153 results on '"Young MK"'
Search Results
2. Two years of enhanced surveillance of sexually transmitted Chlamydia in southeast Queensland
- Author
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McCall, BJ, Young, MK, and Jardine, D
- Published
- 2006
3. A family cluster of serogroup C meningococcal disease
- Author
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Looke, D, Young, MK, McCall, BJ, and Smith, HV
- Published
- 2004
4. Trends in potential exposure to Australian bat lyssavirus in South East Queensland, 1996 to 2003
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McCall, BJ and Young, MK
- Published
- 2004
5. Marker placement for movement analysis in scoliotic patients: a critical analysis of existing systems.
- Author
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Chockalingam N, Chevalier TL, Young MK, and Dangerfield PH
- Published
- 2008
6. Postherpetic neuralgia in older adults: culture, quality of life, and the use of alternative/complementary therapies.
- Author
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Young MK, Wood M, and Jean-Noel N
- Abstract
The purpose of this article is to describe current knowledge and standards of care for postherpetic neuralgia (PHN) among older persons. Three influencing factors are considered: cultural implications, quality of life (QOL), and current practice of alternative/complementary therapy. A review of literature published between 2001 and 2006 was conducted. The findings indicate that PHN has debilitating effects on older adults regardless of culture. The impact of PHN on culture and ethnicity, particularly on the relationship between culture and patient's self-report of herpes zoster and/or PHN, has not been well investigated as evidenced in the literature. PHN is found to be associated with decreased health-related QOL among the elderly, with the most affected domains being sleep, mood, and general activity. Alternative and complementary therapy offers many advantages such as ease of use, availability, and low cost. However, due to lack of controlled trials and insufficient evidence, alternative therapy is not currently used widely and recommended. As the US population ages, the incidence of herpes zoster and PHN is expected to rise. Clinical trials that explore the response of the culturally diverse older adults to current treatment guidelines, strategies for prevention of PHN and its corresponding decrease in QOL, as well as controlled trials of alternative/complementary remedies should be considered. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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7. An anthrone procedure for determination of inulin in biological fluids
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Young Mk and Raisz Lg
- Subjects
Anthracenes ,Chromatography ,Chemistry ,Inulin ,Urine ,Diluted urine ,Anthrone ,General Biochemistry, Genetics and Molecular Biology ,Body Fluids ,chemistry.chemical_compound ,Feces ,Sodium hydroxide ,Reagent ,Biological fluids ,Humans ,Digestion - Abstract
Summary1. A method for the determination of inulin in biological fluids using a modified anthrone reagent is described. 2. This reagent gives a sensitive and reproducible test for inulin in amounts of 15 to 45 μg. 3. Interfering substances are effectively removed from plasma filtrates and diluted urine by sodium hydroxide digestion. Ten to 25% of commercial inulin is found to be alkali-labile. 4. Recoveries from plasma and urine average 97.7 ± 2.5% and 99.7 ± 2.0%, respectively.
- Published
- 1952
8. Oxidation of amino acids by red and white muscle fiber groups
- Author
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Beatty, CH, primary, Curtis, S, additional, Young, MK, additional, and Bocek, RM, additional
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- 1974
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9. Respiration and metabolism by homogenates of various types of muscle
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Beatty, CH, primary, Young, MK, additional, and Bocek, RM, additional
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- 1972
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10. A systematic review and meta-analysis of ambient temperature and precipitation with infections from five food-borne bacterial pathogens.
- Author
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Manchal N, Young MK, Castellanos ME, Leggat P, and Adegboye O
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- Humans, Incidence, Rain, Gastroenteritis epidemiology, Gastroenteritis microbiology, Bacteremia epidemiology, Bacteremia microbiology, Temperature, Foodborne Diseases epidemiology, Foodborne Diseases microbiology
- Abstract
Studies on climate variables and food pathogens are either pathogen- or region-specific, necessitating a consolidated view on the subject. This study aims to systematically review all studies on the association of ambient temperature and precipitation on the incidence of gastroenteritis and bacteraemia from Salmonella , Shigella , Campylobacter , Vibrio , and Listeria species. PubMed, Ovid MEDLINE, Scopus, and Web of Science databases were searched up to 9 March 2023. We screened 3,204 articles for eligibility and included 83 studies in the review and three in the meta-analysis. Except for one study on Campylobacter , all showed a positive association between temperature and Salmonella, Shigella, Vibrio sp. , and Campylobacter gastroenteritis. Similarly, most of the included studies showed that precipitation was positively associated with these conditions. These positive associations were found regardless of the effect measure chosen. The pooled incidence rate ratio (IRR) for the three studies that included bacteraemia from Campylobacter and Salmonella sp. was 1.05 (95 per cent confidence interval (95% CI): 1.03, 1.06) for extreme temperature and 1.09 (95% CI: 0.99, 1.19) for extreme precipitation. If current climate trends continue, our findings suggest these pathogens would increase patient morbidity, the need for hospitalization, and prolonged antibiotic courses.
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- 2024
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11. Comparison of Anti-Hepatitis A Antibody Pharmacokinetics in Healthy Australian Subjects Receiving Standard or Weight-Based Dosing of Polyvalent Immunoglobulin.
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Young MK, Ng SK, Faddy HM, and Nimmo GR
- Abstract
This randomized controlled trial compared two dosing regimens of the polyvalent immunoglobulin available for hepatitis A post-exposure prophylaxis in Australia. Participants were randomized to receive either 270 IU (standard dose) or 3.375 IU/kg (dose by weight). Quantitative serial serum hepatitis A antibody concentrations were measured at baseline and then on days 1, 3, 7, 28, and 50. Fifteen participants completed the trial. Serum hepatitis A antibody concentrations were not different between the study groups at any time point. Pharmacokinetic parameters estimated from participant data were not different between the study groups. The hepatitis A antibody level of all participants exceeded 10 mIU/mL at day 50. While no difference between dosing regimens was found in this study, further research should examine dosing at the lower limit of current Australian recommendations before making policy decisions., (© 2024 The Author(s). The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)
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- 2024
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12. From dusty shelves toward the spotlight: growing evidence for Ap4A as an alarmone in maintaining RNA stability and proteostasis.
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Young MK and Wang JD
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- Escherichia coli genetics, Escherichia coli metabolism, Bacillus subtilis genetics, Bacillus subtilis metabolism, Bacterial Proteins metabolism, Bacterial Proteins genetics, Bacteria metabolism, Bacteria genetics, Stress, Physiological, Dinucleoside Phosphates metabolism, Proteostasis, RNA Stability
- Abstract
Bacteria thrive in diverse environments and must withstand various stresses. A key stress response mechanism is the reprogramming of macromolecular biosynthesis and metabolic processes through alarmones - signaling nucleotides that accumulate intracellularly in response to metabolic stress. Diadenosine tetraphosphate (Ap4A), a putative alarmone, is produced in a noncanonical reaction by universally conserved aminoacyl-tRNA synthetases. Ap4A is ubiquitous across all domains of life and accumulates during heat and oxidative stress. Despite its early discovery in 1966, Ap4A's alarmone status remained inconclusive. Recent discoveries identified Ap4A as a precursor to RNA 5' caps in Escherichia coli. Additionally, Ap4A was found to directly bind to and allosterically inhibit the purine biosynthesis enzyme inosine 5'-monophosphate dehydrogenase, regulating guanosine triphosphate levels and enabling heat resistance in Bacillus subtilis. These findings, along with previous research, strongly suggest that Ap4A plays a crucial role as an alarmone, warranting further investigation to fully elucidate its functions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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13. The impact of existing total anti-toxin B IgG immunity in outcomes of recurrent Clostridioides difficile infection.
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Rigo I, Young MK, Abhyankar MM, Xu F, Ramakrishnan G, Naz F, Madden GR, and Petri WA
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- Humans, Male, Middle Aged, Female, Aged, Bacterial Proteins immunology, Prospective Studies, Antibodies, Neutralizing immunology, Antibodies, Neutralizing blood, Adult, Aged, 80 and over, Clostridium Infections immunology, Clostridium Infections prevention & control, Immunoglobulin G blood, Immunoglobulin G immunology, Bacterial Toxins immunology, Clostridioides difficile immunology, Recurrence, Antibodies, Bacterial blood, Antibodies, Bacterial immunology
- Abstract
Late anti-toxin-B humoral immunity acquired after treatment is important for preventing recurrent Clostridioides difficile infection. We prospectively-measured anti-toxin-B IgG and neutralization titers at diagnosis as potential early predictors of recurrence. High anti-toxin-B-IgG/neutralizing antibodies were associated with short-lasting protection within 6-weeks, however, no difference in recurrence risk was observed by 90-days post-infection., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: William A. Petri Jr is a consultant for TechLab, a company that makes diagnostics for C. difficile. The other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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14. Systemic neutrophil degranulation and emergency granulopoiesis in patients with Clostridioides difficile infection.
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Ramakrishnan G, Young MK, Nayak U, Rigo I, Marrs AS, Gilchrist CA, Behm BW, Madden GR, and Petri WA Jr
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- Humans, Male, Female, Middle Aged, Aged, Biomarkers blood, Adult, Flow Cytometry, Neutrophil Activation, Aged, 80 and over, Cytokines blood, Lipocalin-2 blood, Neutrophils immunology, Cell Degranulation, Clostridium Infections immunology, Clostridium Infections blood, Clostridium Infections microbiology, Clostridioides difficile
- Abstract
Objectives: Clostridioides difficile infection (CDI) is characterized by neutrophilia in blood, with a high leukocyte count accompanying severe infection. In this study, we characterized peripheral blood neutrophil activation and maturity in CDI by (i) developing a method to phenotype stored neutrophils for disease-related developmental alterations and (ii) assessing neutrophil-associated biomarkers., Methods: We stored fixed leukocytes from blood collected within 24 h of diagnosis from a cohort of hospitalized patients with acute CDI. Additional study cohorts included recurrent CDI patients at time of and two months after FMT therapy and a control healthy cohort. We assessed levels of neutrophil surface markers CD66b, CD11b, CD16 and CD10 by flow cytometry. Plasma neutrophil elastase and lipocalin-2 were measured using ELISA, while G-CSF, GM-CSF and cytokines were measured using O-link Proteomic technology., Results: CD66b
+ neutrophil abundance assessed by flow cytometry correlated well with complete blood counts, establishing that neutrophils in stored blood are sufficiently well-preserved for phenotyping by flow cytometry. Neutrophil abundance was significantly increased in CDI patients compared to healthy controls. Emergency granulopoiesis in acute CDI patients was evidenced by lower neutrophil surface expression of CD10, CD11b and CD16. CD10+ staining of neutrophils started to recover within 3-7 days of CDI treatment. Neutrophil activation and degranulation were higher in acute CDI as assessed by plasma neutrophil elastase and lipocalin-2. Biomarker levels in immunocompetent subjects were associated with recurrence and fatal outcomes., Conclusions: Neutrophil activation and emergency granulopoiesis characterize the early immune response in acute CDI, with plasma degranulation biomarkers predictive of disease severity., Competing Interests: Declaration of competing interest WAP has a conflict of interest in that he is a consultant for TechLab, Inc, which makes diagnostic tests for C. difficile infection. The other authors have no conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2024
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15. The unknown unknown: A framework for assessing environmental DNA assay specificity against unsampled taxa.
- Author
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Wilcox TM, Kronenberger JA, Young MK, Mason DH, Franklin TW, and Schwartz MK
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- Animals, Insecta, Fresh Water, DNA, Environmental, Carps, Urochordata
- Abstract
Taxon-specific quantitative PCR (qPCR) assays are commonly used for environmental DNA sampling-based inference of animal presence. These assays require thorough validation to ensure that amplification truly indicates detection of the target taxon, but a thorough validation is difficult when there are potentially many non-target taxa, some of which may have incomplete taxonomies. Here, we use a previously published, quantitative model of cross-amplification risk to describe a framework for assessing qPCR assay specificity when there is missing information and it is not possible to assess assay specificity for each individual non-target confamilial. In this framework, we predict assay specificity against unsampled taxa (non-target taxa without sequence data available) using the sequence information that is available for other confamilials. We demonstrate this framework using four case study assays for: (1) An endemic, freshwater arthropod (meltwater stonefly; Lednia tumana), (2) a globally distributed, marine ascidian (Didemnum perlucidum), (3) a continentally distributed freshwater crustacean (virile crayfish; Faxonius virilis, deanae and nais species complex) and (4) a globally distributed freshwater teleost (common carp; Cyprinus carpio and its close relative C. rubrofuscus). We tested the robustness of our approach to missing information by simulating application of our framework for all possible subsamples of 20-all non-target taxa. Our results suggest that the modelling framework results in estimates which are largely concordant with observed levels of cross-amplification risk using all available sequence data, even when there are high levels of data missingness. We explore potential limitations and extensions of this approach for assessing assay specificity and provide users with an R Markdown template for generating reproducible reports to support their own assay validation efforts., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)
- Published
- 2024
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16. Simultaneous species detection and discovery with environmental DNA metabarcoding: A freshwater mollusk case study.
- Author
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Vanderpool DD, Wilcox TM, Young MK, Pilgrim KL, and Schwartz MK
- Abstract
Environmental DNA (eDNA) sampling is a powerful tool for rapidly characterizing biodiversity patterns for specious, cryptic taxa with incomplete taxonomies. One such group that are also of high conservation concern are North American freshwater gastropods. In particular, springsnails of the genus Pyrgulopsis (Family: Hydrobiidae) are prevalent throughout the western United States where >140 species have been described. Many of the described species are narrow endemics known from a single spring or locality, and it is believed that there are likely many additional species which have yet to be described. The distribution of these species across the landscape is of interest because habitat loss and degradation, climate change, groundwater mining, and pollution have resulted in springsnail imperilment rates as high as 92%. Determining distributions with conventional sampling methods is limited by the fact that these snails are often <5 mm in length with few distinguishing morphological characters, making them both difficult to detect and to identify. We developed an eDNA metabarcoding protocol that is both inexpensive and capable of rapid, accurate detection of all known Pyrgulopsis species. When compared with conventional collection techniques, our pipeline consistently resulted in detection at sites previously known to contain Pyrgulopsis springsnails and at a cost per site that is likely to be substantially less than the conventional sampling and individual barcoding that has been done historically. Additionally, because our method uses eDNA extracted from filtered water, it is non-destructive and suitable for the detection of endangered species where "no take" restrictions may be in effect. This effort represents both a tool which is immediately applicable to taxa of high conservation concern across western North America and a case study in the broader application of eDNA sampling for landscape assessments of cryptic taxa of conservation concern., Competing Interests: The authors declare no conflict of interest., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Ecology and Evolution published by John Wiley & Sons Ltd.)
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- 2024
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17. Pulmonary Function and Survival 1 Year After Dupilumab Treatment of Acute Moderate to Severe Coronavirus Disease 2019: A Follow-up Study From a Phase 2a Trial.
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Hendrick J, Ma JZ, Haughey HM, Coleman R, Nayak U, Kadl A, Sturek JM, Jackson P, Young MK, Allen JE, and Petri WA
- Abstract
Background: We previously conducted a phase 2a randomized placebo-controlled trial of 40 subjects to assess the efficacy and safety of dupilumab use in people hospitalized with coronavirus disease 2019 (COVID-19) (NCT04920916). Based on our preclinical data suggesting that downstream pulmonary dysfunction with COVID-19 induced type 2 inflammation, we contacted patients from our phase 2a study at 1 year for assessment of post-COVID-19 conditions., Methods: Subjects at 1 year after treatment underwent pulmonary function tests, high-resolution computed tomographic imaging, symptom questionnaires, neurocognitive assessments, and serum immune biomarker analysis, with subject survival also monitored. The primary outcome was the proportion of abnormal diffusion capacity for carbon monoxide (DLCO) or 6-minute walk test (6MWT) at the 1-year visit., Results: Of those survivors who consented to 1-year visits (n = 16), subjects who had originally received dupilumab were less likely than those who received placebo to have an abnormal DLCO or 6MWT (Fisher exact P = .011; adjusted P = .058). As a secondary endpoint, we saw that 16% of subjects in the dupilumab group died by 1 year compared to 38% in the placebo group, though this was not statistically significant (log-rank P = .12). We did not find significant differences in neurocognitive testing, symptoms, or chest computed tomography between treatment groups but observed a larger reduction in eotaxin levels in those who received dupilumab., Conclusions: In this observational study, subjects who received dupilumab during acute COVID-19 hospitalization were less likely to have a reduced DLCO or 6MWT, with a nonsignificant trend toward reduced mortality at 1 year compared to placebo., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2024
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18. Field testing Australian bat lyssavirus risk communication resources.
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Uren AM and Young MK
- Abstract
Issue Addressed: Australian bat lyssavirus (ABLV) is a fatal zoonosis, which can be transmitted to humans through scratches or bites from infected bats. Currently, there is a lack of research evaluating risk communication resources about ABLV or the dangers from handling bats. The purpose of this study was to field test resources aimed at educating the public about risks to humans and bats from human-bat interaction, then update these resources based upon feedback to ensure they were relevant and appropriately targeted to the public., Methods: Thirteen semi-structured interviews with a purposive sample of participants chosen for maximum variation of age and sex were conducted. Two investigators analysed the data independently using a deductive approach and then came to consensus by discussion., Results: The main themes were a wide-ranging level of knowledge and opinions about bats, the resources having an effect on people, and messaging in relation to children and pets being particularly important., Conclusion: This study highlighted the complexities of risk communication to a broad audience with varied experience and knowledge about bats, and the importance of evaluation prior to implementation to ensure risk communication is relevant and appealing to the intended audience. SO WHAT?: Field testing of health education material prior to implementation is an effective way to ensure key messages are understood, and is important when communicating about fatal but preventable zoonoses such as ABLV., (© 2023 Australian Health Promotion Association.)
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- 2024
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19. Exploring relationships between pre-service teachers' self-efficacy for writing and instruction provided in simulated elementary writing conferences.
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Gillespie Rouse A, Young MK, and Gifford D
- Abstract
Practice-based opportunities, like teaching simulations, are becoming more prevalent in teacher preparation programs. We sought to examine the instructional moves of 5 pre-service teachers during a simulated elementary writing conference using Mursion technology, a mixed-reality simulation (MRS) that emulates a classroom environment with student avatars. We examined both participants' self-efficacy and their instructional moves during MRS writing conferences. To better understand pre-service teachers' learning, we also examined reflections they wrote about their MRS experience. Results showed that pre-service teachers spent much of their time (31.7%) managing the environment (e.g., setting expectations, addressing student behavior) during MRS writing conferences, followed by nearly one-fourth of their time (24.2%) instructing students on their writing pieces (e.g., adding details, revising, editing), with high levels of teacher talk compared to student talk. Participants' self-efficacy for writing, for teaching writing elements, and for writing instruction were not clearly related to their instructional moves during the MRS experience. However, participants' reflections suggest that pre-service teachers felt the experience gave them the opportunity to practice making in-the-moment decisions and learn from their peers in a way that may allow them to have a more accurate understanding of their abilities to teach writing. Implications from these findings related to teacher self-efficacy, motivation, and teacher preparation programs are presented., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gillespie Rouse, Young and Gifford.)
- Published
- 2023
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20. Pulmonary function and survival one year after dupilumab treatment of acute moderate to severe COVID-19: A follow up study from a Phase IIa trial.
- Author
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Hendrick J, Ma JZ, Haughey HM, Coleman R, Nayak U, Kadl A, Sturek JM, Jackson P, Young MK, Allen JE, and Petri WA Jr
- Abstract
Background: We previously conducted a Phase IIa randomized placebo-controlled trial of 40 subjects to assess the efficacy and safety of dupilumab use in those hospitalized with COVID-19 (NCT04920916). Based on our pre-clinical data suggesting downstream pulmonary dysfunction with COVID-19 induced type 2 inflammation, we contacted patients from our Phase IIa study at 1 year for assessment of Post Covid-19 Conditions (PCC)., Methods: Subjects at 1 year after treatment underwent pulmonary function testing (PFTs), high resolution computed tomography (HRCT) imaging, symptom questionnaires, neurocognitive assessments, and serum immune biomarker analysis, with subject survival also monitored. The primary outcome was the proportion of abnormal PFTs, defined as an abnormal diffusion capacity for carbon monoxide (DLCO) or 6-minute walk testing (6MWT) at the 1-year visit., Results: Sixteen of the 29 one-year survivors consented to the follow up visit. We found that subjects who had originally received dupilumab were less likely to have abnormal PFTs compared to those who received placebo (Fisher's exact p=0.011, adjusted p=0.058). We additionally found that 3 out of 19 subjects (16%) in the dupilumab group died by 1 year compared to 8 out of 21 subjects (38%) in the placebo group (log rank p=0.12). We did not find significant differences in neurocognitive testing, symptoms or CT chest imaging between treatment groups but observed evidence of reduced type 2 inflammation in those who received dupilumab., Conclusions: We observed evidence of reduced long-term morbidity and mortality from COVID-19 with dupilumab treatment during acute hospitalization when added to standard of care regimens., Competing Interests: POTENTIAL CONFLICTS OF INTEREST: The authors have no competing interests to report.
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- 2023
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21. Detection of Leishmania (Mundinia) macropodum (Kinetoplastida: Trypanosomatidae) and heterologous Leishmania species antibodies among blood donors in a region of Australia with marsupial Leishmania endemicity.
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Panahi E, Stanisic DI, Skinner EB, Faddy HM, Young MK, and Herrero LJ
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- Humans, Blood Donors, Australia epidemiology, Immunoglobulin G, Leishmania, Kinetoplastida, Leishmaniasis, Cutaneous epidemiology, Leishmaniasis, Cutaneous veterinary, Leishmaniasis, Cutaneous diagnosis
- Abstract
Objectives: The Australian Leishmania (Mundinia) macropodum parasite causes cutaneous leishmaniasis among marsupial species. Although cutaneous leishmaniasis is a major public health burden worldwide, it is not clear if humans are naturally exposed to the unique L. macropodum. To assess whether humans have an immunoglobulin (Ig) G response to L. macropodum, we examined anti-Leishmania antibodies among humans residing in a region of marsupial Leishmania endemicity in Australia., Methods: Using a serological enzyme-linked immunosorbent assay, we characterized Leishmania-specific IgG and IgG subclass responses to soluble Leishmania antigen from L. macropodum, and other Leishmania species (L. donovani, L. major, and L. mexicana) in 282 blood donor samples., Results: We found that 20.57% of individuals demonstrated a positive total IgG response to L. macropodum. For individuals with antibodies to soluble Leishmania antigen from one Leishmania species, there was no increased likelihood of recognition to other Leishmania species. For samples with detectable L. macropodum IgG, IgG1 and IgG2 were the prevalent subclasses detected., Conclusion: It is not yet clear whether the IgG antibody detection in this study reflects exposure to Leishmania parasites or a cross-reactive immune response that was induced against an unrelated immunogen. Future studies should investigate whether L. macropodum can result in a viable infection in humans., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022. Published by Elsevier Ltd.)
- Published
- 2023
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22. Novel Biomarkers, Including tcdB PCR Cycle Threshold, for Predicting Recurrent Clostridioides difficile Infection.
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Madden GR, Rigo I, Boone R, Abhyankar MM, Young MK, Basener W, and Petri WA Jr
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- Humans, Interleukin-8, Interleukin-6, Bayes Theorem, Endothelial Growth Factors therapeutic use, Epidermal Growth Factor therapeutic use, Biomarkers analysis, Polymerase Chain Reaction, Clostridioides difficile genetics, Bacterial Toxins genetics, Clostridium Infections diagnosis, Clostridium Infections drug therapy
- Abstract
Traditional clinical models for predicting recurrent Clostridioides difficile infection do not perform well, likely owing to the complex host-pathogen interactions involved. Accurate risk stratification using novel biomarkers could help prevent recurrence by improving underutilization of effective therapies (i.e., fecal transplant, fidaxomicin, bezlotoxumab). We used a biorepository of 257 hospitalized patients with 24 features collected at diagnosis, including 17 plasma cytokines, total/neutralizing anti-toxin B IgG, stool toxins, and PCR cycle threshold ( C
T ) (a proxy for stool organism burden). The best set of predictors for recurrent infection was selected by Bayesian model averaging for inclusion in a final Bayesian logistic regression model. We then used a large PCR-only data set to confirm the finding that PCR CT predicts recurrence-free survival using Cox proportional hazards regression. The top model-averaged features were (probabilities of >0.05, greatest to least): interleukin 6 (IL-6), PCR CT , endothelial growth factor, IL-8, eotaxin, IL-10, hepatocyte growth factor, and IL-4. The accuracy of the final model was 0.88. Among 1,660 cases with PCR-only data, cycle threshold was significantly associated with recurrence-free survival (hazard ratio, 0.95; P < 0.005). Certain biomarkers associated with C. difficile infection severity were especially important for predicting recurrence; PCR CT and markers of type 2 immunity (endothelial growth factor [EGF], eotaxin) emerged as positive predictors of recurrence, while type 17 immune markers (IL-6, IL-8) were negative predictors. In addition to novel serum biomarkers (particularly, IL-6, EGF, and IL-8), the readily available PCR CT may be critical to augment underperforming clinical models for C. difficile recurrence.- Published
- 2023
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23. Vulvovaginal erosive lichen planus refractory to topical therapies: What's next? A case report.
- Author
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Young MK, Holder KG, Baker TE, and Kauffman RP
- Abstract
A 60-year-old woman was referred for progressive and severe vulvovaginal pain characterized by erosions and Wickham's stria for the past 7 months. Her condition had not responded to oral fluconazole, topical estrogen cream, and topical clobetasol cream. Vulvar and vaginal biopsies were obtained under general anesthesia to verify the diagnosis of erosive lichen planus given the failed response to ultrapotent topical steroids. Tacrolimus cream was added but not tolerated. Oral and cutaneous lesions of lichen planus also developed. In the absence of evidence-based guidelines, three different systemic treatments were administered sequentially (hydroxychloroquine, mycophenolate, and finally cyclosporin) before a satisfactory, well-tolerated, and sustained clinical response was obtained. Topical betamethasone ointment in a taper was continued to assist in sustaining a vulvovaginal response after cyclosporin was discontinued., (© 2023 The Authors.)
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- 2023
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24. Broad-scale eDNA sampling for describing aquatic species distributions in running waters: Pacific lamprey Entosphenus tridentatus in the upper Snake River, USA.
- Author
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Young MK, Isaak DJ, Nagel D, Horan DL, Carim KJ, Franklin TW, Zeller VA, Roper B, and Schwartz MK
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- United States, Animals, Rivers, Lampreys genetics, Salmon genetics, Ecosystem, DNA, Environmental
- Abstract
One of the most fundamental yet challenging tasks for aquatic ecologists is to precisely delineate the range of species, particularly those that are broadly distributed, require specialized sampling methods, and may be simultaneously declining and increasing in different portions of their range. An exemplar is the Pacific lamprey Entosphenus tridentatus, a jawless anadromous fish of conservation concern that is actively managed in many coastal basins in western North America. To efficiently determine its distribution across the accessible 56,168 km of the upper Snake River basin in the north-western United States, we first delimited potential habitat by using predictions from a species distribution model based on conventionally collected historical data and from the distribution of a potential surrogate, Chinook salmon Oncorhynchus tshawytscha, which yielded a potential habitat network of 10,615 km. Within this area, we conducted a two-stage environmental DNA survey involving 394 new samples and 187 archived samples collected by professional biologists and citizen scientists using a single, standardized method from 2015 to 2021. We estimated that Pacific lamprey occupied 1875 km of lotic habitat in this basin, of which 1444 km may have been influenced by recent translocation efforts. Pacific lamprey DNA was consistently present throughout most river main stems, although detections became weaker or less frequent in the largest and warmest downstream channels and near their headwater extent. Pacific lamprey were detected in nearly all stocked tributaries, but there was no evidence of indigenous populations in such habitats. There was evidence of post-stocking movement because detections were 1.8-36.0 km upstream from release sites. By crafting a model-driven spatial sampling template and executing an eDNA-based sampling campaign led by professionals and volunteers, supplemented by previously collected samples, we established a benchmark for understanding the current range of Pacific lamprey across a large portion of its range in the interior Columbia River basin. This approach could be tailored to refine range estimates for other wide-ranging aquatic species of conservation concern., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA.)
- Published
- 2022
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25. eDNAssay: A machine learning tool that accurately predicts qPCR cross-amplification.
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Kronenberger JA, Wilcox TM, Mason DH, Franklin TW, McKelvey KS, Young MK, and Schwartz MK
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- Benzothiazoles, Diamines, Machine Learning, Oligonucleotides, Quinolines, Real-Time Polymerase Chain Reaction methods, Sensitivity and Specificity, DNA, Environmental
- Abstract
Environmental DNA (eDNA) sampling is a highly sensitive and cost-effective technique for wildlife monitoring, notably through the use of qPCR assays. However, it can be difficult to ensure assay specificity when many closely related species co-occur. In theory, specificity may be assessed in silico by determining whether assay oligonucleotides have enough base-pair mismatches with nontarget sequences to preclude amplification. However, the mismatch qualities required are poorly understood, making in silico assessments difficult and often necessitating extensive in vitro testing-typically the greatest bottleneck in assay development. Increasing the accuracy of in silico assessments would therefore streamline the assay development process. In this study, we paired 10 qPCR assays with 82 synthetic gene fragments for 530 specificity tests using SYBR Green intercalating dye (n = 262) and TaqMan hydrolysis probes (n = 268). Test results were used to train random forest classifiers to predict amplification. The primer-only model (SYBR Green results) and full-assay model (TaqMan probe-based results) were 99.6% and 100% accurate, respectively, in cross-validation. We further assessed model performance using six independent assays not used in model training. In these tests the primer-only model was 92.4% accurate (n = 119) and the full-assay model was 96.5% accurate (n = 144). The high performance achieved by these models makes it possible for eDNA practitioners to more quickly and confidently develop assays specific to the intended target. Practitioners can access the full-assay model online via eDNAssay (https://NationalGenomicsCenter.shinyapps.io/eDNAssay), a user-friendly tool for predicting qPCR cross-amplification., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA.)
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- 2022
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26. Clinical features and predictive biomarkers for bladder cancer in patients with type 2 diabetes presenting with haematuria.
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Tonry CL, Evans RM, Ruddock MW, Duggan B, McCloskey O, Maxwell AP, O'Rourke D, Boyd RE, Watt J, Reid CN, Curry DJ, Stevenson M, Young MK, Jamison CS, Gallagher J, Fitzgerald SP, Lamont J, and Watson CJ
- Subjects
- Biomarkers, Tumor, Hematuria diagnosis, Hematuria etiology, Humans, Vascular Endothelial Growth Factor A, Diabetes Mellitus, Type 2 complications, Renal Insufficiency, Chronic complications, Urinary Bladder Neoplasms complications, Urinary Bladder Neoplasms diagnosis, Urinary Bladder Neoplasms pathology
- Abstract
Aims: To identify clinical features and protein biomarkers associated with bladder cancer (BC) in individuals with type 2 diabetes mellitus presenting with haematuria., Materials and Methods: Data collected from the Haematuria Biomarker (HaBio) study was used in this analysis. A matched sub-cohort of patients with type 2 diabetes and patients without diabetes was created based on age, sex, and BC diagnosis, using approximately a 1:2 fixed ratio. Randox Biochip Array Technology and ELISA were applied for measurement of 66 candidate serum and urine protein biomarkers. Hazard ratios and 95% confidence intervals were estimated by chi-squared and Wilcoxon rank sum test for clinical features and candidate protein biomarkers. Diagnostic protein biomarker models were identified using Lasso-based binominal regression analysis., Results: There was no difference in BC grade, stage, and severity between individuals with type 2 diabetes and matched controls. Incidence of chronic kidney disease (CKD) was significantly higher in patients with type 2 diabetes (p = 0.008), and CKD was significantly associated with BC in patients with type 2 diabetes (p = 0.032). A biomarker model, incorporating two serum (monocyte chemoattractant protein 1 and vascular endothelial growth factor) and three urine (interleukin 6, cytokeratin 18, and cytokeratin 8) proteins, predicted incidence of BC with an Area Under the Curve (AUC) of 0.84 in individuals with type 2 diabetes. In people without diabetes, the AUC was 0.66., Conclusions: We demonstrate the potential clinical utility of a biomarker panel, which includes proteins related to BC pathogenesis and type 2 diabetes, for monitoring risk of BC in patients with type 2 diabetes. Earlier urology referral of patients with type 2 diabetes will improve outcomes for these patients., Trial Registration: http://www.isrctn.com/ISRCTN25823942., (© 2022 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)
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- 2022
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27. Repressed Ang 1-7 in COVID-19 Is Inversely Associated with Inflammation and Coagulation.
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Carpenter RM, Young MK, Petri WAO, Lyons GR, Gilchrist C, Carey RM, and Petri WA Jr
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- Humans, Inflammation, Peptidyl-Dipeptidase A, SARS-CoV-2, Angiotensin-Converting Enzyme 2, COVID-19
- Abstract
The coronavirus SARS-CoV-2 infects host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, which belongs to an anti-inflammatory, anti-thrombotic counter-regulatory arm of the renin-angiotensin system (RAS). ACE2 dysfunction and RAS dysregulation has been explored as a driving force in acute respiratory distress syndrome (ARDS), but data from COVID-19 patients has been inconsistent and inconclusive. We sought to identify disruptions of the classical (ACE)/angiotensin (Ang) II/Ang II type-1 receptor (AT
1 R) and the counter-regulatory ACE2/Ang 1-7/ Mas Receptor ( Mas R) pathways in patients with COVID-19 and correlate these with severity of infection and markers of inflammation and coagulation. Ang II and Ang 1-7 levels in plasma were measured by enzyme-linked immunosorbent assay (ELISA) for 230 patients, 166 of whom were SARS-CoV-2+. Ang 1-7 was repressed in COVID-19 patients compared to that in SARS-CoV-2 negative outpatient controls. Since the control cohort was less sick than the SARS-CoV-2+ group, this association between decreased Ang 1-7 and COVID-19 cannot be attributed to COVID-19 specifically as opposed to critical illness more generally. Multivariable logistic regression analyses demonstrated that every 10-pg/mL increase in plasma Ang 1-7 was associated with a 3% reduction in the odds of hospitalization (adjusted odds ratio [AOR] 0.97, confidence interval [CI] 0.95 to 0.99) and a 3% reduction in odds of requiring oxygen supplementation (AOR 0.97, CI 0.95 to 0.99) and/or ventilation (AOR 0.97, CI 0.94 to 0.99). Ang 1-7 was also inversely associated with pro-inflammatory cytokines and d-dimer in this patient cohort, suggesting that reduced activity in this protective counter-regulatory arm of the RAS contributes to the hyper-immune response and diffuse coagulation activation documented in COVID-19. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a unique disease, COVID-19, which ranges in severity from asymptomatic to causing severe respiratory failure and death. Viral transmission throughout the world continues at a high rate despite the development and widespread use of effective vaccines. For those patients who contract COVID-19 and become severely ill, few therapeutic options have been shown to provide benefits and mortality rates are high. Additionally, the pathophysiology underlying COVID-19 disease presentation, progression, and severity is incompletely understood. The significance of our research is in confirming the role of renin-angiotensin system dysfunction in COVID-19 pathogenesis in a large cohort of patients with diverse disease severity and outcomes. Additionally, to our knowledge, this is the first study to pair angiotensin peptide levels with inflammatory and thrombotic markers. These data support the role of ongoing clinical trials examining renin-angiotensin system-targeted therapeutics for the treatment of COVID-19.- Published
- 2022
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28. Activity in the Dorsomedial Striatum Underlies Serial Reversal Learning Performance Under Probabilistic Uncertainty.
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Young MK, Conn KA, Das J, Zou S, Alexander S, Burne THJ, and Kesby JP
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Background: Corticostriatal circuits, particularly the dorsomedial striatum (DMS) and lateral orbitofrontal cortex, are critical for navigating reversal learning under probabilistic uncertainty. These same areas are implicated in the reversal learning impairments observed in individuals with psychosis as well as their psychotic symptoms, suggesting that they may share a common neurobiological substrate. To address this question, we used psychostimulant exposure and specific activation of the DMS during reversal learning in mice to assess corticostriatal activity., Methods: We used amphetamine treatment to induce psychosis-relevant neurobiology in male mice during reversal learning and to examine pathway-specific corticostriatal activation. To determine the causal role of DMS activity, we used chemogenetics to drive midbrain inputs during a range of probabilistic contingencies., Results: Mice treated with amphetamine showed altered punishment learning, which was associated with decreased shifting after losses and increased perseverative errors after reversals. Reversal learning performance and strategies were dependent on increased activity in lateral orbitofrontal cortex to DMS circuits as well as in the DMS itself. Specific activation of midbrain to DMS circuits also decreased shifting after losses and reversal learning performance. However, these alterations were dependent on the probabilistic contingency., Conclusions: Our work suggests that the DMS plays a multifaceted role in reversal learning. Increasing DMS activity impairs multiple reversal learning processes dependent on the level of uncertainty, confirming its role in the maintenance and selection of incoming cortical inputs. Together, these outcomes suggest that elevated dopamine levels in the DMS could contribute to decision-making impairments in individuals with psychosis., (© 2022 The Authors.)
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- 2022
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29. Diagnostic performance of screening tools for the detection of obstructive sleep apnea in people living with HIV.
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Schmickl CN, Bosompra NO, DeYoung PN, Gilbertson D, Orr JE, Malhotra A, Grant I, Ancoli-Israel S, Young MK, and Owens RL
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- Fatigue complications, Female, Humans, Male, Mass Screening, Polysomnography, Sleepiness, Surveys and Questionnaires, HIV Infections complications, Sleep Apnea, Obstructive complications, Sleep Apnea, Obstructive diagnosis
- Abstract
Study Objectives: Many people living with human immunodeficiency virus (PLWH) have undiagnosed obstructive sleep apnea (OSA), which may contribute to commonly reported fatigue and the high cardiovascular disease burden in this population. Our objective was to assess the utility of traditional OSA screening tools (STOP-BANG, Berlin Questionnaire, and Epworth Sleepiness Scale) for detecting OSA in PLWH., Methods: Adult PLWH were recruited from sleep/ human immunodeficiency virus clinics and the community into a larger clinical trial that included completion of these questionnaires before in-laboratory polysomnography. Discriminatory performance of these screening tools was assessed using area under receiver operating characteristic curves (AUC). The reference standard for the primary analysis was OSA based on an apnea-hypopnea index ≥ 5 events/h using recommended "1A"-criteria (hypopnea with 3% desaturation and/or arousal). Secondary analyses explored acceptable "1B"-criteria (hypopnea with 4% desaturation) and/or higher apnea-hypopnea index cut-offs (≥ 15 events/h)., Results: 120 PLWH were included (mean age: 50 ± 11 years; body mass index: 27 ± 4 kg/m
2 , 84% male) and OSA was diagnosed in 75% using 1A-criteria. In the primary analysis, the discriminatory performance of the 3 screening tools was low (AUCs 0.58 to 0.70) and similar across the tools ( P ≥ .14). In secondary analyses, STOP-BANG showed moderate-high discriminatory ability (AUCs 0.77-0.80) and performed significantly better ( P ≤ .008) than the Berlin Questionnaire or Epworth Sleepiness Scale (AUCs 0.53-0.62)., Conclusions: OSA was highly prevalent in our cohort of PLWH. Although STOP-BANG could reasonably identify moderate-severe OSA, the tools were not reliable for mild disease. Specifically, the questionnaires perform poorly for PLWH with mild OSA manifesting with arousals, yet such people may be at risk of fatigue/sleepiness and impaired memory consolidation., Clinical Trial Registration: Registry: ClinicalTrials.gov; Title: Obstructive Sleep Apnea Endotypes and Impact on Phenotypes of People Living with HIV (PLWH/OSA); Identifier: NCT03575143; URL: https://clinicaltrials.gov/ct2/show/NCT03575143., Citation: Schmickl CN, Bosompra N-O, DeYoung PN, et al. Diagnostic performance of screening tools for the detection of obstructive sleep apnea in people living with HIV. J Clin Sleep Med . 2022;18(7):1797-1804., (© 2022 American Academy of Sleep Medicine.)- Published
- 2022
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30. Do metapopulations and management matter for relict headwater bull trout populations in a warming climate?
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Isaak DJ, Young MK, Horan DL, Nagel D, Schwartz MK, and McKelvey KS
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- Animals, Climate Change, Rivers, Seasons, Ecosystem, Trout
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Mountain headwater streams have emerged as important climate refuges for native cold-water species due to their slow climate velocities and extreme physical conditions that inhibit non-native invasions. Species persisting in refuges often do so as fragmented, relict populations from broader historical distributions that are subject to ongoing habitat reductions and increasing isolation as climate change progresses. Key for conservation planning is determining where remaining populations will persist and how habitat restoration strategies can improve biological resilience to enhance the long-term prospects for species of concern. Studying bull trout, a headwater species in the northwestern USA, we developed habitat occupancy models using a data set of population occurrence in 991 natal habitat patches with a suite of novel geospatial covariates derived from high-resolution hydroclimatic scenarios and other sources representing watershed and instream habitat conditions, patch geometry, disturbance, and biological interactions. The best model correctly predicted bull trout occupancy status in 82.6% of the patches and included effects for: patch size estimated as habitat volume, extent of within-patch reaches <9°C mean August temperature, distance to nearest occupied patch, road density, invasive brook trout prevalence, patch slope, and frequency of high winter flows. The model was used to assess 16 scenarios of bull trout occurrence within the study streams that represented a range of restoration strategies under three climatic conditions (baseline, moderate change, and extreme change). Results suggested that regional improvements in bull trout status were difficult to achieve in realistic restoration strategies due to the pervasive nature of climate change and the limited extent of restoration actions given their high costs. However, occurrence probabilities in a subset of patches were highly responsive to restoration actions, suggesting that targeted investments to improve the resilience of some populations may be contextually beneficial. A possible strategy, therefore, is focusing effort on responsive populations near more robust population strongholds, thereby contributing to local enclaves where dispersal among populations further enhances resilience. Equally important, strongholds constituted a small numerical percentage of patches (5%-21%), yet encompassed the large majority of occupied habitat by volume (72%-89%) and their protection could have significant conservation benefits for bull trout., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA.)
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- 2022
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31. Public health response following an iGAS outbreak in a residential aged care facility in Queensland.
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Van Zeeland JC, Rupasinghe H, and Young MK
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- Aged, Australia epidemiology, Disease Outbreaks prevention & control, Humans, Queensland epidemiology, Public Health, Streptococcus pyogenes
- Abstract
Abstract: During an 18-day period, beginning in April 2020, three residents with invasive group A streptococcal infections (iGAS) were reported at a single residential aged care facility (RACF) in Brisbane's northern geographical region. All three cases were hospitalised with severe illness; two of the cases died as a result of the illness. The Metro North Public Health Unit (PHU) led the public health investigation and response, targeting infection control measures and offering chemoprophylaxis to all 142 staff and 119 residents at the facility. The outbreak was declared over in June, after 30 days of no new cases. Isolates from all three cases were shown to have identical strain typing, emm89. The benefits and challenges of implementing mass chemoprophylaxis in this setting are discussed., (© Commonwealth of Australia CC BY-NC-ND.)
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- 2022
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32. Binary Toxin Expression by Clostridioides difficile Is Associated With Worse Disease.
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Young MK, Leslie JL, Madden GR, Lyerly DM, Carman RJ, Lyerly MW, Stewart DB, Abhyankar MM, and Petri WA Jr
- Abstract
Background: The incidence of Clostridioides difficile infection (CDI) has increased over the past 2 decades and is considered an urgent threat by the Centers for Disease Control and Prevention. Hypervirulent strains such as ribotype 027, which possess genes for the additional toxin C. difficile binary toxin (CDT), are contributing to increased morbidity and mortality., Methods: We retrospectively tested stool from 215 CDI patients for CDT by enzyme-linked immunosorbent assay (ELISA). Stratifying patients by CDT status, we assessed if disease severity and clinical outcomes correlated with CDT positivity. Additionally, we completed quantitative PCR (PCR) DNA extracted from patient stool to detect cdtB gene. Lastly, we performed 16 S rRNA gene sequencing to examine if CDT-positive samples had an altered fecal microbiota., Results: We found that patients with CdtB, the pore-forming component of CDT, detected in their stool by ELISA, were more likely to have severe disease with higher 90-day mortality. CDT-positive patients also had higher C. difficile bacterial burden and white blood cell counts. There was no significant difference in gut microbiome diversity between CDT-positive and -negative patients., Conclusions: Patients with fecal samples that were positive for CDT had increased disease severity and worse clinical outcomes. Utilization of PCR and testing for C. difficile toxins A and B may not reveal the entire picture when diagnosing CDI; detection of CDT-expressing strains is valuable in identifying patients at risk of more severe disease., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2022
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33. Molecular species delimitation refines the taxonomy of native and nonnative physinine snails in North America.
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Young MK, Smith R, Pilgrim KL, and Schwartz MK
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- Animals, North America, Phylogeography, Snails genetics, Introduced Species, Phylogeny, Snails classification
- Abstract
Being able to associate an organism with a scientific name is fundamental to our understanding of its conservation status, ecology, and evolutionary history. Gastropods in the subfamily Physinae have been especially troublesome to identify because morphological variation can be unrelated to interspecific differences and there have been widespread introductions of an unknown number of species, which has led to a speculative taxonomy. To resolve uncertainty about species diversity in North America, we targeted an array of single-locus species delimitation methods at publically available specimens and new specimens collected from the Snake River basin, USA to generate species hypotheses, corroborated using nuclear analyses of the newly collected specimens. A total-evidence approach delineated 18 candidate species, revealing cryptic diversity within recognized taxa and a lack of support for other named taxa. Hypotheses regarding certain local endemics were confirmed, as were widespread introductions, including of an undescribed taxon likely belonging to a separate genus in southeastern Idaho for which the closest relatives are in southeast Asia. Overall, single-locus species delimitation was an effective first step toward understanding the diversity and distribution of species in Physinae and to guiding future investigation sampling and analyses of species hypotheses., (© 2021. The Author(s).)
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- 2021
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34. IL-13 is a driver of COVID-19 severity.
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Donlan AN, Sutherland TE, Marie C, Preissner S, Bradley BT, Carpenter RM, Sturek JM, Ma JZ, Moreau GB, Donowitz JR, Buck GA, Serrano MG, Burgess SL, Abhyankar MM, Mura C, Bourne PE, Preissner R, Young MK, Lyons GR, Loomba JJ, Ratcliffe SJ, Poulter MD, Mathers AJ, Day AJ, Mann BJ, Allen JE, and Petri WA Jr
- Subjects
- Animals, COVID-19 blood, COVID-19 pathology, COVID-19 therapy, Disease Models, Animal, Disease Progression, Female, Humans, Interleukin-13 blood, Lung immunology, Lung pathology, Male, Mice, Mice, Inbred C57BL, Severity of Illness Index, COVID-19 immunology, Interleukin-13 immunology, SARS-CoV-2 immunology
- Abstract
Immune dysregulation is characteristic of the more severe stages of SARS-CoV-2 infection. Understanding the mechanisms by which the immune system contributes to COVID-19 severity may open new avenues to treatment. Here, we report that elevated IL-13 was associated with the need for mechanical ventilation in 2 independent patient cohorts. In addition, patients who acquired COVID-19 while prescribed Dupilumab, a mAb that blocks IL-13 and IL-4 signaling, had less severe disease. In SARS-CoV-2-infected mice, IL-13 neutralization reduced death and disease severity without affecting viral load, demonstrating an immunopathogenic role for this cytokine. Following anti-IL-13 treatment in infected mice, hyaluronan synthase 1 (Has1) was the most downregulated gene, and accumulation of the hyaluronan (HA) polysaccharide was decreased in the lung. In patients with COVID-19, HA was increased in the lungs and plasma. Blockade of the HA receptor, CD44, reduced mortality in infected mice, supporting the importance of HA as a pathogenic mediator. Finally, HA was directly induced in the lungs of mice by administration of IL-13, indicating a new role for IL-13 in lung disease. Understanding the role of IL-13 and HA has important implications for therapy of COVID-19 and, potentially, other pulmonary diseases. IL-13 levels were elevated in patients with severe COVID-19. In a mouse model of the disease, IL-13 neutralization reduced the disease and decreased lung HA deposition. Administration of IL-13-induced HA in the lung. Blockade of the HA receptor CD44 prevented mortality, highlighting a potentially novel mechanism for IL-13-mediated HA synthesis in pulmonary pathology.
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- 2021
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35. Genetic mapping and phenotypic analysis of shot H.3.2 in Drosophila melanogaster .
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Talley EM, Watts CT, Aboyer S, Adamson MG, Akoto HA, Altemus H, Avella PJ, Bailey R, Bell ER, Bell KL, Breneman K, Burkhart JS, Chanley LJ, Cook SS, DesLaurier MT, Dorsey TR, Doyle CJ, Egloff ME, Fasawe AS, Garcia KK, Graves NP, Gray TK, Gustafson EM, Hall MJ, Hayes JD, Holic LJ, Jarvis BA, Klos PS, Kritzmire S, Kuzovko L, Lainez E, McCoy S, Mierendorf JC, Neri NA, Neville CR, Osborn K, Parker K, Parks ME, Peck K, Pitt R, Platta ME, Powell B, Rodriguez K, Ruiz C, Schaefer MN, Shields AB, Smiley JB, Stauffer B, Straub D, Sweeney JL, Termine KM, Thomas B, Toth SD, Veile TR, Walker KS, Webster PN, Woodard BJ, Yoder QL, Young MK, Zeedyk ML, Ziegler LN, Bieser KL, Puthoff DP, Stamm J, Vrailas-Mortimer AD, Kagey JD, and Merkle JA
- Abstract
Genetic screens are used to identify genes involved in specific biological processes. An EMS mutagenesis screen in Drosophila melanogaster identified growth control phenotypes in the developing eye. One mutant line from this screen, H.3.2 , was phenotypically characterized using the FLP/FRT system and genetically mapped by complementation analysis and genomic sequencing by undergraduate students participating in the multi-institution Fly-CURE consortium. H.3.2 was found to have a nonsense mutation in short stop ( shot ), anortholog of the mammalian spectraplakin dystonin ( DST ). shot and DST are involved in cytoskeletal organization and play roles during cell growth and proliferation., (Copyright: © 2021 by the authors.)
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- 2021
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36. Your Call Is Important to Us: COVID-19 and Trends in Public Health Unit Call Service Utilization.
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Horn ZB, Uren AM, and Young MK
- Abstract
Objective: The aim of this study was to analyze coronavirus disease 2019 (COVID-19) -related call data at Metro North Public Health Unit, Brisbane Australia, over the 2020 calendar year to assist surge preparedness., Methods: Call data were retrieved by call category or reference to "COVID" in summaries from the call management system at a large metropolitan public health service. Under a mixed-methods approach, qualitative data (caller, call purpose, and call outcome) were categorized with categories arising de novo. Resulting variables were numerically analyzed to identify trends by categories and time., Results: Of the 3468 calls retrieved, 160 duplicates and 26 irrelevant calls were excluded. Of 3282 included calls, general practitioners, followed by the public, contributed the greatest call volumes. Health-care-related callers and the public made 84.2% of calls. Calls most frequently related to patient testing (40.7%) and isolation/quarantine (23.2%). Education provision accounted for 29.4% of all outcomes. A total of 11.8% of all call outcomes involved applying relevant case definitions, and 49.1% of calls were identified as potentially preventable through effective emergency risk communication and targeted call-handling., Conclusions: This study identified key drivers of public health unit phone service use related to the COVID-19 pandemic throughout 2020. The results highlighted where risk perception influenced call volume and provided important insights for future public health preparedness.
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- 2021
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37. Diverse Humoral Immune Responses in Younger and Older Adult COVID-19 Patients.
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Sasson JM, Campo JJ, Carpenter RM, Young MK, Randall AZ, Trappl-Kimmons K, Oberai A, Hung C, Edgar J, Teng AA, Pablo JV, Liang X, Yee A, Petri WA Jr, and Camerini D
- Subjects
- Adult, Age Factors, Aged, Aged, 80 and over, Antibodies, Viral immunology, COVID-19 immunology, Coronavirus Envelope Proteins immunology, Coronavirus Nucleocapsid Proteins immunology, Female, Humans, Immunoglobulin G immunology, Male, Phosphoproteins immunology, Protein Array Analysis, Severity of Illness Index, Spike Glycoprotein, Coronavirus immunology, Antibodies, Viral blood, Coronavirus NL63, Human immunology, Coronavirus OC43, Human immunology, Cytokines blood, Middle East Respiratory Syndrome Coronavirus immunology, SARS-CoV-2 immunology
- Abstract
We sought to discover links between antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patient clinical variables, cytokine profiles, and antibodies to endemic coronaviruses. Serum samples from 30 patients of younger (26 to 39 years) and older (69 to 83 years) age groups and with varying clinical severities ranging from outpatient to mechanically ventilated were collected and used to probe a novel multi-coronavirus protein microarray. This microarray contained variable-length overlapping fragments of SARS-CoV-2 spike (S), envelope (E), membrane (M), nucleocapsid (N), and open reading frame (ORF) proteins created through in vitro transcription and translation (IVTT). The array also contained SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus OC43 (HCoV-OC43), and HCoV-NL63 proteins. IgG antibody responses to specific epitopes within the S1 protein region spanning amino acids (aa) 500 to 650 and within the N protein region spanning aa 201 to 300 were found to be significantly higher in older patients and further significantly elevated in those older patients who were ventilated. Additionally, there was a noticeable overlap between antigenic regions and known mutation locations in selected emerging SARS-CoV-2 variants of current clinical consequence (B.1.1.7, B1.351, P.1, CAL20.C, and B.1.526). Moreover, the older age group displayed more consistent correlations of antibody reactivity with systemic cytokine and chemokine responses than the younger adult group. A subset of patients, however, had little or no response to SARS-CoV-2 antigens and disproportionately severe clinical outcomes. Further characterization of these slow-low-responding individuals with cytokine analysis revealed significantly higher interleukin-10 (IL-10), IL-15, and interferon gamma-induced protein 10 (IP-10) levels and lower epidermal growth factor (EGF) and soluble CD40 ligand (sCD40L) levels than those of seroreactive patients in the cohort. IMPORTANCE As numerous viral variants continue to emerge in the coronavirus disease 2019 (COVID-19) pandemic, determining antibody reactivity to SARS-CoV-2 epitopes becomes essential in discerning changes in the immune response to infection over time. This study enabled us to identify specific areas of antigenicity within the SARS-CoV-2 proteome, allowing us to detect correlations of epitopes with clinical metadata and immunological signals to gain holistic insight into SARS-CoV-2 infection. This work also emphasized the risk of mutation accumulation in viral variants and the potential for evasion of the adaptive immune responses in the event of reinfection. We additionally highlighted the correlation of antigenicity between structural proteins of SARS-CoV-2 and endemic HCoVs, raising the possibility of cross-protection between homologous lineages. Finally, we identified a subset of patients with minimal antibody reactivity to SARS-CoV-2 infection, prompting discussion of the potential consequences of this alternative immune response.
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- 2021
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38. Optimizing a Multi-Component Intranasal Entamoeba Histolytica Vaccine Formulation Using a Design of Experiments Strategy.
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Abhyankar MM, Orr MT, Kinsey R, Sivananthan S, Nafziger AJ, Oakland DN, Young MK, Farr L, Uddin MJ, Leslie JL, Burgess SL, Liang H, De Lima I, Larson E, Guderian JA, Lin S, Kahn A, Ghosh P, Reed S, Tomai MA, Pedersen K, Petri WA Jr, and Fox CB
- Subjects
- Adjuvants, Immunologic chemistry, Administration, Intranasal, Animals, Antibodies, Protozoan blood, Antibodies, Protozoan immunology, Chemical Phenomena, Cytokines metabolism, Drug Compounding, Entamoebiasis parasitology, Enzyme-Linked Immunosorbent Assay, Humans, Immunogenicity, Vaccine, Immunoglobulin G immunology, Liposomes, Mice, Protozoan Vaccines administration & dosage, Protozoan Vaccines chemistry, Vaccination, Antigens, Protozoan immunology, Entamoeba histolytica immunology, Entamoebiasis immunology, Entamoebiasis prevention & control, Protozoan Vaccines immunology
- Abstract
Amebiasis is a neglected tropical disease caused by Entamoeba histolytic a. Although the disease burden varies geographically, amebiasis is estimated to account for some 55,000 deaths and millions of infections globally per year. Children and travelers are among the groups with the greatest risk of infection. There are currently no licensed vaccines for prevention of amebiasis, although key immune correlates for protection have been proposed from observational studies in humans. We previously described the development of a liposomal adjuvant formulation containing two synthetic TLR ligands (GLA and 3M-052) that enhanced antigen-specific fecal IgA, serum IgG2a, a mixed IFNγ and IL-17A cytokine profile from splenocytes, and protective efficacy following intranasal administration with the LecA antigen. By applying a statistical design of experiments (DOE) and desirability function approach, we now describe the optimization of the dose of each vaccine formulation component (LecA, GLA, 3M-052, and liposome) as well as the excipient composition (acyl chain length and saturation; PEGylated lipid:phospholipid ratio; and presence of antioxidant, tonicity, or viscosity agents) to maximize desired immunogenicity characteristics while maintaining physicochemical stability. This DOE/desirability index approach led to the identification of a lead candidate composition that demonstrated immune response durability and protective efficacy in the mouse model, as well as an assessment of the impact of each active vaccine formulation component on protection. Thus, we demonstrate that both GLA and 3M-052 are required for statistically significant protective efficacy. We also show that immunogenicity and efficacy results differ in female vs male mice, and the differences appear to be at least partly associated with adjuvant formulation composition., Competing Interests: MT is an employee of 3M and 3M-052 is an asset of 3M’s. WP is a consultant for TechLab, Inc. and in addition receives royalties for amebiasis diagnostics that are donated in their entirety to the American Society of Tropical Medicine and Hygiene. KP is an employee of TechLab, Inc. and amebiasis diagnostics are an asset of TechLab’s. CF, RK, SS, HL, IL, EL, JG, SL, AK, and SR are employees of IDRI, which owns assets including patents and patent applications involving formulations of GLA and 3M-052 including what is represented in this article. MA, WP, CF, and SL are inventors on patent/patent application(s) involving the vaccine formulations represented in this article. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Abhyankar, Orr, Kinsey, Sivananthan, Nafziger, Oakland, Young, Farr, Uddin, Leslie, Burgess, Liang, De Lima, Larson, Guderian, Lin, Kahn, Ghosh, Reed, Tomai, Pedersen, Petri and Fox.)
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- 2021
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39. Protocol for Testing Yoga to Reduce Post-Lumbar Spine Surgery Pain: A Methodology Article.
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Sharma NK, Aoyagi K, Crouch Young MK, Parrish A, Smith C, Burton DC, Arnold PM, Colln K, and Colgrove Y
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- Adult, Aged, Aged, 80 and over, Humans, Lumbar Vertebrae surgery, Middle Aged, Pain, Postoperative etiology, Pain, Postoperative therapy, Pilot Projects, Randomized Controlled Trials as Topic, Treatment Outcome, Meditation, Yoga
- Abstract
Currently, acute postoperative pain during hospitalization is primarily managed by medications, and patients must adhere to restrictive postoperative precautions for 3 months following lumbar spine surgeries. Yoga can be an alternative approach to assist in acute and subacute postoperative pain management, anxiety, and return to function. The purpose of the present work was to develop and test the feasibility and explore the effectiveness of a tailored yoga program, delivered in-person during the hospital stay and electronically after hospital discharge, as a potential new avenue for postoperative care. This pilot study will use a crossover randomized controlled design. Individuals aged between 40 and 80 years who are scheduled for lumbar laminectomy and/or fusion, and who have not practiced regular yoga within the past 6 months at the time of enrollment, will be recruited and randomized to either a tailored yoga program (intervention group) or usual care (control group) during the hospital stay (phase one). Bearing in mind postoperative precautions, all subjects will be instructed to perform a home-based tailored yoga program delivered electronically via YouTube links for 8 weeks post-hospital discharge (phase two). The primary outcome measures assessing feasibility are adherence/compliance. Secondary outcome measures include pain, anxiety, function, sleep, perceived stress, and pain-catastrophizing behavior. Length of hospital stay and pain medication use, gait distance, and overall physical activity during hospitalization will also be collected. Finally, a qualitative interview will be obtained after completion of the hospital and home-based programs. This study will determine the feasibility of a tailored yoga program for acute and subacute postoperative lumbar spine surgery pain, anxiety, and functional outcomes.
- Published
- 2021
- Full Text
- View/download PDF
40. IgG Antibodies against SARS-CoV-2 Correlate with Days from Symptom Onset, Viral Load and IL-10.
- Author
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Young MK, Kornmeier C, Carpenter RM, Natale NR, Sasson JM, Solga MD, Mathers AJ, Poulter MD, Qiang X, and Petri WA Jr
- Abstract
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a pandemic of the respiratory disease coronavirus disease 2019 (COVID-19). Antibody testing is essential to identify persons exposed to the virus and potentially in predicting disease immunity. 183 COVID-19 patients (68 of whom required mechanical ventilation) and 41 controls were tested for plasma IgG, IgA and IgM against the SARS-CoV-2 S1, S2, receptor binding domain (RBD) and N proteins using the MILLIPLEX
® SARS-CoV-2 Antigen Panel. Plasma cytokines were concurrently measured using the MILLIPLEX® MAP Human Cytokine/Chemokine/Growth Factor Panel A. As expected the 183 COVID-19 positive patients had high levels of IgG, IgA and IgM anti-SARS-CoV-2 antibodies against each of the viral proteins. Sensitivity of anti-S1 IgG increased from 60% to 93% one week after symptom onset. S1-IgG and S1-IgA had specificities of 98% compared to the 41 COVID-19 negative patients. The 68 ventilated COVID-19 positive patients had higher antibody levels than the 115 COVID-19 positive patients who were not ventilated. IgG antibody levels against S1 protein had the strongest positive correlation to days from symptom onset. There were no statistically significant differences in IgG, IgA and IgM antibodies against S1 based on age. We found that patients with the highest levels of anti-SARS-CoV-2 antibodies had the lowest viral load in the nasopharynx. Finally there was a correlation of high plasma IL-10 with low anti-SARS-CoV-2 antibodies. Anti-SARS-CoV-2 antibody levels, as measured by a novel antigen panel, increased within days after symptom onset, achieving > 90% sensitivity and specificity within one week, and were highest in patients who required mechanical ventilation. Antibody levels were inversely associated with viral load but did not differ as a function of age. The correlation of high IL-10 with low antibody response suggests a potentially suppressive role of this cytokine in the humoral immune response in COVID-19., Competing Interests: Conflicts of Interest- The authors have no conflicts of interest to report.- Published
- 2020
- Full Text
- View/download PDF
41. Pharmacokinetic modeling to determine the minimum effective dose of disease-specific antibodies for preventing hepatitis A post-exposure.
- Author
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Young MK, Ng SK, Nimmo GR, and Cripps AW
- Subjects
- Australia, Biological Availability, Body Weight, Dose-Response Relationship, Drug, Humans, Immunization, Passive, Immunoglobulins metabolism, Immunologic Factors administration & dosage, Immunologic Factors pharmacokinetics, Injections, Intramuscular, Post-Exposure Prophylaxis methods, Antibodies, Viral blood, Hepatitis A prevention & control, Immunoglobulins administration & dosage, Models, Biological
- Abstract
Background: The minimum effective dose of intramuscular polyvalent immune globulin for prevention of hepatitis A post-exposure is unknown. In Australia current dosing is according to weight category., Methods: The peak concentration and decay of hepatitis A antibodies after intramuscular dosing of immune globulin in adults was modeled utilizing published parameters. Models simulated dosing according to current Australian guidelines, then adjusted the dose in clinically relevant increments to estimate the optimal dose of hepatitis A antibodies for post-exposure prophylaxis of nonimmune individuals. Optimal dosing assumed a target serum concentration of hepatitis A antibodies of the correlate of protection plus a 10% margin of error at an incubation period. The effect of weight on hepatitis A antibody concentration at an incubation period under current guidelines was examined by fixing weight in 5 kg increments., Results: Current dosing guidelines in Australia may underdose people who weigh in excess of 85 kg. The optimal dose of hepatitis A-specific antibodies according to the model was 3.6, 2.5, and 1.9 IU/kg assuming 50%, 75% and 100% bioavailability respectively., Conclusions: For individuals in Australia recommended passive immunization as post-exposure prophylaxis and weighing in excess of 85 kg, conservative management would include dosing between 2.5 and 3.6 IU hepatitis A antibodies/kg.
- Published
- 2020
- Full Text
- View/download PDF
42. Pliocene-Early Pleistocene Geological Events Structure Pacific Martens (Martes caurina).
- Author
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Schwartz MK, Walters AD, Pilgrim KL, Moriarty KM, Slauson KM, Zielinski WJ, Aubry KB, Sacks BN, Zarn KE, Quinn CB, and Young MK
- Subjects
- Animals, Conservation of Natural Resources, Evolution, Molecular, Forests, Geology, Microsatellite Repeats, North America, Phylogeny, Phylogeography, Sequence Analysis, DNA, Genetics, Population, Genome, Mitochondrial, Mustelidae genetics
- Abstract
The complex topography, climate, and geological history of Western North America have shaped contemporary patterns of biodiversity and species distributions in the region. Pacific martens (Martes caurina) are distributed along the northern Pacific Coast of North America with disjunct populations found throughout the Northwestern Forested Mountains and Marine West Coast Forest ecoregions of the West Coast. Martes in this region have been classified into subspecies; however, the subspecific designation has been extensively debated. In this study, we use genomic data to delineate conservation units of Pacific marten in the Sierra-Cascade-Coastal montane belt in the western United States. We analyzed the mitochondrial genome for 94 individuals to evaluate the spatial distribution and divergence times of major lineages. We further genotyped 401 individuals at 13 microsatellite loci to investigate major patterns of population structure. Both nuclear and mitochondrial DNA suggest substantial genetic substructure concordant with historical subspecies designations. Our results revealed that the region contains 2 distinct mitochondrial lineages: a Cascades/Sierra lineage that diverged from the Cascades/coastal lineage 2.23 (1.48-3.14 mya), consistent with orogeny of the Cascade Mountain chain. Interestingly, Pacific Martes share phylogeographic patterns similar with other sympatric taxa, suggesting that the complex geological history has shaped the biota of this region. The information is critical for conservation and management efforts, and further investigation of adaptive diversity is warranted following appropriate revision of conservation management designations., (Published by Oxford University Press on behalf of The American Genetic Association 2020.)
- Published
- 2020
- Full Text
- View/download PDF
43. Clinical experience of intramuscular immunoglobulin for measles prophylaxis in children: Is it practical?
- Author
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Philips L, Young MK, Wallace J, and Dobinson HC
- Subjects
- Australia, Child, Humans, Immunoglobulin G, Injections, Intramuscular, Vaccination, Measles prevention & control
- Abstract
Measles continues to be a public health concern world-wide. Vulnerable individuals including those in which vaccinations is contraindicated, may be reliant on normal human immunoglobulin (NHIG) prophylaxis in an aim to prevent disease. This paper will summarise and discuss a tertiary paediatric hospital's clinical experience and the practicalities of administering intramuscular (IM) NHIG to paediatric patients as per the current measles prophylaxis guidelines in Australia. Following potential exposure within the emergency department, 17 paediatric patients (0-15 years) were recommended IM NHIG for prophylaxis. The dose of NHIG ranged from 0.6 to 15 mL and required multiple (2-8) injections. Two patients required sedation for staff to safely administer the injections. Staff involved with these cases reported administering multiple injections to paediatric patients to be a traumatising experience. They also expressed views that the injection of large volumes via the IM route was an impractical method of administration. Based on this experience, we recommend intravenous immunoglobulin be considered when large volumes of NHIG are recommended intramuscularly., (© 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)
- Published
- 2020
- Full Text
- View/download PDF
44. IL-33 drives group 2 innate lymphoid cell-mediated protection during Clostridium difficile infection.
- Author
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Frisbee AL, Saleh MM, Young MK, Leslie JL, Simpson ME, Abhyankar MM, Cowardin CA, Ma JZ, Pramoonjago P, Turner SD, Liou AP, Buonomo EL, and Petri WA Jr
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Anti-Bacterial Agents adverse effects, Bacterial Toxins immunology, Bacterial Toxins metabolism, Clostridioides difficile pathogenicity, Colon cytology, Colon immunology, Colon microbiology, Colon pathology, Disease Models, Animal, Enterocolitis, Pseudomembranous microbiology, Enterocolitis, Pseudomembranous mortality, Enterocolitis, Pseudomembranous therapy, Fecal Microbiota Transplantation, Female, Gastrointestinal Microbiome drug effects, Gastrointestinal Microbiome immunology, Gene Expression Profiling, Humans, Interleukin-33 immunology, Lymphocytes metabolism, Male, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Up-Regulation drug effects, Up-Regulation immunology, Virulence immunology, Young Adult, Clostridioides difficile immunology, Enterocolitis, Pseudomembranous immunology, Immunity, Innate, Interleukin-33 metabolism, Lymphocytes immunology
- Abstract
Clostridium difficile (C. difficile) incidence has tripled over the past 15 years and is attributed to the emergence of hypervirulent strains. While it is clear that C. difficile toxins cause damaging colonic inflammation, the immune mechanisms protecting from tissue damage require further investigation. Through a transcriptome analysis, we identify IL-33 as an immune target upregulated in response to hypervirulent C. difficile. We demonstrate that IL-33 prevents C. difficile-associated mortality and epithelial disruption independently of bacterial burden or toxin expression. IL-33 drives colonic group 2 innate lymphoid cell (ILC2) activation during infection and IL-33 activated ILC2s are sufficient to prevent disease. Furthermore, intestinal IL-33 expression is regulated by the microbiota as fecal microbiota transplantation (FMT) rescues antibiotic-associated depletion of IL-33. Lastly, dysregulated IL-33 signaling via the decoy receptor, sST2, predicts C. difficile-associated mortality in human patients. Thus, IL-33 signaling to ILC2s is an important mechanism of defense from C. difficile colitis.
- Published
- 2019
- Full Text
- View/download PDF
45. Decreased total psoas muscle area after neoadjuvant therapy is a predictor of increased mortality in patients undergoing oesophageal cancer resection.
- Author
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Yassaie SS, Keane C, French SJH, Al-Herz FAJ, Young MK, and Gordon AC
- Subjects
- Aged, Esophageal Neoplasms complications, Esophageal Neoplasms mortality, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Neoadjuvant Therapy, New Zealand epidemiology, Organ Size, Postoperative Complications epidemiology, Predictive Value of Tests, Reproducibility of Results, Retrospective Studies, Risk Factors, Sarcopenia complications, Sarcopenia mortality, Survival Rate trends, Tomography, X-Ray Computed, Esophageal Neoplasms therapy, Esophagectomy methods, Postoperative Complications etiology, Psoas Muscles diagnostic imaging, Risk Assessment methods, Sarcopenia diagnosis
- Abstract
Background: Oesophagectomy for locally advanced cancer carries high rates of morbidity and mortality. Patients require a thorough risk assessment alongside preoperative counselling. Total psoas area (TPA) measurements have been used as a surrogate marker of sarcopenia to predict post-operative complications in oesophageal cancer patients. No studies to date have determined whether there is an association between the proportion of TPA lost during neoadjuvant therapy and post-operative outcomes., Methods: Clinical data and imaging of patients who underwent neoadjuvant therapy followed by open two-stage oesophagectomy between January 2008 and April 2018 were analysed retrospectively. Patients who did not undergo restaging computed tomography scan prior to surgery were excluded from the study. The TPA was measured on two cross-sectional slices at L4 on computed tomography scans pre- and post-neoadjuvant therapy., Results: A total of 53 patients who met inclusion criteria were identified. The mean loss of TPA was 7.3%. Patients who had a decrease of TPA of more than 4% had significantly increased 30-day mortality compared to those who lost 4% or less (24% versus 0%, P = 0.02). Patients aged over 65 years who also had a loss of TPA >4% had significantly increased 30-day mortality (37% versus 2.9%, odds ratio 19, P = 0.008)., Conclusion: A decrease in TPA of >4% is associated with a significantly higher risk of post-operative mortality in patients undergoing neoadjuvant therapy followed by oesophagectomy. Measuring the loss of TPA during neoadjuvant treatment could be a novel aid to preoperative risk assessment., (© 2019 Royal Australasian College of Surgeons.)
- Published
- 2019
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- View/download PDF
46. The use of normal human immunoglobulin (NHIG) for public health purposes in Queensland 2004-2014 and Australia 2014-2016
- Author
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Young MK, Cripps AW, and Nimmo GR
- Abstract
Objective To describe the use of normal human immunoglobulin (NHIG) recommended for public health purposes in Queensland and Australia. Methods Queensland public health unit (PHU) data on notified cases of measles, rubella and hepatitis A from 2004 to 2014 were examined; particularly regarding the number of contacts offered NHIG and the volume recommended per contact. The National Blood Authority (NBA) provided unidentified data from NHIG order form inception (June 2014) through December 2016. Queensland orders were compared to PHU data where the data timeframes overlapped. Results NHIG usage varied by condition. For hepatitis A, usage declined after the introduction of vaccination for contacts in 2010. Usage fluctuated across the study period for measles and was not recommended for rubella. Average volumes per contact for hepatitis A and measles were 1.6mL and 11.9mL respectively based on PHU data. PHU data approximated NBA data on NHIG usage for hepatitis A and rubella contacts. Calculated volumes of NHIG per measles contact were also similar, but PHU data underestimated the number of measles contacts for whom NHIG was ordered. Discussion This study is the first to document the use of NHIG for public health purposes in Australia. Results will be valuable for national blood sufficiency planning and cost effectiveness studies in the event of alterations to NHIG dosage recommendations., (© Commonwealth of Australia CC BY-NC-ND)
- Published
- 2019
- Full Text
- View/download PDF
47. Integrative taxonomy refutes a species hypothesis: The asymmetric hybrid origin of Arsapnia arapahoe (Plecoptera, Capniidae).
- Author
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Young MK, Smith RJ, Pilgrim KL, Fairchild MP, and Schwartz MK
- Abstract
Molecular tools are commonly directed at refining taxonomies and the species that constitute their fundamental units. This has been especially insightful for groups for which species hypotheses are ambiguous and have largely been based on morphological differences between certain life stages or sexes, and has added importance when taxa are a focus of conservation efforts. Here, we examine the taxonomic status of Arsapnia arapahoe , a winter stonefly in the family Capniidae that is a species of conservation concern because of its limited abundance and restricted range in northern Colorado, USA. Phylogenetic analyses of sequences of mitochondrial and nuclear genes of this and other capniid stoneflies from this region and elsewhere in western North America indicated extensive haplotype sharing, limited genetic differences, and a lack of reciprocal monophyly between A. arapahoe and the sympatric A. decepta , despite distinctive and consistent morphological differences in the sexual apparatus of males of both species. Analyses of autosomal and sex-linked single nucleotide polymorphisms detected using genotyping by sequencing indicated that all individuals of A. arapahoe consisted of F
1 hybrids between female A. decepta and males of another sympatric stonefly, Capnia gracilaria . Rather than constitute a self-sustaining evolutionary lineage, A. arapahoe appears to represent the product of nonintrogressive hybridization in the limited area of syntopy between two widely distributed taxa. This offers a cautionary tale for taxonomists and conservation biologists working on the less-studied components of the global fauna.- Published
- 2019
- Full Text
- View/download PDF
48. The indications and safety of polyvalent immunoglobulin for post-exposure prophylaxis of hepatitis A, rubella and measles.
- Author
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Young MK
- Subjects
- Australia, Canada, Humans, New Zealand, Practice Guidelines as Topic, United Kingdom, United States, Antibodies, Viral administration & dosage, Hepatitis A prevention & control, Immunization, Passive, Measles prevention & control, Post-Exposure Prophylaxis standards, Rubella prevention & control
- Abstract
Derived from pooled blood donations, polyvalent immunoglobulins are used for post-exposure prophylaxis as one aspect of the public health management of hepatitis A, rubella and measles. This review summarizes the safety profile of these blood products and the current recommendations for their use for the prevention of hepatitis A, rubella and measles among people who have been exposed to these diseases. The current recommendations are drawn from the most recent publicly available national guidelines of the United States, Australia, New Zealand, Canada and the United Kingdom as accessed in February 2019.
- Published
- 2019
- Full Text
- View/download PDF
49. qPCR detection of Sturgeon chub (Macrhybopsis gelida) DNA in environmental samples.
- Author
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Mason DH, Dysthe JC, Franklin TW, Skorupski JA, Young MK, McKelvey KS, and Schwartz MK
- Subjects
- Animals, Geography, Reproducibility of Results, Cyprinidae genetics, Real-Time Polymerase Chain Reaction
- Abstract
The Sturgeon chub (Macrhybopsis gelida) is a cyprinid fish native to the Missouri and Mississippi River basins of the U.S. Suspected long-term declines in the size of its distribution have prompted a review of its conservation status by the U.S. Fish and Wildlife Service, a process which depends on reliable methods to delineate the distribution and status of extant populations. To facilitate monitoring of Sturgeon chub populations, we developed a quantitative PCR assay to detect Sturgeon chub DNA in environmental samples. The assay consistently detected Sturgeon chub DNA in concentrations as low as 2 copies per reaction, and did not amplify DNA from non-target fish species that are sympatric in the upper Missouri River basin. Field tests of this assay with environmental samples successfully detected Sturgeon chub from sites known to be occupied. This assay offers an extremely sensitive methodology that can be applied to determine the range of Sturgeon chub, regardless of variation in habitat characteristics., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
- Full Text
- View/download PDF
50. An improved environmental DNA assay for bull trout (Salvelinus confluentus) based on the ribosomal internal transcribed spacer I.
- Author
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Dysthe JC, Franklin TW, McKelvey KS, Young MK, and Schwartz MK
- Subjects
- Animals, DNA, Mitochondrial genetics, Ribosomes genetics, Species Specificity, Trout classification, DNA, Ribosomal Spacer genetics, Metagenomics methods, Phylogeny, Trout genetics
- Abstract
The majority of environmental DNA (eDNA) assays for vertebrate species are based on commonly analyzed regions of the mitochondrial genome. However, the high degree of mitochondrial similarity between two species of charr (Salvelinus spp.), southern Dolly Varden (S. malma lordii) and bull trout (Salvelinus confluentus), precludes the development of a mitochondrial eDNA assay to distinguish them. Presented here is an eDNA assay to detect bull trout based on the first ribosomal internal transcribed spacer (ITSI), a nuclear marker. This assay successfully detects bull trout and avoids detecting Dolly Varden as well as brook trout (S. fontinalis), Arctic char (S. alpinus), and lake trout (S. namaycush). In addition, this assay was compared with an extensively used mitochondrial bull trout assay and it was found that the ITSI-based assay produced higher detectability. Our results suggest this assay should out-perform the published mtDNA assay across the range of bull trout, while the added specificity allows reliable bull trout detection in areas where bull trout co-occur with other charr such as Dolly Varden. While clearly a superior assay in this instance, basing assays on ITSI is not without problems. For vertebrates, there are fewer ITSI sequences available than commonly sequenced regions of the mitochondrial genome. Thus, the initial in silico screening of candidate assays must be preceded by much more extensive sampling and sequencing of sympatric or closely related taxa. Further, all copies of the internal transcribed spacers within an individual may not be identical, which can lead to complications. Lastly, the copy number for ITSI varies widely across taxa; the greater detectability associated with this assay cannot be assumed for other species., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
- Full Text
- View/download PDF
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