Travel Distance and Time to Pulsed Dye Laser Treatment for Port-Wine Birthmark in the Pediatric Population.

Prior research has demonstrated that early treatment of port-wine birthmark (PWB) with pulsed dye laser (PDL) yields optimal patient outcomes. Given the known variations in practice patterns among dermatologists offering PDL, we conducted a cross-sectional analysis in order to determine the travel distance and time to practice locations offering PDL therapy for PWB among the pediatric population. We determined the travel time and distance from each county population center in the United States to the nearest PDL site using ArcGIS and linked the data to demographic characteristics in each census tract. 1,243 practice sites were identified that offer PDL treatment for PWB for patients under the age of 18. Children living in urban areas were found to have a significantly shorter median travel time and distance to PDL sites (6.1 miles, 11.8 minutes) compared to children living in rural areas (60.9 miles, 66.7 minutes). Additionally, uninsured children were found to travel longer average distances (32.2 miles) than insured children (24.2 miles). These findings suggest that certain socioeconomically disadvantaged groups have increased travel burden when obtaining PDL treatment for PWB. Transportation resources and support may need to be given to certain patients to ensure timely and effective PDL treatment.

Differential patient travel distance and time to psoriasis clinical trial sites.

Considering the known disparities in racial representation in psoriasis clinical trials, this study sought to characterize travel distance and time to reach a psoriasis clinical trial site as a potential barrier to trial participation for multiple demographic and geographic variables. We determined travel distance and time from every census tract population center in the United States to the nearest psoriasis clinical trial site using ArcGIS and linked travel estimates to demographic characteristics in each census tract based on 2020 American Community Survey. The average distance and time traveled to reach a psoriasis clinical trial site nationally were 45.6 miles and 51.8 min, respectively. Urban residence and Northeast location had significantly lower travel distance and time relative to their geographic counterparts. Travel burden was significantly greater among Native American and Black races, individuals without college education and Veterans Affairs beneficiaries relative to their counterparts. These findings reveal disparate access regarding rurality, race, education and insurance type, which may encourage investigators to increase travel funding for underrepresented groups and diversity recruitment efforts to promote access to psoriasis clinical trials.

Travel distance and time to dermatology clinical trial sites: a cross-sectional geospatial analysis.

Despite increasing calls for diversity in clinical trial recruitment, data are lacking regarding disparities in access to dermatologic clinical trials. The objective of this study was to characterize travel distance and time to reach a dermatology clinical trial site considering patient demographic and location characteristics. We determined travel distance and time from every census tract population center in the United States to the nearest dermatologic clinical trial site using ArcGIS and linked travel estimates to demographic characteristics in each census tract based on 2020 American Community Survey. Nationally, patients travel an average of 14.3 miles and 19.7 min to reach a dermatologic clinical trial site. Significantly shorter travel distance and time were observed for urban and Northeast residence, White and Asian race and private insurance relative to rural and Southern residence, Native American and Black race and public insurance (p < 0.001). These findings reveal disparate access regarding geographic region, rurality, race and insurance type, which may encourage investigators to allocate funding for travel assistance for underrepresented and disadvantaged groups to promote access and diversity in dermatologic clinical trials.

Modeling the iron storage protein ferritin reveals how residual ferrihydrite iron determines initial ferritin iron sequestration kinetics.

Computational models can be created more efficiently by composing them from smaller, well-defined sub-models that represent specific cellular structures that appear often in different contexts. Cellular iron metabolism is a prime example of this as multiple cell types tend to rely on a similar set of components (proteins and regulatory mechanisms) to ensure iron balance. One recurrent component, ferritin, is the primary iron storage protein in mammalian cells and is necessary for cellular iron homeostasis. Its ability to sequester iron protects cells from rising concentrations of ferrous iron limiting oxidative cell damage. The focus of the present work is establishing a model that tractably represents the ferritin iron sequestration kinetics such that it can be incorporated into larger cell models, in addition to contributing to the understanding of general ferritin iron sequestration dynamics within cells. The model's parameter values were determined from published kinetic and binding experiments and the model was validated against independent data not used in its construction. Simulation results indicate that FT concentration is the most impactful on overall sequestration dynamics, while the FT iron saturation (number of iron atoms sequestered per FT cage) fine tunes the initial rates. Finally, because this model has a small number of reactions and species, was built to represent important details of FT kinetics, and has flexibility to include subtle changes in subunit composition, we propose it to be used as a building block in a variety of specific cell type models of iron metabolism.

Distinguishing annular pustular psoriasis from subcorneal pustular dermatosis-A diagnostic dilemma in a 10-year-old boy.

Subcorneal pustular dermatosis (SPD) and annular pustular psoriasis (APP) are very rare in childhood and difficult to differentiate both clinically and histopathologically. We report the case of a 10-year-old male with a 9-year history of erythematous scaly annular plaques with scattered pustules on the trunk. Although initially diagnosed as SPD, a lack of response to dapsone, presence of spongiosis on histology, and early age of disease onset led to consideration of APP. The patient was subsequently treated with adalimumab 80 mg weekly and completely cleared. This case illustrates the overlapping features of SPD and APP and suggests that the two disorders may represent a spectrum of the same disease.

Computational Modeling of Macrophage Iron Sequestration during Host Defense against Aspergillus.

Iron is essential to the virulence of Aspergillus species, and restricting iron availability is a critical mechanism of antimicrobial host defense. Macrophages recruited to the site of infection are at the crux of this process, employing multiple intersecting mechanisms to orchestrate iron sequestration from pathogens. To gain an integrated understanding of how this is achieved in aspergillosis, we generated a transcriptomic time series of the response of human monocyte-derived macrophages to Aspergillus and used this and the available literature to construct a mechanistic computational model of iron handling of macrophages during this infection. We found an overwhelming macrophage response beginning 2 to 4 h after exposure to the fungus, which included upregulated transcription of iron import proteins transferrin receptor-1, divalent metal transporter-1, and ZIP family transporters, and downregulated transcription of the iron exporter ferroportin. The computational model, based on a discrete dynamical systems framework, consisted of 21 3-state nodes, and was validated with additional experimental data that were not used in model generation. The model accurately captures the steady state and the trajectories of most of the quantitatively measured nodes. In the experimental data, we surprisingly found that transferrin receptor-1 upregulation preceded the induction of inflammatory cytokines, a feature that deviated from model predictions. Model simulations suggested that direct induction of transferrin receptor-1 (TfR1) after fungal recognition, independent of the iron regulatory protein-labile iron pool (IRP-LIP) system, explains this finding. We anticipate that this model will contribute to a quantitative understanding of iron regulation as a fundamental host defense mechanism during aspergillosis. IMPORTANCE Invasive pulmonary aspergillosis is a major cause of death among immunosuppressed individuals despite the best available therapy. Depriving the pathogen of iron is an essential component of host defense in this infection, but the mechanisms by which the host achieves this are complex. To understand how recruited macrophages mediate iron deprivation during the infection, we developed and validated a mechanistic computational model that integrates the available information in the field. The insights provided by this approach can help in designing iron modulation therapies as anti-fungal treatments.

mol2sphere: spherical decomposition of multi-domain molecules for visualization and coarse grained spatial modeling.

Motivation: Proteins, especially those involved in signaling pathways are composed of functional modules connected by linker domains with varying degrees of flexibility. To understand the structure-function relationships in these macromolecules, it is helpful to visualize the geometric arrangement of domains. Furthermore, accurate spatial representation of domain structure is necessary for coarse-grain models of the multi-molecular interactions that comprise signaling pathways. Results: We introduce a new tool, mol2sphere, that transforms the atomistic structure of a macromolecule into a series of linked spheres corresponding to domains. It does this with a k-means clustering algorithm. It may be used for visualization or for coarse grain modeling and simulation. Availability and implementation: PyMOL plugin, source, and documentation.https://nmrbox.org/registry/mol2sphere. SpringSaLaD executables and documentation: http://vcell.org/ssalad, SpringSaLaD v.2 source: https://github.com/jmasison/SpringSaLaD.