Single-cell RNA analysis of chromodomain-encoding genes in mesenchymal stromal cells of the mouse dental pulp.

The chromodomain helicase DNA-binding (CHD) and chromobox (CBX) families of proteins play crucial roles in cell fate decisions, differentiation, and cell proliferation in a broad variety of tissues and cell types. CHD proteins are ATP-dependent epigenetic enzymes actively engaged in transcriptional regulation, DNA replication, and DNA damage repair, whereas CBX proteins are transcriptional repressors mainly involved in the formation of heterochromatin. The pleiotropic effects of CHD and CBX proteins are largely dependent on their versatility to interact with other key components of the epigenetic and transcriptional machinery. Although the function and regulatory modes of CHD and CBX factors are well established in many cell types, little is known about their roles during osteogenic differentiation. A single-cell RNA-sequencing analysis of the mouse incisor dental pulp revealed distinct spatiotemporal expression patterns of CHD- and CBX-encoding genes within different clusters of mesenchymal stromal cells (MSCs) representing various stages of osteogenic differentiation. Additionally, genes encoding interaction partners of CHD and CBX proteins, such as subunits of the trithorax-COMPASS and polycomb chromatin remodeling complexes, exhibited differential co-expression behaviors within MSC subpopulations. Thus, CHD- and CBX-encoding genes show partially overlapping but distinct expression patterns in MSCs, suggesting their differential roles in osteogenic cell fate decisions.

Digital Media-related Problems Contributing to Psychiatric Hospitalizations Among Children and Adolescents Before and After the Onset of the COVID-19 Pandemic.

The role of digital media in crises leading to youth psychiatric admissions is understudied and digital media use increased during the COVID-19 pandemic. In this cross-sectional study, demographics, clinical characteristics, and digital media-related problems (DMRPs; sub-coded as cyberbullying, online communication problems, triggering content, and limit-setting problems) were extracted from hospital records of youth (n = 1,101) admitted to a pediatric psychiatric unit from May 2018 to November 2021. DMRPs were identified in 127 admissions (11.5%), led by the online communication problems and limit-setting subtypes (both 4-5%). Significantly more overall problems were identified following the pandemic onset (13.9% of admissions vs. 9.1% before, p < 0.05). The limit-setting subtype specifically increased post-COVID-19 (6.0% vs. 2.7%, p < 0.01), and was associated with prior admissions, suicide attempts, and impulse control/behavioral disorders. Online communication problems were significantly more common among girls and youth with a history of trauma. Interventions in acute settings to mitigate consequences of DMRPs are needed.

Application of 3D printing to create an in vitro aneurysm rupture model.

Currently available benchtop (in vitro) aneurysm models are inadequate for testing the efficacy of endovascular device treatments. Specifically, current models do not represent the mechanical instability of giant aneurysms (defined as aneurysms with 25 mm in height or width) and do not predictably rupture under simulated physiological conditions. Hence, in vitro aneurysm models with biomechanically relevant material properties and a predictable rupture timeframe are needed to accurately assess the efficacy of new medical device treatment options. Understanding the material properties of an aneurysm (e.g., shear and compression modulus) as it approaches rupture is a crucial step toward creating a pathologically relevant and sophisticated in vitro aneurysm rupture model. We investigated the change in material properties of a blood vessel, via enzymatic treatment, to simulate the degradation of an aneurysm wall and used this information to create a sophisticated aneurysm rupture model using the latest in additive manufacturing technologies (3D printing) with tissue-like materials. Mechanical properties (shear and compression modulus) of swine carotid vessels were evaluated before and after incubation with collagenase D enzyme (30 min at 37°C) to simulate the effect of biochemical activity on aneurysm wall approaching rupture compared to control vessels (untreated). Mechanical strength of a soft and flexible 3D-printed material (VCA-A30: 30 shore A hardness) was tested for comparison to these arterial vessels. This material was then used to create spherical shaped, giant-sized (25-mm diameter) aneurysm phantoms and were run under neurovascular pressures (120/80 ± 5 mmHg), beats per minute (BPM = 70) and flows representing the middle cerebral artery [MCA: 142.67 (±20.13) mL/min] using a blood analog [3.6 (±0.4) cP viscosity] with non-Newtonian shear-thinning properties. The shear modulus of swine carotid vessel before treatment was 12.2 (±2.7) KPa and compression modulus was 663.5 (±111.6) KPa. After enzymatic treatment by collagenase D, shear modulus of animal tissues reduced by 33% (p-value = .039) while compression modulus remained statistically unchanged (p-value = .615). Control group (untreated vessels) showed minimal reduction (13%, p-value = .226) in shear modulus and 78% increase (p-value = .034) in compression modulus. The shear modulus of the 3D-printed material was 228.59 (±24.82) KPa while its compression modulus was 668.90 (±13.16) KPa. This material was used to prototype a sophisticated in vitro giant aneurysm rupture model. When subjected to physiological pressures and flow rates, the untreated models consistently ruptured at ~12 min. These results indicate that aneurysm rupture can be recreated consistently in a benchtop in vitro model, utilizing the latest 3D-printed materials, connected to a physiologically relevant programmable pump. Further studies will investigate the optimization of various aneurysm dome thickness regions within the aneurysm, with tunable rupture times for comparison of aneurysm device deployment and benchtop controls based on the measurable effects of pressure and flow changes within the aneurysm models. These optimized in vitro rupture models could ultimately be used to test the efficacy of device treatment options and rupture risk by quantifying specific device rupture times and aneurysm rupture position.

The ACS-NSQIP Analysis of Negative Pressure Wound Therapy Following Pancreatectomy for Pancreatic Diagnoses.

Introduction Surgical site infections (SSIs) continue to be a challenging issue among patients undergoing pancreatectomy. Anecdotally, the use of negative pressure wound therapy (NPWT) following pancreatectomy for cancer has been associated with decreased SSIs. The objective of this study was to compare the postoperative outcomes of NPWT and non-NPWT for incisional wound care following distal pancreatectomy or pancreatoduodenectomy for pancreatic diagnoses using a national surgical database. Methods The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) was queried from 2005 to 2019 for patients undergoing distal pancreatectomy or pancreaticoduodenectomy for pancreatic diagnoses using primary Current Procedural Terminology (CPT) codes. The primary outcome was surgical site infection rates between NPWT and non-NPWT patient groups. Secondary outcomes include sepsis, septic shock, readmission, and reoperation. Outcomes of interest were compared using multivariate logistic regression. Results A total of 54,457 patients underwent pancreatectomy with 131 receiving NPWT. Multivariate analysis, while accounting for patient characteristics, including wound classification, showed no difference in postoperative superficial SSI, deep SSI, sepsis, septic shock, or readmission between the NPWT and non-NPWT groups. Organ space SSI was higher in the NPWT group (21% vs 12%, p=0.001). Reoperation related to procedure was also high in the NPWT group (14% vs 4.3%, p<0.001). Conclusion The use of NPWT in distal pancreatectomies and pancreatoduodenectomies is associated with increased organ space SSIs and reoperation rates, with no difference in superficial SSI, deep SSI, or readmission. This large sample study shows no significant benefit of using NPWT incisional wound care after pancreatectomy.

Predictors and Correlates of Positive Urine Drug Screening in a Retrospective Cohort Analysis of Child and Adolescent Psychiatry Inpatients Throughout the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES: Youth substance use is associated with significant psychological, neurological, and medical complications. Risk factors for substance use among children and adolescents in the general population include peer and/or parental substance use, certain psychiatric illnesses (eg, Attention-Deficit/Hyperactivity Disorder, depression), and history of maltreatment. Co-occurring substance use and psychiatric illness have been associated with increased suicidality, but few prior studies have characterized substance use among child/adolescent inpatients. As such, it remains unclear how substance use contributing to acute psychiatric presentations has changed since the start of the COVID-19 pandemic. METHODS: This is a retrospective cohort study of 816 unique child/adolescent psychiatry inpatients with urine drug screening (UDS) results from a diverse urban setting. Charts of patients hospitalized between June 1, 2018 and November 30, 2021 were reviewed for sociodemographic characteristics, indication for admission, psychiatric history, hospital course, treatment plan, and discharge diagnosis. Differences in sociodemographic and clinical characteristics, such as age, race, and diagnoses, between patients with and without positive UDS were explored throughout various periods of the COVID-19 pandemic. Descriptive and comparative statistics were performed, as well as a logistic regression model to identify the predictors of positive UDS. RESULTS: Of the study sample, 18% had a positive UDS. Older age, diagnosis of impulsive or behavioral disorder, and a history of violence were found to be predictors of positive UDS. Asian/South Asian or Hispanic/LatinX race and history of a developmental or intellectual disability were found to be negative predictors. The frequency of positive UDS in this population did not change based on COVID-19. DISCUSSION AND CONCLUSIONS: Multiple factors may predispose children and adolescents to substance use. Though no impact of COVID-19 was found in this sample, longer-term studies are needed. SCIENTIFIC SIGNIFICANCE: This study identifies independent predictors of active substance use in the child and adolescent psychiatric inpatient population.

Development of physiologically relevant synthetic thrombus for use in visual analysis of in vitro mechanical thrombectomy device testing.

BACKGROUND: Ischemic stroke is a leading cause of death and significant long-term disability worldwide. Mechanical thrombectomy is emerging as a standard treatment for eligible patients. As clinical implementation of stent retrieval and aspiration thrombectomy increases, there is a need for physiologically relevant in vitro device efficacy testing. Critical to this testing is the development of standardized 'soft' and 'hard' synthetic blood clots that mimic the properties of human thrombi and are compatible with imaging technologies. Synthetic clots allow researchers to extract information regarding clot integration, model hemodynamics, and quantify the physics of thrombectomy. METHODS: This work develops polyacrylamide and alginate-based synthetic clots that are compatible with particle image velocimetry (PIV) and radiographic imaging techniques while maintaining mechanical properties of 'soft' and 'hard' human clots. Dynamic mechanical analysis testing using an HR2-Rheometer demonstrates comparable mechanical properties to human clots previously tested by this research group and provided in existing literature. RESULTS: The synthetic clots are formulated with either 0.5% w/v polyethylene microspheres for PIV visualization or 20% w/v barium sulfate for angiographic visualization, enabling real-time imaging of clot behavior during thrombectomy simulations. The soft formulation shows compressive and shear properties of ~12 kPa and 2-3 kPa, respectively. The hard clots are 3-4 times stiffer, with compressive and shear properties of 41-42 kPa and 8-9 kPa, respectively. CONCLUSION: Standardized synthetic clots offer a platform for reproducible device testing. This provides a greater understanding of mechanical thrombectomy device efficacy, which may lead to quantifiable advances in device development and eventual improved clinical outcomes.