Challenges and strategies for generating therapeutic patient-specific hemangioblasts and hematopoietic stem cells from human pluripotent stem cells

Recent characterization of hemangioblasts differentiated from human embryonic stem cells (hESC) has further confirmed evidence from murine, zebrafish and avian experimental systems that hematopoietic and endothelial lineages arise from a common progenitor. Such progenitors may provide a valuable resource for delineating the initial developmental steps of human hemato-endotheliogenesis, which is a process normally difficult to study due to the very limited accessibility of early human embryonic/fetal tissues. Moreover, efficient hemangioblast and hematopoietic stem cell (HSC) generation from patient-specific pluripotent stem cells has enormous potential for regenerative medicine, since it could lead to strategies for treating a multitude of hematologic and vascular disorders. However, significant scientific challenges remain in achieving these goals, and the generation of transplantable hemangioblasts and HSC derived from hESC currently remains elusive. Our previous work has suggested that the failure to derive engraftable HSC from hESC is due to the fact that current methodologies for differentiating hESC produce hematopoietic progenitors developmentally similar to those found in the human yolk sac, and are therefore too immature to provide adult-type hematopoietic reconstitution. Herein, we outline the nature of this challenge and propose targeted strategies for generating engraftable human pluripotent stem cell-derived HSC from primitive hemangioblasts using a developmental approach. We also focus on methods by which reprogrammed somatic cells could be used to derive autologous pluripotent stem cells, which in turn could provide unlimited sources of patient-specific hemangioblasts and HSC

Optical Voltammetry of Polymer-Encapsulated Single-Walled Carbon Nanotubes

The semiconducting single-walled carbon nanotube (SWCNT), noncovalently wrapped by a polymeric monolayer, is a nanoscale semiconductor-electrolyte interface under investigation for sensing, photonics, and photovoltaic applications. SWCNT complexes are routinely observed to sensitize various electrochemical/redox phenomena, even in the absence of an external field. While the photoluminescence response to gate voltage depends on the redox potential of the nanotube, analogous optical voltammetry of functionalized carbon nanotubes could be conducted in suspension without applying voltage but by varying the solution conditions as well as the chemistry of the encapsulating polymer. Steady-state photoluminescence, absorbance, and in situ measurements of O2/H2O reactivity show correlation with the pH/pKa-dependent reactivity of π-rich coatings. The nanotube emission responses suggest that the presence of photogenerated potential may explain the observed coating electrochemical reactivity. This work finds that electronic and chemical interactions of the nanotube with the encapsulating polymer may play a critical role in applications that depend on radiative recombination, such as optical sensing

A Social Media Quality Review of Popular Sinusitis Videos on TikTok

Objective: Social media may inform health care decisions among younger patient populations. TikTok is a social media platform that allows users to post short-form videos. This study aimed to assess the quality of sinusitis-related videos on TikTok. Study Design: We searched TikTok on January 29, 2023, for sinusitis-related hashtags: #sinusitis, #sinus, #sinusinfection. Setting: Internet. Methods: The number of views/shares per day, uploader type (nonmedical influencer, lay individual, and medical professional) content categories (medical advice, marketing, comedy, and lifestyle/acceptability), and content type (educational vs factual) were collected. The Patient Education Materials Assessment Tool for Audiovisual Material and Journal of the American Medical Association criteria score was used to measure understandability, actionability, and reliability. The Global Quality Scale (GQS) was used to evaluate the quality of videos; the harm/benefit score was used to evaluate causative effects. Analyses were performed using analysis of variance (α = .05). Results: There were 221 videos identified, which garnered over 300 million views and 1 million shares. Almost half of the videos were published by nonmedical influencers. When controlling for covariates, nonmedical influencers and lay uploaders were more likely to have harmful harm/benefit scores, less understandable videos, and lower GQS scores compared to medical professionals. Less than half of videos posted by nonmedical influencers categorized as educational were factual (46.7%); lay individuals and medical professionals had higher rates of factual educational content (79.9% and 83.7%, respectively). Conclusion: Most nonmedical influencer-posted TikTok videos about sinusitis are inaccurate, despite being portrayed as medical advice/educational. Rhinologists must find modern ways to disseminate true disease-related content via social media to combat medical misinformation.</p

Special Considerations in Pediatric Endoscopic Skull Base Surgery.

Originally pioneered in adults, endoscopic endonasal approaches for skull base pathology are being increasingly applied as a minimally invasive alternative for young children. Intrinsic anatomic differences between these patient populations have sparked discussions on the feasibility, safety, and efficacy of these techniques in pediatric patients. This work aims to serve as a primer for clinicians engaged in the rapidly evolving field of pediatric endoscopic skull base surgery. A succinct overview of relevant embryology, sinonasal anatomy, and diagnostic workup is presented to emphasize key differences and unique technical considerations. Additional discussions regarding select skull base lesions, reconstructive paradigms, potential surgical complications, and postoperative care are also highlighted in the setting of multidisciplinary teams

Impact of social determinants of health on access to rhinology care and patient outcomes: A pilot study

Objective: This novel pilot study constructs a social deprivation index (SDI) and utilizes an area deprivation index (ADI) to evaluate the link between social determinants of health and rhinology patient experiences. Methods: Adult patients undergoing outpatient care of chronic rhinitis and chronic rhinosinusitis at a tertiary academic medical center were recruited to participate in a telephone survey assessing symptoms, social/emotional consequences of disease, and barriers to care on a 5-point Likert scale. Sociodemographic characteristics were utilized to rate SDI on an 8-point scale. ADI was obtained by area code of residence. Ordered logistic regression was used to examine associations between the SDI/ADI and perceptions of rhinology care. Results: Fifty patients were included. Individuals with higher SDI scores (i.e., more socially deprived) experienced more severe nasal congestion (p = .007). Furthermore, higher national ADI correlated with increased severity of smell changes (p = .050) and facial pressure (p = .067). No association was seen between either deprivation index and global/psychiatric symptoms. While no correlations were found between higher SDI and difficulties with the costs of prescriptions, rhinologist's visits, or saline, higher SDI was correlated with decreased difficulty with surgery costs (p = .029), and individuals with higher national ADI percentile had increased difficulties obtaining nasal saline (p = .029). Conclusion: Worse social deprivation is associated with difficulties obtaining saline rinses and increased severity of nasal/sinus symptoms in an urban, underserved, majority-Black population. These findings suggest social factors affect access to and quality of rhinology care in a complex and nuanced way and highlight the need for a specific SDI to further study social determinants of health in rhinology. Level of Evidence: 2c.</p

Cell Membrane Proteins Modulate the Carbon Nanotube Optical Bandgap <i>via</i> Surface Charge Accumulation

Cell adhesion is a protein-mediated process intrinsic to most living organisms. Dysfunction in cell adhesion processes is implicated in various diseases, including thrombosis and metastatic cancers. Using an approach to resolve spectral features from cell membrane-associated photoluminescent single-walled carbon nanotubes, we found that nanotube optical bandgaps respond to the electrostatic potential of the cell surface, which corresponds to cell adhesion properties. We studied the carbon nanotube emission energy response to solution ionic potentials, which suggests sensitivity to local charge accumulation. We conclude that nanotubes respond to cell surface electrostatic potentials that are mediated by membrane proteins, which vary significantly across cell types. These findings portend the optical measurement of surface electrostatic potentials for biophysical measurements and biomedical applications

A Carbon Nanotube Optical Reporter Maps Endolysosomal Lipid Flux

Lipid accumulation within the lumen of endolysosomal vesicles is observed in various pathologies including atherosclerosis, liver disease, neurological disorders, lysosomal storage disorders, and cancer. Current methods cannot measure lipid flux specifically within the lysosomal lumen of live cells. We developed an optical reporter, composed of a photoluminescent carbon nanotube of a single chirality, that responds to lipid accumulation via modulation of the nanotube’s optical band gap. The engineered nanomaterial, composed of short, single-stranded DNA and a single nanotube chirality, localizes exclusively to the lumen of endolysosomal organelles without adversely affecting cell viability or proliferation or organelle morphology, integrity, or function. The emission wavelength of the reporter can be spatially resolved from within the endolysosomal lumen to generate quantitative maps of lipid content in live cells. Endolysosomal lipid accumulation in cell lines, an example of drug-induced phospholipidosis, was observed for multiple drugs in macrophages, and measurements of patient-derived Niemann–Pick type C fibroblasts identified lipid accumulation and phenotypic reversal of this lysosomal storage disease. Single-cell measurements using the reporter discerned subcellular differences in equilibrium lipid content, illuminating significant intracellular heterogeneity among endolysosomal organelles of differentiating bone-marrow-derived monocytes. Single-cell kinetics of lipoprotein-derived cholesterol accumulation within macrophages revealed rates that differed among cells by an order of magnitude. This carbon nanotube optical reporter of endolysosomal lipid content in live cells confers additional capabilities for drug development processes and the investigation of lipid-linked diseases

Embolization in Juvenile Nasopharyngeal Angiofibroma Surgery: A Systematic Review and Meta-Analysis

Objective: To compare outcomes of juvenile nasopharyngeal angiofibroma (JNA) resection between embolized and non-embolized cohorts, and between transarterial embolization (TAE) and direct puncture embolization (DPE). Data sources: Per PRISMA guidelines, PubMed, Embase, Web of Science, Scopus, and Cochrane databases were searched for publications prior to or in 2021. Materials and methods: Original English manuscripts investigating the resection of JNA with and without preoperative embolization were included. Embolization type, recurrence rate, complication rates, blood loss, and transfusions were extracted. Risk of bias was assessed by the Risk of Bias in Non-randomized Studies-of Interventions method. Results: There were 61 studies with 917 patients included. Preoperative embolization was performed in 79.3% of patients. Of those embolized, 75.8% (N = 551) underwent TAE and 15.8% (N = 115) underwent DPE. JNA recurrence in embolized patients was lower than in non-embolized patients (9.3% vs. 14.4%; odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.35, 1.06). DPE resulted in lower rates of disease recurrence (0% vs. 9.5%; OR: 0.066, 95% CI: 0.016, 0.272) and complications (1.8% vs. 21.9%; OR: 0.07, 95% CI: 0.02, 0.3) than TAE. A random effects Bayesian model was performed to analyze the difference in mean blood loss in 6 studies that included both embolized and non-embolized patients. This analysis showed a mean reduction in blood loss of 798 mL in the embolized group. Conclusions: We found embolization decreases blood loss in JNA resection. DPE led to improved recurrence and complication rates when compared to TAE, but future prospective studies are needed to further evaluate which embolization technique can optimize outcomes in JNA. Level of evidence: NA Laryngoscope, 2023.</p