe the teamwork mechanisms that develop as teams use these strategies, which ultimately makes the dyads effective in the organisation. Dyad leaders who use these strategies will develop their teamwork behaviours and teamwork processes to reduce conflict and sustain the viability of their team to complete their goals, benefiting the patient, the team, and the organisation.

COVID-19 is a global pandemic caused by a novel zoonotic RNA virus named SARS-CoV-2. Various cutaneous manifestations associated with COVID-19 have been described, including urticarial rash, confluent erythematous rash, papulovesicular exanthem, chilblain-like acral pattern, livedo reticularis, and purpuric vasculitis pattern. Here, we are presenting a case of a 45-year-old male with mucocutaneous features of Stevens-Johnson syndrome.

Encapsulating peritoneal sclerosis (EPS) is a serious complication of chronic peritoneal dialysis (PD) that results in encapsulation of the bowel in a thick, fibrocollagenous membrane. Given its rare and complex nature, diagnosis of EPS often arises late in the disease process or intraoperatively. We report the case of an 86-year-old male with a history of renal failure managed with PD who presented with multiple hospital admissions for recurrent abdominal pain and symptoms of small bowel obstruction. Open laparotomy revealed encasement of the entire abdominal cavity in a cocoon-like membrane, consistent with EPS, which was successfully managed with extensive excision and adhesiolysis. This discussion, enriched by unique radiographic insights and delineation of a surgical strategy, seeks to enhance the understanding of this underreported disease characterized by a lack of definitive treatment and an enigmatic pathophysiology.

Marijuana is the most widely used illicit drug in the United States. As marijuana becomes legalized in more states and its use increases among adolescents, pediatricians must be aware of the impact of marijuana on pediatric health. Marijuana smoking as well as cigarette smoking has been associated with numerous lung diseases, including chronic bronchitis and bullous lung diseases. This case report postulates that regular marijuana smoking may be associated with pulmonary Langerhans cell histiocytosis, a severe lung disease that lacks definitive treatment and can cause respiratory failure. Given the potential risk of life-threatening lung diseases, pediatricians must screen adolescents with respiratory symptoms for marijuana use. In addition, this case underscores the need for further research and improved understanding of the relationship between marijuana smoking and lung disease.

Hereditary spherocytosis (HS) is a hereditary hematologic disorder characterized by fragile spherical red blood cells that are susceptible to hemolysis. HS patients are often asymptomatic or present with anemia; however, serious complications of chronic hemolysis can include cholelithiasis and aplastic crisis. Splenectomy is considered the standard surgical treatment in moderate and severe forms of HS, with the main complication being a life-long risk of infection. Interestingly, our case suggests a possibility of secondary hemochromatosis as a complication of chronic hemolysis seen in HS. A vast majority of hemochromatosis patients possess a genetic predisposition, which increases their serum iron level and iron storage within the reticuloendothelial system. However, we present a case in which the genetic panel for common mutations associated with hemochromatosis resulted as negative. This case emphasizes the need for increased awareness regarding the potential development of idiopathic hemochromatosis in patients with long-standing HS, allowing for prompt intervention and preventing the associated complications.

We describe a case where the patient presented to the emergency department (ED) with ocular irritation in the right eye with concomitant blurry vision that had been persistent for a week. The cause of this patient's ocular irritation and worsening visual acuity was determined to be a retained foreign body of the limbus. The foreign body had been in the patient's eye for about four months before he began to experience these symptoms. The four-month duration was established based on initial symptoms and a prior ED visit with no noted eye injury or foreign body detection, as well as the degree of overlying epithelization. This case highlights the importance of obtaining a thorough history and physical examination while emphasizing the high index of suspicion needed for translucent foreign bodies. Here, an inert foreign body erupted four months after injury. Additionally, this case stresses the importance of transition of care for ophthalmologic conditions. Consideration of any social determinants of health that could prevent as an example.

The use of digital technology in pediatric asthma management has emerged as a potential tool for improving asthma management. However, the use of digital tools has the potential to contribute to the inequitable delivery of asthma care because of existing social factors associated with asthma disparities. Our study focused on parents' chosen language and sociodemographic factors that might shape the use of digital technology in asthma self-management. This study aims to estimate and compare patient, family, and technology-related characteristics by parents' chosen language (English or Spanish) and compare a digital literacy measure by sociodemographic factors. Survey data were collected from July to December 2021 from parents of children with asthma who were seen by a Chicago pediatric health system pulmonary provider. Questions assessed patient and family characteristics, digital technology use, and digital literacy, measured using the validated eHealth Literacy Scale (eHEALS). Chi-square tests and multivariable logistic regression were used for comparisons, and Kruskal-Wallis tests were used for comparing median eHEALS scores by social characteristics. Of the 197 parents surveyed, 24.4% (n=49) of parents identified as a race categorized as other, 37.1% (n=67) as White, and 38.6% (n=75) as Black; 47.2% (n=93) identified as Hispanic/Latino/Latina. Additionally, 79.7% (n=157) of parents preferred English, and 20.3% (n=40) preferred Spanish. English-speaking parents were more likely to report having a data plan for their smartphone (117/157, 74.5%) or high-speed internet (138/157, 87.9%) compared to Spanish-speaking parents (smartphone: 23/40, 58%; P=.03; internet: 27/40, 68%; P=.002). Compared with Spanish-speaking parents, English-speaking parents were less likely to report having a lot or some concern about paying for internet (28/40, 70% vs 83/157, 52.9%; P=.046) or about data privacy (35/40, 88% vs 105/157, 67.5%; P=.01). Digital literacy scores differed significantly by race, income, education level, and language. In a multivariable model, language was not a significant factor for having high-speed internet service (P=.12) or concern about paying for internet at home (P=.60), but it was a significant factor for concerns about data privacy (P=.04). The significant differences in technology-related characteristics suggest that digital connectivity, affordability, and data privacy may also be important factors in considering digital technology use in asthma care.

To understand how extracellular vesicle (EV) subtypes differentially activate monocytes, a series of studies were performed. We found that plasma-EVs biased monocytes toward an M1 profile. Culturing monocytes with granulocyte-, monocyte-, and endothelial-EVs induced several pro-inflammatory cytokines. By contrast, platelet-EVs induced TGF-β and GM-CSF, and red blood cell (RBC)-EVs did not activate monocytes . The scavenger receptor CD36 was important for binding of RBC-EVs to monocytes, while blockade of CD36, CD163, CD206, TLR1, TLR2, and TLR4 did not affect binding of plasma-EVs to monocytes . To identify mortality risk factors, multiple soluble factors and EV subtypes were measured in patients' plasma at intensive care unit admission. Of 43 coagulation factors and cytokines measured, two were significantly associated with mortality, tissue plasminogen activator and cystatin C. Of 14 cellular markers quantified on EVs, 4 were early predictors of mortality, including the granulocyte marker CD66b. In conclusion, granulocyte-EVs have potent pro-inflammatory effects on monocytes . Furthermore, correlation of early granulocyte-EV levels with mortality in critically ill patients provides a potential target for intervention in management of the pro-inflammatory cascade associated with critical illness.