Search

Megan C Riddle,1,* Jiahui Lin,3,* Jonathan B Steinman,2 Joshua D Salvi,2 Margaret M Reynolds,3 Anne S Kastor,3,† Christina Harris,4 Carla Boutin-Foster3 1Department of Psychiatry and Behavioral Sciences, University of Washington, 2Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD–PhD Program, 3Department of Internal Medicine, Weill Cornell Medical College, New York, NY, 4Department of Medicine, Division of General Internal Medicine, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA, LA, USA *These authors contributed equally to this work †Anne S Kastor passed away on July 5, 2013. Abstract: As the health care delivery landscape changes, medical schools must develop creative strategies for preparing future physicians to provide quality care in this new environment. Despite the growing prominence of the patient-centered medical home (PCMH) as an effective model for health care delivery, few medical schools have integrated formal education on the PCMH into their curricula. Incorporating the PCMH model into medical school curricula is important to ensure that students have a comprehensive understanding of the different models of health care delivery and can operate effectively as physicians. The authors provide a detailed description of the process by which the Weill Cornell Community Clinic (WCCC), a student-run free clinic, has integrated PCMH principles into a service-learning initiative. The authors assessed patient demographics, diagnoses, and satisfaction along with student satisfaction. During the year after a PCMH model was adopted, 112 students and 19 licensed physicians volunteered their time. A review of the 174 patients seen from July 2011 to June 2012 found that the most common medical reasons for visits included management of hypertension, hyperlipidemia, diabetes, gastrointestinal conditions, arthritis, anxiety, and depression. During the year after the adoption of the PCMH model, 87% were very or extremely satisfied with their care, and 96% of the patients would recommend the WCCC to others. Students who participate in the WCCC gain hands-on experience in coordinating care, providing continuity of care, addressing issues of accessibility, and developing quality and safety metrics. The WCCC experience provides an integrative model that links service-learning with education on health care delivery in a primary care setting. The authors propose that adoption of this approach by other student-run clinics provides a substantial opportunity to improve medical education nationwide and better prepare future physicians to practice within this new model of health care delivery. Keywords: medical education, patient-centered medical home, medical students, service-learning, student-run free clinic.

Background: Whether optical computed tomography (OCT) and magnetic resonance imaging (MRI) findings are associated with final visual acuity in children with myelin oligodendrocyte glycoprotein antibody disease (MOGAD) optic neuritis is unclear., Methods: We retrospectively reviewed the charts of pediatric patients with MOGAD optic neuritis seen at St. Louis Children's Hospital/Barnes Jewish Hospital since 2016., Results: In the 12 patients in this study, presenting visual acuity was worse in the optic neuritis-affected eyes but significantly improved from presentation to follow-up, such that, at last follow-up, there was no longer a statistical difference between the affected and unaffected eyes. The number of affected eyes with nerve enhancement and the amount of optic nerve affected, as well as thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and macula, decreased from presentation to follow-up. Ultimately, none of these variables were associated with final visual acuity., Conclusion: In this cohort, pediatric MOGAD optic neuritis patients had positive visual outcomes despite significant RNFL thinning and involvement of the optic nerve on MRI, leading to a lack of correlation between follow-up visual acuity and OCT and MRI measures of disease severity, respectively., (Copyright © 2024 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Context: Social determinants of health are finally getting much-needed policy attention, but their political origins remain underexplored. In this article, the authors advance a theory of political determinants as accruing along three pathways of welfare state effects (redistribution, poverty reduction, and status preservation), and they test these assumptions by examining impacts of policy generosity on life expectancy (LE) over the last 40 years., Methods: The authors merge new and existing welfare policy generosity data from the Comparative Welfare Entitlement Project with data on LE spanning 1980-2018 across 21 countries in the Organization for Economic Cooperation and Development. They then examine relationships between five welfare policy generosity measures and LE using cross-sectional differencing and autoregressive lag models., Findings: The authors find consistent and positive effects for total generosity (an existing measure of social insurance generosity) on LE at birth across different model specifications in the magnitude of an increase in LE at birth of 0.10-0.15 years (p < 0.05) as well as for a measure of status preservation (0.11, p < 0.05). They find less consistent support for redistribution and poverty reduction measures., Conclusions: The authors conclude that in addition to generalized effects of policy generosity on health, status-preserving social insurance may be an important, and relatively overlooked, mechanism in increasing LE over time in advanced democracies., (Copyright © 2024 by Duke University Press.)

Purpose: Coats' disease can be difficult to differentiate from retinoblastoma. While MR imaging of retinoblastoma and Coats' disease have been examined for differentiating features such as eye size, vitreous seeding, and shape of retinal detachment, there is a lack of data on apparent diffusion coefficient (ADC). ADC is a measure of the diffusion (of water molecules) within tissue, and is commonly clinically calculated using MRI., Design: Retrospective cross-sectional study., Methods: Patient or study population: Children < 18 diagnosed with Coats disease or Retinoblastoma between January 1, 2018 and January 8, 2022 who had MRI imaging that was reviewable., Main Outcome Measure: Apparent diffusion coefficient (ADC) of the intraocular lesion. Retrospective brain MRIs were obtained from records of 5 eyes of 5 Coats' patients and 29 eyes of 23 patients with retinoblastoma. All MRIs were obtained prior to treatment. The eyedropper tool in Epic's default viewer (Ambra DICOM) was used to measure the ADC of five to eight randomly sampled points within the eye lesions seen on MRI. Average ADC was calculated for each affected eye. Internal reliability was confirmed by re-measuring mean ADC for a random sample of patients masked to their diagnosis and prior measurements. T-test was used to determine if ADC values differ between groups., Results: The mean ADC for retinoblastoma patients (442 +/- 210 mm 2 /s) differed significantly from the mean for Coats' patients (1364 +/- 309 mm 2 /s), (P < .001). T-test between baseline and repeat measurements was not significantly different. Since ADC values can differ between different scanners and DW MRI pulse sequences, an ADC threshold may be difficult to generalize across institutes, in our data set a threshold of 900 mm 2 /s was useful in separating the two diagnoses with a high degree of accuracy., Conclusions: Clinical features of retinoblastoma and Coats' disease often resemble each other and can lead to misdiagnosis. Since ADCs are derived from diffusion-weighted MRI as an objective parameter, it has the potential to aid in establishing or confirming the diagnosis when retinoblastoma and/or Coats' disease are suspected., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Retinopathy of prematurity (ROP) is a vision-threatening disease of premature infants. Practice guidelines recommend that all infants screened for ROP receive follow-up eye examinations to screen for ophthalmic complications. 1 The purpose of this study was to identify risk factors for the development of strabismus, amblyopia, high refractive error, and cataracts among ROP-screened, non-treated infants., Methods: Retrospective single-centre study of ROP-screened, non-treated premature infants with ophthalmic follow-up. Clinical variables were screened for association with ocular findings at follow-up. Multivariable logistic regression was used to determine the risk factors associated with ocular findings., Results: 309 patients were seen for follow-up at 0.97 (0.69) [mean (SD)] years after neonatal intensive care unit (NICU) discharge. Strabismus was predicted by occipitofrontal circumference (OFC) z-score at NICU discharge (OR 0.61; 95% CI [0.42, 0.88]; p = 0.008), intraventricular haemorrhage (IVH) grade III or IV (OR 3.18; 95% CI [1.18, 8.54]; p = 0.02), and exclusive formula feeding at NICU discharge (OR 2.20; 95% CI [1.07, 4.53]; p = 0.03). Significant predictors of amblyopia were OFC z-score at discharge (OR 0.55; 95% CI [0.31, 0.96]; p = 0.03) and necrotising enterocolitis (NEC) (OR 6.94; 95% CI [1.38, 35.00]; p = 0.02). NEC was a significant risk factor for high refractive error (OR 7.27; 95% CI [1.39, 37.94]; p = 0.02)., Conclusions: Among premature infants screened but not treated for ROP, severe IVH, NEC, low OFC z-score, and exclusive formula feeding at NICU discharge were risk factors for ocular morbidity. These findings affirm the value of ophthalmic follow-up for all ROP-screened infants, particularly those with the identified risk factors., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

The copper-based metal-organic framework (MOF), CuBTC (where H 3 BTC = benzene-1,3,5-tricarboxylate), has been reported as a reusable heterogeneous catalyst for the Friedländer synthesis of substituted quinolines, which are desirable targets in the pharmaceutical industry. Because of this application, we further investigated the CuBTC-catalyzed Friedländer synthesis of 3-acetyl-2-methyl-4-phenylquinoline. CuBTC was synthesized in-house and used as a catalyst for the Friedländer synthesis. Fresh and used CuBTC were analyzed using scanning electron microscopy (SEM), powder X-ray diffraction (pXRD), and X-ray photoelectron spectroscopy (XPS). The used CuBTC shows structural breakdown in pXRD patterns and SEM images. Despite the structural breakdown, the desired product, 3-acetyl-2-methyl-4-phenylquinoline, is still produced in a moderate yield (76.3% ± 0.2), as confirmed via time-of-flight mass spectrometry and nuclear magnetic resonance spectroscopy. Inductively coupled plasma atomic emission spectroscopy of the recovered supernatant solution indicates the presence of copper(II) ions in solution. Thus, we hypothesized that the standard Friedländer conditions may degrade the CuBTC framework, resulting in copper(II) ions in solution. Control experiments with copper(II) from Cu(NO 3 ) 2 ·3H 2 O catalyzes the Friedländer reaction in yields (75.6% ± 0.1) equal to that of the CuBTC MOF. Overall, our findings suggest that CuBTC acts as a copper(II) source, and the copper(II) ions originating from the CuBTC MOF are responsible for the observed catalysis.

Purpose/aim: To report the birth prevalence and natural history of congenital corneal opacities among a population-based cohort of children., Materials and Methods: The medical records of patients <5 years diagnosed with a congenital onset corneal opacity while residing in Olmsted County, Minnesota, from January 1, 1977, through December 31, 2016, were retrospectively reviewed., Results: Fourteen patients were diagnosed with a congenital corneal opacity during the 40-year study period for a birth prevalence of 1 in 5188 live births. The mean age at diagnosis was 7.5 months (range 0-48 months) and 9 (64.3%) were males. Four patients had congenital glaucoma, 4 had limbal dermoids, 2 had sclerocornea, and 1 patient each had Descemet's tear from birth trauma, herpes simplex virus type 1 keratitis, corneal leukoma, and an undiagnosed scar. Six (42.8%) patients required treatment for their underlying corneal opacity including the four patients with congenital glaucoma. The other 8 (57.1%) patients had a clear central axis. Four (28.6%) of 14 patients required amblyopia therapy, and 4 (28.6%) developed strabismus. Four (28.6%) patients had associated systemic conditions. During a mean follow up of 5.4 years (range 1.3-27.0 years), the median best corrected visual acuity (BCVA) was logmar 0.16 (20/25) (range 20/20-hand motion) with one patient with unilateral BCVA less than 20/60 and one patient with bilateral BCVA less than 20/60., Conclusions: In this 40-year cohort, congenital corneal opacities were relatively rare and the result of a variety of disorders. Although amblyopia and strabismus occurred commonly, most patients had good visual outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We report the design of a blood-contacting glucose monitor with a nitric oxide (NO)-releasing metal-organic framework (MOF) embedded within the outer polymer layer of a glucose sensor to promote the release of NO from endogenous NO donors. The sensors were tested by using amperometry across a range of glucose concentrations to assess whether the presence of either the MOF or NO decreased the performance of the glucose monitor. Even though signal response was diminished, the sensors maintained a good regression fit ( R 2 = 0.9944) and a similar dynamic range and reproducibility in the presence of S -nitrosoglutathione.

The copper-based metal-organic framework (MOF) CuBTC (where H 3 BTC = benzene-1,3,5-tricarboxylate) has been shown to be an efficient heterogeneous catalyst for the generation of 1,8-dioxo-octa-hydro xanthene derivatives, which are valuable synthetic targets for the pharmaceutical industry. We have applied this catalytic capability of CuBTC to a continuous flow system to produce the open chain form of 3,3,6,6-tetramethyl-9-phenyl-3,4,5,6,7,9-hexahydro-1 H -xanthene-1,8(2 H )-dione, a xanthene derivative from benzaldehyde and dimedone. An acid work-up after producing the open chain form of the xanthene derivative was used to achieve ring closure and form the final xanthene product. The CuBTC used to catalyze the reaction under continuous flow was confirmed to be stable throughout this process via analysis by SEM, pXRD, and FT-IR spectroscopy, elemental analysis, and XPS. The reaction to produce the open-chain form of the xanthene derivative produced an average yield of 33% ± 14% under the continuous flow (compared to 33% ± 0.12% of performing it under batch conditions). Based on the data obtained from this work, the continuous flow system required 22.5x less time to produce the desired xanthene derivative at comparable yields to batch reaction conditions. These results would allow for the xanthene derivative to be produced much faster, at a lower cost, and require less personal time while also removing the need to perform catalyst remove post reaction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Thai, Roach and Reynolds.)

Device-induced thrombosis remains a major complication of extracorporeal life support (ECLS). To more thoroughly understand how blood components interact with the artificial surfaces of ECLS circuit components, assessment of clot deposition on these surfaces following clinical use is urgently needed. Scanning electron microscopy (SEM), which produces high-resolution images at nanoscale level, allows visualization and characterization of thrombotic deposits on ECLS circuitry. However, methodologies to increase the quantifiability of SEM analysis of ECLS circuit components have yet to be applied clinically. To address these issues, we developed a protocol to quantify clot deposition on ECLS membrane oxygenator gas transfer fiber sheets through digital and SEM imaging techniques. In this study, ECLS membrane oxygenator fiber sheets were obtained, fixed, and imaged after use. Following a standardized process, the percentage of clot deposition on both digital images and SEM images was quantified using ImageJ through blind reviews. The interrater reliability of quantitative analysis among reviewers was evaluated. Although this protocol focused on the analysis of ECLS membrane oxygenators, it is also adaptable to other components of the ECLS circuits such as catheters and tubing. Key features • Quantitative analysis of clot deposition using digital and scanning electron microscopy (SEM) techniques • High-resolution images at nanoscale level • Extracorporeal life support (ECLS) devices • Membrane oxygenators • Blood-contacting surfaces Graphical overview., Competing Interests: Competing interestsThere are no conflicts of interest., (©Copyright : © 2023 The Authors; This is an open access article under the CC BY-NC license.)

The authors review the phenomenon of third ventricular dilation causing chiasmal compression and vision loss, emphasize the need for further study given continued poor outcomes, and, in a patient case, illustrate the value of obtaining magnetic resonance imaging and nerve and macular optical coherence tomography in a patient with an unclear mechanism of vision loss. [ J Pediatr Ophthalmol Strabismus . 2023;60(5):e49-e54.] .

Purpose: Trachoma, the world's leading infectious cause of blindness, has been targeted by the WHO for elimination through the SAFE strategy: surgery, antibiotics, facial cleanliness, and environmental improvement. Although significant progress has been made, there remains a gap in care. This project studied the association of geographical distribution of the remaining need for trachoma intervention and its association with access to basic handwashing facilities at home, as an indicator of water/sanitation infrastructure. We hypothesized that poor water sanitation would correspond to areas where trachoma intervention is still required., Design: Retrospective analysis using the WHO Global Health Observatory. Spatial, correlation, and simple and multivariable regression analyses were used., Methods: Using data from the WHO Global Health Observatory, a total of 194 countries were analyzed. Two choropleth maps were created, with inset maps focused on the South Pacific region, where the top 5 countries with the greatest population proportion requiring trachoma intervention are located., Results: Correlations and the simple regression model of total population with access to handwashing facilities as the only risk factor were insignificant. However, the multivariable regression models with access to handwashing facilities (total, urban, and rural) and population density as risk factors for trachoma intervention were significant., Conclusion: Poor water/sanitation infrastructure correlates with trachoma burden. Therefore, water/sanitation infrastructure improvement is a worthwhile target in the efforts toward trachoma elimination, but further research on the association between these important public health indicators is warranted.

Coating all portions of an extracorporeal membrane oxygenation (ECMO) circuit with materials exhibiting inherent, permanent antithrombotic properties is an essential step to prevent thrombus-induced complications. However, developing antithrombotic coatings for oxygenator fibers within membrane oxygenators of ECMO systems has proven challenging. We have used polydopamine (PDA) to coat oxygenator fibers and immobilize a Cu-based metal-organic framework (MOF) on the surface to act as a nitric oxide (NO) catalyst. Importantly, the PDA/MOF coating will produce NO indefinitely from endogenous S -nitrosothiols and it has not previously been applied to ECMO oxygenator fibers.

The controlled generation of nitric oxide (NO) from endogenous sources, such as S -nitrosoglutathione (GSNO), has significant implications for biomedical implants due to the vasodilatory and other beneficial properties of NO. The water-stable metal-organic framework (MOF) Cu-1,3,5-tris[1 H -1,2,3-triazol-5-yl]benzene has been shown to catalyze the production of NO and glutathione disulfide (GSSG) from GSNO in aqueous solution as well as in blood. Previous experimental work provided kinetic data for the catalysis of the 2GSNO → 2NO + GSSG reaction, leading to various proposed mechanisms. Herein, this catalytic process is examined using density functional theory. Minimal functional models of the Cu-MOF cluster and glutathione moieties are established, and three distinct catalytic mechanisms are explored. The most thermodynamically favorable mechanism studied is consistent with prior experimental findings. This mechanism involves coordination of GSNO to copper via sulfur rather than nitrogen and requires a reductive elimination that produces a Cu(I) intermediate, implicating a redox-active copper site. The experimentally observed inhibition of reactivity at high pH values is explained in terms of deprotonation of a triazole linker, which decreases the structural stability of the Cu(I) intermediate. These fundamental mechanistic insights may be generally applicable to other MOF catalysts for NO generation.

Background: Cannabis sativa L. also known as industrial hemp, is primarily cultivated as source material for cannabinoids cannabidiol (CBD) and ∆9-tetrahydrocannabinol (∆9-THC). Pesticide contamination during plant growth is a common issue in the cannabis industry which can render plant biomass and products made from contaminated material unusable. Remediation strategies to ensure safety compliance are vital to the industry, and special consideration should be given to methods that are non-destructive to concomitant cannabinoids. Preparative liquid chromatography (PLC) is an attractive strategy for remediating pesticide contaminants while also facilitating targeted isolation cannabinoids in cannabis biomass., Methods: The present study evaluated the benchtop-scale suitability of pesticide remediation by liquid chromatographic eluent fractionation, by comparing retention times of 11 pesticides relative to 26 cannabinoids. The ten pesticides evaluated for retention times are clothianidin, imidacloprid, piperonyl butoxide, pyrethrins (I/II mixture), diuron, permethrin, boscalid, carbaryl, spinosyn A, and myclobutanil. Analytes were separated prior to quantification on an Agilent Infinity II 1260 high performance liquid chromatography with diode array detection (HPLC-DAD). The detection wavelengths used were 208, 220, 230, and 240 nm. Primary studies were performed using an Agilent InfinityLab Poroshell 120 EC-C18 3.0 × 50 mm column with 2.7 μm particle diameter, using a binary gradient. Preliminary studies on Phenomenex Luna 10 μm C18 PREP stationary phase were performed using a 150 × 4.6 mm column., Results: The retention times of standards and cannabis matrices were evaluated. The matrices used were raw cannabis flower, ethanol crude extract, CO 2 crude extract, distillate, distillation mother liquors, and distillation bottoms. The pesticides clothianidin, imidacloprid, carbaryl, diuron, spinosyn A, and myclobutanil eluted in the first 3.6 min, and all cannabinoids (except for 7-OH-CBD) eluted in the final 12.6 min of the 19-minute gradient for all matrices evaluated. The elution times of 7-OH-CBD and boscalid were 3.44 and 3.55 min, respectively., Discussion: 7-OH-CBD is a metabolite of CBD and was not observed in the cannabis matrices evaluated. Thus, the present method is suitable for separating 7/11 pesticides and 25/26 cannabinoids tested in the six cannabis matrices tested. 7-OH-CBD, pyrethrins I and II (RT A : 6.8 min, RT B : 10.5 min), permethrin (RT A : 11.9 min, RT B : 12.2 min), and piperonyl butoxide (RT A : 8.3 min, RT B : 11.7 min), will require additional fractionation or purification steps., Conclusions: The benchtop method was demonstrated have congruent elution profiles using preparative-scale stationary phase. The resolution of pesticides from cannabinoids in this method indicates that eluent fractionation is a highly attractive industrial solution for pesticide remediation of contaminated cannabis materials and targeted isolation of cannabinoids., (© 2023. The Author(s).)

Importance: The options for genetic testing continue to grow for ocular conditions, including optic atrophy, anterior segment dysgenesis, cataracts, corneal dystrophy, nystagmus, and glaucoma. Gene panels can vary in content and coverage, as we and others have evaluated in inherited retinal disease (IRD)., Objective: To describe gene panel testing options for inherited eye disease phenotypes and their differences. This review is important for making diagnostic decisions., Evidence Review: A licensed, certified genetic counselor (RP) used Concert Genetics and the search terms optic atrophy, corneal dystrophy, cataract, glaucoma, anterior segment dysgenesis, microphthalmia/anophthalmia, and nystagmus to identify available testing options performed by CLIA-certified commercial genetic testing laboratories. Other co-authors were surveyed with respect to genetic panels used for the indications of interest. Ophthalmic panels were then compared using Concert Genetics in addition to their own websites., Findings: Panels from each clinical category were included and summarized. This comparison highlighted the differences and similarities between panels so that clinicians can make informed decisions., Conclusions: Access to genetic testing is increasing. The diagnostic yield of genetic testing is increasing. Each panel is different, so phenotyping or characterizing clinical characteristics that may help predict a specific genotype, as well as pre-test hypotheses regarding a genotype, should shape the choice of panels.

Research suggests that generous social welfare programs play a role in maternal and child health. However, most studies examine a single policy in isolation. Drawing from research documenting low-income families 'packaging' of social policies, we create a novel measure summarizing the value of a collection of income support policies for the working poor. This collection includes: the Supplemental Nutrition Assistance Program (SNAP), the Earned Income Tax Credit (EITC), the minimum wage, and the unemployment insurance (UI) program. Using U.S. state-level administrative data from 1996 to 2014, we estimate fixed effects regression models to examine the relationship between birth outcomes and income support policies (individually and combined). We find that increases in the combined value of the four income supports are significantly associated with reductions in preterm births and low birthweight births, but not infant mortality rates. States with the highest observed levels of combined income support had 14% fewer PTBs and 7% fewer LBWs than states with the lowest levels of income support. Of the four individual income support policies, only unemployment insurance has no significant independent effects. SNAP benefits have the largest and most consistent effects, reducing poor birth outcomes across all three indicators. An annual increase of $1000 in SNAP benefits is associated with a 3% decline in infant deaths, 5% decline in preterm births, and 2% decline in low birthweight births. These results suggest that increasing the generosity of income support policies may be a promising strategy for improving birth outcomes in the United States., Competing Interests: The authors declare no conflict or competing interests as a result of this funding or otherwise.

Purpose: To update the incidence of uveitis in a Midwestern U.S. county population., Methods: Retrospective population-based cohort study. All Olmsted County, Minnesota residents diagnosed with uveitis from January 1, 2006 to December 31, 2015 were identified via the Rochester Epidemiology Project. Diagnoses were confirmed by a uveitis specialist., Results: There were 371 incident uveitis cases, yielding an overall age- and sex-adjusted incidence rate of 26.9 per 100,000 per year (95% CI: 24.1-29.7). Females accounted for 202 (54.4%) cases, 306 (82.5%) were White, and 299 (80.6%) were anterior uveitis. Highest incidence was observed in patients ≥65 years old. No difference in incidence existed between sexes ( p = .17). Incidence rates increased with age for uveitis overall (all anatomic subtypes) ( p < .001), anterior uveitis ( p < .001), and posterior uveitis ( p < .001). Idiopathic uveitis accounted for 168 (45.3%) cases, more frequently diagnosed in females (50.0%) than males (39.6%) ( p = .05)., Conclusion: Uveitis incidence increased 1.6-fold over a 50-year span in this predominately White U.S. Midwestern county population.

Medical devices that require substantial contact between blood and a foreign surface would be dramatically safer if constructed from materials that prevent clot formation and coagulation disturbance at the blood-biomaterial interface. Nitric oxide (NO), an endogenous inhibitor of platelet activation in the vascular endothelium, could provide anticoagulation at the blood-surface interface when applied to biomaterials. We investigated an application of a copper-based metal-organic framework, H 3 [(Cu 4 Cl) 3 (BTTri) 8 -(H 2 O) 12 ]·72H 2 O where H 3 BTTri = 1,3,5-tris(1 H -1,2,3-triazole-5-yl)benzene] (CuBTTri), which has been shown to be an effective catalyst to generate NO from S -nitrosothiols that are endogenously present in blood. A method was developed to apply a CuBTTri composite coating to Tygon medical tubing used for extracorporeal lung support devices. The stability and activity of the coating were evaluated during 72 h dynamic saline flow testing (1.5-2.5 L/min, n = 3) with scanning electron microscopy imaging and inductively coupled mass-spectroscopy analysis. Compatibility of the coating with whole blood was assessed with a panel of hemocompatibility tests during 6 h circulation of swine donor blood in an ex vivo circulation loop constructed with CuBTTri tubing or unmodified Tygon (1.5 L/min blood flow rate, n = 8/group). Thrombus deposition and catalytic activity of the CuBTTri tubing were assessed following blood exposure. The coating remained stable during 72 h saline flow experiments at clinically relevant flow rates. No adverse effects were observed relative to controls during blood compatibility testing, to include no significant changes in platelet count ( p = 0.42), platelet activation indicated by P-selectin expression ( p = 0.57), coagulation panel values, or methemoglobin fraction ( p = 0.18) over the 6 h circulation period. CuBTTri within the coating generated NO following blood exposure in the presence of biologically relevant concentrations of an NO donor. CuBTTri composite coating was stable and blood compatible in this pilot study and requires further investigation of efficacy using in vivo models conducted with clinically relevant blood flow rates and study duration.

This paper investigated whether the commonly observed immigrant health advantage persists among undocumented immigrants in the U.S. and provides nationally representative evidence on the health of this vulnerable population. Data were derived from pooled cross-sections of the National Health Interview Survey (NHIS, 2000-2018). The legal status of foreign-born NHIS respondents is imputed using a non-parametric machine learning model built based on information from the 2004, 2008 and 2014 cohorts of the Survey of Income and Program Participation (SIPP). Multivariate logistic regression analysis indicated that, despite exposure to numerous additional risk factors, the undocumented population experienced a more pronounced Healthy Migrant Effect, with lower odds of reporting fair or poor self-rated health, any physician-diagnosed chronic conditions or being obese. The observed patterns in undocumented health outcomes may be related to the additional challenges and exclusionary policies associated with undocumented migration that could in turn lead to a more pronounced selection of healthy and resilient individuals., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To describe the incidence, prevalence, and clinical characteristics of presumed ocular histoplasmosis syndrome (POHS) in a Histoplasma endemic region., Methods: The International Classification of Diseases, 9 th and 10 th Revision codes were used to search the Rochester Epidemiology Project, a record-linkage system for medical care provided in Olmsted County, MN. Medical records were reviewed to confirm POHS diagnoses in county residents from January 1, 2006, to December 31, 2015. Age- and sex-adjusted incidence rates were calculated and adjusted to the 2010 U.S. White population., Results: There were 18 incident cases (30 eyes) and 87 prevalent cases (131 eyes). The incidence rate was 1.35 per 100,000 per year. The mid-study prevalence rate was 0.064%. Choroidal neovascularization (CNV) occurred in 17.4% of the affected eyes. At the last follow-up, 16.8% of the affected eyes had POHS-related decreased visual acuity (<20/40)., Conclusion: This study assesses the epidemiology and clinical features of POHS in a Midwestern U.S. county., Abbreviations/acronyms: POHS = Presumed ocular histoplasmosis syndrome; ICD = International Classification of Diseases; CI = Confidence interval; VA = Visual acuity; Anti-VEGF = Anti-vascular endothelial growth factor; REP = Rochester Epidemiology Project, CNV = Choroidal neovascularization.

Cannabinoids are important industrial analytes commonly assayed with high-pressure liquid chromatography (HPLC). In this study, we evaluate the suitability of MIL-53(Al), a commercially available metal-organic framework (MOF), as a stationary phase for cannabinoid separations. The suitability of an MOF for a given separation is hypothesized to be limited by the ability of a given molecule to enter the pore of the MOF. To evaluate the extent of possible adsorptive interactions between cannabinoids and the interior surface area of MIL-53(Al), the radii of gyration ( R g ) and solvent-accessible surface areas were calculated for three cannabinoids, namely, cannabidiol, cannabinol, and Δ9-tetrahydrocannabinol, as well as the MOF. These values were used to calculate the theoretical adsorption capacity of the MOF, using four competing adsorption models. The R g of cannabinoids (4.1 Å) is larger than one MOF pore aperture dimension (4.0 × 5.0 Å). The adsorption capacity was measured by relating a decrease in the cannabinoid concentration in acetonitrile when exposed to 100 mg of MOF. The cannabinoid uptake by the MOF was estimated using the relative standard deviation (RSD) of the soaking solution assay, as the decomposition-corrected RSD as uptake (DCRU). The DCRU was calculated as 0.007 ± 0.004 μg cannabinoids /mg MOF . These findings indicate that most of the MOF surface area was inaccessible for adsorption by cannabinoids due to size-exclusion effects. The implication of this work is that the suitability of an MOF for adsorptive separations, such as liquid chromatography, must have an upper limit for the size of the analyte. Additionally, MOFs may generally be more suitable for separations in the gas phase, where adsorbates are not hindered by the presence of a solvation shell.

Link and Phelan's pioneering 1995 theory of fundamental causes urged health scholars to consider the macro-level contexts that "put people at risk of risks." Allied research on the political economy of health has since aptly demonstrated how institutions contextualize risk factors for health. Yet scant research has fully capitalized on either fundamental cause or political economy of health's allusion to power relations as a determinant of persistent inequalities in population health. I address this oversight by advancing a theory of health power resources that contends that power relations distribute and translate the meaning (i.e., necessity, value, and utility) of socioeconomic and health-relevant resources. This occurs through stratification, commodification, discrimination, and devitalization. Resurrecting historical sociological emphases on power relations provides an avenue through which scholars can more fully understand the patterning of population health and better connect the sociology of health and illness to the central tenets of the discipline.

Despite enormous advances in the detection and treatment of breast cancer, it still remains the leading cancer diagnosis and has the second highest mortality rate. Thus, breast cancer research is a high priority for academics and clinicians alike. Based on previous research indicating the potential of nitric oxide (NO) and SMYD-3 inhibition, this work sought to expand upon these concepts and combine the two approaches. Both NO (from S -Nitrosoglutathione (GSNO)), termed Group 1, and a combination therapeutic, inhibitor-4 (SMYD-3 inhibitor) plus NO (from GSNO), termed Group 2, were evaluated for their efficacy on breast carcinoma cell lines MCF7 and MDA-MB-231, and the normal MCF10A breast cell line, using cellular viability, colony formation capacity, cytotoxicity, and cellular apoptosis analysis. These results indicated that, in Group 1, breast carcinoma lines MCF7 and MDA-MB-231, cells experienced a moderate reduction in cellular viability (~20-25%), a large reduction in colony formation capacity (~80-90%), a moderate increase in the relative number of dead cells, and a moderate increase in cellular apoptosis. Group 2 was significantly more impactful, with a ~50% knockdown in cellular viability, a 100% reduction in colony formation capacity, a large increase in the relative number of dead cells, and a large increase in cellular apoptosis. Additionally, Group 2 induced a very small impact on the normal MCF10A cell line. Cumulatively, this work revealed the exciting impact of this combination therapeutic, indicating its potential for clinical application and further research.

Herein, we establish a method to quantitatively monitor a metal-organic framework (MOF)-catalyzed, biomedically relevant reaction directly in blood plasma, specifically, the generation of nitric oxide (NO) from the endogenous substrate S -nitrosoglutathione (GSNO) catalyzed by H 3 [(Cu 4 Cl) 3 -(BTTri) 8 ] (CuBTTri). The reaction monitoring method uses UV-vis and 1 H NMR spectroscopies along with a nitric oxide analyzer (NOA) to yield the reaction stoichiometry and catalytic rate for GSNO to NO conversion catalyzed by CuBTTri in blood plasma. The results show 100% loss of GSNO within 16 h and production of 1 equiv. of glutathione disulfide (GSSG) per 2 equiv. of GSNO. Only 78 ± 10% recovery of NO(g) was observed, indicating that blood plasma can scavenge the generated NO before it can escape the reaction vessel. Significantly, to best apply and understand reaction systems with biomedical importance, such as NO release catalyzed by CuBTTri, methods to study the reaction directly in biological solvents must be developed.

Purpose: The purpose of this retrospective cohort study was to report the outcomes of high AC/A ratio accommodative esotropia (AET) among children., Methods: The medical records of all children <19 years diagnosed with accommodative esotropia and a high AC/A ratio while residing in Olmsted County, Minnesota, from January 1, 1975, through December 31, 2004, were retrospectively reviewed., Results: A total of 512 patients were diagnosed with AET during the 30-year study period, of which 395 (77.1%) had fully accommodative ET, 117 (22.8%) had partially accommodative ET and 106 (20.5%) had a high AC/A ratio. Of the 93 (87.7 %) high AC/A patients managed with bifocals, 50 (53.8 %) discontinued their use after a mean of 58.7 (range: 5.6-229) months. The Kaplan-Meier rate of discontinuing bifocals was 24.5% at 3 years, 36.4% at 5 years, and 61.4% at 10 years. Patients who discontinued bifocals were more likely to have had strabismus surgery (44% vs 18.6%, p  = 0.009) than those who did not discontinue bifocals. The high AC/A patients managed with bifocals achieved similar stereoacuity outcomes to those who did not wear bifocals ( p  = 0.65) and were no more likely to require surgery ( p  = 0.13)., Conclusion: Among this cohort of children with accommodative esotropia and a high AC/A ratio, bifocal use was discontinued in the majority of children within 10 years, and more commonly among those who underwent strabismus surgery. The use of bifocals was not associated with a higher likelihood of undergoing surgery or enhanced stereopsis compared to those who did not use them.

Purpose: Differing techniques have been reported for focal laser therapy for patients with small and medium retinoblastoma. We report the technique used at our center; and report the functional and anatomical outcomes for small and medium retinoblastomas treated with focal laser therapy with or without systemic chemotherapy., Methods: A retrospective case study was conducted including pediatric patients with macular retinoblastoma treated with systemic chemotherapy and laser ablation from July 1990 to July 2015 at Washington University School of Medicine/Saint Louis Children's Hospital., Results: Fourteen eyes (11 patients) with small and medium retinoblastoma tumors were treated with repetitive indirect laser hyperthermia and seven of those patients were treated with systemic chemotherapy as well. Using the International Retinoblastoma classification, one eye was stage A, 10 eyes were stage B, and three eyes were stage C. The mean follow-up time was 7.7 years. There were no recurrences of tumor in the patients. Final visual acuity outcomes were 20/20 to 20/50 in four eyes, 20/60 to 20/200 in four eyes, and 20/400 or less in six eyes. None of the patients developed metastatic disease., Conclusions: The evidence for systemic chemotherapy and diode laser therapy is limited to case series and retrospective reviews, but evidence suggests that it is an effective treatment for small and medium sized retinoblastoma tumors involving the macula with the potential for good visual outcomes.

Proteoglycans (PGs) play many important roles in biology, contributing to the mechanical properties of tissues, helping to organize extracellular matrix components, and participating in signaling mechanisms related to mechanotransduction, cell differentiation, immune responses, and wound healing. Our lab has designed two different types of PG mimics: polyelectrolyte complex nanoparticles (PCNs) and PG-mimetic graft copolymers (GCs), both of which are prepared using naturally occurring glycosaminoglycans. This work evaluates the enzymatic stability of these PG mimics using hyaluronidases (I-S, IV-S, and II), chondroitinase ABC, and lysozyme, for PG mimics suspended in solution and adsorbed onto surfaces. Hyaluronan (HA)- and chondroitin sulfate (CS)-containing PG mimics are degraded by the hyaluronidases. PCNs prepared with CS and GCs prepared with heparin are the only CS- and HA-containing PG mimics protected from chondroitinase ABC. None of the materials are measurably degraded by lysozyme. Adsorption to polyelectrolyte multilayer surfaces protects PG mimics from degradation, compared to when PG mimics are combined with enzymes in solution; all surfaces are still intact after 21 days of enzyme exposure. This work reveals how the stability of PG mimics is controlled by both the composition and macromolecular assembly of the PG mimic and also by the size and specificity of the enzyme. Understanding and tuning these degradation susceptibilities are essential for advancing their applications in cardiovascular materials, orthopedic materials, and growth factor delivery applications.

Several species of fungus from the genus Aspergillus are implicated in pulmonary infections in immunocompromised patients. Broad screening methods for fungal infections are desirable, as cultures require a considerable amount of time to provide results. Herein, we developed degradation and detection methods to produce and detect D-glucosamine (GlcN) from Aspergillus niger, a species of filamentous fungus. Ultimately, these techniques hold the potential to contribute to the diagnosis of pulmonary fungal infections in immunocompromised patients. In the following studies, we produced GlcN from fungal-derived chitin to serve as a marker for Aspergillus niger. To accomplish this, A. niger cells were lysed and subjected to a hydrochloric acid degradation protocol. Products were isolated, reconstituted in aqueous solutions, and analyzed using hydrophilic interaction liquid chromatography (HILIC) in tandem with electrospray ionization time-of-flight mass spectrometry. Our results indicated that GlcN was produced from A. niger. To validate these results, products obtained via fungal degradation were compared to products obtained from the degradation of two chitin polymers. The observed retention times and mass spectral extractions provided a two-step validation confirming that GlcN was produced from fungal-derived chitin. Our studies qualitatively illustrate that GlcN can be produced from A. niger; applying these methods to a more diverse range of fungi offers the potential to render a broad screening method for fungal detection pertinent to diagnosis of fungal infections.

When flowing whole blood contacts medical device surfaces, the most common blood-material interactions result in coagulation, inflammation, and infection. Many new blood-contacting biomaterials have been proposed based on strategies that address just one of these common modes of failure. This study proposes to mitigate unfavorable biological reactions that occur with blood-contacting medical devices by designing multifunctional surfaces, with features optimized to meet multiple performance criteria. These multifunctional surfaces incorporate the release of the small molecule hormone nitric oxide (NO) with surface chemistry and nanotopography that mimic features of the vascular endothelial glycocalyx. These multifunctional surfaces have features that interact with coagulation components, inflammatory cells, and bacterial cells. While a single surface feature alone may not be sufficient to achieve multiple functions, the release of NO from the surfaces along with their modification to mimic the endothelial glycocalyx synergistically improves platelet-, leukocyte-, and bacteria-surface interactions. This work demonstrates that new blood-compatible materials should be designed with multiple features, to better address the multiple modes of failure of blood-contacting medical devices., (© 2021 Wiley-VCH GmbH.)

The most common extracranial solid tumor in childhood, paediatric neuroblastoma, is frequently diagnosed at advanced stages and identified as high risk. High risk neuroblastoma is aggressive and unpredictable, resulting in poor prognosis and only ∼40% five-year survival rates. Herein, nitric oxide (NO) delivered via the S -nitrosothiol, S -nitrosoglutathione (GSNO), is explored as an anticancer therapeutic in various neuroblastoma lines. After 24 h of treatment with GSNO, cell viability assays, as assessed by resazurin and MTT ((3-4,5-dimethylthiazol-2-yl)-2,5-diphyltetrazolium bromide), consistently identified a moderate, ∼13-29%, decrease in metabolic activity, colony formation assays revealed notably significant reduction of clonogenic activity, and cytotoxicity assays revealed a visibly significant reduction of total number of cells and live cells as well as an increase in number of dead cells in treated cells versus untreated cells. Thrillingly, RNA-sequence analysis provided highly valuable information regarding the differentially expressed genes in treated samples versus control samples as well as insight into the mechanism of action of NO as an anticancer therapeutic. Favorably, the collective results from these analyses exhibited tumoricidal, non-tumour promoting, and discriminatory characteristics, illuminating the feasibility and significance of NO as a cytotoxic adjuvant in neuroblastoma treatment., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose: We sought to evaluate whether additional topical anesthetic, specifically proparacaine 0.5%, improved patient experience with intravitreal injections without hindering antisepsis., Methods: A prospective, randomized controlled trial was conducted including 36 eyes of 36 patients undergoing intravitreal injections. Patients were randomized to treatment with additional topical proparacaine 0.5% versus control after undergoing informed consent. All patients prior to intravitreal injection underwent conjunctival culture after one drop of topical proparacaine 0.5% was placed. Half of patients then received an additional drop of proparacaine and then underwent a second conjunctival culture. The other half of patients had a drop of povidone iodine and then a second conjunctival culture. Intravitreal injection followed conjunctival cultures. To evaluate their experience, patients were provided with a survey., Results: In total, 36 patients were enrolled in the study. Three of 36 (8.3%) patients had positive conjunctival cultures after proparacaine eye drops alone. One of 17 (5.8%) patients had a positive conjunctival culture after a second drop of proparacaine. One of 19 (5.3%) patients had a positive culture after proparacaine and povidone iodine. By noninferiority analysis, proparacaine was inferior to povidone iodine ( p  = .28). Patient experience surveys did not differ between groups., Conclusion: Patient perception did not significantly differ whether or not additional proparacaine drops were used prior to intravitreal injection in a randomized controlled trial. While proparacaine has some antiseptic properties, these were found to be inferior to those of povidone iodine. Therefore, while povidone iodine is essential for antisepsis, additional proparacaine drops should not interfere with antisepsis.

The metal-organic framework (MOF) H 3 [(Cu 4 Cl) 3 -(BTTri) 8 , H 3 BTTri = 1,3,5-tris( 1 H-1,2,3-triazol-5-yl)benzene] (CuBTTri) is a precatalyst for biomedically relevant nitric oxide (NO) release from S- nitrosoglutathione (GSNO). The questions of the number and nature of the catalytically most active, kinetically dominant sites are addressed. Also addressed is whether or not the well-defined structural geometry of MOFs (as solid-state analogues of molecular compounds) can be used to generate specific, testable hypotheses about, for example, if intrapore vs exterior surface metal sites are more catalytically active. Studies of the initial catalytic rate vs CuBTTri particle external surface area to interior volume ratio show that intrapore copper sites are inactive within the experimental error (≤1.7 × 10 -5% of the observed catalytic activity)-restated, the traditional MOF intrapore metal site catalysis hypothesis is disproven for the current system. All observed catalysis occurs at exterior surface Cu sites, within the experimental error. Fourier transform infrared (FT-IR) analysis of CN - -poisoned CuBTTri reveals just two detectable Cu sites at a ca. ≥0.5% detection limit, those that bind three or one CN - ("Cu(CN) 3 " and "CuCN"), corresponding to the CN - binding expected for exterior surface, 3-coordinate (Cu surface ) and intrapore, 5-coordinate (Cu pore ) sites predicted by the idealized, metal-terminated crystal structure. Two-coordinate Cu defect sites are ruled out at the ≥0.5% FT-IR detection limit as such defect sites would have been detectable by the FT-IR studies of the CN - -poisoned catalyst. Size-selective poisoning studies of CuBTTri exterior surface sites reveal that 1.3 (±0.4)% of total copper in 0.6 ± 0.4 μm particles is active. That counting of active sites yields a normalized turnover frequency (TOF), TOF norm = (4.9 ± 1.2) × 10 - 2 mol NO (mol Cu surface ) -1 s -1 (in water, at 20 min, 25 °C, 1 mM GSNO, 30% loss of GSNO, and 1.3 ± 0.4 mol % Cu surface )-a value ∼100× higher than the TOF calculated without active site counting. Overall, Ockham's razor interpretation of the data is that exterior surface, Cu surface sites are the catalytically most active sites present at a 1.3 (±0.4)% level of total Cu.

Despite engagement with the construct of power relations, research on the political economy of health has largely overlooked organized labor as a determinant of well-being. Grounded in the theory of power resources, our study aims to fill this gap by investigating the link between country-level union density and mental health while accounting for the compositional effects of individual-level union membership. We use three waves of the European Social Survey (N = 52,737) and a variation on traditional random-effects models to estimate both the contextual and change effects of labor unions on depressive symptoms. We find that country-level union density is associated with fewer depressive symptoms and that this is true irrespective of union membership. We discuss our findings vis-à-vis the literatures on the political economy of health, power resources, and fundamental causes of disease.

Purpose: To determine the population-based incidence and disease associations of episcleritis and scleritis in a midwestern U.S., Design: Population-based retrospective cohort study., Methods: All residents of Olmsted County, Minnesota from 2006 to 2015 were identified by using the Rochester Epidemiology Project. A total of 223 episcleritis cases and 77 scleritis cases were identified. The incidence and disease associations of episcleritis and scleritis were assessed, as well as scleritis recurrence rates, treatment, and complications., Results: Incidence rates for episcleritis and scleritis were 15.39 and 5.54 per 100,000 per year, respectively. Females accounted for 60.1% of episcleritis and 51.9% of scleritis cases. The mean age at diagnosis was 40.2 years of age for episcleritis and 48.8 years of age for scleritis. In the episcleritis cases, the incidence in females was higher (P = .01). There were no significant differences between sexes for scleritis incidence (P = .75); 23.4% of scleritis patients had an associated systemic disease. Patients with systemic disease showed a trend toward an increased risk of recurrence, but it was not statistically significant. There was a slightly decreased risk of scleritis recurrence with older age at diagnosis (hazard ratio [HR]: 0.73; P = .058; 95% confidence interval [CI]: 0.52-1.01). At last follow-up, most eyes with scleritis (90.4%) had good visual acuity (better than 20/40), and 92.3% had stable or improved visual acuity., Conclusions: The Olmsted County, Minnesota population had a lower incidence of episcleritis and a higher incidence of scleritis than populations in previous studies. The population-based results from the current study may provide information that is more applicable to a primary eye care setting., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Bacterial infections occurring on medical devices are incredibly difficult to treat, highlighting the urgency for progress in developing antibiotics and antibacterial materials. This work describes the preparation of an antibacterial prodrug polymer composite material for use as an antibacterial coating for medical devices to prevent infections. Polyvinyl chloride and polyurethane films are prepared containing a bacterial nitroreductase enzyme-activated diazeniumdiolate that releases nitric oxide (NO), a known potent antimicrobial agent. Characterization of the surface of the composite materials by scanning electron microscopy (SEM) and energy-dispersive X-ray analysis (EDS) reveals that the surface of the materials is composed of high amounts of nitrogen due to incorporation of the NO donor compound, up to 13.2% nitrogen on the surface of the 2.5% w/v diazeniumdiolate composite. NO release from the composite films is observed only after metabolism by a bacterial nitroreductase enzyme isolated from E. coli , demonstrating the prodrug nature of the polymer composite materials. Antibacterial efficacy experiments resulted in up to a 66% reduction in E. coli after exposure to the diazeniumdiolate-composite materials. This work details the first illustration of an antibacterial enzyme-activated NO-releasing polymer, a material with potential application as a medical device coating to prevent device-associated infections and improve patient outcomes.

The beneficial effects provided by chitosan oligosaccharides (COS) make them of interest in medical research. The monomers that constitute COS confer distinct properties, so controlling COS composition during their production is significant. In this work, we degraded chitin and chitosan polymers and identified low molecular weight products such as COS that formed, using electrospray ionization time-of-flight mass spectrometry. Our results show that hydrochloric acid, hydrogen peroxide, and nitrous acid generate distinct products from chitin and chitosan. Hydrochloric acid degrades chitin and chitosan to produce glucosamine (GlcN) monomers and oligomers. Hydrogen peroxide degrades chitosan to produce GlcN and N-acetyl-d-glucosamine (GlcNAc) monomers and oligomers, and nitrous acid degrades chitosan to produce 2,5-anhydro- d-mannose. Our studies show that COS composition is dictated by both the degradation protocol and the starting polymer. Additionally, our results enable selection of degradation protocols based on their ability to degrade chitin and chitosan and facilitate the production of COS with desired compositions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Medical device-associated bacterial infections remain a significant complication for patients on extracorporeal organ support. Device-specific bacterial infections occur when bacteria enter the host tissue and attach to the devices, enabling bacteria to colonize and multiply rapidly. Preventing bacterial attachment would efficiently inhibit colonization and biofilm formation. In this study, a copper-based metal-organic framework (MOF) with demonstrated stability under physiological conditions was dispersed in a polymer solution and applied to the interior surface of seven-foot-long medical circulation tubing via a custom-designed coating system. The resulting MOF coating was thin and uniform along the entire length of the tubing. The coating was stable after dynamic flow without degradation or changes to the surface morphology. Bacterial attachment studies were performed on MOF-embedded medical tubing and uncoated control tubing under static and dynamic flow conditions for 24 h. Staphylococcus aureus ( S. aureus ) attachment was reduced by 52 ± 15% (static conditions) and 53 ± 29% (dynamic conditions) on the MOF-coated tubing compared to uncoated controls. In addition, S. aureus attachment was reduced by 52 ± 12% (MOF coating) and 52 ± 30% (uncoated controls) under dynamic flow conditions compared to static conditions. This study is the first to show the promising antibacterial performance of a MOF coating on medical tubing under both static and dynamic flow conditions.

Neuroblastoma, the most common extracranial solid tumor in children, accounts for 15% of all pediatric cancer deaths. Pharmaceutical applications of S-Nitrosylation, which, under normal conditions is involved with a host of epigenetic and embryological development pathways, have exhibited great potential for use as adjuvant therapeutics in the clinical management of cancer. Herein, an evaluation of the impact of nitric oxide (NO) as a potent anticancer agent on murine neuroblastoma cells is presented. Excitingly cell viability, colony formation, and non-carcinogenic cell analysis illustrate the significance and practicality of NO as a cytotoxic anticancer therapeutic. Resazurin, WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt), and MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphyltetrazolium bromide) assays consistently displayed a moderate, ~20-25% reduction in cell viability after exposure to 1 mM S -Nitrosoglutathione (GSNO). A colony formation assay demonstrated that treated cells no longer exhibited colony formation capacity. Identically GSNO-treated Adult Human Dermal Fibroblasts (HDFa) exhibited no decrease in viability, indicating potential discrimination between neoplastic and normal cells. Collectively, our findings indicate a potential application for NO as an adjuvant therapeutic in the clinical management of neuroblastoma.

Melanoma-associated retinopathy (MAR) is a rare paraneoplastic retinal disorder usually occurring in the context of metastatic melanoma. Patients present with night blindness, photopsias and a constriction of the visual field. MAR is an auto-immune disorder characterized by the production of autoantibodies targeting retinal proteins, especially autoantibodies reacting to the cation channel TRPM1 produced in melanocytes and ON-bipolar cells. TRPM1 has at least three different isoforms which vary in the N-terminal region of the protein. In this study, we report the case of three new MAR patients presenting different anti-TRPM1 autoantibodies reacting to the three isoforms of TRPM1 with variable binding affinity. Two sera recognized all isoforms of TRPM1, while one recognized only the two longest isoforms upon immunolocalization studies on overexpressing cells. Similarly, the former two sera reacted with all TRPM1 isoforms on western blot, but an immunoprecipitation enrichment step was necessary to detect all isoforms with the latter serum. In contrast, all sera labelled ON-bipolar cells on Tprm1+/+ but not on Trpm1-/- mouse retina as shown by co-immunolocalization. This confirms that the MAR sera specifically detect TRPM1. Most likely, the anti-TRPM1 autoantibodies of different patients vary in affinity and concentration. In addition, the binding of autoantibodies to TRPM1 may be conformation-dependent, with epitopes being inaccessible in some constructs (truncated polypeptides versus full-length TRPM1) or applications (western blotting versus immunohistochemistry). Therefore, we propose that a combination of different methods should be used to test for the presence of anti-TRPM1 autoantibodies in the sera of MAR patients., Competing Interests: The authors have declared that no competing interests exist.

Thermogravimetric analysis (TGA) is a technique which can probe chemisorption of substrates onto metal organic frameworks. A TGA method was developed to examine the catalytic oxidation of S -nitrosoglutathione (GSNO) by the MOF H 3 [(Cu 4 Cl) 3 (BTTri) 8 ] (abbr. Cu-BTTri; H 3 BTTri = 1,3,5-tris(1 H -1,2,3-triazol-5-yl)benzene), yielding glutathione disulfide (GSSG) and nitric oxide (NO). Thermal analysis of reduced glutathione (GSH), GSSG, GSNO, and Cu-BTTri revealed thermal resolution of all four analytes through different thermal onset temperatures and weight percent changes. Two reaction systems were probed: an aerobic column flow reaction and an anaerobic solution batch reaction with gas agitation. In both systems, Cu-BTTri was reacted with a 1 mM GSH, GSSG, or GSNO solution, copiously rinsed with distilled-deionized water (dd-H 2 O), dried (25 °C, < 1 Torr), and assessed by TGA. Additionally, stock, effluent or supernatant, and rinse solutions for each glutathione derivative within each reaction system were assessed by mass spectrometry (MS) to inform on chemical transformations promoted by Cu-BTTri as well as relative analyte concentrations. Both reaction systems exhibited chemisorption of glutathione derivatives to the MOF by TGA. Mass spectrometry analyses revealed that in both systems, GSH was oxidized to GSSG, which chemisorbed to the MOF whereas GSSG remained unchanged during chemisorption. For GSNO, chemisorption to the MOF without reaction was observed in the aerobic column setup, whereas conversion to GSSG and subsequent chemisorption was observed in the anaerobic batch setup. These findings suggest that within this reaction system, GSSG is the primary adsorbent of concern with regards to strong binding to Cu-BTTri. Development of similar thermal methods could allow for the probing of MOF reactivity for a wide range of systems, informing on important considerations such as reduced catalytic efficiency from poisoning, recyclability, and loading capacities of contaminants or toxins with MOFs.

Immigrant health research has highlighted the relevance of socioeconomic, health services, and immigration-related factors in explaining disparities in health screening rates between native- and foreign-born individuals. This study advances knowledge in this area by investigating the explanatory strength of such factors for cardiovascular risk screening across eight immigrant groups. Using nationally representative data from the National Health Interview Survey, we test the hypothesis that known correlates of preventive healthcare seeking differ in their ability to predict screening behavior depending on region of origin. Results show that health service factors (lack of insurance and no place for care) are fairly consistent predictors of preventive screening while socioeconomic and immigration-related factors are less so. These findings surface the complex processes underlying observed differentials in health-seeking behaviors and illuminate potential targets for public health and clinical intervention.

Background: The Supplementary Nutrition Assistance Program (SNAP) is a critical lifeline for millions of low-income US families, but some studies suggests that it may inadvertently increase obesity risk. Building on research contesting the SNAP-obesity link, we examine the effect of SNAP participation on BMI among multiyear participants at varying levels of SNAP benefit levels to provide some of the first evidence on the relationship between SNAP participation, state-level SNAP resources, and body weight. We focus on children given the strong links between early-life obesity and later-life health., Methods: Linking state-level data on SNAP benefit levels with three waves of longitudinal individual-level data from the Child Development Supplement of the Panel Study of Income Dynamics, we use child- and state-level fixed effects to examine whether exogenous differences in SNAP benefit allotments influence the relationship between SNAP participation and weight gain., Results: Lower SNAP benefit levels were associated with only modest increases in BMI among children; higher benefit levels showed no association with BMI., Conclusions: Although concerns that more food assistance promotes obesity have spurred calls for cuts in the SNAP program, we find the opposite - that SNAP participation is associated with an increase in childhood BMI only when benefit levels are low. This study adds to the mounting evidence suggesting that SNAP does not cause obesity. It also contributes to the literature on the political economy of health, especially that pertaining to social policy variation across US states., Competing Interests: None., (© 2020 Published by Elsevier Ltd.)

The developing antibiotic resistance crisis creates a serious need for new antimicrobial agents. In this work, novel nitroaromatic-protected piperazine diazeniumdiolate (nitric oxide donor) prodrugs are synthesized to release nitric oxide upon enzyme activation to kill bacteria. Antibacterial prodrugs could help reduce side effects due to antibiotics, only releasing the therapeutic where infections are concentrated. The nitroreductase enzyme, which is found almost exclusively in bacteria, reduces the nitroaromatic-protecting group of the synthesized compounds and catalyzes the release of nitric oxide. This paper shows that nitric oxide release from the synthesized compounds only occurs in the presence of a bacteria-derived nitroreductase enzyme, demonstrating the possibility of site-specific delivery of an antibacterial therapeutic. The amount of nitric oxide release is measured at concentrations of 0.01, 0.1, and 1 mM, and is well within antibacterial levels at concentrations of 0.1 and 1 mM. The antibacterial activity of the compounds is demonstrated after exposure of the compounds to Escherichia coli, a nitroreductase-producing bacterial species, leading to up to a 94% reduction in the number of viable bacteria after 24 h at 1 mM concentrations of the prodrug. This study is the first example of an antibacterial diazeniumdiolate prodrug activated by a nitroreductase enzyme, and further demonstrates the possibilities of antibacterial prodrugs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

S-Nitrosothiols (RSNOs) such as S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP) are susceptible to decomposition by stimuli including heat, light, and trace metal ions. Using stepwise isothermal thermogravimetric analysis (TGA), we observed that NO-forming homolytic cleavage of the S-N bond occurs at 134.7 ± 0.8 °C in GSNO and 132.8 ± 0.9 °C in SNAP, contrasting with the value of 150 °C that has been previously reported for both RSNOs. Using mass spectrometry (MS), nuclear magnetic resonance (NMR), and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), we analyzed the decomposition products from TGA experiments. The organic product of GSNO decomposition was glutathione disulfide, while SNAP decomposed to form N-acetylpenicillamine disulfide as well as other products, including tri- and tetrasulfides. In addition, we assessed the relative solution stabilities of GSNO and SNAP under common laboratory conditions, which include variable temperature, pH, and light exposure with rigorous exclusion of trace metal ions by chelation. GSNO exhibited greater stability than SNAP over a 7-day period except in one instance. Both RSNOs demonstrated an inverse relationship between solution stability and temperature, with refrigeration considerably extending shelf life. A decrease in pH from 7.4 to 5.0 also enhanced the stability of both RSNOs. A further decrease in pH from 5.0 to 3.0 resulted in decreased stability for both RSNOs, and is notably the only occasion in which SNAP proved more stable than GSNO. After 1 h of exposure to overhead fluorescent lighting, both RSNOs displayed high susceptibility to light-induced decomposition. After 7 h, GSNO and SNAP decomposed 19.3 ± 0.5% and 30 ± 2%, respectively., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Copper containing compounds catalyze decomposition of S-Nitrosoglutathione (GSNO) in the presence of glutathione (GSH) yielding glutathione disulfide (GSSG) and nitric oxide (NO). Extended NO generation from an endogenous source is medically desirable to achieve vasodilation, reduction in biofilms on medical devices, and antibacterial activity. Homogeneous and heterogeneous copper species catalyze release of NO from endogenous GSNO. One heterogeneous catalyst used for GSNO decomposition in blood plasma is the metal-organic framework (MOF), H 3 [(Cu 4 Cl) 3 -(BTTri) 8 , H 3 BTTri = 1,3,5-tris( 1 H-1,2,3-triazol-5-yl) benzene] (CuBTTri). Fundamental questions about these systems remain unanswered, despite their use in biomedical applications, in part because no method previously existed for simultaneous tracking of [GSNO], [GSH], and [GSSG] in water. Tracking these reactions in water is a necessary step towards study in biological media (blood is approximately 80% water) where NO release systems must operate. Even the balanced stoichiometry remains unknown for copper-ion and CuBTTri catalyzed GSNO decomposition. Herein, we report a direct 1 H NMR method which: simultaneously monitors [GSNO], [GSH], and [GSSG] in water; provides the experimentally determined stoichiometry for copper-ion vs CuBTTri catalyzed GSNO decomposition; reveals that the CuBTTri-catalyzed reaction reaches 10% GSNO decomposition (16 h) without added GSH, yet the copper-ion catalyzed reaction reaches 100% GSNO decomposition (16 h) without added GSH; and shows 100% GSNO decomposition upon addition of stoichiometric GSH to the CuBTTri catalyzed reaction. These observations provide evidence that copper-ion and CuBTTri catalyzed GSNO decomposition in water operate through different reaction mechanisms, the details of which can now be probed by 1 H NMR kinetics and other needed studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Metal-organic frameworks (MOFs) are powerful chemosensors when designed to undergo a detectable change in optical properties upon interacting with target analytes. This work contributes to the overall understanding of metal-ion interactions with MOFs to elicit changes in fluorescence emission, a necessary step en route to developing more sensitive and selective systems for metal-ion sensing. Toward this goal, the photophysical properties of an amino-containing MOF, Cu 3 (NH 2 BTC) 2 , were investigated. The MOF was highly sensitive for the detection of Fe 2+ and Fe 3+ exhibiting the most intense fluorescence quenching with the lowest detectable change in signal occurring at 1.55 ppm (27.8 μM) at room temperature in minutes. Other metal ions, including Pb 2+ , Cu 2+ , Mn 2+ , Ni 2+ , and Co 2+ , were also detected at 5.7, 12, 3.0, 1.6, and 0.2 ppm, respectively, demonstrating the range of sensing capabilities. Additional experiments were performed to elucidate the pathway of metal-ion detection, including the investigation of photoluminescent changes upon the introduction of acids (HCl, ZrCl 4 , and AlCl 3 ) and several anions (CO 3 2- , OAc - , and Cr 2 O 7 2- ). To determine the influence of the amino functional group on interactions with the analytes, isoreticular Cu 3 BTC 2 and postsynthetically modified Cu 3 (NH 2 BTC) 2 (to hinder access to the free-amine moiety) were also investigated, revealing that the free amine is essential for the detection of the anions and is likely involved in the detection of several divalent metal ions. On the other hand, divalent metal ion Fe 2+ likely induces an emission intensity change by interaction with the carboxylate of the MOF ligand or the open Cu 2+ sites. Taken together, this report demonstrates that Cu 3 (NH 2 BTC) 2 has unique photoluminescent properties and likely elicits detection of ions (ppm, μM) via multiple pathways. As such, future development of MOF-based sensors should include MOFs with free accessible functional handles (such as an amine) to be strategically modified to selectively detect specific metal ions.