Publications by authors named "Elizabeth Wilson"

249 Publications

Sleep Apnea and Fetal Growth Restriction (SAFER) study: protocol for a pragmatic randomised clinical trial of positive airway pressure as an antenatal therapy for fetal growth restriction in maternal obstructive sleep apnoea.

BMJ Open 2021 06 29;11(6):e049120. Epub 2021 Jun 29.

Anesthesiology, Washington University in St Louis School of Medicine, St Louis, Missouri, USA

Introduction: Fetal growth restriction (FGR) is a major contributor to fetal and neonatal morbidity and mortality with intrauterine, neonatal and lifelong complications. This study explores maternal obstructive sleep apnoea (OSA) as a potentially modifiable risk factor for FGR. We hypothesise that, in pregnancies complicated by FGR, treating mothers who have OSA using positive airway pressure (PAP) will improve birth weight and neonatal outcomes.

Methods And Analysis: The Sleep Apnea and Fetal Growth Restriction study is a prospective, block-randomised, single-blinded, multicentre, pragmatic controlled trial. We enrol pregnant women aged 18-50, between 22 and 31 weeks of gestation, with established FGR based on second trimester ultrasound, who do not have other prespecified known causes of FGR (such as congenital anomalies or intrauterine infection). In stage 1, participants are screened by questionnaire for OSA risk. If OSA risk is identified, participants proceed to stage 2, where they undergo home sleep apnoea testing. Participants are determined to have OSA if they have an apnoea-hypopnoea index (AHI) ≥5 (if the oxygen desaturation index (ODI) is also ≥5) or if they have an AHI ≥10 (even if the ODI is <5). These participants proceed to stage 3, where they are randomised to nightly treatment with PAP or no PAP (standard care control), which is maintained until delivery. The primary outcome is unadjusted birth weight; secondary outcomes include fetal growth velocity on ultrasound, enrolment-to-delivery interval, gestational age at delivery, birth weight corrected for gestational age, stillbirth, Apgar score, rate of admission to higher levels of care (neonatal intensive care unit or special care nursery) and length of neonatal stay. These outcomes are compared between PAP and control using intention-to-treat analysis.

Ethics And Dissemination: This study has been approved by the Institutional Review Boards at Washington University in St Louis, Missouri; Hadassah Hebrew University Medical Center, Jerusalem; and the University of Rochester, New York. Recruitment began in Washington University in November 2019 but stopped from March to November 2020 due to COVID-19. Recruitment began in Hadassah Hebrew University in March 2021, and in the University of Rochester in May 2021. Dissemination plans include presentations at scientific conferences and scientific publications.

Trial Registration Number: NCT04084990.
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http://dx.doi.org/10.1136/bmjopen-2021-049120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245445PMC
June 2021

Comparing performance on the Months of the Year Backwards test in hospitalised patients with delirium, dementia, and no cognitive impairment: an exploratory study.

Eur Geriatr Med 2021 Jun 22. Epub 2021 Jun 22.

Geriatric Medicine, Edinburgh Delirium Research Group, Usher Institute, University of Edinburgh, Edinburgh, Scotland, UK.

Purpose: To investigate performance of the Months of the Year Backwards (MOTYB) test in older hospitalised patients with delirium, dementia, and no cognitive impairment.

Methods: Secondary analysis of data from a case-control study of 149 hospitalised patients aged ≥ 65 years with delirium [with or without dementia (N = 50)], dementia [without delirium (N = 46)], and no cognitive impairment (N = 53). Verbatim transcripts of MOTYB audio recordings were analysed to determine group differences in response patterns.

Results: In the total sample [median age 85y (IQR 80-88), 82% female], patients with delirium were more often unable to recite months backward to November (36/50 = 72%) than patients with dementia (21/46 = 46%; p < 0.01) and both differed significantly from patients without cognitive impairment (2/53 = 4%; p's < 0.001). 121/149 (81%) of patients were able to engage with the test. Patients with delirium were more often unable to engage with MOTYB (23/50 = 46%; e.g., due to reduced arousal) than patients with dementia (5/46 = 11%; p < 0.001); both groups differed significantly (p's < 0.001) from patients without cognitive impairment (0/53 = 0%). There was no statistically significant difference between patients with delirium (2/27 = 7%) and patients with dementia (8/41 = 20%) in completing MOTYB to January, but performance in both groups differed (p < 0.001 and p < 0.02, respectively) from patients without cognitive impairment (35/53 = 66%).

Conclusion: Delirium was associated with inability to engage with MOTYB and low rates of completion. In patients able to engage with the test, error-free completion rates were low in delirium and dementia. Recording of engagement and patterns of errors may add useful information to MOTYB scoring.
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http://dx.doi.org/10.1007/s41999-021-00521-4DOI Listing
June 2021

The Meaning of Consent and Its Implications for Anesthesiologists.

Adv Anesth 2020 Dec 14;38:1-22. Epub 2020 Aug 14.

Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA. Electronic address:

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http://dx.doi.org/10.1016/j.aan.2020.07.001DOI Listing
December 2020

Negative Regulation of Human Hepatic Constitutive Androstane Receptor by Cholesterol Synthesis Inhibition: Role of Sterol Regulatory Element Binding Proteins.

Drug Metab Dispos 2021 May 19. Epub 2021 May 19.

Wayne State University, United States

The squalene synthase inhibitor squalestatin 1 (Squal1) is a potent and efficacious inducer of CYP2B expression in primary cultured rat hepatocytes and rat liver. To determine whether Squal1 is also an inducer of human CYP2B, the effects of Squal1 treatment were evaluated in primary cultured human hepatocytes, differentiated HepaRG cells, and humanized mouse livers. Squal1 treatment did not increase CYP2B6 mRNA levels in human hepatocytes or HepaRG cells and only slightly and inconsistently increased CYP2B6 mRNA content in humanized mouse liver. However, treatment with farnesol, which mediates Squal1's effect on rat CYP2B expression, increased CYP2B6 mRNA levels in HepaRG cells expressing the constitutive androstane receptor (CAR) but not in cells with knocked-down CAR. To determine the impact of cholesterol biosynthesis inhibition on CAR activation, the effects of pravastatin (Prava) were determined on CITCO-mediated gene expression in primary cultured human hepatocytes. Prava treatment abolished CITCO-inducible CYP2B6 expression, but had less effect on rifampicin-mediated CYP3A4 induction, and CITCO treatment did not affect Prava-inducible HMG-CoA reductase (HMGCR) expression. Treatment with inhibitors of different steps of cholesterol biosynthesis attenuated CITCO-mediated CYP2B6 induction in HepaRG cells, and Prava treatment increased HMGCR expression and inhibited CYP2B6 induction with comparable potency. Transfection of HepG2 cells with transcriptionally active sterol responsive element binding proteins (SREBPs) reduced CAR-mediated transactivation, and inducible expression of transcriptionally active SREBP2 attenuated CITCO-inducible CYP2B6 expression in HepaRG cells. These findings suggest that Squal1 does not induce CYP2B6 in human hepatocytes because Squal1's inhibitory effect on cholesterol biosynthesis interferes with CAR activation. The cholesterol biosynthesis inhibitor squalestatin 1 induces rat hepatic CYP2B expression indirectly, by causing accumulation of an endogenous isoprenoid that activates the constitutive androstane receptor (CAR). This study demonstrates that squalestatin 1 does not similarly induce CYP2B6 expression in human hepatocytes. Rather, inhibition of cholesterol biosynthesis interferes with CAR activity, likely by activating sterol regulatory element binding proteins. These findings increase our understanding of the endogenous processes that modulate human drug-metabolizing gene expression.
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http://dx.doi.org/10.1124/dmd.120.000341DOI Listing
May 2021

Risk factors for persistent pain after breast and thoracic surgeries: a systematic literature review and meta-analysis.

Pain 2021 Apr 5. Epub 2021 Apr 5.

Saint Louis University School of Medicine, St. Louis, MO, United States University of Sydney School of Medicine, Sydney, Australia MCPHS University, Boston, MA, United States Department of Anesthesiology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States Becker Medical Library, Washington University in St. Louis School of Medicine, St. Louis, MO, United States Departments of Anesthesiology & Perioperative Medicine, Biomedical & Molecular Sciences, Centre for Neuroscience Studies, and School of Policy Studies, Queen's University, Kingston, Ontario, Canada Department of Clinical Medicine, Danish Pain Research Center, Aarhus University, Aarhus, Denmark.

Abstract: Persistent postsurgical pain (PPSP) is common after breast and thoracic surgeries. Understanding which risk factors consistently contribute to PPSP will allow clinicians to apply preventive strategies, as they emerge, to high-risk patients. The objective of this work was to systematically review and meta-analyze the literature on risk factors of PPSP after breast and thoracic surgeries. A systematic literature search using Ovid Medline, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Embase, PsycINFO, and Scopus databases was conducted. Study screening with inclusion and exclusion criteria, data extraction, and risk of bias assessment was performed independently by 2 authors. The data for each surgical group were analyzed separately and meta-analyzed where possible. The literature search yielded 5584 articles, and data from 126 breast surgery and 143 thoracic surgery articles were considered for meta-analysis. In breast surgery, younger age, higher body mass index, anxiety, depression, diabetes, smoking, preoperative pain, moderate to severe acute postoperative pain, reoperation, radiotherapy, and axillary lymph node dissection were the main factors associated with higher risk of PPSP. In thoracic surgery, younger age, female sex, hypertension, preoperative pain, moderate to severe acute postoperative pain, surgical approach, major procedure, and wound complications were associated with PPSP. This systematic review demonstrated certain consistent risk factors of PPSP after breast and thoracic surgeries, as well as identified research gaps. Understanding the factors that increase susceptibility to PPSP can help selectively allocate resources to optimize perioperative care in high-risk patients and help develop targeted, risk-stratified interventions for PPSP prevention.
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http://dx.doi.org/10.1097/j.pain.0000000000002301DOI Listing
April 2021

Perioperative sleep in geriatric cardiac surgical patients: a feasibility study using a wireless wearable device.

Br J Anaesth 2021 06 1;126(6):e205-e208. Epub 2021 Apr 1.

Department of Anesthesiology, Washington University School of Medicine in St Louis, St Louis, MO, USA; Department of Psychiatry, Washington University School of Medicine in St Louis, St Louis, MO, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine in St Louis, St Louis, MO, USA; Department of Biomedical Engineering, Washington University in St Louis, St Louis, MO, USA. Electronic address:

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http://dx.doi.org/10.1016/j.bja.2021.02.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258967PMC
June 2021

Characterization of a Regional Childhood Obesity Prevention and Treatment System.

Child Obes 2021 Jun 31;17(4):291-297. Epub 2021 Mar 31.

Midwest Center for Nonprofit Leadership, University of Missouri-Kansas City, Kansas City, MO, USA.

This project characterized the system of childhood obesity-related programs and functions based on a socioecological framework within the Kansas City region to determine strengths, weaknesses, and leverage points for informing collective impact. A mixed-method approach was employed to identify and collect data ∼260 childhood obesity-related programs provided by 89 organizations. Findings indicated no major gaps in population or location served although few programs specifically focused on service to minority groups or neighborhoods. The region has many programs working within the system, yet the distribution of programs does not occur as expected throughout the dimensions of a standard socioecological model or community health system. In addition, several organizations perform certain leadership functions such as coordination, resource allocation, or monitoring, but none perform all, indicating the lack of a traditional "backbone" organization. These findings demonstrate how a region's childhood obesity prevention and treatment programs can be evaluated using a socioecological framework.
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http://dx.doi.org/10.1089/chi.2020.0294DOI Listing
June 2021

The Impact of Rejection Sensitivity on Self-Disclosure Within the Context of Online Dating.

Cyberpsychol Behav Soc Netw 2021 Feb 22. Epub 2021 Feb 22.

Department of Psychology, Arkansas State University, Jonesboro, Arkansas, USA.

Prior research suggests that rejection sensitive individuals may find it easier to express their true selves in an online environment. The purpose of the present study was to examine the extent to which rejection sensitivity (RS) and true self influence self-disclosure within the context of online dating. We collected data from a total of 1,295 individuals who completed an online survey. For those who engaged in online dating, RS was not directly related to self-disclosure in online dating profiles or in communicating with individuals met through online dating sites/apps, but true self was. In addition, there was an indirect relationship between RS and self-disclosure in the context of online dating through true self. These findings suggest that rejection sensitive individuals who feel more comfortable revealing aspects of their "true" selves online may be more likely to engage in self-disclosure within the context of online dating, which could potentially offer some clue as to why rejection sensitive individuals may be somewhat more likely to engage in online dating than less rejection sensitive individuals. That is, rejection sensitive individuals are perhaps more likely to engage in online dating because it may facilitate representation of their "true" selves and may thus increase dating success.
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http://dx.doi.org/10.1089/cyber.2020.0257DOI Listing
February 2021

Novel Solutions to Student Problems: A Phenomenological Exploration of a Single Session Approach to Art Therapy With Creative Arts University Students.

Authors:
Elizabeth Wilson

Front Psychol 2020 18;11:600214. Epub 2021 Jan 18.

Creative Arts and Music Therapy Research Unit, Faculty of Fine Arts and Music, University of Melbourne, Melbourne, VIC, Australia.

Within the Australian university context, research has uncovered increasing levels of psychological distress, in the form of stress, anxiety and depression. Higher rates of psychological distress have been reported in undergraduate students specifically enrolled in creative arts programs. Despite these increasing levels of psychological distress, university students are reluctant to engage with mental health and wellbeing supports. To explore ways to meet the mental health and wellbeing needs of creative arts university students, the Creative Arts and Music Therapy Research Unit at The University of Melbourne commenced a project exploring the benefits and pitfalls of a brief creative arts therapies approach for students attending a campus based wellbeing clinic. This exploratory research study formed the art therapy component of this much broader research endeavor. Creative arts students in this research study were invited to participate in a single session art therapy encounter that involved the visual exploration of the miracle question, asking students to visually depict "what the problem looks like and how it will look when the problem is resolved or you feel like you can cope with it better?" The descriptive findings of this exploratory research study revealed how the combination of art therapy used within a single session framework was able to afford students a novel means to externalize problems, leading students to forming a less internalized view of the self.
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http://dx.doi.org/10.3389/fpsyg.2020.600214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847986PMC
January 2021

Molecular Targeting of RRM2, NF-κB, and Mutant TP53 for the Treatment of Triple-Negative Breast Cancer.

Mol Cancer Ther 2021 04 3;20(4):655-664. Epub 2021 Feb 3.

Department of Physiology and Pharmacology, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, California.

Doxorubicin and other anthracycline derivatives are frequently used as part of the adjuvant chemotherapy regimen for triple-negative breast cancer (TNBC). Although effective, doxorubicin is known for its off-target and toxic side effect profile, particularly with respect to the myocardium, often resulting in left ventricular (LV) dysfunction and congestive heart failure when used at cumulative doses exceeding 400 mg/m Previously, we have observed that the ribonucleotide reductase subunit M2 (RRM2) is significantly overexpressed in estrogen receptor (ER)-negative cells as compared with ER-positive breast cancer cells. Here, we inhibited RRM2 in ER-negative breast cancer cells as a target for therapy in this difficult-to-treat population. We observed that through the use of didox, a ribonucleotide reductase inhibitor, the reduction in RRM2 was accompanied by reduced NF-κB activity When didox was used in combination with doxorubicin, we observed significant downregulation of NF-κB proteins accompanied by reduced TNBC cell proliferation. As well, we observed that protein levels of mutant p53 were significantly reduced by didox or combination therapy Xenograft studies showed that combination therapy was found to be synergistic , resulting in a significantly reduced tumor volume as compared with doxorubicin monotherapy. In addition, the use of didox was also found to ameliorate the toxic myocardial effects of doxorubicin as measured by heart mass, LV diameter, and serum troponin T levels. The data present a novel and promising approach for the treatment of TNBC that merits further clinical evaluation in humans.
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http://dx.doi.org/10.1158/1535-7163.MCT-20-0373DOI Listing
April 2021

Developing an OPAT service that meets the ever-changing needs of patients.

Authors:
Elizabeth Wilson

Br J Nurs 2021 Jan;30(2):S12-S14

Lead Nurse, Outpatient Parenteral Antimicrobial Therapy, Manchester University NHS Foundation Trust.

, Lead Nurse, Outpatient Parenteral Antimicrobial Therapy, Manchester University NHS Foundation Trust ([email protected]), BJN Awards 2020 Vascular Access Nurse of the Year runner-up.
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http://dx.doi.org/10.12968/bjon.2021.30.2.S12DOI Listing
January 2021

Protocol for the Prognosticating Delirium Recovery Outcomes Using Wakefulness and Sleep Electroencephalography (P-DROWS-E) study: a prospective observational study of delirium in elderly cardiac surgical patients.

BMJ Open 2020 12 13;10(12):e044295. Epub 2020 Dec 13.

Department of Anesthesiology, Washington University in Saint Louis School of Medicine, Saint Louis, Missouri, USA

Introduction: Delirium is a potentially preventable disorder characterised by acute disturbances in attention and cognition with fluctuating severity. Postoperative delirium is associated with prolonged intensive care unit and hospital stay, cognitive decline and mortality. The development of biomarkers for tracking delirium could potentially aid in the early detection, mitigation and assessment of response to interventions. Because sleep disruption has been posited as a contributor to the development of this syndrome, expression of abnormal electroencephalography (EEG) patterns during sleep and wakefulness may be informative. Here we hypothesise that abnormal EEG patterns of sleep and wakefulness may serve as predictive and diagnostic markers for postoperative delirium. Such abnormal EEG patterns would mechanistically link disrupted thalamocortical connectivity to this important clinical syndrome.

Methods And Analysis: P-DROWS-E (Prognosticating Delirium Recovery Outcomes Using Wakefulness and Sleep Electroencephalography) is a 220-patient prospective observational study. Patient eligibility criteria include those who are English-speaking, age 60 years or older and undergoing elective cardiac surgery requiring cardiopulmonary bypass. EEG acquisition will occur 1-2 nights preoperatively, intraoperatively, and up to 7 days postoperatively. Concurrent with EEG recordings, two times per day postoperative Confusion Assessment Method (CAM) evaluations will quantify the presence and severity of delirium. EEG slow wave activity, sleep spindle density and peak frequency of the posterior dominant rhythm will be quantified. Linear mixed-effects models will be used to evaluate the relationships between delirium severity/duration and EEG measures as a function of time.

Ethics And Dissemination: P-DROWS-E is approved by the ethics board at Washington University in St. Louis. Recruitment began in October 2018. Dissemination plans include presentations at scientific conferences, scientific publications and mass media.

Trial Registration Number: NCT03291626.
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http://dx.doi.org/10.1136/bmjopen-2020-044295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737109PMC
December 2020

Developmental Changes in Tongue Strength, Swallow Pressures, and Tongue Endurance.

Dysphagia 2020 Nov 10. Epub 2020 Nov 10.

Department of Speech and Hearing Sciences, Elson S. Floyd College of Medicine, Washington State University Spokane, PO Box 1495, Spokane, WA, 99210-1495, USA.

Maximum tongue strength, mean swallow pressures, and tongue endurance were measured in 324 children ages 6-12 years. The purpose of this study was to measure saliva swallow pressures in absolute terms (i.e., kilopascals) and as a percentage of maximum tongue strength to determine functional reserve in across ages in children and to examine factors that may influence tongue strength and swallow pressures including age, tongue endurance, and tongue-tie. The study results showed that maximum tongue strength and swallow pressures increased with age, while tongue endurance did not. Swallow pressures averaged 44% of maximum tongue strength across ages, indicating that children typically have a functional reserve of 56%. Tongue strength and swallow pressures were not decreased in the 20 children with tongue-tie. A sample clinical case is discussed.
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http://dx.doi.org/10.1007/s00455-020-10200-4DOI Listing
November 2020

The Effect of Simple Cost Effective Interventions in Improving Enhanced Recovery in Neck of Femur Fracture Care.

Cureus 2020 Oct 28;12(10):e11217. Epub 2020 Oct 28.

Trauma and Orthopaedics, Bristol Royal Infirmary, Bristol, GBR.

Aim Due to the frequency and high mortality and morbidity associated with neck of femur fractures, pathways of care have been established in the United Kingdom. These include the Enhanced Recovery Program (ERP), which aims to maximise the quality of care whilst reducing their length of stay, and the Best Practice Tariff (BPT) which if adhered to warrants £1335 per neck of femur fracture. We conducted a prospective audit to assess adherence to these pathways in a trauma unit. Methods An audit was carried out between November 2015 and May 2016. The information was obtained from neck of femur fracture proformas, anaesthetic charts and drug charts by two investigators. Results Nine out of the 10 ERP components were adhered to in all 31 patients. This highlighted a deficiency in requesting day one post-operative osteoporosis bloods, which was only carried out in 61.3% of patients. As an intervention, a reminder sticker was placed on the operation note as an intervention. Re-audit following the introduction of the stickers showed a marked improvement of 90%. During the initial admission 38.7% of patients adhered to the BPT. The main area for improvement was fracture prevention assessment, specifically Fracture Risk Assessment Tool (FRAX) scores and Nottingham Hip Fracture Scores. To improve this these sections were highlighted in the proformas to promote their importance. Additionally, a smartphone application was made available to doctors to aid with ease of calculation. Following these interventions, 93% of patients had this data entered, with an improvement in overall tariff attainment to 63.3%. Conclusions The introduction of simple measures is beneficial both for patient safety and economically for hospitals.
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http://dx.doi.org/10.7759/cureus.11217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594660PMC
October 2020

Plasma and Urinary FGF-2 and VEGF-A Levels Identify Children at Risk for Severe Bleeding after Pediatric Cardiopulmonary Bypass: A Pilot Study.

Med Res Arch 2020 Jun 18;8(6). Epub 2020 Jun 18.

Nephrology, Department of Pediatrics, Children's National Health System, 111 Michigan Ave NW, Washington, DC 20010.

Severe bleeding after cardiothoracic surgery with cardiopulmonary bypass (CPB) is associated with increased morbidity and mortality in adults and children. Fibroblast Growth Factor-2 (FGF-2) and Vascular Endothelial Growth Factor-A (VEGF-A) induce hemorrhage in murine models with heparin exposure. We aim to determine if plasma and urine levels of FGF-2 and VEGF-A in the immediate perioperative period can identify children with severe bleeding after CPB. We performed a prospective, observational biomarker study in 64 children undergoing CPB for congenital heart disease repair from June 2015 - January 2017 in a tertiary pediatric referral center. Primary outcome was severe bleeding defined as ≥ 20% estimated blood volume loss within 24-hours. Independent variables included perioperative plasma and urinary FGF-2 and VEGF-A levels. Analyses included comparative (Wilcoxon rank sum, Fisher's exact, and Student's tests) and discriminative (receiver operator characteristic [ROC] curve) analyses. Forty-eight (75%) children developed severe bleeding. Median plasma and urinary FGF-2 and VEGF-A levels were elevated in children with severe bleeding compared to without bleeding (preoperative: plasma FGF-2 = 16[10-35] vs. 9[2-13] pg/ml; urine FGF-2= 28[15-76] vs. 14.5[1.5-22] pg/mg; postoperative: plasma VEGF-A = 146[34-379] vs. 53 [0-134] pg/ml; urine VEGF-A = 132 [52-257] vs. 45[0.1-144] pg/mg; all < 0.05). ROC curve analyses of combined plasma and urinary FGF-2 and VEGF-A levels discriminated severe postoperative bleeding (AUC: 0.73-0.77) with mean sensitivity and specificity above 80%. We conclude that the perioperative plasma and urinary levels of FGF-2 and VEGF-A discriminate risk of severe bleeding after pediatric CPB.
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http://dx.doi.org/10.18103/mra.v8i6.2134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546309PMC
June 2020

Prescription opioid misuse among university students: A systematic review.

J Am Coll Health 2020 Aug 11:1-19. Epub 2020 Aug 11.

Department of Psychology, University of Rhode Island, Kingston, Rhode Island, USA.

Misuse of prescription opioids has substantially increased in the past decade among the general population, including among university students. Relative to the literature concerning opioid misuse among the general population, little information is available regarding the college student population. The purpose of the present study was to conduct a systematic review of the literature concerning the prevalence of prescription opioid misuse among the university student population. The lifetime estimate for prescription opioid misuse among general populations of students ranged from 4% to 19.7%, with higher estimates for special student populations. Students most at risk for misuse of prescription opioids are those who report higher rates of psychological distress, depression, and suicidal thoughts and behaviors, and white, male students who use alcohol and illicit drugs. Findings from this study underscore the need for opioid prevention and intervention programs on university campuses.
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http://dx.doi.org/10.1080/07448481.2020.1786095DOI Listing
August 2020

Rheumatic fever recurrences in New Zealand 2010-14.

N Z Med J 2020 06 12;133(1516):47-57. Epub 2020 Jun 12.

Consultant Paediatric Cardiologist, Green Lane Paediatric & Congenital Cardiac Services, Starship Children's Hospital and Honorary Clinical Associate Professor, University of Auckland, Auckland.

Aim: To describe the epidemiology and clinical characteristics of recurrences of acute rheumatic fever (ARF) in New Zealand 2010-14.

Method: Retrospective hospital chart review for ARF with repeat hospital admissions from 2010-14, to identify recurrences of ARF. Definitions of recurrence as per NZ Heart Foundation Guidelines.

Results: There were 65 episodes of recurrent ARF among 60 patients. Māori 51%, Pacific 49%. Arthritis and carditis were the most common major manifestations. Median age at recurrence 21.6 years, (8-42 years), with 83% patients over 15 years. There were 841 first episodes of ARF in New Zealand in 2010-4. Overall New Zealand ARF recurrence rate was 7.2% (CI 5.5-8.9%). The recurrence rate was 4% for those under 16 years, 16% for those aged 16-20 and 25% for those >20 years (p<0.05). Seventy-three percent of recurrences occurred in the Auckland region. Recurrences of ARF were strongly associated with RHD progression.

Conclusion: The risk of recurrence of ARF in New Zealand is low for children. In contrast, recurrences of ARF in New Zealand occur predominantly after age 15, and disproportionately in the Auckland DHBs. Current medical systems and registers may not be meeting the needs of adolescents and adults requiring secondary prophylaxis.
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June 2020

Anesthesia residency training in regional anesthesiology and acute pain medicine: a competency-based model curriculum.

Reg Anesth Pain Med 2020 08 30;45(8):660-667. Epub 2020 May 30.

Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.

The Accreditation Council for Graduate Medical Education has shifted to competency-based medical education. This educational framework requires the description of educational outcomes based on the knowledge, skills and behaviors expected of competent trainees. It also requires an assessment program to provide formative feedback to trainees as they progress to competency in each outcome. Critical to the success of a curriculum is its practical implementation. This article describes the development of model curricula for anesthesiology residency training in regional anesthesia and acute pain medicine (core and advanced) using a competency-based framework. We further describe how the curricula were distributed through a shared web-based platform and mobile application.
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http://dx.doi.org/10.1136/rapm-2020-101480DOI Listing
August 2020

Persistence of Varicella-Zoster Virus-Specific Plasma Cells in Adult Human Bone Marrow following Childhood Vaccination.

J Virol 2020 06 16;94(13). Epub 2020 Jun 16.

Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA

Childhood immunization with the live-attenuated varicella-zoster virus (VZV) vaccine induces protective immune responses. Routine VZV vaccination started only 2 decades ago, and thus, there are few studies examining the longevity of vaccine-induced immunity. Here, we analyzed the quantity of VZV-specific plasma cells (PCs) and CD4 T cells in the bone marrow (BM) of healthy young adults ( = 15) following childhood VZV immunization. Long-lived BM resident plasma cells constitutively secrete antibodies, and we detected VZV-specific PCs in the BM of all subjects. Anti-VZV plasma antibody titers correlated positively with the number of VZV-specific BM PCs. Furthermore, we quantified the number of interferon gamma (IFN-γ)-producing CD4 T cells specific for VZV glycoprotein E and all other structural and nonstructural VZV proteins in both BM and blood (peripheral blood mononuclear cells [PBMCs]). The frequency of VZV-specific IFN-γ-producing CD4 T cells was significantly higher in PBMCs than BM. Our study shows that VZV-specific PCs and VZV-specific CD4 memory T cells persist up to 20 years after vaccination. These findings indicate that childhood VZV vaccination can elicit long-lived immune memory responses in the bone marrow. Childhood varicella-zoster virus (VZV) immunization induces immune memory responses that protect against primary VZV infection, chicken pox. In the United States, routine childhood VZV vaccination was introduced only 2 decades ago. Hence, there is limited information on the longevity of B and CD4 T cell memory, which are both important for protection. Here, we showed in 15 healthy young adults that VZV-specific B and CD4 T cell responses are detectable in bone marrow (BM) and blood up to 20 years after vaccination. Specifically, we measured antibody-secreting plasma cells in the BM and VZV-specific CD4 T cells in BM and blood. These findings suggest that childhood VZV vaccination induces long-lived immunity.
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http://dx.doi.org/10.1128/JVI.02127-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307153PMC
June 2020

Noncoding Microdeletion in Mouse Disrupts Neural Crest Migration into the Stria Vascularis, Reduces the Endocochlear Potential, and Suggests the Neuropathology for Human Nonsyndromic Deafness DFNB39.

J Neurosci 2020 04 9;40(15):2976-2992. Epub 2020 Mar 9.

Auditory Development and Restoration Program,

Hepatocyte growth factor (HGF) is a multifunctional protein that signals through the MET receptor. HGF stimulates cell proliferation, cell dispersion, neuronal survival, and wound healing. In the inner ear, levels of HGF must be fine-tuned for normal hearing. In mice, a deficiency of HGF expression limited to the auditory system, or an overexpression of HGF, causes neurosensory deafness. In humans, noncoding variants in are associated with nonsyndromic deafness However, the mechanism by which these noncoding variants causes deafness was unknown. Here, we reveal the cause of this deafness using a mouse model engineered with a noncoding intronic 10 bp deletion (del10) in Male and female mice homozygous for del10 exhibit moderate-to-profound hearing loss at 4 weeks of age as measured by tone burst auditory brainstem responses. The wild type (WT) 80 mV endocochlear potential was significantly reduced in homozygous del10 mice compared with WT littermates. In normal cochlea, endocochlear potentials are dependent on ion homeostasis mediated by the stria vascularis (SV). Previous studies showed that developmental incorporation of neural crest cells into the SV depends on signaling from HGF/MET. We show by immunohistochemistry that, in del10 homozygotes, neural crest cells fail to infiltrate the developing SV intermediate layer. Phenotyping and RNAseq analyses reveal no other significant abnormalities in other tissues. We conclude that, in the inner ear, the noncoding del10 mutation in leads to developmental defects of the SV and consequently dysfunctional ion homeostasis and a reduction in the EP, recapitulating human DFNB39 nonsyndromic deafness. Hereditary deafness is a common, clinically and genetically heterogeneous neurosensory disorder. Previously, we reported that human deafness DFNB39 is associated with noncoding variants in the 3'UTR of a short isoform of encoding hepatocyte growth factor. For normal hearing, HGF levels must be fine-tuned as an excess or deficiency of HGF cause deafness in mouse. Using a mutant mouse with a small 10 bp deletion recapitulating a human noncoding variant, we demonstrate that neural crest cells fail to migrate into the stria vascularis intermediate layer, resulting in a significantly reduced endocochlear potential, the driving force for sound transduction by inner ear hair cells. HGF-associated deafness is a neurocristopathy but, unlike many other neurocristopathies, it is not syndromic.
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http://dx.doi.org/10.1523/JNEUROSCI.2278-19.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141880PMC
April 2020

A smartphone-based test for the assessment of attention deficits in delirium: A case-control diagnostic test accuracy study in older hospitalised patients.

PLoS One 2020 24;15(1):e0227471. Epub 2020 Jan 24.

Edinburgh Delirium Research Group, University of Edinburgh, Edinburgh, Scotland, United Kingdom.

Background: Delirium is a common and serious acute neuropsychiatric syndrome which is often missed in routine clinical care. Inattention is the core cognitive feature. Diagnostic test accuracy (including cut-points) of a smartphone Delirium App (DelApp) for assessing attention deficits was assessed in older hospital inpatients.

Methods: This was a case-control study of hospitalised patients aged ≥65 years with delirium (with or without pre-existing cognitive impairment), who were compared to patients with dementia without delirium, and patients without cognitive impairment. Reference standard delirium assessment, which included a neuropsychological test battery, was based on Diagnostic and Statistical Manual of Mental Disorders-5 criteria. A separate blinded assessor administered the DelApp arousal assessment (score 0-4) and attention task (0-6) yielding an overall score of 0 to 10 (lower scores indicate poorer performance). Analyses included receiver operating characteristic curves and sensitivity and specificity. Optimal cut-points for delirium detection were determined using Youden's index.

Results: A total of 187 patients were recruited, mean age 83.8 (range 67-98) years, 152 (81%) women; n = 61 with delirium; n = 61 with dementia without delirium; and n = 65 without cognitive impairment. Patients with delirium performed poorly on the DelApp (median score = 4/10; inter-quartile range 3.0, 5.5) compared to patients with dementia (9.0; 5.5, 10.0) and those without cognitive impairment (10.0; 10.0, 10.0). Area under the curve for detecting delirium was 0.89 (95% Confidence Interval 0.84, 0.94). At an optimal cut-point of ≤8, sensitivity was 91.7% (84.7%, 98.7%) and specificity 74.2% (66.5%, 81.9%) for discriminating delirium from the other groups. Specificity was 68.3% (56.6%, 80.1%) for discriminating delirium from dementia (cut-point ≤6).

Conclusion: Patients with delirium (with or without pre-existing cognitive impairment) perform poorly on the DelApp compared to patients with dementia and those without cognitive impairment. A cut-point of ≤8/10 is suggested as having optimal sensitivity and specificity. The DelApp is a promising tool for assessment of attention deficits associated with delirium in older hospitalised adults, many of whom have prior cognitive impairment, and should be further validated in representative patient cohorts.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227471PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980392PMC
April 2020

Development and Psychometric Properties of the Self-Blame Attributions for Cancer Scale.

Oncol Nurs Forum 2020 01;47(1):79-88

University of Missouri-Kansas City.

Objectives: To adapt the Cardiac Self-Blame Attributions Scale into the Self-Blame Attributions for Cancer Scale (SBAC) for use in patients with cancer and analyze its psychometric properties.

Sample & Setting: 113 patients receiving radiation therapy at the University of Kansas Cancer Center.

Methods & Variables: The SBAC and other self-report measures were administered during outpatient oncology appointments for radiation therapy to establish the psychometric properties of the SBAC.

Results: A two-factor structure represented behavioral and characterological self-blame attributions. Reliability estimates for each factor were excellent and evidence of convergent and discriminant validity was found, indicating support for the SBAC as a valid and reliable measure of self-blame attributions in patients with cancer.

Implications For Nursing: The SBAC may help healthcare providers, including nursing staff, to identify the self-blame patterns exhibited by patients with cancer. Future research can assess the reliability and validity of SBAC across stages of treatment and establish the predictive validity of the scale in individuals with cancer.
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http://dx.doi.org/10.1188/20.ONF.79-88DOI Listing
January 2020

Use of carotid and axillary artery approach for stenting the patent ductus arteriosus in infants with ductal-dependent pulmonary blood flow: A multicenter study from the congenital catheterization research collaborative.

Catheter Cardiovasc Interv 2020 03 9;95(4):726-733. Epub 2019 Dec 9.

Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia.

Background: Carotid artery (CA) and axillary artery (AA) access are increasingly used for transcatheter stenting of the patent ductus arteriosus (PDA), although reports are limited.

Methods: The Congenital Catheterization Research Collaborative (CCRC) reviewed multicenter data from infants who underwent PDA stenting via the CA or AA approach from 2008 to 2017, and compared outcomes to those of infants undergoing PDA stenting via the femoral artery (FA) approach. Post-procedure ultrasound (US) imaging was reviewed.

Results: Forty-nine infants underwent PDA stenting from the CA (n = 43) or AA (n = 6) approach, compared with 55 infants who underwent PDA stenting from the FA approach. The PDA was the sole pulmonary blood flow (PBF) source in 61% of infants in the CA/AA cohort, compared with 33% of the FA cohort (p < .01). Ductal tortuosity for CA/AA cohort was Type I (straight) in 10 (20%), Type II (one turn) in 17 (35%), and Type III (multiple turns) in 22 (45%) infants and reflected a greater degree of tortuosity when compared to the FA cohort (p < .01). In 17 infants with CA/AA approach, the "flip technique" was used, and was associated with shorter procedure times for highly tortuous PDA (Type III) patients. Rates of procedural complications were similar across access sites. Most common complications were access site injury (thrombus or bleeding) and stent malposition. No complications were specifically related to the "flip technique."

Conclusions: Use of CA and AA approach for PDA stenting was found to be more commonly employed in sole source PBF and highly tortuous PDAs. Procedural modifications such as the "flip technique" may lead to shorter procedure times. CA and AA approaches are associated with a similar burden of procedural or late complications. Post-procedural surveillance of the CA and AA is suggested, given the incidence of vascular findings on US.
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http://dx.doi.org/10.1002/ccd.28631DOI Listing
March 2020

Insights From Liver-Humanized Mice on Cholesterol Lipoprotein Metabolism and LXR-Agonist Pharmacodynamics in Humans.

Hepatology 2020 08 23;72(2):656-670. Epub 2020 Mar 23.

Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska Institute, Stockholm, Sweden.

Background And Aims: Genetically modified mice have been used extensively to study human disease. However, the data gained are not always translatable to humans because of major species differences. Liver-humanized mice (LHM) are considered a promising model to study human hepatic and systemic metabolism. Therefore, we aimed to further explore their lipoprotein metabolism and to characterize key hepatic species-related, physiological differences.

Approach And Results: Fah , Rag2 , and Il2rg knockout mice on the nonobese diabetic (FRGN) background were repopulated with primary human hepatocytes from different donors. Cholesterol lipoprotein profiles of LHM showed a human-like pattern, characterized by a high ratio of low-density lipoprotein to high-density lipoprotein, and dependency on the human donor. This pattern was determined by a higher level of apolipoprotein B100 in circulation, as a result of lower hepatic mRNA editing and low-density lipoprotein receptor expression, and higher levels of circulating proprotein convertase subtilisin/kexin type 9. As a consequence, LHM lipoproteins bind to human aortic proteoglycans in a pattern similar to human lipoproteins. Unexpectedly, cholesteryl ester transfer protein was not required to determine the human-like cholesterol lipoprotein profile. Moreover, LHM treated with GW3965 mimicked the negative lipid outcomes of the first human trial of liver X receptor stimulation (i.e., a dramatic increase of cholesterol and triglycerides in circulation). Innovatively, LHM allowed the characterization of these effects at a molecular level.

Conclusions: LHM represent an interesting translatable model of human hepatic and lipoprotein metabolism. Because several metabolic parameters displayed donor dependency, LHM may also be used in studies for personalized medicine.
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http://dx.doi.org/10.1002/hep.31052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496592PMC
August 2020

Multicentre collaborative cohort study of the use of Kirschner wires for the management of supracondylar fractures in children.

Chin J Traumatol 2019 Oct 5;22(5):249-254. Epub 2019 Aug 5.

University of Bristol, Senate House, Tyndall Ave, Bristol, BS8 1TH, UK; Bristol Royal Hospital for Children, Maudlin St, Bristol, BS2 8BJ, UK.

Purpose: Supracondylar fractures of the humerus cause significant morbidity in children. Nerve damage and loss of fracture reduction are common recognised complications in patients with this injury. Uncertainty surrounds the optimal Kirschner wire configuration and diameter for closed reduction and pinning of these fractures. This study describes current practice and examined the association between wire configuration or diameter and outcomes (clinical and radiological) in the operative management of paediatric supracondylar fractures.

Methods: Children presenting with Gartland II or III supracondylar fractures at five hospitals in south-west England were eligible for inclusion. Collaborators scrutinised paper and electronic case notes. Outcome measures were maintenance of reduction and iatrogenic nerve injury.

Results: Altogether 209 patients were eligible for inclusion: 15.7% had a documented neurological deficit at presentation; 3.9% who were neurologically intact at presentation sustained a new deficit caused by treatment and 13.4% experienced a clinically significant loss of reduction following fixation. Maintenance of reduction was significantly better in patients treated specifically with crossed ×3 Kirschner wire configuration compared to all other configurations. The incidence of iatrogenic nerve injury was not significantly different between groups treated with different wire configurations.

Conclusion: We present a large multicentre cohort study showing that crossed ×3 Kirschner wires are associated with better maintenance of reduction than crossed ×2 or lateral entry wires. Greater numbers would be required to properly investigate nerve injury relating to operative management of supracondylar fractures. We found significant variations in practice and compliance with the British Orthopaedic Association Standard for Trauma (BOAST) 11 guidelines.
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http://dx.doi.org/10.1016/j.cjtee.2019.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823708PMC
October 2019

Updated good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) in adults and children in the UK.

JAC Antimicrob Resist 2019 Sep 26;1(2):dlz026. Epub 2019 Aug 26.

Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow, UK.

UK good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) were published in 2012 and 2015 for adult and paediatric patients, respectively. Here we update the initial good practice recommendations in a combined document based on a further review of the OPAT literature and an extensive consultation process. As with the previous good practice recommendations, these updated recommendations are intended to provide pragmatic guidance for new and established OPAT services across a range of settings and to act as a set of quality indicators for service evaluation and quality improvement.
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http://dx.doi.org/10.1093/jacamr/dlz026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209972PMC
September 2019

Changes in Anesthetic and Postoperative Sedation-Analgesia Practice Associated With Early Extubation Following Infant Cardiac Surgery: Experience From the Pediatric Heart Network Collaborative Learning Study.

Pediatr Crit Care Med 2019 10;20(10):931-939

Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA.

Objectives: The Pediatric Heart Network sponsored the multicenter Collaborative Learning Study that implemented a clinical practice guideline to facilitate early extubation in infants after repair of isolated coarctation of the aorta and tetralogy of Fallot. We sought to compare the anesthetic practice in the operating room and sedation-analgesia management in the ICU before and after the implementation of the guideline that resulted in early extubation.

Design: Secondary analysis of data from a multicenter study from January 2013 to April 2015. Predefined variables of anesthetic, sedative, and analgesia exposure were compared before and after guideline implementation. Propensity score weighted logistic regression analysis was used to determine the independent effect of intraoperative dexmedetomidine administration on early extubation.

Setting: Five children's hospitals.

Patients: A total of 240 study subjects who underwent repair of coarctation of the aorta or tetralogy of Fallot (119 preguideline implementation and 121 postguideline implementation).

Interventions: None.

Measurements And Main Results: Clinical practice guideline implementation was accompanied by a decrease in the median total intraoperative dose of opioids (49.7 vs 24.0 µg/kg of fentanyl equivalents, p < 0.001) and benzodiazepines (1.0 vs 0.4 mg/kg of midazolam equivalents, p < 0.001), but no change in median volatile anesthetic agent exposure (1.3 vs 1.5 minimum alveolar concentration hr, p = 0.25). Intraoperative dexmedetomidine administration was associated with early extubation (odds ratio 2.5, 95% CI, 1.02-5.99, p = 0.04) when adjusted for other covariates. In the ICU, more patients received dexmedetomidine (43% vs 75%), but concomitant benzodiazepine exposure decreased in both the frequency (66% vs 57%, p < 0.001) and cumulative median dose (0.5 vs 0.3 mg/kg of ME, p = 0.003) postguideline implementation.

Conclusions: The implementation of an early extubation clinical practice guideline resulted in a reduction in the dose of opioids and benzodiazepines without a change in volatile anesthetic agent used in the operating room. Intraoperative dexmedetomidine administration was independently associated with early extubation. The total benzodiazepine exposure decreased in the early postoperative period.
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http://dx.doi.org/10.1097/PCC.0000000000002005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776694PMC
October 2019

Hydrophilic Small Molecules That Harness Transthyretin To Enhance the Safety and Efficacy of Targeted Chemotherapeutic Agents.

Mol Pharm 2019 07 13;16(7):3237-3252. Epub 2019 Jun 13.

The hydrophobicity of many chemotherapeutic agents usually results in their nonselective passive distribution into healthy cells and organs causing collateral toxicity. Ligand-targeted drugs (LTDs) are a promising class of targeted anticancer agents. The hydrophilicity of the targeting ligands in LTDs limits its nonselective passive tissue distribution and toxicity to healthy cells. In addition, the small size of LTDs allows for better tumor penetration, especially in the case of solid tumors. However, the short circulation half-life of LTDs, due to their hydrophilicity and small size, remains a significant challenge for achieving their full therapeutic potential. Therefore, extending the circulation half-life of targeted chemotherapeutic agents while maintaining their hydrophilicity and small size will represent a significant advance toward effective and safe cancer treatment. Here, we present a new approach for enhancing the safety and efficacy of targeted chemotherapeutic agents. By endowing hydrophobic chemotherapeutic agents with a targeting moiety and a hydrophilic small molecule that binds reversibly to the serum protein transthyretin, we generated small hydrophilic drug conjugates that displayed enhanced circulation half-life in rodents and selectivity to cancer cells. To the best of our knowledge, this is the first demonstration of a successful approach that maintains the small size and hydrophilicity of targeted anticancer agents containing hydrophobic payloads while at the same time extending their circulation half-life. This was demonstrated by the superior in vivo efficacy and lower toxicity of our conjugates in xenograft mouse models of metastatic prostate cancer.
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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607395PMC
July 2019

Non-radiometric Cell-free Assay to Measure the Effect of Molecular Chaperones on AMP-activated Kinase Activity.

Bio Protoc 2019 Apr;9(8)

McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

AMP-activated kinase (AMPK) is a trimeric protein holoenzyme with kinase activity. AMPK plays an important role in cellular metabolism and is thought to function as a fuel sensor within the cell, exerting kinase activity to activate energy-conserving pathways and simultaneously inhibit energy-consuming pathways. Traditional methods to measure AMPK activity to test potential agonists or antagonists utilize radiolabeled ATP with a peptide substrate. Although radiolabeling provides a high level of sensitivity, this approach is not ideal for medium to high-throughput screening, dose-response curves, or kinetic analyses. Our protocol utilizes Invitrogen's Z'-LYTE™ Kinase Assay Kit (Ser/Thr 23 Peptide) to measure changes in the enzymatic activity of AMPKɑ2β1γ1 in the presence of a molecular chaperone. The Z'-LYTE™ platform is based on Fluorescence Resonance Energy Transfer (FRET). The AMPK peptide substrate (S/T 23 peptide: MRPRKRQGSVRRRV) is a self-contained FRET system, using coumarin as the donor and fluorescein as the acceptor. When the peptide is phosphorylated, it is sensitive to cleavage by a site-specific protease. The cleavage of the phospho-peptide eliminates the FRET pair, and the ratiometric analysis of FRET is used as an indirect measure of AMPK kinase activity. This method does not require the use of radiolabeling or antibodies and is used in a multi-well format, with high reproducibility and throughput capabilities.
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http://dx.doi.org/10.21769/BioProtoc.3218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534159PMC
April 2019

The effect of salts in aqueous media on the formation of the BSA corona on SiO nanoparticles.

Colloids Surf B Biointerfaces 2019 Jul 6;179:374-381. Epub 2019 Apr 6.

Department of Chemical and Biochemical Engineering, 4133 Seamans Center for the Engineering Arts and Sciences, The University of Iowa, Iowa City, IA, USA. Electronic address:

Protein-nanoparticle interactions are garnering attention due to their potential impacts on human health and environmental contamination. The colloidal properties of nanoparticles (NPs) in aqueous media may differ in the presence of natural materials such as salts and proteins. In this study, the interactions between bovine serum albumin (BSA) and fumed hydrophilic silicon dioxide (SiO) NPs were studied in aqueous solutions under variable pH or ion composition. Investigation of hydrodynamic diameter and zeta potential changes to nanoparticles upon addition of BSA, the adsorption of BSA to the SiO NP surface, and the interaction energy between particles revealed that buffered solutions promote protein adsorption onto NPs and particle agglomeration. The effects of ionic salt solutions were dependent on the ion charge, with negatively charged ions stabilizing the system and positively charged ions promoting protein-nanoparticle interactions. These data highlight that physiologically relevant salts affect protein corona formation on non-toxic, amorphous SiO NPs and spur the need for well-defined characterization conditions when determining potential toxicity of NPs upon human or animal exposure.
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http://dx.doi.org/10.1016/j.colsurfb.2019.04.012DOI Listing
July 2019
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