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Objective: To determine the association of patient race, patient-provider racial congruence, patient ethnicity, and family primary language with patient family experience (PFE) survey responses., Methods: Cross-sectional review of PFE survey responses from all ambulatory medical encounters at a large, urban children's hospital system June 1, 2020-May 31, 2022. Exposures were patient race, patient-provider racial congruence, patient ethnicity, and family primary language. We adjusted analyses for neighborhood-level socioeconomic deprivation, patient sex and age, encounter specialty, and location of care. Outcomes were PFE survey scores for five questions focused on overall experience, respect, and safety; categorized using industry standard metric of presence of a "top-box" score, defined as a nine or 10 for questions on an 11-point scale or as four on a four-point scale., Results: We included 89,175 surveys (15.6% response rate). The odds of having optimal, "top-box" responses for several assessed questions were lower for patients identified as Asian (eg, adjusted odds ratio [OR] 0.46; 95% confidence interval [CI] 0.40, 0.52) or Black (eg, OR 0.65; CI 0.60, 0.70) compared to White, and for Hispanic (eg, OR 0.84; CI 0.72, 0.97) compared to non-Hispanic. Similarly, the odds of having "top-box" scores were lower for Spanish-primary-language (eg, OR 0.38; CI 0.30, 0.48) compared to English-primary-language patients. Patient-provider racial congruence had higher odds of "top-box" responses for two of five assessed questions (eg, OR 1.18; CI 1.04, 1.35)., Conclusions: We found previously unreported inequities in ambulatory pediatric PFE outcomes, with worse experiences reported by Asian, Black, Hispanic, and Spanish-language patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy of Resident Education And Counseling on Household (REACH) Firearm Safety, a novel virtual reality (VR) intervention., Methods: We conducted a single-center, randomized controlled trial among pediatric residents in a Midwestern academic primary care center comparing REACH Firearm Safety with didactic training (intervention) to didactic training alone (control). In the intervention arm, participants practiced firearm safety counseling with virtual characters and received immediate feedback. All residents completed audio-recorded standardized patient (SP) encounters before and after the training as well as a retrospective pre-post survey. Two reviewers, blinded to the allocation arm, used a standardized assessment tool to generate performance scores. Outcomes of interest included the difference between groups in SP performance scores and self-reported confidence., Results: From March to July 2023, 62% of eligible pediatric residents (n = 47/76) completed the allocated study tasks (intervention 19, control 28). In both groups, SP performance scores and self-reported confidence improved. Compared to the control group, the intervention group demonstrated improvement in sharing information on secure storage devices (P = 0.009) and increased confidence in providing information on secure storage (P = 0.002)., Conclusions: Compared with didactic training alone, a VR intervention using deliberate practice improved residents' skills and confidence related to firearm safety counseling., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objective: Central odontogenic fibromas (COF) are rare, benign tumors derived from dental mesenchymal tissue that may occur in the maxilla or mandible. This report describes primary and recurrent COF in the mandible of a patient with nevoid basal cell carcinoma syndrome (NBCCS)., Study Design: A 36-year-old African American male presented with a COF and its recurrence 17 months later. Tissue pieces were obtained from both occurrences with IRB-approved signed consent. Collected tissue pieces were dissected; one portion was formalin-fixed and paraffin-embedded, and the other was cultured for the isolation of cell populations from the primary (COdF-1) and recurrent (COdF-1a) tumors. Quantification real-time polymerase chain reaction (qRT-PCR), immunohistochemistry, and DNA sequencing were used for gene and protein analysis of the primary tumor and cell populations., Results: Histopathologic analysis of the tumor showed sparse odontogenic epithelial cords in fibrous connective tissue, and qRT-PCR analysis of tumor and cell populations (COdF-1 and COdF-1a) detected VIM, CK14, CD34, CD99 and ALPL mRNA expression. Protein expression was confirmed by immunohistochemistry. CD34 expression in primary tissues was higher than in tumor cells due to tumor vascularization. DNA sequencing indicated the patient had PTCH1 mutations., Conclusions: Histopathology, mRNA, and protein expression indicate the rare occurrence of COF in a patient with mutated PTCH1 gene and NBCCS., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: The authors declared no conflict of interests.

Background: Moral distress (MD) refers to psychological unease when healthcare professionals identify morally correct actions to take but are constrained in their ability to take those actions., Methods: This study evaluated the relationship between out-of-hours decisions and MD among 40 Foundation Year 2 (FY2) doctors. They were asked to choose the 'expected' and the 'right' management options for five out-of-hours scenarios and complete an adapted Measure of Moral Distress for Health Professionals (MMD-HP) questionnaire., Results: 28/40 (70%) reported discordance between 'expected' and 'right' options more frequently than concordance. The mean total MMD-HP score was low: 64.9 ( SD  = 26.9), range 13-143, maximum 288. The association between decision-making discordance and MMD-HP score was weak., Conclusion: Out-of-hours decisions by FY2 doctors were characterised by doing what is 'expected' rather than what is perceived to be 'right'. Providing guidance regarding decision-making in deteriorating patients is needed for patient safety and staff well-being., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

When main-sequence stars expand into red giants, they are expected to engulf close-in planets 1-5 . Until now, the absence of planets with short orbital periods around post-expansion, core-helium-burning red giants 6-8 has been interpreted as evidence that short-period planets around Sun-like stars do not survive the giant expansion phase of their host stars 9 . Here we present the discovery that the giant planet 8 Ursae Minoris b 10 orbits a core-helium-burning red giant. At a distance of only 0.5 AU from its host star, the planet would have been engulfed by its host star, which is predicted by standard single-star evolution to have previously expanded to a radius of 0.7 AU. Given the brief lifetime of helium-burning giants, the nearly circular orbit of the planet is challenging to reconcile with scenarios in which the planet survives by having a distant orbit initially. Instead, the planet may have avoided engulfment through a stellar merger that either altered the evolution of the host star or produced 8 Ursae Minoris b as a second-generation planet 11 . This system shows that core-helium-burning red giants can harbour close planets and provides evidence for the role of non-canonical stellar evolution in the extended survival of late-stage exoplanetary systems., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Tooth agenesis (TA) is the developmental absence of one or more teeth and is the most common craniofacial disorder in humans. Maxillary lateral incisor agenesis (MLIA) is a specific subtype of TA and can have esthetic, functional, and psychosocial implications for patients. The aim of this study was to evaluate the prevalence of MLIA amongst patients with non-syndromic tooth agenesis, as well as its association with other dental anomalies., Materials and Methods: The dental records of 240 patients with non-syndromic congenitally missing teeth treated at the University of Alabama at Birmingham Department of Orthodontics were reviewed. Dolphin Imaging software was used to identify missing teeth, microdonts, peg laterals, impactions, and transpositions. Data were analyzed using chi-square or Fisher's exact test. All the tests were two-sided at the significance level of 0.05 (SAS 9.4)., Results: In the patient cohort, MLIA prevalence was 37.5% (second most common) and no gender or ethnic differences were identified. We also observed the bilaterally missing lateral incisors more frequently than the unilateral presentation (p = 0.0006). Additionally, 62.5% of patients with unilateral MLIA displayed a contralateral tooth that was a peg (p = 0.0001); however, no association was found with other microdonts. Furthermore, of the 90 patients missing at least one maxillary lateral incisor, 42.2% were missing another tooth type and 10% of MLIA patients also had an impacted tooth (mainly maxillary canines). However, these were not statistically significant. Finally, no transposed teeth were found in our patients., Conclusions: This study found that maxillary lateral incisors were the second most frequently missing teeth. When clinicians diagnose congenital absence of a maxillary lateral incisor, the patient should be evaluated for other missing teeth, peg lateral incisors, or potential impactions, especially maxillary canines., (© 2022. The Author(s).)

Diabetic nephropathy is a leading cause of end-stage renal disease, characterized by endothelial dysfunction and a compromised glomerular permeability barrier. Dysregulation of the angiopoietin 1 (ANGPT1)/angiopoietin 2 (ANGPT2) signaling axis is implicated in disease progression. We recently described the discovery of an IgG 1 antibody, O010, with therapeutic potential to elevate circulating endogenous ANGPT1, a tyrosine kinase with Ig and epidermal growth factor (EGF) homology domains-2 (TIE2) agonist. Studies are described that detail the effect of various ANGPT1-elevating strategies to limit progression of renal dysfunction in diabetic-obese (db/db) mice. Results demonstrate that adeno-associated virus- or DNA minicircle-directed overexpression of ANGPT1 elicits a reduction in albuminuria (56%-73%) and an improvement in histopathology score (18% reduction in glomerulosclerosis). An improved acetylcholine response in isolated aortic rings was also observed indicative of a benefit on vascular function. In separate pharmacokinetic studies, an efficacious dose of the ANGPT1 DNA minicircle increased circulating levels of the protein by >80%, resulting in a concomitant suppression of ANGPT2. At a dose of O010-producing maximal elevation of circulating ANGPT1 achievable with the molecule (60% increase), no suppression of ANGPT2 was observed in db/db mice, suggesting insufficient pathway engagement; no reduction in albuminuria or improvement in histopathological outcomes were observed. To pinpoint the mechanism resulting in lack of efficacy, we demonstrate, using confocal microscopy, an interference with TIE2 translocation to adherens junctions, resulting in a loss of protection against vascular permeability normally conferred by ANGPT1. Results demonstrated the essential importance of ANGPT1 to maintain the glomerular permeability barrier, and, due to interference of O010 with this process, led to the discontinuation of the molecule for clinical development. SIGNIFICANCE STATEMENT: This body of original research demonstrates that elevation of systemic angiopoietin 1 (ANGPT1) is protective against diabetic nephropathy. However, using a novel biotherapeutic approach to elevate systemic ANGPT1 renoprotection was not observed; we demonstrate that protection was lost due to interference of the therapeutic with ANGPT1/ tyrosine kinase with Ig and EGF homology domains-2 translocation to adherens junctions. Thus, the clinical development of the antibody was terminated., (Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics.)

BMP signaling plays an important role in dentin development. BMPs and antagonists regulate odontoblast differentiation and downstream gene expression via canonical Smad and non-canonical Smad signaling pathways. The interaction of BMPs with their receptors leads to the formation of complexes and the transduction of signals to the canonical Smad signaling pathway (for example, BMP ligands, receptors, and Smads) and the non-canonical Smad signaling pathway (for example, MAPKs, p38, Erk, JNK, and PI3K/Akt) to regulate dental mesenchymal stem cell/progenitor proliferation and differentiation during dentin development and homeostasis. Both the canonical Smad and non-canonical Smad signaling pathways converge at transcription factors, such as Dlx3, Osx, Runx2, and others, to promote the differentiation of dental pulp mesenchymal cells into odontoblasts and downregulated gene expressions, such as those of DSPP and DMP1. Dysregulated BMP signaling causes a number of tooth disorders in humans. Mutation or knockout of BMP signaling-associated genes in mice results in dentin defects which enable a better understanding of the BMP signaling networks underlying odontoblast differentiation and dentin formation. This review summarizes the recent advances in our understanding of BMP signaling in odontoblast differentiation and dentin formation. It includes discussion of the expression of BMPs, their receptors, and the implicated downstream genes during dentinogenesis. In addition, the structures of BMPs, BMP receptors, antagonists, and dysregulation of BMP signaling pathways associated with dentin defects are described.

While the respiratory tract is the primary route of entry for SARS-CoV-2, evidence shows that the virus also impacts the central nervous system. Intriguingly, case reports have documented SARS-CoV-2 patients presenting with demyelinating lesions in the brain, spinal cord, and optic nerve, suggesting possible implications in neuroimmune disorders such as multiple sclerosis (MS) and other related neuroimmune disorders. However, the cellular mechanisms underpinning these observations remain poorly defined. The goal of this paper was to review the literature to date regarding possible links between SARS-CoV-2 infection and neuroimmune demyelinating diseases such as MS and its related disorders, with the aim of positing a hypothesis for disease exacerbation. The literature suggests that SARS-CoV, SARS-CoV-2, and orthologous murine coronaviruses invade the CNS via the olfactory bulb, spreading to connected structures via retrograde transport. We hypothesize that a glial inflammatory response may contribute to damaged oligodendrocytes and blood brain barrier (BBB) breakdown, allowing a second route for CNS invasion and lymphocyte infiltration. Potential for molecular mimicry and the stimulation of autoreactive T cells against myelin is also described. It is imperative that further studies on SARS-CoV-2 neuroinvasion address the adverse effects of the virus on myelin and exacerbation of MS symptoms, as nearly 3 million people suffer from MS worldwide., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 MacDougall, El-Hajj Sleiman, Beauchemin and Rangachari.)

Objective: To optimize and compare the isolation of platelet-rich plasma (PRP) and its cryopreserved derivative, platelet lysate (PL), to a commercial human platelet lysate (HPL) product PLUS and investigate their proliferative stimulation on primary human endometrial cells in vitro., Design: Basic research., Setting: Academic fertility center., Patient(s): Three healthy blood donors and eight patients with a history of recurrent implantation failure., Interventions(s): Stimulated proliferation of isolated primary endometrial epithelial cells and endometrial stromal cells in vitro with autologous and nonautologous HPL (PLUS; Compass Biomedical)., Main Outcome Measure(s): Platelet-derived growth factor BB homodimer protein content in isolated PRP/PL and commercial HPL and endometrial epithelial cell and endometrial stromal cell proliferation after 24- or 48-hour stimulation with PL (measured by metabolic activity and Ki67 expression)., Result(s): To optimize and compare the isolation of autologous PRP/PL, three double-centrifugation protocols were assessed by flow cytometry for platelet yield (CD45 - CD41 + CD61 + ) and platelet-derived growth factor BB homodimer protein content by enzyme-linked immunosorbent assay. Cryopreserved PL, especially isolated by our fastest protocol, contained higher protein concentrations and, thus, was optimal for experimental flexibility compared with fresh PRP. The autologous and commercial PLs displayed comparable immune and growth factor content and stimulation of cell proliferation in vitro., Conclusion(s): Our results provide the groundwork for the isolation and use of HPL to stimulate endometrial growth. Furthermore, commercial PL consistently stimulated cell proliferation and may allow standardization of clinical treatment for recurrent implantation failure., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)