Publications by authors named "B Rhiannon Noble"

370 Publications

Long-term functional alterations following prenatal GLP-1R activation.

Neurotoxicol Teratol 2021 Apr 14:106984. Epub 2021 Apr 14.

Department of Biomedical Sciences and Center for Brain Repair, Florida State University College of Medicine, Tallahassee, FL 32306, United States of America. Electronic address:

Evidence supporting the use of glucagon-like peptide-1 (GLP-1) analogues to pharmacologically treat disorders beyond type 2 diabetes and obesity is increasing. However, little is known about how activation of the GLP-1 receptor (GLP-1R) during pregnancy affects maternal and offspring outcomes. We treated female C57Bl/6 J mice prior to conception and throughout gestation with a long-lasting GLP-1R agonist, Exendin-4. While GLP-1R activation has significant effects on food and drug reward, depression, locomotor activity, and cognition in adults, we found few changes in these domains in exendin-4-exposed offspring. Repeated injections of Exendin-4 had minimal effects on the dams and may have enhanced maternal care. Offspring exposed to the drug weighed significantly more than their control counterparts during the preweaning period and demonstrated alterations in anxiety-like outcomes, which indicate a developmental role for GLP-1R modulation in the stress response that may be sex-specific.
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http://dx.doi.org/10.1016/j.ntt.2021.106984DOI Listing
April 2021

Interfacility transfer communication of multidrug-resistant organism colonization or infection status: Practices and barriers in the acute-care setting.

Infect Control Hosp Epidemiol 2021 Apr 16:1-6. Epub 2021 Apr 16.

Department of Pharmacy Practice, Oregon State University College of Pharmacy, Portland, Oregon.

Objective: To describe interfacility transfer communication (IFTC) methods for notification of multidrug-resistant organism (MDRO) status in a diverse sample of acute-care hospitals.

Design: Cross-sectional survey.

Participants: Hospitals within the Society for Healthcare Epidemiology of America (SHEA) Research Network (SRN).

Methods: SRN members completed an electronic survey on protocols and methods for IFTC. We assessed differences in IFTC frequency, barriers, and perceived benefit by presence of an IFTC protocol.

Results: Among 136 hospital representatives who were sent the survey, 54 (40%) responded, of whom 72% reported having an IFTC protocol in place. The presence of a protocol did not differ significantly by hospital size, academic affiliation, or international status. Of those with IFTC protocols, 44% reported consistent notification of MDRO status (>75% of the time) to receiving facilities, as opposed to 13% from those with no IFTC protocol (P = .04). Respondents from hospitals with IFTC protocols reported significantly fewer barriers to communication compared to those without (2.8 vs 4.3; P = .03). Overall, however, most respondents (56%) reported a lack of standardization in communication. Presence of an IFTC protocol did not affect whether respondents perceived IFTC protocols as having a significant impact on infection prevention or antimicrobial stewardship.

Conclusions: Most respondents reported having an IFTC protocol, which was associated with reduced communication barriers at transfer. Standardization of protocols and clarity about expectations for sending and receipt of information related to MDRO status may facilitate IFTC and promote appropriate and timely infection prevention practices.
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http://dx.doi.org/10.1017/ice.2021.131DOI Listing
April 2021

Decreasing Trends in Opioid Prescribing on Discharge to Hospice Care.

J Pain Symptom Manage 2021 Apr 10. Epub 2021 Apr 10.

Division of General Internal Medicine & Geriatrics, Department of Medicine, Oregon Health & Science University, Portland, OR.

Context: There are concerns that policies aimed to prevent opioid misuse may unintentionally reduce access to opioids for patients at end-of-life.

Objective: We assessed trends in opioid prescribing among patients on discharge from the hospital to hospice care.

Methods: This was a retrospective cohort study among adult (age ≥18 years) patients discharged from a 544-576 bed, academic medical center to hospice care between January 1, 2010 to December 31, 2018. Study data were collected from a repository of patients' electronic health record data. Our primary outcome was the frequency of opioid prescribing on discharge to hospice care. Our primary exposure was the calendar year of discharge. We also investigated non-opioid analgesic prescribing and stratified opioid prescribing trends by patient characteristics (e.g. demographics, cancer diagnosis, and location of hospice care).

Results: Among 2,648 discharges to hospice care, mean (standard deviation) age was 65.8 (16.0) years, 46.3% were female, and 58.7% had a cancer diagnosis. Opioid prescribing on discharge to hospice care decreased significantly from 91.2% (95% confidence interval (CI) = 87.1% to 94.1%) in 2010 to 79.3% (95% CI = 74.3% to 83.5%) in 2018 adjusting for age, sex, cancer diagnosis, and location of hospice care. Prescribing of non-opioid analgesic medications increased over the same time period.

Conclusions: We observed a statistically significant decreasing trend in opioid prescribing on discharge to hospice care. Further research should aim to confirm these findings and to identify opportunities to ensure optimal pain management among patients transitioning to hospice care.
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http://dx.doi.org/10.1016/j.jpainsymman.2021.03.025DOI Listing
April 2021

Relationship of antibody responses to paediatric asthma severity.

BMJ Open Respir Res 2021 Mar;8(1)

Center for Vaccines and Immunology, University of Georgia College of Veterinary Medicine, Athens, Georgia, USA

Background: Although asthma is the most commonly diagnosed respiratory disease, its pathogenesis is complex, involving both genetic and environmental factors. A role for the respiratory microbiome in modifying asthma severity has been recently recognised. Airway colonisation by has previously been associated with multiple chronic lung diseases, including chronic obstructive pulmonary disease (COPD) and severe asthma (SA). Decreased incidence of pneumonia in HIV-infected individuals and reduced severity of COPD is associated with naturally occurring antibody responses to the antigen, Kexin (KEX1).

Methods: 104 paediatric patients were screened for KEX1 IgG reciprocal end point titre (RET), including 51 with SA, 20 with mild/moderate asthma, 20 non-asthma and 13 with cystic fibrosis (CF) in a cross-sectional study.

Results: Patients with SA had significantly reduced KEX1 titres compared with patients with mild/moderate asthma (p=0.018) and CF (p=0.003). A binary KEX1 RET indicator was determined at a threshold of KEX1 RET=1000. Patients with SA had 4.40 (95% CI 1.28 to 13.25, p=0.014) and 17.92 (95% CI 4.15 to 66.62, p<0.001) times the odds of falling below that threshold compared with mild/moderate asthma and patients with CF, respectively. Moreover, KEX1 IgG RET did not correlate with tetanus toxoid IgG (r=0.21, p=0.82) or total IgE (r=0.03, p=0.76), indicating findings are specific to antibody responses to KEX1.

Conclusions: Paediatric patients with SA may be at higher risk for chronic infections and asthma symptom exacerbation due to reduced levels of protective antibodies. Plasma KEX1 IgG titre may be a useful parameter in determining the clinical course of treatment for paediatric patients with asthma.
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http://dx.doi.org/10.1136/bmjresp-2020-000842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993353PMC
March 2021

Predicting wavelength-dependent photochemical reactivity and selectivity.

Nat Commun 2021 03 16;12(1):1691. Epub 2021 Mar 16.

School of Chemistry and Physics, Queensland University of Technology (QUT), Brisbane, QLD, Australia.

Predicting the conversion and selectivity of a photochemical experiment is a conceptually different challenge compared to thermally induced reactivity. Photochemical transformations do not currently have the same level of generalized analytical treatment due to the nature of light interaction with a photoreactive substrate. Herein, we bridge this critical gap by introducing a framework for the quantitative prediction of the time-dependent progress of photoreactions via common LEDs. A wavelength and concentration dependent reaction quantum yield map of a model photoligation, i.e., the reaction of thioether o-methylbenzaldehydes via o-quinodimethanes with N-ethylmaleimide, is initially determined with a tunable laser system. Combined with experimental parameters, the data are employed to predict LED-light induced conversion through a wavelength-resolved numerical simulation. The model is validated with experiments at varied wavelengths. Importantly, a second algorithm allows the assessment of competing photoreactions and enables the facile design of λ-orthogonal ligation systems based on substituted o-methylbenzaldehydes.
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http://dx.doi.org/10.1038/s41467-021-21797-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966369PMC
March 2021

Acute post-injury blockade of α2δ-1 calcium channel subunits prevents pathological autonomic plasticity after spinal cord injury.

Cell Rep 2021 Jan;34(4):108667

Department of Neuroscience, Belford Center for Spinal Cord Injury, The Ohio State University, Columbus, OH 43210, USA. Electronic address:

After spinal cord injury (SCI), normally innocuous visceral or somatic stimuli can trigger uncontrolled reflex activation of sympathetic circuitry, causing pathological dysautonomia. We show that remarkable structural remodeling and plasticity occur within spinal autonomic circuitry, creating abnormal sympathetic reflexes that promote dysautonomia. However, when mice are treated early after SCI with human-equivalent doses of the US Food and Drug Administration (FDA)-approved drug gabapentin (GBP), it is possible to block multi-segmental excitatory synaptogenesis and abolish sprouting of autonomic neurons that innervate immune organs and sensory afferents that trigger pain and autonomic dysreflexia (AD). This "prophylactic GBP" regimen decreases the frequency and severity of AD and protects against SCI-induced immune suppression. These benefits persist even 1 month after stopping treatment. GBP could be repurposed to prevent dysautonomia in at-risk individuals with high-level SCI.
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http://dx.doi.org/10.1016/j.celrep.2020.108667DOI Listing
January 2021

Variation in Hospice Patient and Admission Characteristics by Referral Location.

Med Care 2020 12;58(12):1069-1074

Department of Population and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA.

Background: Little is known regarding differences between patients referred to hospice from different care locations.

Objective: The objective this study was to describe the associations between hospice referral locations and hospice patient and admission characteristics.

Research Design: Cross-sectional analysis of hospice administrative data.

Subjects: Adult (age older than 18 y) decedents of a national, for-profit, hospice chain across 19 US states who died between January 1, 2012, and December 31, 2016.

Measures: Patients' primary hospice diagnosis, hospice length stay, and hospice care site. We also determined the frequency of opioid prescriptions with and without a bowel regimen on hospice admission.

Results: Among 78,647 adult decedents, the mean age was 79.2 (SD=13.5) years, 56.4% were female, and 69.9% were a non-Hispanic White race. Most hospice referrals were from the hospital (51.9%), followed by the community (21.9%), nursing homes (17.4%), and assisted living (8.8%). Cancer (33.6%) was the most prevalent primary hospice diagnosis; however, this varied significantly between referral locations (P<0.001). Similarly, home hospice (32.8%) was the most prevalent site; however, this also varied significantly between referral locations (P<0.001). More hospital-referred patients (55.6%) had a hospice length of stay <7 days compared with patients referred from nursing homes (30.3%), the community (28.9%), or assisted living (18.7%), P<0.001. Hospital-referred patients also had the lowest frequency (58.4%) of coprescribed opioids and bowel regimen on hospice admission compared with other referral locations.

Conclusion: We observed significant differences in hospice patient and admission characteristics by referral location.
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http://dx.doi.org/10.1097/MLR.0000000000001415DOI Listing
December 2020

Opioid prescribing on discharge to skilled nursing facilities.

Pharmacoepidemiol Drug Saf 2020 09 29;29(9):1183-1188. Epub 2020 Jul 29.

Department of Pharmacy Practice, Oregon State University College of Pharmacy, Portland, Oregon, USA.

Purpose: Skilled nursing facility (SNF) residents are at increased risk for opioid-related harms. We quantified the frequency of opioid prescribing among patients discharged from an acute care hospital to SNFs.

Methods: This was a retrospective cohort study among adult (≥18 years) inpatients discharged from a quaternary-care academic referral hospital in Portland, OR to a SNF between January 1, 2017 and December 31, 2018. Our primary outcome was receipt of an opioid prescription on discharge to a SNF. Our exposures included patient demographics (eg, age, sex), comorbid illnesses, surgical diagnosis related group (DRG), receiving opioids on the first day of the index hospital admission, and inpatient hospital length of stay.

Results: Among 4374 patients discharged to a SNF, 3053 patients (70%) were prescribed an opioid on discharge. Among patients prescribed an opioid, 61% were over the age of 65 years, 50% were male, and 58% had a surgical Medicare severity diagnosis related group (MS-DRG). Approximately 70% of patients discharged to a SNF were prescribed an opioid on discharge, of which 68% were for oxycodone, and 52% were for ≥90 morphine milligram equivalents per day. Surgical DRG, diagnoses of cancer or chronic pain, last pain score, and receipt of an opioid on first day of the index hospital admission were independently associated with being prescribed an opioid on discharge to a SNF.

Conclusion: Opioids were frequently prescribed at high doses to patients discharged to a SNF. Efforts to improve opioid prescribing safety during this transition may be warranted.
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http://dx.doi.org/10.1002/pds.5075DOI Listing
September 2020

N-Acetylcysteine Nanocarriers Protect against Oxidative Stress in a Cellular Model of Parkinson's Disease.

Antioxidants (Basel) 2020 Jul 9;9(7). Epub 2020 Jul 9.

School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK.

Oxidative stress is a key mediator in the development and progression of Parkinson's disease (PD). The antioxidant n-acetylcysteine (NAC) has generated interest as a disease-modifying therapy for PD but is limited due to poor bioavailability, a short half-life, and limited access to the brain. The aim of this study was to formulate and utilise mitochondria-targeted nanocarriers for delivery of NAC alone and in combination with the iron chelator deferoxamine (DFO), and assess their ability to protect against oxidative stress in a cellular rotenone PD model. Pluronic F68 (P68) and dequalinium (DQA) nanocarriers were prepared by a modified thin-film hydration method. An MTT assay assessed cell viability and iron status was measured using a ferrozine assay and ferritin immunoassay. For oxidative stress, a modified cellular antioxidant activity assay and the thiobarbituric acid-reactive substances assay and mitochondrial hydroxyl assay were utilised. Overall, this study demonstrates, for the first time, successful formulation of NAC and NAC + DFO into P68 + DQA nanocarriers for neuronal delivery. The results indicate that NAC and NAC + DFO nanocarriers have the potential characteristics to access the brain and that 1000 μM P68 + DQA NAC exhibited the strongest ability to protect against reduced cell viability ( = 0.0001), increased iron ( = 0.0033) and oxidative stress ( ≤ 0.0003). These NAC nanocarriers therefore demonstrate significant potential to be transitioned for further preclinical testing for PD.
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http://dx.doi.org/10.3390/antiox9070600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402157PMC
July 2020

Computational Optimization of Alkoxyamine-based Electrochemical Methylation.

J Phys Chem A 2020 Jul 13;124(29):6104-6110. Epub 2020 Jul 13.

ARC Centre of Excellence for Electromaterials Science, Research School of Chemistry, Australian National University, Canberra Australian Capital Territory 2601, Australia.

Computational chemistry at the G3(MP2)-RAD//M06-2X/6-31+G(d,p)//SMD level of theory was used to study the oxidation of a test set of methyl adducts of nitroxide radicals and methyl adducts of Blatter's radical, a Kuhn verdazyl and two oxo-verdazyls. The barriers and the reaction energies of the S2 reactions of the oxidized species with pyridine were also studied with a view to identify species with both low oxidation potentials and low S2 barriers, so as to broaden the functional group tolerance of in situ electrochemical methylation compared with TEMPO-Me (1-methoxy-2,2,6,6-tetramethylpiperidine). Within the alkoxyamines, the oxidation potentials covered a range of 0.5 V, with trends explicable in terms of electrostatics, ring strain, and charge transfer. The oxidation potentials of oxo-verdazyl adducts, verdazyl adducts, and particularly the methyl adducts of Blatter's radical were considerably low due to the ability of their extensive π-systems to stabilize a positive charge. As expected, the S2 reaction energies of the oxidized substrate became less favorable as the oxidation potential decreases. Unfortunately, this also meant that the barriers increased due to the excellent Evans-Polanyi correlation ( = 0.92). Nonetheless, 7-methoxy-7-azadispiro[5.1.5.3]hexadecane, ,-di--butyl--methylhydroxylamine, and particularly 1-methoxy-2,2,5,5-tetramethylpyrrolidine were identified as suitable candidates for broadening the scope of in situ electrochemical methylation while maintaining comparable kinetics to known reagents.
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http://dx.doi.org/10.1021/acs.jpca.0c05169DOI Listing
July 2020

Electrostatic Activation of Tetrazoles.

J Org Chem 2020 08 15;85(15):10091-10097. Epub 2020 Jul 15.

ARC Centre of Excellence for Electromaterials Science, Research School of Chemistry, Australian National University, Canberra, Australian Capital Territory 2601, Australia.

Photoactivation of tetrazoles to form nitrile imines primed for 1,3-dipolar cycloaddition reactions is of widespread utility in chemistry. In contrast, the corresponding thermal reactions usually possess prohibitively high barriers and have garnered significantly less attention. Here, computational chemistry at the M06-2X/6-31+G(d,p) level of theory with SMD solvent corrections is used to show that these thermal activation barriers can be significantly reduced through the use of nonconjugated charged functional groups (CFGs). For 2,5-dimethyl-tetrazole, a positive CFG on the -methyl (2-position) lowers the fragmentation barrier by around 80 kJ mol in the gas phase, while a negative charge has a smaller opposite effect. These CFG effects remain significant even in polar solvents, with barrier lowering on the order of 30 kJ mol in dimethyl sulfoxide and acetonitrile. In practical terms, the positive CFG decreases the fragmentation half-life of 2,5-dimethyl-tetrazole in refluxing o-xylene from 300,000 years to 1 week. While the resulting nitrile imine is stabilized, its subsequent 1,3-cycloaddition with -methylmaleimide remains highly facile. Electrostatic effects on a range of 2-phenyl-5-methyltetrazoles, 2-methyl-5-phenyl-tetrazoles, and 2,5-diphenyl-tetrazoles follow similar trends and are explicable largely in terms of the stabilization of the developing dipole in the transition state.
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http://dx.doi.org/10.1021/acs.joc.0c01354DOI Listing
August 2020

Acute hepatopancreatic necrosis disease (VP), a chronic disease in shrimp (Penaeus vannamei) population raised in latin America.

J Invertebr Pathol 2020 07 11;174:107424. Epub 2020 Jun 11.

School of Animal and Comparative Biomedical Sciences, University of Arizona, 1041 E. Lowell Street, Tucson, AZ 85721, USA.

In Latin American shrimp farming, acute hepatopancreatic necrosis disease (AHPND) does not cause the acute mortalities observed in SE Asia. Herein we report for the first time a new phase of infection of AHPND, a chronic phase based on two experimental AHPND-challenge trials using shrimp lines from Latin America. Three shrimp lines of Penaeus vannamei were challenged with a highly pathogenic strain of Vibrio parahaemolyticus causing AHPND (VP). PCR and histopathology assays were used for confirmation of AHPND in the trials. The first study was to compare survival between the lines. A follow-up trial was conducted to document hepatopancreas heterotrophic bacterial count and to measure the expression of VP binary toxin genes (pirAB genes) at 24 h.p.i. One of the Latin American shrimp lines, APE1, had significantly higher survival than recorded for the other two lines (APE2 & APE3) and the specific-pathogen-free positive control line. Histopathology showed typical AHPND acute and terminal phase lesions in VP challenged groups, although destructive cellular changes were more pronounced in the SPF line. Histopathology of animals surviving AHPND revealed a unique chronic phase of infection that resembles septic hepatopancreatic necrosis (SHPN), recognized as diagnostic of digestive tract vibriosis. Data to support our finding, including a quantitative RT-PCR assay, confirmed the expression of pirAB genes and the differential hepatopancreas heterotrophic plate count (HPC) among the different lines challenged. The results explain in part why the shrimp industry in some Latin American countries continues to grow despite the presence of AHPND. In addition, the biology and pathology of AHPND resistant/tolerant shrimp appear to be quite unique in this Latin American shrimp population.
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http://dx.doi.org/10.1016/j.jip.2020.107424DOI Listing
July 2020

Cytomegalovirus serologic matching in deceased donor kidney allocation optimizes high- and low-risk (D+R- and D-R-) profiles and does not adversely affect transplant rates.

Am J Transplant 2020 12 23;20(12):3502-3508. Epub 2020 Jun 23.

Division of Nephrology, Oregon Health and Science University, Portland, Oregon, USA.

Cytomegalovirus (CMV) is a major cause of infection-related morbidity and mortality in kidney transplantation. The most significant risk for developing CMV infection after transplant depends upon donor (D) and recipient (R) CMV serostatus. In 2012, our Organ Procurement Organization (OPO) began a novel pretransplant CMV prevention strategy via matching deceased kidney donors and recipients by CMV serostatus. Prior to the matching protocol, our distribution of seropositive and seronegative donors and recipients was similar to the United States at large. After the matching protocol, high-risk D+R- were reduced from 18.5% to 2.9%, whereas low-risk D-R- were increased from 13.5% to 24%. There was no adverse effect on transplant rates and no differential effect on waiting times for R+ vs R- after the protocol was implemented. This protocol could be implemented on a regional or national level to optimize low and high-risk CMV seroprofiles and potentially improve CMV-related outcomes in kidney transplantation.
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http://dx.doi.org/10.1111/ajt.15976DOI Listing
December 2020

A Multicomponent Nonpharmacological Intervention to Prevent Delirium for Hospitalized People with Advanced Cancer: A Phase II Cluster Randomized Waitlist Controlled Trial (The PRESERVE Pilot Study).

J Palliat Med 2020 10 24;23(10):1314-1322. Epub 2020 Apr 24.

IMPACCT, Faculty of Health, University of Technology Sydney, Ultimo, New South Wales, Australia.

Delirium is a common debilitating complication of advanced cancer. To determine if a multicomponent nonpharmacological delirium prevention intervention was feasible for adult patients with advanced cancer, before a phase III (efficacy) trial. Phase II (feasibility) cluster randomized controlled trial. All sites implemented delirium screening and diagnostic assessment. Strategies within sleep, vision and hearing, hydration, orientation, mobility, and family domains were delivered to enrolled patients at intervention site admission days 1-7. Control sites then implemented the intervention ("waitlist sites"). Four Australian palliative care units. The primary outcome was adherence, with an endpoint of at least 60% patients achieving full adherence. Secondary outcomes were interdisciplinary care delivery, delirium measures, and adverse events, analyzed descriptively and inferentially. Sixty-five enrolled patients (25 control, 20 intervention, and 20 waitlist) had 98% delirium screens and 75% diagnostic assessments completed. Nurses (67%), physicians (16%), allied health (8.4%), family (7%), patients (1%), and volunteers (0.5%) delivered the intervention. There was full adherence for 5% patients at intervention sites, partial for 25%. Both full and partial adherence were higher at waitlist sites: 25% and 45%, respectively. One-third of control site patients (32%) became delirious within seven days of admission compared to one-fifth (20%) at both intervention and waitlist sites ( = 0.5). Mean (standard deviation) Delirium Rating Scale-Revised-1998 scores were 16.8 + 12.0 control sites versus 18.4 + 8.2 ( = 0.6) intervention and 18.7 + 7.8 ( = 0.5) waitlist sites. The intervention caused no adverse events. The intervention requires modification for optimal adherence in a phase III trial.
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http://dx.doi.org/10.1089/jpm.2019.0632DOI Listing
October 2020

A novel mouse model of glucagon-like peptide-1 receptor expression: A look at the brain.

J Comp Neurol 2020 10 29;528(14):2445-2470. Epub 2020 Mar 29.

Department of Biomedical Sciences and Center for Brain Repair, Florida State University College of Medicine, Tallahassee, Florida, USA.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone with a number of functions to maintain energy homeostasis and contribute to motivated behavior, both peripherally and within the central nervous system (CNS). These functions, which include insulin secretion, gastric emptying, satiety, and the hedonic aspects of food and drug intake, are primarily mediated through stimulation of the GLP-1 receptor. While this receptor plays an important role in a variety of physiological outcomes, data regarding its CNS expression has been primarily limited to regional receptor binding and single-label transcript expression studies. We thus developed a bacterial artificial chromosome transgenic mouse, in which expression of a red fluorescent protein (mApple) is driven by the GLP-1R promoter. Using this reporter mouse, we characterized the regional and cellular expression patterns of GLP-1R expressing cells in the CNS, using double-label immunohistochemistry and in situ hybridization. GLP-1R-expressing cells were enriched in several key brain regions and circuits, including the lateral septum, hypothalamus, amygdala, bed nucleus of the stria terminalis, hippocampus, ventral midbrain, periaqueductal gray, and cerebral cortex. In most regions, GLP-1R primarily colocalized with GABAergic neurons, except within some regions such as the hippocampus, where it was co-expressed in glutamatergic neurons. GLP-1R-mApple cells were highly co-expressed with 5-HT3 receptor-containing neurons within the cortex and striatum, as well as with dopamine receptor- and calbindin-expressing cells within the lateral septum, the brain region in which GLP-1R is most highly expressed. In this manuscript, we provide detailed images of GLP-1R-mApple expression and distribution within the brain and characterization of these neurons.
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http://dx.doi.org/10.1002/cne.24905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392814PMC
October 2020

Assessment of transmission risk in WSSV-infected shrimp Litopenaeus vannamei upon cooking.

J Fish Dis 2020 Apr 11;43(4):403-411. Epub 2020 Feb 11.

Aquaculture Pathology Laboratory, School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ, USA.

White spot syndrome virus has been a threat to the global shrimp industry since it was discovered in Taiwan in 1992. Thus, shrimp-producing countries have launched regulations to prevent import of WSSV-infected commodity shrimp from endemic areas. Recently, cooked shrimp that is infected with WSSV tested positive by PCR. However, there is no study to determine the infectivity of WSSV in cooked shrimp that tested positive by PCR. In the present study, WSSV-infected shrimp were cooked at boiling temperature for different times including 0, 1, 3, 5, 10 and 30 min. Upon exposure to boiling temperature, WSSV-infected shrimp were fed to SPF shrimp (Litopenaeus vannamei). The result showed experimentally challenged shrimp from 0-min treatment (positive control) indeed got infected with WSSV. However, experimentally challenged shrimp that were fed tissues boiled at 1, 3, 5, 10 and 30 min were not infected with WSSV. Mortality data showed that only the positive control (0-min) treatment displayed high mortality, whereas no mortality was observed in any other treatment category. These findings suggest that cooking shrimp at boiling temperature for at least 1 min might prevent any potential spread of WSSV from endemic countries to other geographical areas where WSSV has not yet been reported.
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http://dx.doi.org/10.1111/jfd.13128DOI Listing
April 2020

Health Care Worker Perceptions of Gaps and Opportunities to Improve Hospital-to-Hospice Transitions.

J Palliat Med 2020 07 31;23(7):900-906. Epub 2019 Dec 31.

Department of Pharmacy Practice, Oregon State University College of Pharmacy, Portland, Oregon, USA.

Care transitions from the hospital to hospice are a difficult time, and gaps during this transitions could cause poor care experiences and outcomes. However, little is known about what gaps exist in the hospital-to-hospice transition. To understand the process of hospital-to-hospice transition and identify common gaps in the transition that result in unsafe or poor patient and family caregiver experiences. We conducted a qualitative descriptive study using semistructured interviews with health care workers who are directly involved in hospital-to-hospice transitions. Participants were asked to describe the common practice of discharging patients to hospice or admitting patients from a hospital, and share their observations about hospital-to-hospice transition gaps. Fifteen health care workers from three hospitals and three hospice programs in Portland, Oregon. All interviews were audio recorded and analyzed using qualitative descriptive methods to describe current practices and identify gaps in hospital-to-hospice transitions. Three areas of gaps in hospital-to-hospice transitions were identified: (1) low literacy about hospice care; (2) changes in medications; and (3) hand-off information related to daily care. Specific concerns included hospital providers giving inaccurate descriptions of hospice; discharge orders not including comfort medications for the transition and inadequate prescriptions to manage medications at home; and lack of information about daily care hindering smooth transition and continuity of care. Our findings identify gaps and suggest opportunities to improve hospital-to-hospice transitions that will serve as the basis for future interventions to design safe and high-quality hospital-to-hospice care transitions.
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http://dx.doi.org/10.1089/jpm.2019.0513DOI Listing
July 2020

Mechanistic Insights into -Acyloxyamine-Initiated Controlled Degradation of Polypropylene: The Unexpected Role of Keto-Enol Tautomerization in Carboxylate Radical Chemistry.

J Org Chem 2020 Feb 7;85(4):2338-2346. Epub 2020 Jan 7.

ARC Centre of Excellence for Electromaterials Science, Research School of Chemistry , Australian National University , Canberra , Australian Capital Territory 2601 , Australia.

Controlled degradation of polypropylene (PP) is used industrially to improve the properties of crude PP. While this degradation is traditionally initiated by organic peroxides, -acyloxyamines are now preferred due to their greater stability. However, their mechanism of action remains unclear. Using high-level ab initio calculations, we show that N-O homolysis is the most likely fragmentation pathway available to -acyloxyamines, in contrast to the more usual C-O homolysis observed for the closely related -alkoxyamines. This would, in theory, generate aminyl and carboxylate radicals, with the latter undergoing decarboxylation to generate methyl radicals. However, the enol forms of -acyloxyamines are significantly less thermally stable, having bond dissociation free energies that are over 50 kJ/mol below those of their keto equivalents. Under conditions where keto-enol tautomerism is feasible, enol N-O homolysis, which forms the more stable acetic acid radical, would be the dominant degradation pathway. This reveals the crucial and underappreciated role that polar impurities play in the initiation process of enolizable initiators and may explain contradictory observations in the experimental literature. The product aminyl radicals are susceptible to β-fragmentation, releasing alkyl radicals and affording imines, which in turn are susceptible to allylic H-abstraction and further β-fragmentation leading to dialkylpyridines as the ultimate degradation products.
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http://dx.doi.org/10.1021/acs.joc.9b03052DOI Listing
February 2020

Oriented Internal Electrostatic Fields Cooperatively Promote Ground- and Excited-State Reactivity: A Case Study in Photochemical CO Capture.

J Am Chem Soc 2020 Jan 20;142(1):606-613. Epub 2019 Dec 20.

ARC Centre of Excellence for Electromaterials Science, Research School of Chemistry , Australian National University , Canberra , Australian Capital Territory 2601 , Australia.

Oriented electrostatic fields can exert catalytic effects upon both the kinetics and the thermodynamics of chemical reactions; however, the vast majority of studies thus far have focused upon ground-state chemistry and rarely consider any more than a single class of reaction. In the present study, we first use density functional theory (DFT) calculations to clarify the mechanism of CO storage via photochemical carboxylation of -alkylphenyl ketones, originally proposed by Murakami et al. (, , 14063); we then demonstrate that oriented internal electrostatic fields arising from remote charged functional groups (CFGs) can selectively and cooperatively promote both ground- and excited-state chemical reactivity at all points along the revised mechanism, in a manner otherwise difficult to access via classical substituent effects. What is particularly striking is that electrostatic field effects upon key photochemical transitions are predictably enhanced in increasingly polar solvents, thus overcoming a central limitation of the electrostatic catalysis paradigm. We explain these observations, which should be readily extendable to the ground state.
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http://dx.doi.org/10.1021/jacs.9b12186DOI Listing
January 2020

Rational Design of Highly Activating Ligands for Cu-Based Atom Transfer Radical Polymerization.

J Org Chem 2019 Dec 18;84(23):15624-15632. Epub 2019 Nov 18.

ARC Centre of Excellence for Electromaterials Science, Research School of Chemistry , Australian National University , Canberra , Australian Capital Territory 2601 , Australia.

Atom transfer radical polymerization (ATRP) is the most commonly utilized technique in controlled radical polymerization. However, the identification of more active catalysts could further increase its scope, both for polymerization and small-molecule synthesis more generally. To this end, a series of novel ligands were designed on the basis of two strategies: replacing nitrogen-based ligands with their phosphorus equivalents and rigidifying the ligand cap of nitrogen-based ligands so as to enforce short Cu-cap distances. Each ligand was assessed using accurate computational chemistry, which was used to compute the thermodynamics and, in selected cases, kinetics of an ATRP reaction with a model methyl methacrylate propagating radical. In principle, the use of phosphorus ligand caps was found to be a powerful strategy for increasing catalyst activity. Unfortunately, in practice, speciation issues sacrificed much of their advantage. In contrast, cap rigidification increases the activity of nitrogen-based ligands, well beyond existing ATRP ligands such as TPMA. The effectiveness of these ligands was further demonstrated for hard-to-activate initiating systems based on ethylene, vinyl chloride, and vinyl acetate polymerization. Several of these improved ligands are synthetically accessible, with rigid piperidine or quinuclidine analogues of TPMA possessing improved thermodynamic and kinetic activity by 2 to 3 orders of magnitude.
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http://dx.doi.org/10.1021/acs.joc.9b02915DOI Listing
December 2019

Incorporating social dimensions in hydrological and water quality modeling to evaluate the effectiveness of agricultural beneficial management practices in a Prairie River Basin.

Environ Sci Pollut Res Int 2020 May 12;27(13):14271-14287. Epub 2019 Oct 12.

School of Environment and Sustainability, University of Saskatchewan, Room 323, Kirk Hall, 117 Science Place, Saskatoon, SK, S7N 5C8, Canada.

There is growing interest to develop processes for creating user-informed watershed scale models of hydrology and water quality and to assist in decision-making for balanced policies for managing watersheds. Watershed models can be enhanced with the incorporation of social dimensions of watershed management as brought forward by participants such as the perspectives, values, and norms of people that depend on the land, water, and ecosystems for sustenance, economies, and overall wellbeing. In this work, we explore the value of combining both qualitative and quantitative methods and social science data to enhance salience and legitimacy of watershed models so that end-users are more engaged. We discuss pilot testing and engagement workshops for building and testing a systems dynamics model of the Qu'Appelle Valley to gather insights from local farmers and understand their perceptions of Beneficial Management Practices (BMPs). Mixed-method workshops with agricultural producers in the Qu'Appelle Watershed gathered feedback on the developing model and the incorporation of social determinants affecting decision-making. Analysis of focus groups and factor analysis of Q-sorts were used to identify the desired components of the model, and whether it supported farmers' understanding of the potential effects of BMPs on water quality. We explored farmers' engagement with models testing BMPs and the potential of incorporating their decision processes within the model itself. Finally, we discuss the reception of the process and the practicality of the approach in providing legitimate and credible decision support tools for a community of farmers.
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http://dx.doi.org/10.1007/s11356-019-06325-1DOI Listing
May 2020

Compliance with statewide regulations for communication of patients' multidrug-resistant organism and Clostridium difficile status during transitions of care.

Am J Infect Control 2020 04 8;48(4):451-453. Epub 2019 Oct 8.

Department of Pharmacy Practice, Oregon State University/Oregon Health & Science University College of Pharmacy, Portland, OR. Electronic address:

In 2014, Oregon implemented an interfacility transfer communication law requiring notification of multidrug-resistant organism status on patient transfer. Based on 2015 and 2016 statewide facility surveys, compliance was 77% and 87% for hospitals, and 67% and 68% for skilled nursing facilities. Methods for complying with the rule were heterogeneous, and fewer than half of all facilities surveyed reported use of a standardized interfacility transfer communication form to assess a patient's multidrug-resistant organism status on transfer.
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http://dx.doi.org/10.1016/j.ajic.2019.08.025DOI Listing
April 2020

Flood Risk Management in Canada's Prairie Provinces: an Analysis of Decision-Maker Priorities and Policy Preferences.

Environ Manage 2019 Nov 30;64(5):608-625. Epub 2019 Sep 30.

Department of Geography and Planning, University of Saskatchewan, Kirk Hall, 117 Science Place, Saskatoon, SK, S7N 5C8, Canada.

If the aim of flood risk management (FRM) is to increase society's resilience to floods, then a holistic treatment of flood risk is required that addresses flood prevention, defence, mitigation, preparation, and response and recovery. Progressing resilience-based management to flood risk requires both diversity and coordination of policy across multiple jurisdictions. Decision makers and the types of FRM policy decisions they make play a key role in implementing FRM policies and strategies that progress flood resilience. This paper explores how policy preferences held by FRM decision makers relate to the characteristics of resilient FRM policy. The research was conducted in three flood-prone provinces in western Canada using a multi-criteria analytical approach. The results show that while decision maker FRM priorities are similar across the Canadian Prairies, their preferred FRM policies differ. Further, preferred FRM policies were largely resistance-based and influenced at least as much by flood experiences and perceptions of flood risk as by more obvious administrative pressures such as cost, public acceptability, and environmental protection. Several observations emerge from these results for advancing a coordinated, diversified approach to FRM which is required for resilience, both for western Canada and for FRM more broadly.
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http://dx.doi.org/10.1007/s00267-019-01208-0DOI Listing
November 2019

TEMPO-Me: An Electrochemically Activated Methylating Agent.

J Am Chem Soc 2019 09 13;141(38):15450-15455. Epub 2019 Sep 13.

ARC Centre of Excellence for Electromaterials Science & Research School of Chemistry , Australian National University , Canberra , Australian Capital Territory 2601 , Australia.

Bench- and air-stable 1-methoxy-2,2,6,6-tetramethylpiperidine (TEMPO-Me) is relatively unreactive at ambient temperature in the absence of an electrochemical stimulus. In this report, we demonstrate that the one-electron electrochemical oxidation of TEMPO-Me produces a powerful electrophilic methylating agent in situ. Our computational and experimental studies are consistent with methylation proceeding via a S2 mechanism, with a strength comparable to the trimethyloxonium cation. A protocol is developed for the electrochemical methylation of aromatic acids using TEMPO-Me.
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http://dx.doi.org/10.1021/jacs.9b08634DOI Listing
September 2019

Familial Intracranial Aneurysm in Newfoundland: Clinical and Genetic Analysis.

Can J Neurol Sci 2019 09 8;46(5):518-526. Epub 2019 Aug 8.

Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.

Objective: Intracranial aneurysm (IA) is an expansion of the weakened arterial wall that is often asymptomatic until rupture, resulting in subarachnoid hemorrhage. Here we describe the high prevalence of familial IA in a cohort of Newfoundland ancestry. We began to investigate the genetic etiology of IA in affected family members, as the inheritance of this disease is poorly understood.

Methods: Whole exome sequencing was completed for a cohort of 12 affected individuals from two multiplex families with a strong family history of IA. A filtering strategy was implemented to identify rare, shared variants. Filtered variants were prioritized based on validation by Sanger sequencing and segregation within the families.

Results: In family R1352, six variants passed filtering; while in family R1256, 68 variants remained, so further filtering was pursued. Following validation by Sanger sequencing, top candidates were investigated in a set of population controls, namely, C4orf6 c.A1G (p.M1V) and SPDYE4c.C103T (p.P35S). Neither was detected in 100 Newfoundland control samples.

Conclusion: Rare and potentially deleterious variants were identified in both families, though incomplete segregation was identified for all filtered variants. Alternate methods of variant prioritization and broader considerations regarding the interplay of genetic and environmental factors are necessary in future studies of this disease.
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http://dx.doi.org/10.1017/cjn.2019.230DOI Listing
September 2019

Water Quality Monitoring to Support Cumulative Effects Assessment and Decision Making in the Mackenzie Valley, Northwest Territories, Canada.

Integr Environ Assess Manag 2019 Nov 13;15(6):988-999. Epub 2019 Sep 13.

Center for Environmental Assessment Research, University of British Columbia, Vancouver, British Columbia, Canada.

Project proponent- and government-led environmental monitoring are required to identify, understand, and manage cumulative effects (CE), yet such monitoring initiatives are rarely mutually supportive. Notwithstanding the need for a more integrated and complementary approach to monitoring, monitoring efforts are often less effective than intended for addressing CE. This paper examines current monitoring programs in the Mackenzie Valley, Northwest Territories, Canada, based on 7 attributes: consistency, compatibility, observability, detectability, adaptability, accessibility, and usability. Results indicate a tenuous link between and across proponent-led monitoring requirements under project-specific water licenses and government-led monitoring of regional baseline conditions. There is some consistency in what is monitored, but data are often incompatible, insufficient to understand baseline change, not transferable across projects or scales, inaccessible to end users, and ultimately unsuitable to understanding CE. Lessons from the Mackenzie Valley highlight the need for improved alignment of monitoring efforts across programs and scales, characterized by a set of common parameters that are most useful for early detection of cumulative change and supporting regulatory decisions at the project scale. This alignment must be accompanied by more open and accessible data for both proponents and regulators, while protecting the sensitivity of proprietary information. Importantly, there must be conceptual guidance for CE, such that the role of monitoring is clear, providing the types of CE questions to be asked, identifying the hypotheses to be tested, and ensuring timely and meaningful results to support regulatory decisions. © 2019 SETAC.
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http://dx.doi.org/10.1002/ieam.4179DOI Listing
November 2019

Polymer Spreading on Unidirectionally Nanotextured Substrates Using Molecular Dynamics.

Langmuir 2019 Jul 21;35(26):8784-8789. Epub 2019 Jun 21.

Department of Mechanical Engineering , University of Utah , Salt Lake City , Utah 84112 , United States.

A unidirectional nanotexture alters the wettability of a substrate and can be used to create patterned polymer films, tailored polymer coverage/reflow, or aligned polymer molecules. However, the physical mechanisms underlying polymer spreading on nanoscale textures are not well-understood, and competing theories exist to explain how texture peaks and grooves alter the wettability of a substrate. We use molecular dynamics to simulate polymer spreading on substrates with unidirectional nanoscale textures as a function of texture shape and size and compare to polymer spreading on a flat substrate. We show that the texture groove shape is the primary factor that modifies polymer spreading on unidirectionally nanotextured substrates because the texture groove shape determines the minimum potential energy of a substrate. At the texture groove, the energy potentials of several surfaces combine, which increases polymer attraction and drives spreading along the texture groove. A texture groove also acts as a sink that inhibits polymer spreading perpendicular to the texture. Texture peaks create energy barriers that inhibit polymer spreading perpendicular to the texture, but this is a secondary mechanism that does not significantly affect anisotropic spreading. This research unifies competing theories of anisotropic liquid spreading documented in the literature and aims to aid in the design of nanoscale textures and ultrathin liquid film systems.
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http://dx.doi.org/10.1021/acs.langmuir.9b01050DOI Listing
July 2019

Detection of Enterocytozoon hepatopenaei using an invasive but non-lethal sampling method in shrimp (Penaeus vannamei).

J Microbiol Methods 2019 07 17;162:38-41. Epub 2019 May 17.

Aquaculture Pathology Laboratory, School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ, USA. Electronic address:

The detection of enteric pathogens that cause diseases in shrimp involves the sacrifice of the host to obtain tissue samples for diagnosis. In this study, we describe an invasive but non-lethal sampling methodology using a syringe to collect biopsy samples from the hepatopancreas (HP) of Penaeus vannamei to detect the microsporidian pathogen, Enterocytozoon hepatopenaei (EHP), by qPCR and transmission electron microscopy. EHP was detected in all the infected shrimp by qPCR. The shrimp infected by the microsporidian showed 65% survival at 7 days post-sampling. Transmission electron microscopic examination of the biopsy samples revealed numerous spores of the pathogen. The presence of EHP was further confirmed by histology and in situ hybridization from HP tissue samples. The data shows that a hepatopancreas biopsy could be a viable means of detecting enteric pathogens in shrimp, and the method could be valuable in sampling broodstock and natural populations without the need to sacrifice the animals.
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http://dx.doi.org/10.1016/j.mimet.2019.05.008DOI Listing
July 2019

Assessing the Accuracy of Citizen Scientist Reported Measurements for Agrichemical Contaminants.

Environ Sci Technol 2019 05 9;53(10):5633-5640. Epub 2019 May 9.

Department of Civil Engineering , University of Nebraska Lincoln , Omaha , Nebraska 68182 , United States.

Citizen science is a research tool capable of addressing major environmental challenges, including contamination of water resources by agrichemicals, such as nutrients and pesticides. The objectives of this study were (1) to identify the proportion of accurate observations by citizen scientists using rapid assessment water quality tools, and (2) to characterize how a user's prior experience with water quality tools was associated with the accuracy of citizen scientists. To achieve these objectives, we conducted group testing with over 136 citizen scientists and compared their results from water quality testing of water samples to results obtained using laboratory analytical methods. Following brief training, we observed that accuracy of reported results varies based on the user's experience level where experienced and expert users shared consistent and reliable measurements. Where erroneous measures were reported, citizen scientists tend to overestimate contaminant concentrations when using colorimetric water quality tools. Additionally, we identified differences in accuracy related to the types of water quality assessment tools used by citizen scientists from each experience group. This study demonstrates the importance of evaluating participant background experience in designing citizen science campaigns.
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http://dx.doi.org/10.1021/acs.est.8b06707DOI Listing
May 2019

Isavuconazole Prophylaxis in Patients With Hematologic Malignancies and Hematopoietic Cell Transplant Recipients.

Clin Infect Dis 2020 02;70(5):723-730

Division of Infectious Diseases, Oregon Health and Science University, Portland.

Background: Isavuconazole (ISA) is an attractive candidate for primary mold-active prophylaxis in high-risk patients with hematologic malignancies or hematopoietic cell transplant (HCT) recipients. However, data supporting the use of ISA for primary prophylaxis in these patients are lacking.

Methods: We conducted a retrospective review of breakthrough invasive fungal infections (bIFIs) among adult hematologic malignancy patients and HCT recipients who received ≥7 days of ISA primary prophylaxis between 1 September 2016 and 30 September 2018. The incidence of bIFIs in patients receiving ISA was compared to those receiving posaconazole (POS) and voriconazole (VOR) during the same time period.

Results: One hundred forty-five patients received 197 courses of ISA prophylaxis. Twelve bIFIs (Aspergillus fumigatus [5], Aspergillus species [2], Mucorales [2], Fusarium species [2], and Candida glabrata [1]) occurred, representing 8.3% of patients and 6.1% of courses, after a median duration of 14 days of ISA prophylaxis. All bIFIs occurred during periods of neutropenia. Seven patients (58.3%) died within 42 days of onset of bIFI. In addition, bIFIs complicated 10.2% of ISA, 4.1% of POS, and 1.1% of VOR courses among patients with de novo or relapsed/refractory acute myeloid leukemia during the study period, with invasive pulmonary aspergillosis (IPA) complicating 6.8% of ISA, 1.3% of POS, and zero VOR courses.

Conclusions: Although ISA has been approved for treatment of invasive Aspergillus and mucormycosis, we observed an increased rate of bIFI, notably IPA, using ISA for primary prophylaxis. These results support the need for further study to determine the role of ISA as primary prophylaxis.
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http://dx.doi.org/10.1093/cid/ciz282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931837PMC
February 2020