Search

OBJECTIVE: To examine linguistic disparities between English- and Spanish-speaking patients in access to care, satisfaction, and telehealth appointment attendance. DESIGN: Retrospective study recording demographics for non-attendance analysis and conducting phone surveys assessing satisfaction with telehealth. SETTING: Data was collected between March and December 2020 at the UCSF Craniofacial Center (CFC), a multidisciplinary pediatric clinic. Patients: English- and Spanish-speaking patients with a telehealth appointment. Interventions: The CFC offered language-concordant outreach, assistance with the telehealth platform, and interpreters at all telehealth appointments. MAIN OUTCOME MEASURES: Demographics and patient-reported satisfaction with telehealth, barriers, and instruction clarity. RESULTS: Medicaid insurance was the only predictor of non-attendance. Surveys revealed that Spanish-speakers had 12.4 times the odds of lacking access to telehealth technology and 10.7 times the odds of needing help with logging on compared to English-speakers. There were no significant differences in satisfaction outcomes. CONCLUSIONS: We attribute this equity in satisfaction to our language-concordant outreach efforts.

BACKGROUND: Side effects of opioid pain management after surgical repair of cleft lips are numerous and affect postoperative course. We compared opioid versus opioid-free pain management regimens for infants who underwent cleft lip repair to evaluate the impact on postoperative recovery. METHODS: Cleft lip repairs at our institution from December 2016 to February 2021 were retrospectively reviewed, comparing patients who received opioids to patients receiving a nonopioid pain control regimen. Data collected include length of stay, oral morphine equivalents (OME) received on day of surgery (DOS)/postoperative day (POD) 1, time to and volume of first oral feed, and Face/Legs/Activity/Cry/Consolability (FLACC) scores. RESULTS: Seventy-three infants were included (47 opioid and 26 nonopioid). The opioid group received average 1.75 mg OME on DOS and 1.04 mg OME on POD1. Average DOS FLACC scores were similar between groups [1.57 ± 1.18 nonopioid versus 1.76 ± 0.94 (SD) opioid; P = 0.46]. Average POD1 FLACC scores were significantly lower for the nonopioid group (0.73 ± 1.05 versus 1.35 ± 1.06; P = 0.022). Median time to first PO (min) was similar [178 (interquartile range [IQR] 66-411) opioid versus 147 (IQR 93-351) nonopioid; P = 0.65]. Median volume of first feed (mL) was twice as high for the nonopioid group [90 (IQR 58-120) versus 45 (IQR 30-60); P = 0.003]. CONCLUSIONS: Nonopioid postoperative pain management was more effective than opioids for pain management in infants after cleft lip repair, as evidenced by FLACC scores and increased volume of the first oral feed.

Stem cell behavior is tightly regulated by spatiotemporal signaling from the niche, which is a four-dimensional microenvironment that can instruct stem cells to remain quiescent, self-renew, proliferate, or differentiate. In this review, we discuss recent advances in understanding the signaling cues provided by the stem cell niche in two contrasting adult tissues, the rapidly cycling intestinal epithelium and the slowly renewing skeletal muscle. Drawing comparisons between these two systems, we discuss the effects of niche-derived growth factors and signaling molecules, metabolic cues, the extracellular matrix and biomechanical cues, and immune signals on stem cells. We also discuss the influence of the niche in defining stem cell identity and function in both normal and pathophysiologic states.

Although heterogeneity is recognized within the murine satellite cell pool, a comprehensive understanding of distinct subpopulations and their functional relevance in human satellite cells is lacking. We used a combination of single cell RNA sequencing and flow cytometry to identify, distinguish, and physically separate novel subpopulations of human PAX7+ satellite cells (Hu-MuSCs) from normal muscles. We found that, although relatively homogeneous compared to activated satellite cells and committed progenitors, the Hu-MuSC pool contains clusters of transcriptionally distinct cells with consistency across human individuals. New surface marker combinations were enriched in transcriptional subclusters, including a subpopulation of Hu-MuSCs marked by CXCR4/CD29/CD56/CAV1 (CAV1+). In vitro, CAV1+ Hu-MuSCs are morphologically distinct, and characterized by resistance to activation compared to CAV1- Hu-MuSCs. In vivo, CAV1+ Hu-MuSCs demonstrated increased engraftment after transplantation. Our findings provide a comprehensive transcriptional view of normal Hu-MuSCs and describe new heterogeneity, enabling separation of functionally distinct human satellite cell subpopulations.

Rotator cuff (RC) tears are frequently complicated by muscle atrophy. Muscle stem cells (MuSCs) repair damaged myofibers following injury, but their role in the prevention or pathogenesis of atrophy following RC tears remains undefined. We hypothesized that the RC MuSC population would be affected by supraspinatus (SS) and infraspinatus (IS) tendon transection (TT) compared to uninjured muscle in a mouse model of RC tear. C57BL6/J mice underwent unilateral SS and IS TT and contralateral sham surgery. At 3, 8, or 14 weeks after injury, mice were euthanized, and SS and IS were harvested for FACS sorting of CD31-/CD45-/Sca1-/ITGa7+/VCAM+ MuSCs or histological analysis. Ki-67+ MuSCs from injured muscle increased 3.4-fold at 3 weeks (p = 0.03) and 8.1-fold at 8 weeks (p = 0.04) following TT injury, but returned to baseline by 14 weeks (p = 0.91). Myod1 remained upregulated 3.3-fold at 3 weeks (p = 0.03) and 2.0-fold at 14 weeks (p = 0.0003), respectively. Myofiber cross-sectional area was decreased at both 3 and 14 weeks after injury, but the number of MuSCs per fiber remained relatively constant at 3 (p = 0.3) and 14 (p = 0.6) weeks after TT. In this study, we characterized the longitudinal effect of RC tendon injury on the MuSC population in supraspinatus and infraspinatus muscles. MuSCs are transiently activated, and are not depleted, in spite of persistent muscle atrophy. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1370-1376, 2018.

Investigation of human muscle regeneration requires robust methods to purify and transplant muscle stem and progenitor cells that collectively constitute the human satellite cell (HuSC) pool. Existing approaches have yet to make HuSCs widely accessible for researchers, and as a result human muscle stem cell research has advanced slowly. Here, we describe a robust and predictable HuSC purification process that is effective for each human skeletal muscle tested and the development of storage protocols and transplantation models in dystrophin-deficient and wild-type recipients. Enzymatic digestion, magnetic column depletion, and 6-marker flow-cytometric purification enable separation of 104 highly enriched HuSCs per gram of muscle. Cryostorage of HuSCs preserves viability, phenotype, and transplantation potential. Development of enhanced and species-specific transplantation protocols enabled serial HuSC xenotransplantation and recovery. These protocols and models provide an accessible system for basic and translational investigation and clinical development of HuSCs.

Although human induced pluripotent stem cells (hiPSCs) hold great potential for the study of human diseases affecting disparate cell types, they have been underutilized in seeking mechanistic insights into the pathogenesis of congenital craniofacial disorders. Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder caused by mutations in EFNB1 and characterized by craniofacial, skeletal, and neurological anomalies. Heterozygous females are more severely affected than hemizygous males, a phenomenon termed cellular interference that involves mosaicism for EPHRIN-B1 function. Although the mechanistic basis for cellular interference in CFNS has been hypothesized to involve Eph/ephrin-mediated cell segregation, no direct evidence for this has been demonstrated. Here, by generating hiPSCs from CFNS patients, we demonstrate that mosaicism for EPHRIN-B1 expression induced by random X inactivation in heterozygous females results in robust cell segregation in human neuroepithelial cells, thus supplying experimental evidence that Eph/ephrin-mediated cell segregation is relevant to pathogenesis in human CFNS patients.

Background: Accurate diagnosis and spatial characterization of craniofacial fractures is critical for treatment planning and precise fracture reduction. Since augmented reality (AR) has potential for better diagnostic evaluation than traditional three-dimensional (3D) reformats, we tested whether our accessible mobile-based AR model improves diagnostic accuracy, spatial understanding, and decreases task cognitive load when clinicians evaluate facial fractures. Methods: Clinicians (n = 30) in specialties managing craniofacial trauma assessed a database of mandibular and maxillofacial complex fractures of varying severity using computed-tomography slices supplemented with either traditional 3D reformats (control) or the AR model (experimental), completed diagnostic and spatial characterization tasks, and were evaluated quantitatively and qualitatively on diagnostic accuracy, task cognitive load, and weighted preference for the traditional versus AR model. Results: Most clinicians (83%) preferred the AR model overall. Control and experimental groups had equivalent diagnostic sensitivity and specificity. Less experienced clinicians found the AR model required less effort, was less frustrating, and was preferred for fracture displacement characterization. The AR model had no significant impact on more experienced clinicians. All clinicians found the AR model allowed more intuitive manipulation of the 3D object. Those with less experience preferred the AR model over traditional imaging for diagnostic and educational purposes, whereas more experienced clinicians found that the AR model did not significantly alter their established approach to fracture evaluation. Conclusions: Our mobile-based AR model may be preferable to traditional 3D formats for spatial assessment tasks and decreasing task cognitive load, most notably for less experienced clinicians for whom perioperative practices are less established. [ABSTRACT FROM AUTHOR]

The control of proliferation and differentiation by tumor suppressor genes suggests that evolution of divergent tumor suppressor repertoires could influence species regenerative capacity. To directly test that premise, we humanized the zebrafish p53 pathway by introducing regulatory and coding sequences of the human tumor suppressor ARF into the zebrafish genome. ARF was dormant during development, in uninjured adult fins, and during wound healing, but was highly expressed in the blastema during epimorphic fin regeneration after amputation. Regenerative, but not developmental signals resulted in binding of zebrafish E2f to the human ARF promoter and activated conserved ARF-dependent Tp53 functions. The context-dependent activation of ARF did not affect growth and development but inhibited regeneration, an unexpected distinct tumor suppressor response to regenerative versus developmental environments. The antagonistic pleiotropic characteristics of ARF as both tumor and regeneration suppressor imply that inducing epimorphic regeneration clinically would require modulation of ARF -p53 axis activation.

© 2015 The Authors.Summary Identification of human satellite cells that fulfill muscle stem cell criteria is an unmet need in regenerative medicine. This hurdle limits understanding how closely muscle stem cell properties are conserved among mice and human

The control of proliferation and differentiation by tumor suppressor genes suggests that evolution of divergent tumor suppressor repertoires could influence species' regenerative capacity. To directly test that premise, we humanized the zebrafish p53 pathway by introducing regulatory and coding sequences of the human tumor suppressor ARF into the zebrafish genome. ARF was dormant during development, in uninjured adult fins, and during wound healing, but was highly expressed in the blastema during epimorphic fin regeneration after amputation. Regenerative, but not developmental signals resulted in binding of zebrafish E2f to the human ARF promoter and activated conserved ARF-dependent Tp53 functions. The context-dependent activation of ARF did not affect growth and development but inhibited regeneration, an unexpected distinct tumor suppressor response to regenerative versus developmental environments. The antagonistic pleiotropic characteristics of ARF as both tumor and regeneration suppressor imply that inducing epimorphic regeneration clinically would require modulation of ARF -p53 axis activation.

© 2014 Tamaki et al.Background: Human pancreatic islet structure poses challenges to investigations that require specific modulation of gene expression. Yet dissociation of islets into individual cells destroys cellular interactions important to islet phy

Cell-cell fusion is critical to the normal development of certain tissues, yet the nature and degree of conservation of the underlying molecular components remains largely unknown. Here we show that the two guanine-nucleotide exchange factors Brag2 and Dock180 have evolutionarily conserved functions in the fusion of mammalian myoblasts. Their effects on muscle cell formation are distinct and are a result of the activation of the GTPases ARF6 and Rac, respectively. Inhibition of ARF6 activity results in a lack of physical association between paxillin and beta(1)-integrin, and disruption of paxillin transport to sites of focal adhesion. We show that fusion machinery is conserved among distinct cell types because Dock180 deficiency prevented fusion of macrophages and the formation of multinucleated giant cells. Our results are the first to demonstrate a role for a single protein in the fusion of two different cell types, and provide novel mechanistic insight into the function of GEFs in the morphological maturation of multinucleated cells.

We describe the first cases of pediatric melanoma with ALK fusion gene arising within giant congenital melanocytic nevi. Two newborn boys presented with large pigmented nodular plaques and numerous smaller satellite nevi. Additional expansile nodules developed within both nevi and invasive melanomas were diagnosed before 10 months of age in both boys. Oncogenic driver mutations in NRAS and BRAF were absent in both cases. Instead, oncogenic ZEB2::ALK fusion genes were identified in both the nevus and melanoma developing within the nevus. In both cases, tumors were noted by ultrasound in utero, demonstrated significant nodularity at birth, and progressed to melanoma in the first year of life suggesting that congenital nevi with ALK fusion genes may behave more aggressively than those with other mutations. As ALK kinase inhibitors are effective against a range of tumors with similar ALK fusion kinases, identifying ALK fusion genes in congenital melanocytic nevi may provide an opportunity for targeted therapy. [ABSTRACT FROM AUTHOR]

Objective : This study sought to identify disparities in the timing of alveolar bone grafting (ABG) surgery and the replacement strategy for missing maxillary lateral incisors for patients with clefts. Design : A retrospective record review identified patients who underwent ABG. Multivariable regression analyzed the independent contribution of each variable. Setting : This institutional study was performed at the University of California, San Francisco. Participants : Patients who presented under age 12 and underwent secondary ABG between 2012 and 2020 (n = 160). Main Outcome Measures : The age at secondary ABG and the recommended dental replacement treatment for each patient, either dental implantation or canine substitution. Results : The average age at ABG was 10.8 ± 2.1 years, 106 (66.3%) patients were not White, and 80 (50.0%) had private insurance. Independent predictors of older age at ABG included an income below $ 50 000 as estimated from ZIP code (β = 15.0 months, 95% CI, 5.7-24.3, P =.002) and identifying as a race other than White (β = 10.1 months, 95% CI, 2.1-18.0, P =.01). After ABG, patients were more likely to undergo dental implantation over canine substitution if they were female (odds ratio [OR] = 4.3, 95% CI, 1.3-17.1, P =.02) or had private insurance (OR = 12.5, 95% CI, 2.2-143.2, P =.01). Conclusions : Patients who were low-income or not White experienced delays in ABG, whereas dental implantation was more likely to be recommended for patients with private insurance. Understanding the sources of disparities in dental reconstruction of cleft deformities may reveal opportunities to improve equity. [ABSTRACT FROM AUTHOR]