Publications by authors named "William Silvers"

32 Publications

Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT.

Sci Rep 2021 Feb 11;11(1):3622. Epub 2021 Feb 11.

Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Copper-67 (t = 2.58 days) decays by β ([Formula: see text]: 562 keV) and γ-rays (93 keV and 185 keV) rendering it with potential for both radionuclide therapy and single-photon emission computed tomography (SPECT) imaging. Prompted by the recent breakthrough of Cu production with high specific activity, high radionuclidic purity, and sufficient quantities, the interest in the theranostic potential of Cu has been rekindled. This work addresses the practicability of developing Cu-labeled antibodies with substantially improved quality for cancer radioimmunotheranostics. Proof of concept is demonstrated with pertuzumab, a US-FDA-approved monoclonal antibody for combination therapies of HER2-positive breast cancer. With an average number of 1.9 chelators coupled to each antibody, we achieved a two-order of magnitude increase in radiolabeling efficiency compared to literature reports. In a preclinical therapeutic study, mice (n = 4-7/group) bearing HER2 xenografts exhibited a Cu-dose dependent tumor-growth inhibition from Cu-labeled-Pertuzumab co-administered with trastuzumab. Furthermore, greater tumor size reduction was observed with Cu-labeled-pertuzumab formulations of higher specific activity. The potential of SPECT imaging with Cu radiopharmaceuticals was tested after Cu-labeled-Pertuzumab administration. Impressively, all tumors were clearly visualized by SPECT imaging with Cu-labeled-Pertuzumab even at day 5 post injection. This work demonstrates it is practical to use Cu radioimmunoconjugates for cancer radioimmunotheranostics.
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http://dx.doi.org/10.1038/s41598-021-82812-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878802PMC
February 2021

A Call to Commemorate International Holocaust Remembrance Day, January 27, in All Health Science Schools.

AMA J Ethics 2021 01 1;23(1):E75-77. Epub 2021 Jan 1.

Clinical professor of medicine at the University of Colorado School of Medicine in Aurora.

This viewpoint proposes why and how Holocaust Remembrance Day, January 27, should be honored in all health professions schools. A public letter, from which this viewpoint is adapted, has been endorsed by over 50 teachers of medicine, ethics, and history.
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http://dx.doi.org/10.1001/amajethics.2021.75DOI Listing
January 2021

Teaching Health Professions Students About the Holocaust.

AMA J Ethics 2021 01 1;23(1):E26-30. Epub 2021 Jan 1.

Project manager for the Holocaust Genocide and Contemporary Bioethics Program at the University of Colorado Center for Bioethics and Humanities in Aurora.

The legacy of health professionals' roles in the Holocaust is fundamental to understanding modern health care ethics, but teaching it is difficult. The University of Colorado Center for Bioethics and Humanities has developed a program that addresses 4 main pedagogical challenges of this content. This article identifies 3 core lessons and proposes 5 specific learning objectives related to health professionals' involvement in the Holocaust for any health professional training program.
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http://dx.doi.org/10.1001/amajethics.2021.26DOI Listing
January 2021

Attitudes about cannabis mediate the relationship between cannabis knowledge and use in active adult athletes.

J Cannabis Res 2020 May 18;2(1):18. Epub 2020 May 18.

Canna Research Group, 3996 Savannah Ct, Boulder, CO, 80301, USA.

Background: Little is known about how cannabis knowledge and attitudes impact cannabis use behavior.

Objective: To test the knowledge-attitudes-behavior paradigm in active adult athletes.

Design: The Athlete Pain, Exercise, and Cannabis Experience (PEACE) Survey, a cross-sectional survey study, used social media and email blasts to recruit participants and SurveyGizmo to collect data.

Participants: Self-defined active adult athletes (n = 1161).

Main Measures: Knowledge about cannabis was evaluated with four questions. Attitudes toward cannabis was evaluated with 11 questions. The attitudes questions were used in a TwoStep Cluster analysis in SPSS to assign group membership by attitudes. Chi-square was used to determine if there were differences in cluster membership by demographic factors and if knowledge about cannabis differed by cluster membership. Regression analysis was performed to determine if cannabis attitudes mediated the relationship between cannabis knowledge and cannabis use.

Key Results: A three-cluster solution was the best fit to the data. The clusters were named Conservative (n = 374, 32.2%), Unsure (n = 533, 45.9%), and Liberal (n = 254, 21.9). There was a significant difference among the clusters for all 11 attitudes items (all p < 0.001). Attitude cluster membership was significantly different by age (p < 0.001), primary sport (p < 0.05), and knowledge about cannabis (p < 0.001). Athletes in the liberal cluster answered the knowledge questions correctly most often. Attitudes mediated the relationship between cannabis knowledge and cannabis use [Never (32.4%), Past (41.6%), Current (26.0%)] with athletes in the liberal cluster showing more knowledge and greater likelihood to be a current cannabis user (p < 0.001). Among current cannabis users there were differential patterns of cannabis use depending on their attitudes and knowledge; liberal athletes tended to co-use THC and CBD and used cannabis longer. (p < 0.001).

Conclusions: Cannabis education needs to consider attitudes about cannabis, especially among those who might benefit from medical cannabis.
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http://dx.doi.org/10.1186/s42238-020-00023-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819330PMC
May 2020

Cannabis attitudes and patterns of use among followers of the Allergy & Asthma Network.

Ann Allergy Asthma Immunol 2021 Apr 17;126(4):401-410.e1. Epub 2021 Jan 17.

Department of Allergy, Kaiser Permanente Southern California, San Diego, California.

Background: Cannabis use in patients with allergy/asthma, a high-risk group for adverse effects to cannabis, is unknown.

Objective: To determine the patterns of use and attitudes toward cannabis in patients with allergy/asthma.

Methods: An anonymous online survey on cannabis attitudes and use was conducted through the Adult Allergy & Asthma Network. The Asthma Control Test assessed asthma burden. Cluster analyses determined group phenotypes and factor analyses condensed cannabis subjective effects into similar response patterns.

Results: A total of 88 of 489 respondents (18.0%) currently use cannabis with most at the age of less than 50 years old, of female sex, and of White race. Of the noncannabis users (N = 401), 2.5% reported cannabis allergy. Cluster analysis revealed that a liberal attitude toward cannabis was associated with current cannabis use (P < .001). Among current cannabis users, 40.9% of their physicians inquired on cannabis use; only 37.5% of users wanted to discuss cannabis. In addition, 65.9% used cannabis for medical or medical/recreational purposes. Cannabinoids used were tetrahydrocannabinol (33.0%), cannabidiol (19.3%), or both (47.7%). Smoked and vaped cannabis were reported by 53.4% and 35.2%, respectively. Furthermore, 51 cannabis users (58.0%) reported current asthma with 39.2% uncontrolled; of these, 50% smoked cannabis. Compared with current participants with asthma not using cannabis, those currently using cannabis experienced similar levels of asthma control, quality of life, and frequency of asthma exacerbations. Positive effects were endorsed more than negative effects to cannabis (P < .001). Moreover, 19.3% of cannabis users reported coughing that was associated with smoking cannabis (P < .001).

Conclusion: Cannabis was used by less than 20% of the respondents with positive effects more frequent than negative effects. Half of cannabis users with uncontrolled asthma smoke cannabis, but only a minority of the physicians inquire about its use.
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http://dx.doi.org/10.1016/j.anai.2021.01.014DOI Listing
April 2021

Occupational Allergies to Cannabis.

J Allergy Clin Immunol Pract 2020 Nov - Dec;8(10):3331-3338

Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Philadelphia, Pa; Jane & Leonard Korman Respiratory Institute, Thomas Jefferson University, Philadelphia, Pa; Center for Translational Medicine, Thomas Jefferson University, Philadelphia, Pa. Electronic address:

Within the last decade there has been a significant expansion in access to cannabis for medicinal and adult nonmedical use in the United States and abroad. This has resulted in a rapidly growing and diverse workforce that is involved with the growth, cultivation, handling, and dispensing of the cannabis plant and its products. The objective of this review was to educate physicians on the complexities associated with the health effects of cannabis exposure, the nature of these exposures, and the future practical challenges of managing these in the context of allergic disease. We will detail the biological hazards related to typical modern cannabis industry operations that may potentially drive allergic sensitization in workers. We will highlight the limitations that have hindered the development of objective diagnostic measures that are essential in separating "true" cannabis allergies from nonspecific reactions/irritations that "mimic" allergy-like symptoms. Finally, we will discuss recent advances in the basic and translational scientific research that will aid the development of diagnostic tools and therapeutic standards to serve optimal management of cannabis allergies across the occupational spectrum.
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http://dx.doi.org/10.1016/j.jaip.2020.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837257PMC
June 2020

Is the compleat allergist an integrative physician?

Ann Allergy Asthma Immunol 2020 10 27;125(4):378-379. Epub 2020 Jul 27.

University of North Carolina, Charlotte, North Carolina; Allergy Asthma and Immunology Relief, Charlotte, North Carolina; Allergy Asthma and Immunology Research Institute, Charlotte, North Carolina.

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http://dx.doi.org/10.1016/j.anai.2020.07.024DOI Listing
October 2020

Cannabis: An Emerging Occupational Allergen?

Ann Work Expo Health 2020 08;64(7):679-682

Department of Medicine, Center for Translational Medicine and Division of Pulmonary Allergy and Critical Care Medicine, Jane and Leonard Korman Respiratory Institute, Thomas Jefferson University, Philadelphia, PA, USA.

Cannabis is the most commonly used psychoactive drug. In recent years, Cannabis access has expanded for both medicinal and non-medicinal has grown. This is also marked with an increasing number of individuals gaining employment in this emerging industry. In this article, we briefly discuss the health hazards associated with Cannabis exposure with an emphasis on the potential for allergic reactions in workers who handle and process Cannabis plant.
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http://dx.doi.org/10.1093/annweh/wxaa043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407602PMC
August 2020

Age related differences in cannabis use and subjective effects in a large population-based survey of adult athletes.

J Cannabis Res 2019 Jul 29;1(1). Epub 2019 Jul 29.

Canna Research Group, 3996 Savannah Ct., Boulder, CO, 80301, USA.

Background: There is a paucity of information regarding cannabis use behaviors in adult community-based athletes as most research in athletes has focused on misuse of cannabis in elite, adolescent, university-based athletes. We aimed to determine whether age related differences exist in patterns of cannabis use and subjective effects to cannabis in adult athletes.

Methods: The Athlete PEACE Survey used mainly social media and email blasts to recruit and SurveyGizmo to collect data. Cannabis patterns of use (duration of use, frequency of use, routes of administration, cannabinoid used, concurrent use with exercise), benefits, and adverse effects were reported. Age was reported by decade from 21 to ≥60. Age trends in cannabis use patterns and subjective effects were assessed using linear trend analysis.

Results: Of the 1161 participants, 301 (26%) athletes currently used cannabis. Younger athletes compared to older athletes reported significantly more positive and adverse subjective effects to cannabis, used cannabis longer, and used both tetrahydrocannabinol and cannabidiol for medical and recreational purposes. Younger athletes used cannabis concurrently with exercise more often than older athletes and consumed edibles, vaporized, and smoked more than older athletes.

Conclusions: We found age-related cannabis patterns of use and subjective effects to cannabis. Concerns about cannabis mis-use and abuse in athletes maybe overstated with the potential benefits (improved sleep, decreased anxiety, less pain) outweighing the adverse effects (increased anxiety, increased appetite, difficulty concentrating).
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http://dx.doi.org/10.1186/s42238-019-0006-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819305PMC
July 2019

Cannabis use in active athletes: Behaviors related to subjective effects.

PLoS One 2019 28;14(6):e0218998. Epub 2019 Jun 28.

Canna Research Group, Boulder, CO, United States of America.

Cannabis use has not been well characterized in athletes. Studies primarily examine problematic use or its categorization by anti-doping bodies as a banned substance. Patterns of use, reasons for use, and responses to cannabis consumption have not been studied in a community-based sample of adult athletes. The Athlete PEACE Survey examined cannabis use patterns and subjective effects to cannabis in a community-based cohort of adult athletes. We used mainly social media and email blasts to recruit and SurveyGizmo to collect data. 1,161 (91.1%) of the 1,274 athletes taking the survey completed it. Current cannabis use was evaluated by asking "In the past two weeks, have you used marijuana (including THC and/or CBD)?" and cannabis type used was assessed by asking "What do you primarily use THC, CBD, or both?". Cannabis benefits and adverse effects (i.e. subjective effects) and patterns of use were reported. 302 athletes (26%) currently use cannabis of whom 301 had complete data for cluster analysis. Cluster analysis was used to determine cannabis user phenotypes and exploratory factor analysis (EFA) was used to create subjective effects factors. Associations between cannabis user phenotype clusters and the subjective effects factors were explored using multivariate analysis. Cluster analysis identified three statistically distinct cannabis user phenotypes: (1) older athletes who primarily use medical CBD, (2) mixed age athletes who use cannabis mainly recreationally with both THC and CBD use, and (3) mixed age athletes who used cannabis the longest with primary THC and CBD use. EFA showed three subjective effects factors: (1) Well-being, (2) Calm, and (3) Adverse. Mean positive subjective were higher than mean adverse subjective effects (p<0.001). The cluster using THC and CBD showed the highest mean scores for all three subjective effects factors (p<0.001). Athletes who use a combination of THC and CBD exhibited the most benefit to well-being and calm with minimal adverse effects. Our methodology can be used to develop real-world evidence to inform future use of medical cannabis products.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218998PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598761PMC
February 2020

Exercise-Induced Bronchoconstriction: Background, Prevalence, and Sport Considerations.

Immunol Allergy Clin North Am 2018 05 2;38(2):205-214. Epub 2018 Mar 2.

University of Colorado School of Medicine, 13001 E 17th Place, Aurora, CO 80045, USA.

The transient airway narrowing that occurs as a result of exercise is defined as exercise-induced bronchoconstriction (EIB). The prevalence of EIB has been reported to be up to 90% in asthmatic patients, reflecting the level of disease control. However, EIB may develop even in subjects without clinical asthma, particularly in children, athletes, patients with atopy or rhinitis, and following respiratory infections. The intensity, duration, and type of training have been associated with the occurrence of EIB. In athletes, EIB seems to be only partly reversible, and exercise seems to be a causative factor of airway inflammation and symptoms.
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http://dx.doi.org/10.1016/j.iac.2018.01.007DOI Listing
May 2018

Conducting an Integrative Health Interview.

J Allergy Clin Immunol Pract 2018 Mar - Apr;6(2):436-439.e3. Epub 2018 Feb 1.

Division of Allergy Clinical Immunology, Department of Medicine, University of Colorado Denver School of Medicine, Aurora, Colo.

Complementary medicine incorporates the use of non-evidence-based complementary modalities into conventional (Western) medicine. Alternative medicines are approaches that are used in place of conventional medicine. Integrative medicine is the synthesis of conventional medical treatments with "evidence-based" complementary medical practices. When complementary approaches are incorporated into mainstream health care, it is called integrative health (IH). Among children and adults, IH is common despite not all therapies being safe and/or effective. Clinicians have suboptimal knowledge of their patients' IH use because, in part, they do not know what questions to ask and/or do not have a standard intake form to collect an IH history, as recently demonstrated by an American Academy of Allergy, Asthma, and Immunology membership survey. To address this unmet need, a group of Complementary and Alternative Practice in Allergy Committee members and interprofessional collaborators reviewed the existing literature to locate IH history forms that could assist in identifying patients' IH use. When none was located, the group created 3 templates for the systematic collection and documentation of IH practices: 2 general screening surveys that could be given to patients to complete before an appointment and a third template that provides the clinician with open-ended questions to help uncover IH practices in culturally diverse patient populations. Specialists, already acknowledged as skillful interviewers, can expand their patient-centered expertise by developing their own IH competencies.
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http://dx.doi.org/10.1016/j.jaip.2017.11.029DOI Listing
November 2019

PD-L1 on host cells is essential for PD-L1 blockade-mediated tumor regression.

J Clin Invest 2018 02 16;128(2):580-588. Epub 2018 Jan 16.

Department of Pathology, University of Texas (UT) Southwestern Medical Center, Dallas, Texas, USA.

Programmed death-ligand 1 (PD-L1) expression on tumor cells is essential for T cell impairment, and PD-L1 blockade therapy has shown unprecedented durable responses in several clinical studies. Although higher expression of PD-L1 on tumor cells is associated with a better immune response after Ab blockade, some PD-L1-negative patients also respond to this therapy. In the current study, we explored whether PD-L1 on tumor or host cells was essential for anti-PD-L1-mediated therapy in 2 different murine tumor models. Using real-time imaging in whole tumor tissues, we found that anti-PD-L1 Ab accumulates in tumor tissues, regardless of the status of PD-L1 expression on tumor cells. We further observed that, while PD-L1 on tumor cells was largely dispensable for the response to checkpoint blockade, PD-L1 in host myeloid cells was essential for this response. Additionally, PD-L1 signaling in defined antigen-presenting cells (APCs) negatively regulated and inhibited T cell activation. PD-L1 blockade inside tumors was not sufficient to mediate regression, as limiting T cell trafficking reduced the efficacy of the blockade. Together, these findings demonstrate that PD-L1 expressed in APCs, rather than on tumor cells, plays an essential role in checkpoint blockade therapy, providing an insight into the mechanisms of this therapy.
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http://dx.doi.org/10.1172/JCI96061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785245PMC
February 2018

Spectrum and prevalence of reactions to marijuana in a Colorado allergy practice.

Ann Allergy Asthma Immunol 2017 12;119(6):570-571

Greenwood Village, Colorado.

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http://dx.doi.org/10.1016/j.anai.2017.10.028DOI Listing
December 2017

Exercise-induced bronchoconstriction update-2016.

J Allergy Clin Immunol 2016 11 21;138(5):1292-1295.e36. Epub 2016 Sep 21.

The first practice parameter on exercise-induced bronchoconstriction (EIB) was published in 2010. This updated practice parameter was prepared 5 years later. In the ensuing years, there has been increased understanding of the pathogenesis of EIB and improved diagnosis of this disorder by using objective testing. At the time of this publication, observations included the following: dry powder mannitol for inhalation as a bronchial provocation test is FDA approved however not currently available in the United States; if baseline pulmonary function test results are normal to near normal (before and after bronchodilator) in a person with suspected EIB, then further testing should be performed by using standardized exercise challenge or eucapnic voluntary hyperpnea (EVH); and the efficacy of nonpharmaceutical interventions (omega-3 fatty acids) has been challenged. The workgroup preparing this practice parameter updated contemporary practice guidelines based on a current systematic literature review. The group obtained supplementary literature and consensus expert opinions when the published literature was insufficient. A search of the medical literature on PubMed was conducted, and search terms included pathogenesis, diagnosis, differential diagnosis, and therapy (both pharmaceutical and nonpharmaceutical) of exercise-induced bronchoconstriction or exercise-induced asthma (which is no longer a preferred term); asthma; and exercise and asthma. References assessed as relevant to the topic were evaluated to search for additional relevant references. Published clinical studies were appraised by category of evidence and used to document the strength of the recommendation. The parameter was then evaluated by Joint Task Force reviewers and then by reviewers assigned by the parent organizations, as well as the general membership. Based on this process, the parameter can be characterized as an evidence- and consensus-based document.
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http://dx.doi.org/10.1016/j.jaci.2016.05.029DOI Listing
November 2016

Crystal Structure of Carboxyltransferase from Staphylococcus aureus Bound to the Antibacterial Agent Moiramide B.

Biochemistry 2016 08 10;55(33):4666-74. Epub 2016 Aug 10.

Department of Radiology, University of Texas Southwestern Medical Center , Dallas, Texas 75390, United States.

The dramatic increase in the prevalence of antibiotic-resistant bacteria has necessitated a search for new antibacterial agents against novel targets. Moiramide B is a natural product, broad-spectrum antibiotic that inhibits the carboxyltransferase component of acetyl-CoA carboxylase, which catalyzes the first committed step in fatty acid synthesis. Herein, we report the 2.6 Å resolution crystal structure of moiramide B bound to carboxyltransferase. An unanticipated but significant finding was that moiramide B bound as the enol/enolate. Crystallographic studies demonstrate that the (4S)-methyl succinimide moiety interacts with the oxyanion holes of the enzyme, supporting the notion that an anionic enolate is the active form of the antibacterial agent. Structure-activity studies demonstrate that the unsaturated fatty acid tail of moiramide B is needed only for entry into the bacterial cell. These results will allow the design of new antibacterial agents against the bacterial form of carboxyltransferase.
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http://dx.doi.org/10.1021/acs.biochem.6b00641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226424PMC
August 2016

A Colorado allergist's experience with marijuana legalization.

Ann Allergy Asthma Immunol 2016 Feb;116(2):175-7

Allergy Asthma Colorado PC, Englewood, Colorado. Electronic address:

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http://dx.doi.org/10.1016/j.anai.2015.11.014DOI Listing
February 2016

Design, radiosynthesis, and evaluation of radiotracers for positron emission tomography imaging of stearoyl-CoA desaturase-1.

Bioorg Med Chem Lett 2016 Feb 19;26(3):924-927. Epub 2015 Dec 19.

Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Design, radiosynthesis, and biological evaluation of two radiotracers (N-(3-[(18)F]fluoropropyl)-6-(4-(trifluoromethyl)benzoyl)-piperazin-1-yl)pyridazine-3-carboxamide ((18)F-FPPPT) and (N-(4-[(18)F]fluoroaniline)-6-(4-(trifluoromethyl)benzoyl)-piperazin-1-yl)pyridazine-3-carboxamide ((18)F-FAPPT)) are described for noninvasive assessment of stearoyl-CoA desaturase-1 (SCD-1). The overexpression of SCD-1 in multiple solid tumors associates with poor survival in cancer patients. The two radiotracers, (18)F-FPPPT and (18)F-FAPPT, were each prepared in three steps in radiochemical yields of 21% and 3%, respectively. The practicality of imaging SCD-1 with (18)F-FPPPT was tested in two mouse models bearing xenograft tumors with different levels of SCD-1 expression, which afforded a 1.8-fold uptake difference correspondingly. Our work indicates that it is possible to develop SCD-1 specific imaging probes from previously reported SCD-1 inhibitors.
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http://dx.doi.org/10.1016/j.bmcl.2015.12.062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728040PMC
February 2016

Comparative Evaluation of Two Venous Sampling Techniques for the Assessment of Pancreatic Insulin and Zinc Release upon Glucose Challenge.

J Diabetes Res 2015 27;2015:789359. Epub 2015 Jul 27.

Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Advances in noninvasive imaging modalities have provided opportunities to study β cell function through imaging zinc release from insulin secreting β cells. Understanding the temporal secretory pattern of insulin and zinc corelease after a glucose challenge is essential for proper timing of administration of zinc sensing probes. Portal venous sampling is an essential part of pharmacological and nutritional studies in animal models. The purpose of this study was to compare two different percutaneous image-guided techniques: transhepatic ultrasound guided portal vein access and transsplenic fluoroscopy guided splenic vein access for ease of access, safety, and evaluation of temporal kinetics of insulin and zinc release into the venous effluent from the pancreas. Both techniques were safe, reproducible, and easy to perform. The mean time required to obtain desired catheter position for venous sampling was 15 minutes shorter using the transsplenic technique. A clear biphasic insulin release profile was observed in both techniques. Statistically higher insulin concentration but similar zinc release after a glucose challenge was observed from splenic vein samples, as compared to the ones from the portal vein. To our knowledge, this is the first report of percutaneous methods to assess zinc release kinetics from the porcine pancreas.
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http://dx.doi.org/10.1155/2015/789359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530279PMC
August 2016

How do U.S. and Canadian medical schools teach about the role of physicians in the Holocaust?

Acad Med 2015 Jun;90(6):699-700

Director, Center for Bioethics and Humanities, University of Colorado, Aurora, Colorado; Clinical professor of medicine, University of Colorado, Aurora, Colorado. Clinical professor of psychiatry, University of Colorado, Aurora, Colorado.

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http://dx.doi.org/10.1097/ACM.0000000000000724DOI Listing
June 2015

Oxidoreductase-Facilitated Visualization and Detection of Human Cancer Cells.

Anal Chem 2015 Jun 5;87(12):6411-8. Epub 2015 Jun 5.

Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803-1804, United States.

Unlabelled: Achieving highly selective and sensitive detection/visualization of intracellular biological events through the use of cell-penetrable, bioanalyte-activatable, turn-on probes is dependent on the presence of specific event-linked cellular biomarkers, if and only if there exist activatable probes that appropriately respond to the biomarker analyte. Here is described the evaluation of, and use in cellular imaging studies, a previously undisclosed naphthalimide probe QMeNN, whose fluorescence is deactivated by photoinduced electron transfer (PeT) quenching that results from the presence of a covalently linked biomarker-specific quinone trigger group. Highly selective and rapid activation of the quinone group by the human cancer tumor-linked

Nad(p)h: quinone oxido-reductase isozyme 1 (hNQO1) results in fast trigger group removal to yield a highly fluorescent green-energy-range reporter that possesses a high molar absorptivity; there is a 136-fold increase in brightness for the enzymatically produced reporter versus probe precursor, a value 4 times greater than previously reported for the hNQO1 analyte. The novel probe is taken up and activated rapidly within only hNQO1-positive human cancer cells; addition of an hNQO1 inhibitor prevents the selective activation of the probe. Comparison of cytosolic fluorescence intensity in positive cells versus background in negative cells yields a quantitative metric (positive-to-negative ratio, PNR) for judging hNQO1 activity. We show it is possible to determine hNQO1 presence in previously studied colorectal cancer cells and the unexplored ovarian cancer cell line NIH:OVCAR-3, with respective PNR values of 926 and 34 being obtained. Even with 10 min probe incubation, ready discrimination of positive cells from negative cells is achieved. Cell viability is unaffected by probe presence, thereby highlighting the practicality of probe use in live-cell imaging applications.
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http://dx.doi.org/10.1021/acs.analchem.5b01615DOI Listing
June 2015

Improving screening and diagnosis of exercise-induced bronchoconstriction: a call to action.

J Allergy Clin Immunol Pract 2014 May-Jun;2(3):275-80.e7. Epub 2014 Feb 4.

BioMedEcon, LLC, Moss Beach, Calif.

This article summarizes the findings of an expert panel of nationally recognized allergists and pulmonologists who met to discuss how to improve detection and diagnosis of exercise-induced bronchoconstriction (EIB), a transient airway narrowing that occurs during and most often after exercise in people with and without underlying asthma. EIB is both commonly underdiagnosed and overdiagnosed. EIB underdiagnosis may result in habitual avoidance of sports and physical activity, chronic deconditioning, weight gain, poor asthma control, low self-esteem, and reduced quality of life. Routine use of a reliable and valid self-administered EIB screening questionnaire by professionals best positioned to screen large numbers of people could substantially improve the detection of EIB. The authors conducted a systematic review of the literature that evaluated the accuracy of EIB screening questionnaires that might be adopted for widespread EIB screening in the general population. Results of this review indicated that no existing EIB screening questionnaire had adequate sensitivity and specificity for this purpose. The authors present a call to action to develop a new EIB screening questionnaire, and discuss the rigorous qualitative and quantitative research necessary to develop and validate such an instrument, including key methodological pitfalls that must be avoided.
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http://dx.doi.org/10.1016/j.jaip.2013.11.001DOI Listing
January 2015

Integrative approach to allergy and asthma using complementary and alternative medicine.

Ann Allergy Asthma Immunol 2014 Apr;112(4):280-5

Allergy Asthma Colorado, PC, Englewood, Colorado.

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http://dx.doi.org/10.1016/j.anai.2014.01.020DOI Listing
April 2014

A World Allergy Organization international survey on physical activity as a treatment option for asthma and allergies.

World Allergy Organ J 2014 27;7(1):34. Epub 2014 Nov 27.

Institute of Translational Pharmacology, National research Council, Rome, Italy ; Department of Internal Medicine, Second University of Naples, Naples, Italy.

Background: Physical exercise has been shown to improve asthma symptoms, QoL, exercise capacity, bronchial hyperresponsiveness and lung function and is recommended as a supplementary treatment to pharmacotherapy for asthma. Clinicians are well placed to promote physically active lifestyles, but their role and practice towards promoting physically active lifestyles among patients has not been fully investigated. This study was designed to investigate the knowledge, propensity, attitude and practices of clinicians towards the promotion of physical activity among patients with asthma and allergies.

Methods: Two hundred and eighty clinicians (mean age; 46 ± 13 years; with a clinical experience of practice for 15 ± 7 years) participated in a global survey. The survey comprised a 29-item questionnaire, which gathered information on attitudes of the clinicians towards promoting physical activity, their knowledge and their beliefs regarding evidence for benefits of physical activity as a supplementary treatment in patients with asthma and allergies.

Results: Almost all respondents were aware of the strong evidence in favor of physical activity for the psychological well-being, weight control, decreased risk of diabetes, ischemic heart disease and arterial hypertension. Evidence for reduction in the risk for developing asthma and for better asthma control were reported by 60.0% and 85.4% of participants, respectively. The majority (85.0%) of clinicians strongly agreed that promoting physical activity is important to health care, although 95.5% considered they required more educational training. Although two thirds of them usually recommended exercise to their asthmatic/allergic patients, only 24.0% reported having previous training on the subject of such counseling. Almost all believed that effective counseling about a healthy diet, exercise and weight management would be easier if the clinician himself/herself was physically fit and healthy.

Conclusions: The results of this global survey indicate that clinicians working in the field of allergy and respiratory diseases are well aware of the evidence supporting the benefits of physical activity for asthma and allergic diseases although they need more training in such counseling. Therefore, concerted efforts are needed towards educating clinicians towards promoting physical activity and weight management, as a supplementary treatment for asthma and allergies.
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http://dx.doi.org/10.1186/1939-4551-7-34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363188PMC
April 2015

Profluorogenic reductase substrate for rapid, selective, and sensitive visualization and detection of human cancer cells that overexpress NQO1.

J Am Chem Soc 2013 Jan 27;135(1):309-14. Epub 2012 Dec 27.

Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803-1804, United States.

Achieving the vision of identifying and quantifying cancer-related events and targets for future personalized oncology is predicated on the existence of synthetically accessible and economically viable probe molecules fully able to report the presence of these events and targets in a rapid and highly selective and sensitive fashion. Delineated here are the design and evaluation of a newly synthesized turn-on probe whose intense fluorescent reporter signature is revealed only through probe activation by a specific intracellular enzyme present in tumor cells of multiple origins. Quenching of molecular probe fluorescence is achieved through unique photoinduced electron transfer between the naphthalimide dye reporter and a covalently attached, quinone-based enzyme substrate. Fluorescence of the reporter dye is turned on by rapid removal of the quinone quencher, an event that immediately occurs only after highly selective, two-electron reduction of the sterically and conformationally restricted quinone substrate by the cancer-associated human NAD(P)H:quinone oxidoreductase isozyme 1 (hNQO1). Successes of the approach include rapid differentiation of NQO1-expressing and -nonexpressing cancer cell lines via the unaided eye, flow cytometry, fluorescence imaging, and two-photon microscopy. The potential for use of the turn-on probe in longer-term cellular studies is indicated by its lack of influence on cell viability and its in vitro stability.
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http://dx.doi.org/10.1021/ja309346fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703112PMC
January 2013

Shedding light by cancer redox-human NAD(P)H:quinone oxidoreductase 1 activation of a cloaked fluorescent dye.

Chem Commun (Camb) 2011 Oct 19;47(40):11264-6. Epub 2011 Sep 19.

Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803-1804, USA.

A new quinone propionic acid-cloaked rhodamine fluorophore has its fluorescence revealed (de-cloaked) upon activation by human NAD(P)H:quinone oxidoreductase 1 (hNQO1), an upregulated enzyme in cancer cells and tumors.
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http://dx.doi.org/10.1039/c1cc14578aDOI Listing
October 2011

Clinical observations and seven-and-one-half-year follow-up of patients using an integrative holistic approach for treating chronic sinusitis.

Altern Ther Health Med 2009 Jan-Feb;15(1):36-43

Department of Otolaryngology, University of Colorado Health Sciences Center, Denver, Colorado, USA.

Context: Despite the widespread popularity of alternative medical approaches to respiratory and allergic disorders, there is a lack of scientific substantiation of their benefits.

Objective: Assessment of the therapeutic benefit of an integrative holistic approach to the treatment of chronic sinusitis.

Design: Patients began a 5-month program consisting of 5 evening sessions of 2 hours each in October of 1999.

Setting: The program was held in the offices of one of the authors (WSS).

Patients: Ten patients of an allergist-immunologist specialist (WSS), symptomatic despite aggressive conventional treatment for their chronic sinusitis, were recruited to participate in an integrative holistic medical education and treatment program consisting of 5 sessions and evaluated at a 1-year follow-up. Sessions consisted of education in lifestyle and indoor-air modification, nasal hygiene, and treatment with fluconazole. Eight of 9 subjects were located and provided feedback 7 years and 6 months later, in June 2007.

Main Outcome Measures: Health-related quality of life (QOL) was assessed using the short-form QOL survey (SF-12) and rhinitis QOL by the Rhinitis Quality of Life Questionnaire (RQLQ).

Results: No significant differences emerged in the SF-12 or mini-RQLQ scores comparing visit 2 with visit 1. Statistically significant improvement for physical and mental subscales of the SF-12 emerged comparing the results of visit 4 with visit 2 after the addition offluconazole treatment to the regimen, persisting through an additional year of follow-up. Feedback at 7.5 years confirmed marked long-term improvement in chronic sinusitis symptoms compared to their pre-study condition.
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March 2009