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1.
Transplantation ; 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38564451

ABSTRACT

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease and frequently recurs after kidney transplantation. Recurrent FSGS (rFSGS) is associated with poor allograft and patient outcomes. Bleselumab, a fully human immunoglobulin G4 anti-CD40 antagonistic monoclonal antibody, disrupts CD40-related processes in FSGS, potentially preventing rFSGS. METHODS: A phase 2a, randomized, multicenter, open-label study of adult recipients (aged ≥18 y) of a living or deceased donor kidney transplant with a history of biopsy-proven primary FSGS. The study assessed the efficacy of bleselumab combined with tacrolimus and corticosteroids as maintenance immunosuppression in the prevention of rFSGS >12 mo posttransplantation, versus standard of care (SOC) comprising tacrolimus, mycophenolate mofetil, and corticosteroids. All patients received basiliximab induction. The primary endpoint was rFSGS, defined as proteinuria (protein-creatinine ratio ≥3.0 g/g) with death, graft loss, or loss to follow-up imputed as rFSGS, through 3 mo posttransplant. RESULTS: Sixty-three patients were followed for 12 mo posttransplantation. Relative decrease in rFSGS occurrence through 3 mo with bleselumab versus SOC was 40.7% (95% confidence interval, -89.8 to 26.8; P = 0.37; absolute decrease 12.7% [95% confidence interval, -34.5 to 9.0]). Central-blinded biopsy review found relative (absolute) decreases in rFSGS of 10.9% (3.9%), 17.0% (6.2%), and 20.5% (7.5%) at 3, 6, and 12 mo posttransplant, respectively; these differences were not statistically significant. Adverse events were similar for both treatments. No deaths occurred during the study. CONCLUSIONS: In at-risk kidney transplant recipients, bleselumab numerically reduced proteinuria occurrence versus SOC, but no notable difference in occurrence of biopsy-proven rFSGS was observed.

2.
Sci Rep ; 14(1): 9158, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38644405

ABSTRACT

A circular economy based on symbiotic relationships among sectors, where the waste from one is resource to another, holds promise for cost-effective and sustainable production. This research explores such a model for the agriculture, energy, and construction sectors in California. Here, we develop new an understanding for the synergistic utilization mechanisms for rice hull, a byproduct from rice production, as a feedstock for electricity generation and rice hull ash (RHA) used as a supplementary cementitious material in concrete. A suite of methods including experimental analysis, techno-economic analysis (TEA), and life-cycle assessment (LCA) were applied to estimate the cost and environmental performance of the system. TEA results showed that the electricity price required for break even on expenses without selling RHA is $0.07/kWh, lower than the market price. As such, RHA may be available at little to no cost to concrete producers. Our experimental results showed the viability of RHA to be used as a supplementary cementitious material, meaning it can replace a portion of the cement used in concrete. LCA results showed that replacing 15% of cement with RHA in concrete can reduce carbon dioxide equivalent (CO2e) emissions by 15% while still meeting material performance targets. While the substitution rate of RHA for cement may be modest, RHA generated from California alone could mitigate 0.2% of total CO2e from the entire cement production sector in the United States and 1% in California.

3.
Am J Nephrol ; 54(3-4): 156-164, 2023.
Article in English | MEDLINE | ID: mdl-37019091

ABSTRACT

INTRODUCTION: Coronavirus disease (COVID-19) is a global pandemic which continues to cause systemic inflammation, leading to multi-system organ damage including acute kidney injury (AKI) and thrombotic complications. We hypothesize that D-dimer level predicts an increased risk of AKI and thrombotic complications in COVID-19. METHODS: This was a retrospective cohort study performed at a single-center academic center. Patients hospitalized with COVID-19 between January 1, 2020, and January 1, 2021, were included in the analysis. Demographics and associated medical records were reviewed from the electronic medical record. Statistical analysis was done to determine the incidence of AKI and thrombosis and if D-dimer was predictive of an adverse event. RESULTS: The study included 389 patients with the diagnosis of COVID-19 who were hospitalized. AKI was evident in 143 patients with 59 experiencing a thrombotic event. Factors associated with AKI included age, chronic kidney disease, proteinuria, use of outpatient angiotensin-blocking medications, and D-dimer greater than 1.75 (p < 0.05). Factors associated with thrombosis included use of outpatient anticoagulants, elevated WBC, interleukin-6 (IL-6), and D-dimer greater than 1.75 (p < 0.05). When D-dimer was dichotomized at the median value for the entire dataset (value greater than 1.75), there was good discrimination for AKI and very good discrimination for thrombosis. CONCLUSIONS: Complications of acute renal failure and thrombosis are common in patients presenting with COVID-19. D-dimer was found to be predictive of both. Future studies to validate the association of these two events in patients presenting with COVID-19 are warranted as early treatment with antithrombotic agents may have a role in preventing adverse sequelae and outcomes.


Subject(s)
Acute Kidney Injury , COVID-19 , Thrombosis , Humans , COVID-19/complications , Retrospective Studies , SARS-CoV-2 , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Thrombosis/etiology , Thrombosis/complications
4.
Nat Commun ; 12(1): 4372, 2021 07 16.
Article in English | MEDLINE | ID: mdl-34272370

ABSTRACT

Intrarenal B cells in human renal allografts indicate transplant recipients with a poor prognosis, but how these cells contribute to rejection is unclear. Here we show using single-cell RNA sequencing that intrarenal class-switched B cells have an innate cell transcriptional state resembling mouse peritoneal B1 or B-innate (Bin) cells. Antibodies generated by Bin cells do not bind donor-specific antigens nor are they enriched for reactivity to ubiquitously expressed self-antigens. Rather, Bin cells frequently express antibodies reactive with either renal-specific or inflammation-associated antigens. Furthermore, local antigens can drive Bin cell proliferation and differentiation into plasma cells expressing self-reactive antibodies. These data show a mechanism of human inflammation in which a breach in organ-restricted tolerance by infiltrating innate-like B cells drives local tissue destruction.


Subject(s)
Allografts/immunology , B-Lymphocytes/metabolism , Graft Rejection/immunology , Inflammation/metabolism , Kidney Transplantation/adverse effects , Animals , Autoantibodies/immunology , B-Lymphocytes/immunology , B-Lymphocytes/pathology , Gene Expression Regulation/genetics , Gene Expression Regulation/immunology , Gene Ontology , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class II/immunology , Humans , Immunoglobulin G/immunology , Kidney/immunology , Kidney/metabolism , Mice , Palatine Tonsil/immunology , Palatine Tonsil/metabolism , RNA-Seq , Single-Cell Analysis , Transplantation, Homologous
5.
J Neurophysiol ; 125(2): 476-488, 2021 02 01.
Article in English | MEDLINE | ID: mdl-33146066

ABSTRACT

Activity-dependent changes of synapse strength have been extensively characterized at chemical synapses, but the relationship between physiological forms of activity and strength at electrical synapses remains poorly characterized and understood. For mammalian electrical synapses comprising hexamers of connexin36, physiological forms of neuronal activity in coupled pairs have thus far only been linked to long-term depression; activity that results in strengthening of electrical synapses has not yet been identified. Here, we performed dual whole-cell current-clamp recordings in acute slices of P11-P15 Sprague-Dawley rats of electrically coupled neurons of the thalamic reticular nucleus (TRN), a central brain area that regulates cortical input from and attention to the sensory surround. Using TTA-A2 to limit bursting, we show that tonic spiking in one neuron of a pair results in long-term potentiation of electrical synapses. We use experiments and computational modeling to show that the magnitude of plasticity expressed alters the functionality of the synapse. Potentiation is expressed asymmetrically, indicating that regulation of connectivity depends on the direction of use. Furthermore, calcium pharmacology and imaging indicate that potentiation depends on calcium flux. We thus propose a calcium-based activity rule for bidirectional plasticity of electrical synapse strength. Because electrical synapses dominate intra-TRN connectivity, these synapses and their activity-dependent modifications are key dynamic regulators of thalamic attention circuitry. More broadly, we speculate that bidirectional modifications of electrical synapses may be a widespread and powerful principle for ongoing, dynamic reorganization of neuronal circuitry across the brain.NEW & NOTEWORTHY This work reveals a physiologically relevant form of activity pairing in coupled neurons that results in long-term potentiation of mammalian electrical synapses. These findings, in combination with previous work, allow the authors to propose a bidirectional calcium-based rule for plasticity of electrical synapses, similar to those demonstrated for chemical synapses. These new insights inform the field on how electrical synapse plasticity may modify the neural circuits that incorporate them.


Subject(s)
Electrical Synapses/physiology , Long-Term Potentiation , Thalamus/physiology , Action Potentials , Animals , Female , Male , Rats , Rats, Sprague-Dawley
6.
Ecol Evol ; 10(18): 9827-9840, 2020 Sep.
Article in English | MEDLINE | ID: mdl-33005347

ABSTRACT

The majority of landbird species feed their nestlings arthropods and variation in arthropod populations can impact reproductive outcomes in these species. Arthropod populations in turn are influenced by climate because temperature affects survival and reproduction, and larval development. Thus, climate factors have the potential to influence many bird species during their reproductive phases. In this study, we assessed climate factors that impact the diet of nestling White-headed Woodpecker (Dryobates albolarvatus), an at-risk keystone species in much of its range in western North America. To do this, we measured stable isotope signatures (δ13C and δ15N) in 152 nestlings across six years and linked variation in isotopic values to winter (December-February) and spring (June) precipitation and temperature using mixed effects models. We also explored habitat factors that may impact δ13C and δ15N and the relationship between δ15N and nest productivity. Last, we estimated isotopic niche width for nestlings in different watersheds and years using Bayesian standard ellipses, which allowed us to compare dietary niche width and overlap. We found that colder winter temperatures were associated with an increase in δ15N and δ15N levels had a weak positive relationship with nest productivity. We also found that sites with a more diverse tree community were associated with a broader isotopic niche width in nestlings. Our findings suggest that nestling diet is affected by climate, and under future warming climate scenarios, White-headed Woodpecker nestling diet may shift in favor of lower trophic level prey (prey with lower δ15N levels). The impact of such changes on woodpecker populations merits further study.

7.
ACS Nano ; 14(4): 3847-3857, 2020 Apr 28.
Article in English | MEDLINE | ID: mdl-32105062

ABSTRACT

The morphology of nanocrystals serves as a powerful handle to modulate their functional properties. For semiconducting nanostructures, the shape is no less important than the size and composition, in terms of determining the electronic structure. For example, in the case of nanoplatelets (NPLs), their two-dimensional (2D) electronic structure and atomic precision along the axis of quantum confinement makes them well-suited as pure color emitters and optical gain media. In this study, we describe synthetic efforts to develop ZnSe NPLs emitting in the ultraviolet part of the spectrum. We focus on two populations of NPLs, the first having a sharp absorption onset at 345 nm and a previously unreported species with an absorption onset at 380 nm. Interestingly, we observe that the nanoplatelets are one step in a quantized reaction pathway that starts with (zero-dimensional (0D)) magic-sized clusters, then proceeds through the formation of (one-dimensional (1D)) nanowires toward the (2D) "345 nm" species of NPLs, which finally interconvert into the "380 nm" NPL species. We seek to rationalize this evolution of the morphology, in terms of a general free-energy landscape, which, under reaction control, allows for the isolation of well-defined structures, while thermodynamic control leads to the formation of three-dimensional (3D) nanocrystals.

8.
Am J Kidney Dis ; 75(4): 513-516, 2020 04.
Article in English | MEDLINE | ID: mdl-31866228

ABSTRACT

Thrombotic microangiopathy (TMA) is an emerging complication of oncologic therapy. Cancer-related causes of renal endothelial cell damage include cytotoxic chemotherapies, radiation given for myeloablation, and direct involvement of renal vasculature by tumor cells. Another class of therapeutic agents that has been implicated in TMA is the vascular endothelial growth factor (VEGF) pathway inhibitors, including the anti-VEGF monoclonal antibody bevacizumab and the VEGF receptor tyrosine kinase inhibitor sunitinib. These TMAs have been termed type II cancer drug-induced TMA and are distinguished from those associated with some cytotoxic chemotherapies (ie, type I) in that they are not dose dependent and patients are more likely to demonstrate some recovery of kidney function. Determination of the cause of TMA in oncologic patients often presents a significant challenge because patients frequently receive multiple chemotherapeutic agents simultaneously and clinicopathologic features often demonstrate substantial overlap, regardless of cause. We present a case of TMA with predominantly chronic features in a 70-year-old patient being treated for adenoid cystic carcinoma of the breast with a single agent, a short interfering RNA targeted against Myc (DCR-MYC).


Subject(s)
Proto-Oncogene Proteins c-myc/genetics , RNA, Small Interfering/adverse effects , RNA, Small Interfering/genetics , Thrombotic Microangiopathies/chemically induced , Thrombotic Microangiopathies/genetics , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Chronic Disease , Drug Delivery Systems/adverse effects , Drug Delivery Systems/methods , Fatal Outcome , Female , Gene Targeting/adverse effects , Gene Targeting/methods , Humans , Proto-Oncogene Proteins c-myc/antagonists & inhibitors , RNA, Small Interfering/administration & dosage , Thrombotic Microangiopathies/diagnosis
9.
PLoS One ; 14(9): e0221957, 2019.
Article in English | MEDLINE | ID: mdl-31532792

ABSTRACT

BACKGROUND: Hypertension (HTN) disproportionately affects African Americans (AAs), who respond better to thiazide diuretics than other antihypertensives. Variants of the APOL1 gene found in AAs are associated with a higher rate of kidney disease and play a complex role in cardiovascular disease. METHODS: AA subjects from four HTN trials (n = 961) (GERA1, GERA2, PEAR1, and PEAR2) were evaluated for blood pressure (BP) response based on APOL1 genotype after 4-9 weeks of monotherapy with thiazides, beta blockers, or candesartan. APOL1 G1 and G2 variants were determined by direct sequencing or imputation. RESULTS: Baseline systolic BP (SBP) and diastolic BP (DBP) levels did not differ based on APOL1 genotype. Subjects with 1-2 APOL1 risk alleles had a greater SBP response to candesartan (-12.2 +/- 1.2 vs -7.5 +/- 1.8 mmHg, p = 0.03; GERA2), and a greater decline in albuminuria with candesartan (-8.3 +/- 3.1 vs +3.7 +/- 4.3 mg/day, p = 0.02). APOL1 genotype did not associate with BP response to thiazides or beta blockers. GWAS was performed to determine associations with BP response to candesartan depending on APOL1 genotype. While no SNPs reached genome wide significance, SNP rs10113352, intronic in CSMD1, predicted greater office SBP response to candesartan (p = 3.7 x 10-7) in those with 1-2 risk alleles, while SNP rs286856, intronic in DPP6, predicted greater office SBP response (p = 3.2 x 10-7) in those with 0 risk alleles. CONCLUSIONS: Hypertensive AAs without overt kidney disease who carry 1 or more APOL1 risk variants have a greater BP and albuminuria reduction in response to candesartan therapy. BP response to thiazides or beta blockers did not differ by APOL1 genotype. Future studies confirming this initial finding in an independent cohort are required.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/therapeutic use , Apolipoprotein L1/genetics , Benzimidazoles/therapeutic use , Black or African American/genetics , Hypertension/drug therapy , Tetrazoles/therapeutic use , Adult , Biphenyl Compounds , Female , Genome-Wide Association Study , Genotype , Humans , Hypertension/ethnology , Hypertension/genetics , Male , Middle Aged , Pharmacogenomic Variants , Polymorphism, Single Nucleotide , Sequence Analysis, DNA , Treatment Outcome
10.
Am J Nephrol ; 50(5): 370-374, 2019.
Article in English | MEDLINE | ID: mdl-31553982

ABSTRACT

BACKGROUND: Within-patient tacrolimus level variability >30% has been shown to be a risk factor for de novo donor-specific antibody formation and death-censored graft failure among kidney transplant recipients. The burden of tacrolimus variability and the correlation between variability and subtherapeutic tacrolimus levels were examined in a large national data set. METHODS: All tacrolimus levels drawn at LabCorp® facilities in the United States with a diagnosis code for kidney transplant between November 2011 and September 2017 were examined, excluding values that could represent new allografts. Tacrolimus variability was calculated if at least 3 levels were available. The percentage of subtherapeutic (<4.0 ng/dL) tacrolimus levels (%subT) was also calculated. Interdependence between %subT and tacrolimus variability was assessed with correlation analysis and linear regression. RESULTS: There were 410,257 tacrolimus levels among 27,375 patients, who had 11 (interquartile range [IQR] 6-20) tacrolimus levels over a median follow-up of 26.5 (IQR 12.8-46.1) months. Median tacrolimus variability was 30.6%, and 51.6% of patients exceeded 30% variability. Median %subT was 11.1% (IQR 0-30.8%), and 34.3% of patients had no subtherapeutic levels. The correlation coefficient between tacrolimus variability and %subT was 0.253 (p< 0.001). In linear regression, tacrolimus variability increased 1.86% for each 10% increase in %subT (p < 0.001), but R-squared for this model was only 0.06. CONCLUSION: More than half of established kidney transplant patients from a large national sample exhibited levels of tacrolimus variability that have been associated with inferior transplant outcomes. Tacrolimus variability has a weak association with subtherapeutic levels, but represents a more complicated constellation of clinical factors.


Subject(s)
Biological Variation, Individual , Drug Monitoring/statistics & numerical data , Graft Rejection/prevention & control , Immunosuppressive Agents/pharmacokinetics , Kidney Transplantation/adverse effects , Tacrolimus/pharmacokinetics , Adult , Aged , Datasets as Topic , Female , Follow-Up Studies , Graft Rejection/immunology , Graft Survival/immunology , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Risk Factors , Tacrolimus/therapeutic use , United States
13.
J Cell Sci ; 131(18)2018 09 17.
Article in English | MEDLINE | ID: mdl-30154211

ABSTRACT

Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons, resulting in progressive locomotor dysfunction. Identification of genes required for the maintenance of these neurons should help to identify potential therapeutic targets. However, little is known regarding the factors that render dopaminergic neurons selectively vulnerable to PD. Here, we show that Drosophila melanogaster scarlet mutants exhibit an age-dependent progressive loss of dopaminergic neurons, along with subsequent locomotor defects and a shortened lifespan. Knockdown of Scarlet specifically within dopaminergic neurons is sufficient to produce this neurodegeneration, demonstrating a unique role for Scarlet beyond its well-characterized role in eye pigmentation. Both genetic and pharmacological manipulation of the kynurenine pathway rescued loss of dopaminergic neurons by promoting synthesis of the free radical scavenger kynurenic acid (KYNA) and limiting the production of the free radical generator 3-hydroxykynurenine (3-HK). Finally, we show that expression of wild-type Scarlet is neuroprotective in a model of PD, suggesting that manipulating kynurenine metabolism may be a potential therapeutic option in treating PD.This article has an associated First Person interview with the first author of the paper.


Subject(s)
Drosophila melanogaster/metabolism , Neurodegenerative Diseases/genetics , Parkinson Disease/genetics , Animals , Humans , Neurodegenerative Diseases/pathology , Parkinson Disease/pathology
14.
Hum Pathol ; 76: 47-51, 2018 06.
Article in English | MEDLINE | ID: mdl-29501487

ABSTRACT

Acute T cell-mediated rejection (TCMR) is an important cause of renal allograft loss. The Banff classification for tubulointerstitial (type I) rejection is based on the extent of both interstitial inflammation and tubulitis. Lymphocytes may also be present between parietal epithelial cells and Bowman capsules in this setting, which we have termed "capsulitis." We conducted this study to determine the clinical significance of capsulitis. We identified 42 patients from the pathology archives at The University of Chicago with isolated Banff type I TCMR from 2010 to 2015. Patient demographic data, Banff classification, and graft outcome measurements were compared between capsulitis and noncapsulitis groups using Mann-Whitney U test. Capsulitis was present in 26 (62%) and was more frequently seen in Banff IB than in IA TCMR (88% versus 44%, P = .01). Patients with capsulitis had a higher serum creatinine at biopsy (4.6 versus 2.9 mg/dL, P = .04) and were more likely to progress to dialysis (42% versus 13%, P = .06), with fewer recovering their baseline serum creatinine (12% versus 38%, P = .08). Patients with both Banff IA TCMR and capsulitis have clinical outcomes similar to or possibly worse than Banff IB TCMR compared with those with Banff IA and an absence of capsulitis. Capsulitis is an important pathologic parameter in the evaluation of kidney transplant biopsies with potential diagnostic, prognostic, and therapeutic implications in the setting of TCMR.


Subject(s)
Bowman Capsule/immunology , Graft Rejection/immunology , Immunity, Cellular , Kidney Transplantation/adverse effects , Nephritis/immunology , T-Lymphocytes/immunology , Adult , Allografts , Biopsy , Bowman Capsule/pathology , Chicago , Disease Progression , Female , Graft Rejection/pathology , Graft Rejection/therapy , Humans , Male , Nephritis/pathology , Nephritis/therapy , Predictive Value of Tests , Renal Dialysis , Risk Factors , T-Lymphocytes/metabolism , Treatment Outcome
15.
Sci Data ; 5: 180016, 2018 Feb 20.
Article in English | MEDLINE | ID: mdl-29461513

ABSTRACT

Statistically downscaled climate data have been widely used to explore possible impacts of climate change in various fields of study. Although many studies have focused on characterizing differences in the downscaling methods, few studies have evaluated actual downscaled datasets being distributed publicly. Spatially focusing on the Pacific Northwest, we compare five statistically downscaled climate datasets distributed publicly in the US: ClimateNA, NASA NEX-DCP30, MACAv2-METDATA, MACAv2-LIVNEH and WorldClim. We compare the downscaled projections of climate change, and the associated observational data used as training data for downscaling. We map and quantify the variability among the datasets and characterize the spatio-temporal patterns of agreement and disagreement among the datasets. Pair-wise comparisons of datasets identify the coast and high-elevation areas as areas of disagreement for temperature. For precipitation, high-elevation areas, rainshadows and the dry, eastern portion of the study area have high dissimilarity among the datasets. By spatially aggregating the variability measures into watersheds, we develop guidance for selecting datasets within the Pacific Northwest climate change impact studies.

16.
Int J Biometeorol ; 62(4): 553-564, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29105010

ABSTRACT

Tree cavities provide critical roosting and breeding sites for multiple species, and thermal environments in these cavities are important to understand. Our objectives were to (1) describe thermal characteristics in cavities between June 3 and August 9, 2014, and (2) investigate the environmental factors that influence cavity temperatures. We placed iButtons in 84 different cavities in ponderosa pine (Pinus ponderosa) forests in central Washington, and took hourly measurements for at least 8 days in each cavity. Temperatures above 40 °C are generally lethal to developing avian embryos, and ~ 18% of the cavities had internal temperatures of ≥ 40 °C for at least 1 h of each day. We modeled daily maximum cavity temperature, the amplitude of daily cavity temperatures, and the difference between the mean internal cavity and mean ambient temperatures as a function of several environmental variables. These variables included canopy cover, tree diameter at cavity height, cavity volume, entrance area, the hardness of the cavity body, the hardness of the cavity sill (which is the wood below the cavity entrance which forms the barrier between the cavity and the external environment), and sill width. Ambient temperature had the largest effect size for maximum cavity temperature and amplitude. Larger trees with harder sills may provide more thermally stable cavity environments, and decayed sills were positively associated with maximum cavity temperatures. Summer temperatures are projected to increase in this region, and additional research is needed to determine how the thermal environments of cavities will influence species occupancy, breeding, and survival.


Subject(s)
Microclimate , Pinus ponderosa , Models, Theoretical , Temperature
17.
Prog Transplant ; 27(2): 131-138, 2017 06.
Article in English | MEDLINE | ID: mdl-28617167

ABSTRACT

BACKGROUND: Despite our knowledge of barriers to the early stages of the transplant process, we have limited insight into patient-reported barriers to the prekidney transplant medical evaluation in populations largely at-risk for evaluation failure. METHODS: One-hundred consecutive adults were enrolled at an urban, Midwestern transplant center. Demographic, clinical, and quality of life data were collected prior to patients visit with a transplant surgeon/nephrologist (evaluation begins). Patient-reported barriers to evaluation completion were collected using the Subjective Barriers Questionnaire 90-days after the initial medical evaluation appointment (evaluation ends), our center targeted goal for transplant work-up completion. RESULTS: At 90 days, 40% of participants had not completed the transplant evaluation. Five barrier categories were created from the 85 responses to the Subjective Barriers Questionnaire. Patient-reported barriers included poor communication, physical health, socioeconomics, psychosocial influences, and access to care. In addition, determinants for successful evaluation completion included being of white race, higher income, free of dialysis, a lower comorbid burden, and reporting higher scores on the Kidney Disease Quality of Life subscale role-emotional. CONCLUSION: Poor communication between patients and providers, and among providers, was the most prominent patient-reported barrier identified. Barriers were more prominent in marginalized groups such as ethnic minorities and people with low income. Understanding the prevalence of patient-reported barriers may aid in the development of patient-centered interventions to improve completion rates.


Subject(s)
Communication , Ethnicity , Health Services Accessibility , Income , Kidney Failure, Chronic/therapy , Kidney Transplantation , Minority Groups , Physician-Patient Relations , Renal Dialysis , Adolescent , Adult , Black or African American , Aged , Asian , Cohort Studies , Comorbidity , Female , Health Status , Healthcare Disparities , Hispanic or Latino , Humans , Male , Middle Aged , Poverty , Preoperative Care , Prospective Studies , Quality of Life , Socioeconomic Factors , Surveys and Questionnaires , United States , White People , Young Adult
18.
Int J Mol Sci ; 18(3)2017 Mar 18.
Article in English | MEDLINE | ID: mdl-28335481

ABSTRACT

Colistin sulfate (polymixin E) is an antibiotic prescribed with increasing frequency for severe Gram-negative bacterial infections. As nephrotoxicity is a common side effect, the discovery of pharmacogenomic markers associated with toxicity would benefit the utility of this drug. Our objective was to identify genetic markers of colistin cytotoxicity that were also associated with expression of key proteins using an unbiased, whole genome approach and further evaluate the functional significance in renal cell lines. To this end, we employed International HapMap lymphoblastoid cell lines (LCLs) of Yoruban ancestry with known genetic information to perform a genome-wide association study (GWAS) with cellular sensitivity to colistin. Further association studies revealed that single nucleotide polymorphisms (SNPs) associated with gene expression and protein expression were significantly enriched in SNPs associated with cytotoxicity (p ≤ 0.001 for gene and p = 0.015 for protein expression). The most highly associated SNP, chr18:3417240 (p = 6.49 × 10-8), was nominally a cis-expression quantitative trait locus (eQTL) of the gene TGIF1 (transforming growth factor ß (TGFß)-induced factor-1; p = 0.021) and was associated with expression of the protein HOXD10 (homeobox protein D10; p = 7.17 × 10-5). To demonstrate functional relevance in a murine colistin nephrotoxicity model, HOXD10 immunohistochemistry revealed upregulated protein expression independent of mRNA expression in response to colistin administration. Knockdown of TGIF1 resulted in decreased protein expression of HOXD10 and increased resistance to colistin cytotoxicity. Furthermore, knockdown of HOXD10 in renal cells also resulted in increased resistance to colistin cytotoxicity, supporting the physiological relevance of the initial genomic associations.


Subject(s)
Anti-Bacterial Agents/pharmacology , Colistin/pharmacology , Homeodomain Proteins/genetics , Repressor Proteins/genetics , Transcription Factors/genetics , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/toxicity , Cell Line , Cell Line, Tumor , Colistin/adverse effects , Colistin/toxicity , Drug Resistance/genetics , Genome-Wide Association Study , Humans , Polymorphism, Single Nucleotide , Quantitative Trait Loci
19.
Nurs Econ ; 35(2): 57-63, 2017.
Article in English | MEDLINE | ID: mdl-29985569

ABSTRACT

Upon implementation of the Affordable Care Act (ACA), many managed care organizations (MCOs) initially increased their nurse practitioner (NP) contracting. This trend has not continued, potentially frustrating ACA efforts to expand primary care provider capacity. In this study, about 25% of the responding MCOs did not contract with NPs as primary care providers. only 62.5% of respondent MCOs offering Medicaid products reported contracting with NPs as primary care providers, suggesting this will place a disproportionate burden on low-income patients seeking to access care. Findings from this study also have important geographic implications, suggesting the decision to contract with NPs is made individually, not necessarily influenced by the numbers of newly insured or available primary care physicians.


Subject(s)
Contracts , Managed Care Programs , Nurse Practitioners , Primary Health Care , Humans , Patient Protection and Affordable Care Act , United States , Workforce
20.
ACS Nano ; 10(6): 5769-81, 2016 06 28.
Article in English | MEDLINE | ID: mdl-27203222

ABSTRACT

Semiconductor nanorods can emit linear-polarized light at efficiencies over 80%. Polarization of light in these systems, confirmed through single-rod spectroscopy, can be explained on the basis of the anisotropy of the transition dipole moment and dielectric confinement effects. Here we report emission polarization in macroscopic semiconductor-polymer composite films containing CdSe/CdS nanorods and colloidal CdSe nanoplatelets. Anisotropic nanocrystals dispersed in polymer films of poly butyl-co-isobutyl methacrylate (PBiBMA) can be stretched mechanically in order to obtain unidirectionally aligned arrays. A high degree of alignment, corresponding to an orientation factor of 0.87, was achieved and large areas demonstrated polarized emission, with the contrast ratio I∥/I⊥ = 5.6, making these films viable candidates for use in liquid crystal display (LCD) devices. To some surprise, we observed significant optical anisotropy and emission polarization for 2D CdSe nanoplatelets with the electronic structure of quantum wells. The aligned nanorod arrays serve as optical funnels, absorbing unpolarized light and re-emitting light from deep-green to red with quantum efficiencies over 90% and high degree of linear polarization. Our results conclusively demonstrate the benefits of anisotropic nanostructures for LCD backlighting. The polymer films with aligned CdSe/CdS dot-in-rod and rod-in-rod nanostructures show more than 2-fold enhancement of brightness compared to the emitter layers with randomly oriented nanostructures. This effect can be explained as the combination of linearly polarized luminescence and directional emission from individual nanostructures.

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