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A critical need exists for a robust method that enables early discrimination between superficial-partial and deep-partial thickness burn wounds. In this study, we report on the use of laser speckle imaging (LSI), a simple, non-invasive, optical imaging modality, to measure acute blood flow dynamics in a preclinical burn model. We used a heated brass comb to induce burns of varying severity to nine rats and collected raw speckle reflectance images over the course of three hours after burn. We induced a total of 12 superficial-partial and 18 deep-partial thickness burn wounds. At 3 h after burn we observed a 28% and 44% decrease in measured blood flow for superficial-partial and deep-partial thickness burns, respectively, and that these reductions were significantly different (p = 0.00007). This preliminary data suggests the potential role of LSI in the clinical management of burn wounds.

Background and Objective: Spatial Frequency Domain Imaging (SFDI) is a non-contact wide-field optical imaging technology currently being developed to investigate the feasibility of quantitative non-invasive evaluation of burn wound severity in a rat model. Our objective is to determine the potential of SFDI for mapping quantitative changes in spatially resolved tissue oxygen saturation and water concentration may be indicative of burn wound severity, healing, and further complications. In this portion of the investigation, we focus on the development of a rat burn model and the acute response of tissue to burn wounds. Study Design/Materials and Methods: A controlled burn protocol involving a heated brass comb was applied to 6 rats. Imaging was acquired at 17 evenly spaced wavelengths in the near-infrared from 650 to 970 nm. Over the course of the 3 hour post-burn period, we were able to map quantitative changes in spatially resolved chromophores. Burn severities were verified post-experiment using standard H and E histology and optical microscopy. Results/Conclusion: In total, we were able to induce 12 superficial-partial thickness burns, 8 deep-partial thickness burns, and 4 full thickness burns in our rat models. While several tissue chromophores were tracked, we found that changes in oxygen saturation and water concentration to be sensitive indicators of burn severity. Future work will include additional longitudinal studies over a period of days in order to investigate which parameters are correlated to tissue healing. © 2013 SPIE.

Background and Objective: Spatial Frequency Domain Imaging (SFDI) is a non-contact wide-field optical imaging technology currently being used to study the optical properties and chromophore concentrations of in-vivo malignant melanomas and benign pigmented lesions. Our objective is to develop a motion correction procedure in order to assess the concerns of subject-motion related variables during clinical measurements. Study Design/Materials and Methods: SFDI motion-correction is a two-part procedure which utilizes a fiduciary marker and canny-edge detection in order to reposition and align the frame-to-frame regions-of-interest (ROI). Motioninduced phase-shifts are subsequently sampled before the entire image-set is processed by a modified demodulation formula. By comparing the results of the adjusted processing method with data gathered from the current non-corrected method, we were able to systematically characterize the impact of motion variables on SFDI measurements. Results: Motion-corrected SFDI data from moving phantom measurements and clinical patient measurements showed up to 84.58% decrease in absorption (μa) variance and up to 92.63% decrease in reduced-scattering (μs') variance. Stationary phantom test-measurements showed almost no difference between motion corrected and standard processing. Conclusion: SFDI motion correction is necessary for obtaining high-fidelity in-vivo optical property measurements of pigmented lesions in a clinical setting. © 2011 Copyright SPIE - The International Society for Optical Engineering.

Background: Pharmacogenomic testing can optimize drug efficacy and minimize adverse effects. CYP3A5 polymorphisms affect the metabolism of tacrolimus. We sought to estimate the budget impact of preemptive pharmacogenomic testing for CYP3A5 in pediatric heart transplantation patients from an institutional perspective., Methods: A decision tree was constructed to estimate the budget impact of pediatric heart transplant patients (age ≤18 years) initiated on tacrolimus with and without CYP3A5 pharmacogenomic testing. The budget impact of preemptive pharmacogenomic testing versus no pharmacogenomic testing was calculated. One-way sensitivity analysis and alternative analyses were conducted to assess the robustness of results to changes in model parameters., Results: CYP3A5 genotype-guided dosing provided savings of up to $17 225 per patient compared to standard dosing. These savings decreased to $11 759 when using another institution's data for the standard-dosing group. The time to achieve therapeutic concentration in the poor metabolizer genotype-guided dosing group had the largest impact on cost savings while the cost of the pharmacogenetic test had the smallest impact on cost savings., Conclusion: Implementing CYP3A5 testing could save $17 225 per pediatric heart transplant patient receiving tacrolimus. As pharmacogenomic testing becomes more widespread, institutions should track resource requirements and outcomes to determine the best implementation policies going forward., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Oral commissure stenosis and lower eyelid ectropion from burns are functionally impairing and challenging to treat. Evaluation of various treatment modalities is limited by a lack of preclinical models. Described is a method for inducing controlled, titratable oral commissure and lower eyelid burns in swine for future treatment research., Methods: Burn wounds 3 cm in diameter were applied to the lower eyelid and oral commissure of seven anesthetized Yorkshire swine for 10, 15, 20, or 30 s at 100 °C with a custom designed thermocouple-controlled burn device and observed for 3, 30, or 90 days. Tissue underwent laser speckle imaging (LSI) to assess vascular perfusion and histologic analysis after harvest. Statistical comparisons were calculated using Wilcoxon rank-sum tests., Results: Subdermal extension was noted in oral commissure and lower eyelid burns with contact time of 20 s or greater. Wound area progressively contracted from post-operative day (POD) 0 to 90 in both sites, but this was not statistically significant based on contact time or burn site (p > 0.20). Burns of 20-30 s demonstrated increased neutrophil influx for oral commissure injuries (p < 0.01) and leukocyte and macrophage influx for lower eyelid injuries (p = 0.02). Degree of vascular congestion increased with 20-30 second burns in both the oral commissure (p = 0.015) and lower eyelid (p = 0.04). Normalized LSI readings showed increased speckle size in both oral commissure (4.0-fold increase, p < 0.01) and lower eyelid (3.2-fold increase, p < 0.01) burns on POD 90 compared to pre-injury. No change in oral or ocular function was noted in any of the groups (p = 0.96)., Conclusion: Oral commissure and lower eyelid burns create scars which may be modified by burn duration. This model may evaluate a therapeutic's ability to limit functional impairment from burns., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gregory Dion reports financial support was provided by US Army Institute of Surgical Research., (Published by Elsevier Ltd.)

Background: Pharmacogenomic testing identifies gene polymorphisms impacting drug metabolism, aiding in optimizing treatment efficacy and minimizing toxicity, thus potentially reducing healthcare utilization. 6-Mercaptopurine metabolism is affected by thiopurine methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) polymorphisms. We sought to estimate the budget impact of preemptive pharmacogenomic testing for these genes in pediatric acute lymphoblastic leukemia (ALL) patients from an institutional perspective., Methods: A Markov model was constructed to model the first cycle of the maintenance phase of chemotherapy for pediatric ALL patients transitioning between one of three health states: stable, moderately myelosuppressed, and severely myelosuppressed over 16 weeks, with each health state's associated costs derived from the literature. The patient's likelihood to experience moderate or severe myelosuppression based on metabolism phenotype was calculated from the literature and applied on a weekly basis, and the marginal budget impact of preemptive pharmacogenomic testing vs. no pharmacogenomic testing was calculated. One-way sensitivity analysis was conducted to assess parameter influence on results., Results: Preemptive pharmacogenomic testing of TPMT and NUDT15 provided savings of up to $26 028 per patient during the maintenance phase. In the sensitivity analysis, the cost of outpatient management of moderate myelosuppression had the greatest impact on the budget, resulting in cost savings ranging from $8592 to $30 129 when the minimum and maximum costs of management were used in the model., Conclusion: Preemptive pharmacogenomic testing for TPMT and NUDT15 polymorphisms before initiation of maintenance therapy for pediatric ALL patients yielded considerable cost savings., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Rare-earth triiodides free of donor solvents, LnI 3 (Ln = Sc, Y, La-Lu), have been prepared in quantities as high as 76 g and in yields between 72% (Sc) and 98% (La) by the reaction between the corresponding metal and excess ammonium iodide in a two-step, one-pot procedure that is conducted in borosilicate glassware at temperatures of 350-430 °C in commercial tube furnaces. Procedures for both large-scale and small-scale syntheses are described, with specific examples for Ln = Sc, Y, La, Pr, Nd, Gd, Dy, Ho, and Lu. While the large-scale synthesis described here utilizes specialized glassware, the small-scale preparation may be performed in commercially available glassware.

The complex non-centrosymmetric and chiral nature of helical structures endow materials that possess such motifs with unusual properties. However, despite their ubiquity in biological and organic systems, there is a severe lack of inorganic crystals that display helicity in extended lattices, where these unusual properties are expected to be most pronounced. Here, we report a new inorganic helical structure, gallium sulfur iodide (GaSI), within the exfoliable class of III-VI-VII (1:1:1) one-dimensional (1D) van der Waals (vdW) crystals. Through detailed structural analyses, including single-crystal X-ray diffraction, electron microscopy, and density functional theory (DFT), we elucidate the apparent noncrystallographic screw axis and the first example of an atomic scale helical structure bearing a " squircular " cross-section in GaSI. Crystallizing in the non-centrosymmetric P 4̅ space group, we found that GaSI crystals exhibit pronounced second-harmonic generation. From diffuse reflectance spectroscopy, GaSI displays a sizeable bandgap of 3.69 eV, owing tostrong covalent interactions arising from the smaller sulfur atoms within the helix core. These results position GaSI as a promising exfoliable nonlinear optical material across a broad optical window.

The current toolkit for genetic manipulation in the model animal Drosophila melanogaster is extensive and versatile but not without its limitations. Here, we report a powerful and heritable method to knockdown gene expression in D. melanogaster using the self-cleaving N79 hammerhead ribozyme, a modification of a naturally occurring ribozyme found in the parasite Schistosoma mansoni. A 111-bp ribozyme cassette, consisting of the N79 ribozyme surrounded by insulating spacer sequences, was inserted into 4 independent long noncoding RNA genes as well as the male-specific splice variant of doublesex using scarless CRISPR/Cas9-mediated genome editing. Ribozyme-induced RNA cleavage resulted in robust destruction of 3' fragments typically exceeding 90%. Single molecule RNA fluorescence in situ hybridization results suggest that cleavage and destruction can even occur for nascent transcribing RNAs. Knockdown was highly specific to the targeted RNA, with no adverse effects observed in neighboring genes or the other splice variants. To control for potential effects produced by the simple insertion of 111 nucleotides into genes, we tested multiple catalytically inactive ribozyme variants and found that a variant with scrambled N79 sequence best recapitulated natural RNA levels. Thus, self-cleaving ribozymes offer a novel approach for powerful gene knockdown in Drosophila, with potential applications for the study of noncoding RNAs, nuclear-localized RNAs, and specific splice variants of protein-coding genes., Competing Interests: Conflicts of interest The author(s) declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The monitoring of body temperature is a recent addition to the plethora of parameters provided by wellness and fitness wearable devices. Current wearable temperature measurements are made at the skin surface, a measurement that is impacted by the ambient environment of the individual. The use of near-infrared spectroscopy provides the potential for a measurement below the epidermal layer of skin, thereby having the potential advantage of being more reflective of physiological conditions. The feasibility of noninvasive temperature measurements is demonstrated by using an in vitro model designed to mimic the near-infrared spectra of skin. A miniaturizable solid-state laser-diode-based near-infrared spectrometer was used to collect diffuse reflectance spectra for a set of seven tissue phantoms composed of different amounts of water, gelatin, and Intralipid. Temperatures were varied between 20-24 °C while collecting these spectra. Two types of partial least squares (PLS) calibration models were developed to evaluate the analytical utility of this approach. In both cases, the collected spectra were used without pre-processing and the number of latent variables was the only optimized parameter. The first approach involved splitting the whole dataset into separate calibration and prediction subsets for which a single optimized PLS model was developed. For this first case, the coefficient of determination (R 2 ) is 0.95 and the standard error of prediction (SEP) is 0.22 °C for temperature predictions. The second strategy used a leave-one-phantom-out methodology that resulted in seven PLS models, each predicting the temperatures for all spectra in the held-out phantom. For this set of phantom-specific predicted temperatures, R 2 and SEP values range from 0.67-0.99 and 0.19-0.65 °C, respectively. The stability and reproducibility of the sample-to-spectrometer interface are identified as major sources of spectral variance within and between phantoms. Overall, results from this in vitro study justify the development of future in vivo measurement technologies for applications as wearables for continuous, real-time monitoring of body temperature for both healthy and ill individuals.

Background: Thiopurines such as mercaptopurine (MP) are widely used to treat acute lymphoblastic leukemia (ALL). Thiopurine-S-methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15) inactivate thiopurines, and no-function variants are associated with drug-induced myelosuppression. Dose adjustment of MP is strongly recommended in patients with intermediate or complete loss of activity of TPMT and NUDT15. However, the extent of dosage reduction recommended for patients with intermediate activity in both enzymes is currently not clear., Methods: MP dosages during maintenance were collected from 1768 patients with ALL in Singapore, Guatemala, India, and North America. Patients were genotyped for TPMT and NUDT15, and actionable variants defined by the Clinical Pharmacogenetics Implementation Consortium were used to classify patients as TPMT and NUDT15 normal metabolizers (TPMT/NUDT15 NM), TPMT or NUDT15 intermediate metabolizers (TPMT IM or NUDT15 IM), or TPMT and NUDT15 compound intermediate metabolizers (TPMT/NUDT15 IM/IM). In parallel, we evaluated MP toxicity, metabolism, and dose adjustment using a Tpmt/Nudt15 combined heterozygous mouse model (Tpmt+/-/Nudt15+/-)., Results: Twenty-two patients (1.2%) were TPMT/NUDT15 IM/IM in the cohort, with the majority self-reported as Hispanics (68.2%, 15/22). TPMT/NUDT15 IM/IM patients tolerated a median daily MP dose of 25.7 mg/m2 (interquartile range = 19.0-31.1 mg/m2), significantly lower than TPMT IM and NUDT15 IM dosage (P < .001). Similarly, Tpmt+/-/Nudt15+/- mice displayed excessive hematopoietic toxicity and accumulated more metabolite (DNA-TG) than wild-type or single heterozygous mice, which was effectively mitigated by a genotype-guided dose titration of MP., Conclusion: We recommend more substantial dose reductions to individualize MP therapy and mitigate toxicity in TPMT/NUDT15 IM/IM patients., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The factors affecting the formation and crystal structures of unusual 6d 1 Th(III) square planar aryloxide complexes, as exemplified by [Th(OAr Me ) 4 ] 1- (OAr Me = OC 6 H 2 t Bu 2 -2,6-Me-4), were explored by synthetic and reduction studies of a series of related Th(IV) tetrakis(aryloxide) complexes, Th(OAr R ) 4 (OAr R = OC 6 H 2 t Bu 2 -2,6-R-4). Specifically, electronic, steric, and countercation effects were explored by varying the aryloxide ligand, the alkali metal reducing agent, and the alkali metal chelating agent. Salt metathesis reactions between ThBr 4 (DME) 2 (DME = 1,2-dimethoxyethane) and 4 equiv of the appropriate potassium aryloxide salt were used to prepare a series of Th(IV) aryloxide complexes in high yields: Th(OAr H ) 4 (OAr H = OC 6 H 3 t Bu 2 -2,6), Th(OAr tBu ) 4 (OAr tBu = OC 6 H 2 t Bu 3 -2,4,6), Th(OAr OMe ) 4 (OAr OMe = OC 6 H 2 t Bu 2 -2,6-OMe-4), and Th(OAr Ph ) 4 (OAr Ph = OC 6 H 2 t Bu 2 -2,6-Ph-4). Th(OAr H ) 4 can be reduced by KC 8 , Na, or Li in the absence or presence of 2.2.2-cryptand (crypt) or 18-crown-6 (crown) to form dark purple solutions that have EPR and UV-visible spectra similar to those of the square planar Th(III) complex, [Th(OAr Me ) 4 ] 1- . Hence, the para position of the aryloxide ligand does not have to be alkylated to obtain the Th(III) complexes. Furthermore, reduction of Th(OAr OMe ) 4 , Th(OAr tBu ) 4 , and Th(OAr Ph ) 4 with KC 8 in THF generated purple solutions with EPR and UV-visible spectra that are similar to those of the previously reported Th(III) anion, [Th(OAr Me ) 4 ] 1- . Although many of these reduction reactions did not produce single crystals suitable for study by X-ray diffraction, reduction of Th(OAr H ) 4 , Th(OAr tBu ) 4 , and Th(OAr OMe ) 4 with Li provided X-ray quality crystals whose structures had square planar coordination geometries. Reduction of Th(OAr Ph ) 4 with Li also gave a product with EPR and UV-visible spectra that matched those of [Th(OAr Me ) 4 ] 1- , but X-ray quality crystals of the reduction product were too unstable to provide data. Neither Th(Odipp) 4 (THF) 2 (Odipp = OC 6 H 3 i Pr 2 -2,6) nor Th(Odmp) 4 (THF) 2 (Odmp = OC 6 H 3 Me 2 -2,6) could be reduced to Th(III) products under similar conditions. Reduction of U(OAr H ) 3 (THF) with KC 8 in the presence of 2.2.2-cryptand (crypt) was examined for comparison and formed [K(crypt)][U(OAr H ) 4 ], which has a tetrahedral arrangement of the aryloxide ligands. Moreover, no further reduction was observed when either [K(crypt)][U(OAr H ) 4 ] or [K(crown)(THF) 2 ][U(OAr H ) 4 ] were treated with KC 8 or Li.

Reliable estimates of subnational vaccination coverage are critical to track progress towards global immunisation targets and ensure equitable health outcomes for all children. However, conflict can limit the reliability of coverage estimates from traditional household-based surveys due to an inability to sample in unsafe and insecure areas and increased uncertainty in underlying population estimates. In these situations, model-based geostatistical (MBG) approaches offer alternative coverage estimates for administrative units affected by conflict. We estimated first- and third-dose diphtheria-tetanus-pertussis vaccine coverage in Borno state, Nigeria, using a spatiotemporal MBG modelling approach, then compared these to estimates from recent conflict-affected, household-based surveys. We compared sampling cluster locations from recent household-based surveys to geolocated data on conflict locations and modelled spatial coverage estimates, while also investigating the importance of reliable population estimates when assessing coverage in conflict settings. These results demonstrate that geospatially-modelled coverage estimates can be a valuable additional tool to understand coverage in locations where conflict prevents representative sampling., (© 2023. The Author(s).)

Background: Intramuscular cabotegravir (CAB) and rilpivirine (RPV) is the only long-acting antiretroviral therapy (LA-ART) regimen approved for people with HIV (PWH). Long-acting ART holds promise for improving outcomes among populations with barriers to adherence but is only approved for PWH who have virologic suppression with use of oral ART before initiating injectables., Objective: To examine LA-ART in a population of PWH that includes those with viremia., Design: Observational cohort study., Setting: Urban academic safety-net HIV clinic., Patients: Publicly insured adults living with HIV with and without viral suppression, high rates of unstable housing, mental illness, and substance use., Intervention: Demonstration project of long-acting injectable CAB-RPV., Measurements: Descriptive statistics summarizing cohort outcomes to date, based on pharmacy team logs and electronic medical record data., Results: Between June 2021 and November 2022, 133 PWH at the Ward 86 HIV Clinic were started on LA-ART, 76 of whom had virologic suppression while using oral ART and 57 of whom had viremia. The median age was 46 years (IQR, 25 to 68 years); 117 (88%) were cisgender men, 83 (62%) had non-White race, 56 (42%) were experiencing unstable housing or homelessness, and 45 (34%) had substance use. Among those with virologic suppression, 100% (95% CI, 94% to 100%) maintained suppression. Among PWH with viremia, at a median of 33 days, 54 of 57 had viral suppression, 1 showed the expected 2-log 10 reduction in HIV RNA level, and 2 experienced early virologic failure. Overall, 97.5% (CI, 89.1% to 99.8%) were projected to achieve virologic suppression by a median of 33 weeks. The current virologic failure rate of 1.5% in the cohort is similar to that across registrational clinical trials at 48 weeks., Limitation: Single-site study., Conclusion: This project demonstrates the ability of LA-ART to achieve virologic suppression among PWH, including those with viremia and challenges to adherence. Further data on the ability of LA-ART to achieve viral suppression in people with barriers to adherence are needed., Primary Funding Source: National Institutes of Health, City and County of San Francisco, and Health Resources and Services Administration., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-0788.

As much as half or more of deep partial-thickness burn wounds develop hypertrophic scarring and contracture. Once formed, treatments are only minimally effective. Pirfenidone (Pf), indicated for treatment of idiopathic pulmonary fibrosis, is an anti-inflammatory and anti-fibrotic small molecule that potentially can be repurposed as a preventative against scarring in burn wounds. We present a drug-in-matrix patch with a soft skin adhesive (SSA) wound-contacting layer for multi-day drug delivery of Pf into burn wounds at the point of injury. Our patch construction consists of an SSA adhesive layer (Liveo™ MG7-9850, Dupont, Wilmington, DE, USA) for wound fixation, an acrylic co-polymer drug matrix (DURO-TAK 87-2852, Henkel, Düsseldorf, Germany) as the drug (Pf) reservoir, and an outermost protective polyurethane backing. By employing a drug-in-matrix patch design, Pf can be loaded as high as 2 mg/cm 2 . Compared to the acrylic co-polymer adhesive patch preparations and commercial films, adding an SSA layer markedly reduces skin stripping observed under scanning electron microscopy (SEM). Moreover, the addition of varying SSA thicknesses did not interfere with the in vitro release kinetics or drug permeation in ex vivo porcine skin. The Pf patch can be easily applied onto and removed from deep partial-thickness burn wounds on Duroc pigs. Continuous multi-day dosing of Pf by the patches (>200 μg/cm 2 /day) reduced proinflammatory biomarkers in porcine burn wounds. Pf patches produced by the manual laboratory-scale process showed excellent stability, maintaining intact physical patch properties and in vitro biological activity for up to one year under long-term (25 °C at 60% RH) and 6 months under accelerated (40 °C at 75% RH) test conditions. To manufacture our wound safe-and-extended-release patch, we present scale-up processes using a machine-driven automated roll-to-roll pilot scale coater.

The integration of immunization with other essential health services is among the strategic priorities of the Immunization Agenda 2030 and has the potential to improve the effectiveness, efficiency, and equity of health service delivery. This study aims to evaluate the degree of spatial overlap between the prevalence of children who have never received a dose of the diphtheria-tetanus-pertussis-containing vaccine (no-DTP) and other health-related indicators, to provide insight into the potential for joint geographic targeting of integrated service delivery efforts. Using geospatially modeled estimates of vaccine coverage and comparator indicators, we develop a framework to delineate and compare areas of high overlap across indicators, both within and between countries, and based upon both counts and prevalence. We derive summary metrics of spatial overlap to facilitate comparison between countries and indicators and over time. As an example, we apply this suite of analyses to five countries-Nigeria, Democratic Republic of the Congo (DRC), Indonesia, Ethiopia, and Angola-and five comparator indicators-children with stunting, under-5 mortality, children missing doses of oral rehydration therapy, prevalence of lymphatic filariasis, and insecticide-treated bed net coverage. Our results demonstrate substantial heterogeneity in the geographic overlap both within and between countries. These results provide a framework to assess the potential for joint geographic targeting of interventions, supporting efforts to ensure that all people, regardless of location, can benefit from vaccines and other essential health services.

Introduction: The COVID-19 pandemic has required a shift of many routine primary care visits to telemedicine, potentially widening disparities in care access among vulnerable populations. In a publicly-funded HIV clinic, we aimed to evaluate a pre-visit phone-based planning intervention to address anticipated barriers to telemedicine., Methods: We conducted a pragmatic randomized controlled trial of patients scheduled for a phone-based HIV primary care visit at the Ward 86 HIV clinic in San Francisco from 15 April to 15 May 2020. Once reached by phone, patients were randomized to either have a structured pre-visit planning intervention to address barriers to an upcoming telemedicine visit versus a standard reminder call. The primary outcome was telemedicine visit attendance., Results: Of 476 scheduled telemedicine visits, 280 patients were reached by a pre-visit call to offer enrollment. Patients were less likely to be reached if virally unsuppressed (odds ratio (OR) 0.11, 95% confidence intervals (CI) 0.03-0.48), CD4 < 200 (OR 0.24, 95% CI 0.07-0.85), or were homeless (OR 0.24, 95% CI 0.07-0.87). There was no difference between intervention and control in scheduled visit attendance (83% v. 78%, OR 1.38, 95% CI 0.67-2.81)., Conclusions: A structured phone-based planning call to address barriers to telemedicine in a public HIV clinic was less likely to reach patients with poorly-controlled HIV and patients experiencing homelessness, suggesting additional interventions may be needed in this population to ensure access to telemedicine-based care. Among patients reachable by phone, telemedicine visit attendance was high and not improved with a structured pre-visit intervention, suggesting that standard reminders may be adequate in this population.

Thoughtful integration of interruptive clinical decision support (CDS) alerts within the electronic health record is essential to guide clinicians on the application of pharmacogenomic results at point of care. St. Jude Children's Research Hospital implemented a preemptive pharmacogenomic testing program in 2011 in a multidisciplinary effort involving extensive education to clinicians about pharmacogenomic implications. We conducted a retrospective analysis of clinicians' adherence to 4783 pharmacogenomically guided CDS alerts that triggered for 12 genes and 60 drugs. Clinicians adhered to the therapeutic recommendations provided in 4392 alerts (92%). In our population of pediatric patients with catastrophic illnesses, the most frequently presented gene/drug CDS alerts were TPMT/NUDT15 and thiopurines (n = 3850), CYP2D6 and ondansetron (n = 667), CYP2D6 and oxycodone (n = 99), G6PD and G6PD high-risk medications (n  = 51), and CYP2C19 and proton pump inhibitors (omeprazole and pantoprazole; n = 50). The high adherence rate was facilitated by our team approach to prescribing and our collaborative CDS design and delivery., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Hypertrophic scars are a common negative outcome of deep partial-thickness (DPT) burn wounds resulting in increased dermal thickness, wound area contracture, and inflammation of the affected area. The red Duroc and Yorkshire porcine breeds are common large animal models for studying dermal wounds due to their structural similarities to human skin; however, the porcine transcriptomic profiles of dermal burn wounds and healing process are not well known. In response, a longitudinal transcriptomic comparative study was conducted comparing red Duroc and Yorkshire superficial and DPT burn wounds to their respective control uninjured tissue. Using next-generation RNA sequencing, total RNAs were isolated from burn wound tissue harvested on 0, 3, 7, 15, 30, and 60 days postburn, and mRNA-seq and gene expression read counts were generated. Significant differentially expressed genes relative to uninjured tissue were defined, and active biological processes were determined using gene set enrichment analyses. Additionally, collagen deposition, α-smooth muscle actin (SMA) protein concentration, epidermal and dermal thickness measurements, and wound area changes in response to burn injury were characterized. Overall, the red Duroc pigs, in response to both burn wound types, elicited a more robust and prolonged inflammatory immune response, fibroblast migration, and proliferation, as well as heightened levels of extracellular matrix modulation relative to respective burn types in the Yorkshire pigs. Collectively, the red Duroc DPT burn wounds produce a greater degree of hypertrophic scar-like response compared with Yorkshire DPT burn wounds. These findings will facilitate future porcine burn studies down-selecting treatment targets and determining the effects of novel therapeutic strategies., (Published by Oxford University Press on behalf of the American Burn Association 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

The combination of a boron Lewis acid and a decamethylsamarocene, specifically 9,10-Me 2 -9,10-diboraanthracene with (C 5 Me 5 ) 2 Sm II (THF) 2 , in toluene leads to cooperative reductive capture of N 2 . The product crystallizes as the salt, [(C 5 Me 5 ) 2 Sm III (THF) 2 ][(C 5 Me 5 ) 2 Sm III (η 2 -N 2 B 2 C 14 H 14 )], 1, which formally is comprised of an (NN) 2- moiety sandwiched between a [(C 5 Me 5 ) 2 Sm III ] 1+ metallocene cation and the diboraanthracene ditopic Lewis acid.

: The COVID-19 pandemic is expected to hinder US End the HIV Epidemic goals. We evaluated viral suppression and retention-in-care before and after telemedicine was instituted, in response to shelter-in-place mandates, in a large, urban HIV clinic. The odds of viral nonsuppression were 31% higher postshelter-in-place (95% confidence interval = 1.08-1.53) in spite of stable retention-in-care and visit volume, with disproportionate impact on homeless individuals. Measures to counteract the effect of COVID-19 on HIV outcomes are urgently needed.

Pseudomonas aeruginosa (a Gram-negative bacterium) is an opportunistic pathogen found in many infected wounds and is known to impair healing. To test the hypothesis that knocking out P. aeruginosa genes that are overexpressed during wound infection can cripple a pathogen's ability to impair healing, we assessed two pathways: the Type III secretion system (T3SS) and alginate biosynthesis. We generated single- and double-mutant strains of ExsA (T3SS activator), AlgD (GDP- mannose 6-dehydrogenase of alginate biosynthesis) and their complemented strains and evaluated their pathogenicity in a rabbit ear full-thickness excision-wound infection model. Wounds were inoculated with different strains (wild type, mutants, and complementary strains) at 10 6  CFU/wound on post-wounding day 3. After 24 h, 5 days and 9 days post-infection, wounds were harvested for measuring bacterial counts (viable and total) and wound healing (epithelial gap). On day 9 post-infection, the viable counts of the double mutant, (exsA/algD)‾ were 100-fold lower than the counts of the wild type (PAO1), single mutants, or the complement double-mutant, (exsA/algD)‾ /+ . Also, when compared to wounds infected with wild type or control strains, wounds infected with the double-knockout mutant was less inhibitory to wound healing (p < 0.05). Additionally, the double mutant showed greater susceptibility to macrophage phagocytosis in vitro than all other strains (p < 0.001). In conclusion, compared to single gene knockouts, double knockout of virulence genes in T3SS pathway and alginate biosynthesis pathway is more effective in reducing P. aeruginosa pathogenicity and its ability to impair wound healing. This study highlights the necessity of a dual-targeted anti-virulence strategy to improve healing outcomes of P. aeruginosa-infected wounds., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Skin burns are a significant source of injury in both military and civilian sectors. They are especially problematic in low resource environments where non-fatal injuries can lead to high morbidity rates, prolonged hospitalization, and disability. These multifaceted wounds can be highly complex and must be quickly diagnosed and treated to achieve optimal outcomes. When the appropriate resources are available, the current gold standard for assessing skin burns is through tissue punch biopsies followed by histological analysis. Apart from being invasive, costly, and time-consuming, this method can suffer from heterogeneous sampling errors when interrogating large burn areas. Here we present a practical method for the early visualization of skin burn severity using a topically applied fluorescein-loaded liquid bandage and an unmodified commercial digital camera. Quantitative linear mixed effects models of color images from a four day porcine burn study demonstrate that colorimetric changes within the HSB colorspace can be used to estimate burn depth severity immediately after burning. The finding was verified using fluorescence imaging, tissue cross-sectioning, and histopathology. This low-cost, rapid, and non-invasive color analysis approach demonstrates the potential of dye-loaded liquid bandages as a method for skin burn assessment in settings such as emergency medicine triage and low resource environments.

Genome editing via homology-directed repair (HDR) has made possible precise and deliberate modifications to gene sequences. CRISPR/Cas9-mediated HDR is the simplest means to carry this out. However, technical challenges remain to improve efficiency and broaden applicability to any genetic background of Drosophila melanogaster as well as to other Drosophila species. To address these issues, we developed a two-stage marker-assisted strategy in which embryos are injected with RNPs and pre-screened using T7EI. Using sgRNA in complex with recombinant Cas9 protein, we assayed each sgRNA for genome-cutting efficiency. We then conducted HDR using sgRNAs that efficiently cut target genes and the application of a transformation marker that generates RNAi against eyes absent . This allows for screening based on eye morphology rather than colour. These new tools can be used to make a single change or a series of allelic substitutions in a region of interest, or to create additional genetic tools such as balancer chromosomes.

The cutaneous skin microbiome is host to a vast ensemble of resident microbes that provide essential capabilities including protection of skin barrier integrity and modulation of the host immune response. Cutaneous burn-injury promotes alteration of cutaneous and systemic immune response that can affect both commensal and pathogenic microbes. A cross-sectional study of a limited number of burn patients revealed a difference in the bacteriome of burned versus control participants. Temporal changes of the skin microbiome during health and cutaneous burn-injury remains largely unknown. Furthermore, how this microbial shift relates to community function in the collective metagenome remain elusive. Due to cost considerations and reduced healing time, rodents are frequently used in burn research, despite inherent physiological differences between rodents and human skin. Using a rat burn model, a longitudinal study was conducted to characterize the rat skin bacterial residents and associated community functions in states of health (n = 30) (sham-burned) and when compromised by burn-injury (n = 24). To address the knowledge gap, traumatic thermal injury and disruption of cutaneous surface is associated with genus-level changes in the microbiota, reduced bacterial richness, and altered representation of bacterial genes and associated predicted functions across different skin microbial communities. These findings demonstrate that, upon burn-injury, there is a shift in diversity of the skin's organismal assemblages, yielding a core microbiome that is distinct at the genome and functional level. Moreover, deviations from the core community correlate with temporal changes post-injury and community transition from the state of cutaneous health to disease (burn-injury)., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Burn Association.)

Spherical nucleic acids (SNAs) are nanostructures formed by chemically conjugating short linear strands of oligonucleotides to a nanoparticle template. When made with modified small interfering RNA (siRNA) duplexes, SNAs act as single-entity transfection and gene silencing agents and have been used as lead therapeutic constructs in several disease models. However, the manner in which modified siRNA duplex strands that comprise the SNA lead to gene silencing is not understood. Herein, a systematic analysis of siRNA biochemistry involving SNAs shows that Dicer cleaves the modified siRNA duplex from the surface of the nanoparticle, and the liberated siRNA subsequently functions in a way that is dependent on the canonical RNA interference mechanism. By leveraging this understanding, a class of SNAs was chemically designed which increases the siRNA content by an order of magnitude through covalent attachment of each strand of the duplex. As a consequence of increased nucleic acid content, this nanostructure architecture exhibits less cell cytotoxicity than conventional SNAs without a decrease in siRNA activity., Competing Interests: The authors declare no competing interest.

With a diverse physiological interface to colonize, mammalian skin is the first line of defense against pathogen invasion and harbors a consortium of microbes integral in maintenance of epithelial barrier function and disease prevention. While the dynamic roles of skin bacterial residents are expansively studied, contributions of fungal constituents, the mycobiome, are largely overlooked. As a result, their influence during skin injury, such as disruption of skin integrity in burn injury and impairment of host immune defense system, is not clearly delineated. Burn patients experience a high risk of developing hard-to-treat fungal infections in comparison to other hospitalized patients. To discern the changes in the mycobiome profile and network assembly during cutaneous burn-injury, a rat scald burn model was used to survey the mycobiome in healthy (n = 30) (sham-burned) and burned (n = 24) skin over an 11-day period. The healthy skin demonstrated inter-animal heterogeneity over time, while the burned skin mycobiome transitioned toward a temporally stabile community with declining inter-animal variation starting at day 3 post-burn injury. Driven primarily by a significant increase in relative abundance of Candida, fungal species richness and abundance of the burned skin decreased, especially in days 7 and 11 post-burn. The network architecture of rat skin mycobiome displayed community reorganization toward increased network fragility and decreased stability compared to the healthy rat skin fungal network. This study provides the first account of the dynamic diversity observed in the rat skin mycobiome composition, structure, and network assembly associated with postcutaneous burn injury., (Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology 2019.)

Background: Misidentifying parathyroid glands (PGs) during thyroidectomies or parathyroidectomies could significantly increase postoperative morbidity. Imaging systems based on near infrared autofluorescence (NIRAF) detection can localize PGs with high accuracy. These devices, however, depict NIRAF images on remote display monitors, where images lack spatial context and comparability with actual surgical field of view. In this study, we designed an overlay tissue imaging system (OTIS) that detects tissue NIRAF and back-projects the collected signal as a visible image directly onto the surgical field of view instead of a display monitor, and tested its ability for enhancing parathyroid visualization., Study Design: The OTIS was first calibrated with a fluorescent ink grid and initially tested with parathyroid, thyroid, and lymph node tissues ex vivo. For in vivo measurements, the surgeon's opinion on tissue of interest was first ascertained. After the surgeon looked away, the OTIS back-projected visible green light directly onto the tissue of interest, only if the device detected relatively high NIRAF as observed in PGs. System accuracy was determined by correlating NIRAF projection with surgeon's visual confirmation for in situ PGs or histopathology report for excised PGs., Results: The OTIS yielded 100% accuracy when tested ex vivo with parathyroid, thyroid, and lymph node specimens. Subsequently, the device was evaluated in 30 patients who underwent thyroidectomy and/or parathyroidectomy. Ninety-seven percent of exposed tissue of interest was visualized correctly as PGs by the OTIS, without requiring display monitors or contrast agents., Conclusions: Although OTIS holds novel potential for enhancing label-free parathyroid visualization directly within the surgical field of view, additional device optimization is required for eventual clinical use., (Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Difficulty in identifying the parathyroid gland during neck operations can lead to accidental parathyroid gland excisions and postsurgical hypocalcemia. A clinical prototype called as PTeye was developed to guide parathyroid gland identification using a fiber-optic probe that detects near-infrared autofluorescence from parathyroid glands as operating room lights remain on. An Overlay Tissue Imaging System was designed concurrently to detect near-infrared autofluorescence and project visible light precisely onto parathyroid gland location., Methods: The PTeye and the Overlay Tissue Imaging System were tested in 20 and 15 patients, respectively, and a modified near-infrared imaging system was investigated in 6 patients. All 41 patients underwent thyroidectomy or parathyroidectomy. System accuracy was ascertained with surgeon's visual confirmation for in situ parathyroid glands and histology for excised parathyroid glands., Results: There was no observable difference between near-infrared autofluorescence of healthy and diseased parathyroid glands. The PTeye identified 98% of the parathyroid gland, whereas the near-infrared imaging system and the Overlay Tissue Imaging System identified 100% and 97% of the parathyroid glands, respectively., Conclusion: The PTeye can guide in real-time parathyroid gland identification even with ambient operating room lights. The near-infrared imaging system performs parathyroid gland imaging with high sensitivity, whereas the Overlay Tissue Imaging System enhances parathyroid gland visualization directly within the surgical field without requiring display monitors. These label-free technologies can be valuable adjuncts for identifying parathyroid glands intraoperatively., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Pulmonary infection with the bacterium Francisella tularensis can lead to the serious and potentially fatal disease, tularemia, in humans. Due to the current lack of an approved tularemia vaccine for humans, research is focused on vaccine development utilizing appropriate animal models. The Fischer 344 rat has emerged as a model that reflects human susceptibility to F. tularensis infection, and thus is an attractive model for tularemia vaccine development. Intratracheal inoculation of the Fischer 344 rat with F. tularensis mimics pulmonary exposure in humans. The successful delivery into the rat trachea is critical for pulmonary delivery. A laryngoscope with illumination is used to properly intubate the tracheae of anesthetized rats; the correct placement within the trachea is determined by a simple device to detect breathing. Following intubation, the F. tularensis culture is delivered in a measured dose via syringe. This technique standardizes pulmonary delivery of F. tularensis within the rat trachea to evaluate vaccine efficacy.

The prostate apoptosis response protein 4 (Par-4) is a tumor-suppressor that has been shown to induce cancer-cell selective apoptosis in a variety of cancers. The regulation of Par-4 expression and activity is a relatively understudied area, and identifying novel regulators of Par-4 may serve as novel therapeutic targets. To identify novel regulators of Par-4, a co-immunoprecipitation was performed in colon cancer cells, and co-precipitated proteins were identified by mass-spectometry. TRIM21 was identified as a novel interacting partner of Par-4, and further shown to interact with Par-4 endogenously and through its PRY-SPRY domain. Additional studies show that TRIM21 downregulates Par-4 levels in response to cisplatin, and that TRIM21 can increase the resistance of colon cancer cells to cisplatin. Furthermore, forced Par-4 expression can sensitize pancreatic cancer cells to cisplatin. Finally, we demonstrate that TRIM21 expression predicts survival in pancreatic cancer patients. Our work highlights a novel mechanism of Par-4 regulation, and identifies a novel prognostic marker and potential therapeutic target for pancreatic cancer.

Background and Objective: Soft tissue sarcomas (STS) are a rare and heterogeneous group of malignant tumors that are often treated through surgical resection. Current intraoperative margin assessment methods are limited and highlight the need for an improved approach with respect to time and specificity. Here we investigate the potential of near-infrared Raman spectroscopy for the intraoperative differentiation of STS from surrounding normal tissue., Materials and Methods: In vivo Raman measurements at 785 nm excitation were intraoperatively acquired from subjects undergoing STS resection using a probe based spectroscopy system. A multivariate classification algorithm was developed in order to automatically identify spectral features that can be used to differentiate STS from the surrounding normal muscle and fat. The classification algorithm was subsequently tested using leave-one-subject-out cross-validation., Results: With the exclusion of well-differentiated liposarcomas, the algorithm was able to classify STS from the surrounding normal muscle and fat with a sensitivity and specificity of 89.5% and 96.4%, respectively., Conclusion: These results suggest that single point near-infrared Raman spectroscopy could be utilized as a rapid and non-destructive surgical guidance tool for identifying abnormal tissue margins in need of further excision. Lasers Surg. Med. 48:774-781, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Soft tissue sarcomas (STS) are a rare and heterogeneous group of malignant tumors that are often treated via surgical resection. Inadequate resection can lead to local recurrence and decreased survival rates. In this study, we investigate the hypothesis that near-infrared (NIR) autofluorescence can be utilized for tumor margin analysis by differentiating STS from the surrounding normal tissue. Intraoperative in vivo measurements were acquired from 30 patients undergoing STS resection and were characterized to differentiate between normal tissue and STS. Overall, normal muscle and fat were observed to have the highest and lowest autofluorescence intensities, respectively, with STS falling in between. With the exclusion of well-differentiated liposarcomas, the algorithm's accuracy for classifying muscle, fat, and STS was 93%, 92%, and 88%, respectively. These findings suggest that NIR autofluorescence spectroscopy has potential as a rapid and nondestructive surgical guidance tool that can inform surgeons of suspicious margins in need of immediate re-excision.

Background: To evaluate the effectiveness of the Robert view in assessing trapeziometacarpal arthrosis and to compare the accuracy of the Robert and lateral views in staging trapeziometacarpal (TM) joint arthrosis., Methods: Patient demographics were obtained. Four participating raters reviewed 62 randomly selected thumb x-rays of patients presenting with thumb TM joint pain. Lateral and Robert-hyperpronation views were assessed using an analysis of 13 criteria., Results: X-rays of 62 thumbs for 58 patients were evaluated. The average patients' age was 64 (47-87) and 51 (80%) were females. The majority of X-rays evaluated fell into stage 3. Stage 2 was the second most common level of arthritis encountered and the least was stage 1. More osteophytes were encountered in the trapezium than metacarpal on both the Robert and lateral views. The Robert view was superior in detecting osteophytes on the trapezium than the lateral view. Osteophyte size varied from 1.7 to 2 mm. The lateral view displayed 61 cases with dorsal metacarpal subluxation (98%). The Robert view displayed 48 cases (77%) with radial metacarpal subluxation and 9 cases (15%) with ulnar metacarpal subluxation. Thumb metacarpal adduction deformity was encountered on the lateral view in 20 cases (32%) whereas on the Robert view it was encountered in 14 cases (23%). Subchondral sclerosis was encountered on the Robert view in 56 thumbs (90%) while it was seen on the lateral view in 52 thumbs (84%). Pantrapezial arthritis involving the STT joint was encountered equally in 16 cases (26%) on the Robert view and the lateral views. The study found a moderate level of interrater reliability on both the lateral and Robert views. With the exception of osteophytes encountered on the trapezium versus the metacarpal, there were no other statistically significant findings., Conclusions: This study confirms that each of the Robert and lateral views offer unique information and combining both views enhances the ability to assess radiographic disease severity, and should be the recommended set of X-rays for assessing TM osteoarthrosis.

Francisella tularensis causes the disease tularemia. Human pulmonary exposure to the most virulent form, F. tularensis subsp. tularensis (Ftt), leads to high morbidity and mortality, resulting in this bacterium being classified as a potential biothreat agent. However, a closely-related species, F. novicida, is avirulent in healthy humans. No tularemia vaccine is currently approved for human use. We demonstrate that a single dose vaccine of a live attenuated F. novicida strain (Fn iglD) protects against subsequent pulmonary challenge with Ftt using two different animal models, Fischer 344 rats and cynomolgus macaques (NHP). The Fn iglD vaccine showed protective efficacy in rats, as did a Ftt iglD vaccine, suggesting no disadvantage to utilizing the low human virulent Francisella species to induce protective immunity. Comparison of specific antibody profiles in vaccinated rat and NHP sera by proteome array identified a core set of immunodominant antigens in vaccinated animals. This is the first report of a defined live attenuated vaccine that demonstrates efficacy against pulmonary tularemia in a NHP, and indicates that the low human virulence F. novicida functions as an effective tularemia vaccine platform.

Francisella tularensis is a Gram-negative bacterium responsible for the human disease tularemia. The Francisella pathogenicity island (FPI) encodes a secretion system related to type VI secretion systems (T6SS) which allows F. tularensis to escape the phagosome and replicate within the cytosol of infected macrophages and ultimately cause disease. A lipoprotein is typically found encoded within T6SS gene clusters and is believed to anchor portions of the secretion apparatus to the outer membrane. We show that the FPI protein IglE is a lipoprotein that incorporates (3)H-palmitate and localizes to the outer membrane. A C22G IglE mutant failed to be lipidated and failed to localize to the outer membrane, consistent with C22 being the site of lipidation. Francisella tularensis ssp. novicida expressing IglE C22G is defective for replication in macrophages and unable to cause disease in mice. Bacterial two-hybrid analysis demonstrated that IglE interacts with the C-terminal portion of the FPI inner membrane protein PdpB, and PhoA fusion analysis indicated the PdpB C-terminus is located within the periplasm. We predict this interaction facilitates channel formation to allow secretion through this system., (© 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.)

Extending the wavelength range of spatial frequency domain imaging (SFDI) into the short-wave infrared (SWIR) has the potential to provide enhanced sensitivity to chromophores such as water and lipids that have prominent absorption features in the SWIR region. Here, we present, for the first time, a method combining SFDI with unstructured (zero spatial frequency) illumination to extract tissue absorption and scattering properties over a wavelength range (850 to 1800 nm) largely unexplored by previous tissue optics techniques. To obtain images over this wavelength range, we employ a SWIR camera in conjunction with an SFDI system. We use SFDI to obtain in vivo tissue reduced scattering coefficients at the wavelengths from 850 to 1050 nm, and then use unstructured wide-field illumination and an extrapolated power-law fit to this scattering spectrum to extract the absorption spectrum from 850 to 1800 nm. Our proof-of-principle experiment in a rat burn model illustrates that the combination of multispectral SWIR imaging, SFDI, and unstructured illumination can characterize in vivo changes in skin optical properties over a greatly expanded wavelength range. In the rat burn experiment, these changes (relative to normal, unburned skin) included increased absorption and increased scattering amplitude and slope, consistent with changes that we previously reported in the near-infrared using SFDI.

Frequent monitoring of early-stage burns is necessary for deciding optimal treatment and management. Both superficial and full thickness burns are relatively easy to diagnose based on clinical observation. In between these two extremes are superficial-partial thickness and deep-partial thickness burns. These burns, while visually similar, differ dramatically in terms of clinical treatment and are known to progress in severity over time. The objective of this study was to determine the potential of spatial frequency domain imaging (SFDI) for noninvasively mapping quantitative changes in chromophore and optical properties that may be an indicative of burn wound severity. A controlled protocol of graded burn severity was developed and applied to 17 rats. SFDI data was acquired at multiple near-infrared wavelengths over a course of 3 h. Burn severity was verified using hematoxylin and eosin histology. From this study, we found that changes in water concentration (edema), deoxygenated hemoglobin concentration, and optical scattering (tissue denaturation) to be statistically significant at differentiating superficial partial-thickness burns from deep-partial thickness burns.

Monitoring of tissue blood volume and local oxygen saturation can inform the assessment of tissue health, healing, and dysfunction. These quantities can be estimated from the contribution of oxyhemoglobin and deoxyhemoglobin to the absorption spectrum of the dermis. However, estimation of blood related absorption in skin can be confounded by the strong absorption of melanin in the epidermis and epidermal thickness and pigmentation varies with anatomic location, race, gender, and degree of disease progression. Therefore, a method is desired that decouples the effect of melanin absorption in the epidermis from blood absorption in the dermis for a large range of skin types and thicknesses. A previously developed inverse method based on a neural network forward model was applied to simulated spatial frequency domain reflectance of skin for multiple wavelengths in the near infrared. It is demonstrated that the optical thickness of the epidermis and absorption and reduced scattering coefficients of the dermis can be determined independently and with minimal coupling. Then, the same inverse method was applied to reflectance measurements from a tissue simulating phantom and in vivo human skin. Oxygen saturation and total hemoglobin concentrations were estimated from the volar forearms of weakly and strongly pigmented subjects using a standard homogeneous model and the present two layer model.

Spatial frequency domain imaging (SFDI) is a noncontact and wide-field optical imaging technology currently being used to study the optical properties and chromophore concentrations of in vivo skin including skin lesions of various types. Part of the challenge of developing a clinically deployable SFDI system is related to the development of effective motion compensation strategies, which in turn, is critical for recording high fidelity optical properties. Here we present a two-part strategy for SFDI motion correction. After verifying the effectiveness of the motion correction algorithm on tissue-simulating phantoms, a set of skin-imaging data was collected in order to test the performance of the correction technique under real clinical conditions. Optical properties were obtained with and without the use of the motion correction technique. The results indicate that the algorithm presented here can be used to render optical properties in moving skin surfaces with fidelities within 1.5% of an ideal stationary case and with up to 92.63% less variance. Systematic characterization of the impact of motion variables on clinical SFDI measurements reveals that until SFDI instrumentation is developed to the point of instantaneous imaging, motion compensation is necessary for the accurate localization and quantification of heterogeneities in a clinical setting.

In the USA, the use of the American College of Radiology Breast Imaging-Reporting and Data System (ACR BI-RADS) has served not only as a quality assurance tool and guide to standardizing breast imaging reports but has also improved communication between referring physicians, researchers, and patients. In fact, in the USA, the Mammography Quality Standards Act of 1997 requires that all mammograms be assigned a BI-RADS category based on the finding of most concern. In this manuscript, we aim to review the recommendations provided in the 4 th edition of the ACR BI-RADS for mammography, USG, and MRI. We also review the major controversies surrounding the use of ACR BI-RADS .

A longitudinal epiphyseal bracket (LEB) is a defect of the tubular bones and has been primarily described in the hands and feet, especially the proximal phalanges, metacarpals, and metatarsals. The LEB results from a defective C-shaped secondary ossification center that brackets the diaphysis and metaphysis, causing restricted longitudinal growth in these bones with resultant shortening and angular deformities. Deformities associated with metatarsal epiphyseal bracket include a short, broad metatarsal and medial deviation of the metatarsophalangeal joint (hallux varus deformity). Excision of the cartilaginous LEB has been proposed to prevent future soft tissue contractures and osseous deformities. The LEB has been associated with numerous syndromes including Rubinstein-Taybi syndrome, Cenani-Lenz syndactyly, isolated oligosyndactyly, and Nievergelt syndrome. We describe a two-month-old patient in whom plain film and MR imaging demonstrated bilateral bracketed first metatarsals with associated hallux varus deformities. Bilateral bracket excision was performed with excellent clinical results.