187 results on '"Andersen MJ"'
Search Results
2. P653EAE/ASE guidelines for evaluation of left ventricular diastolic dysfunction in clinical practice
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Andersen, MJ, Ersboell, M, Bro-Jeppesen, J, Gustafsson, F, Koeber, L, Hassager, C, and Moller, JE
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- 2011
3. Housing conditions of urban households with Aboriginal children in NSW Australia: Tenure type matters
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Andersen, MJ, Williamson, AB, Fernando, P, Wright, D, Redman, S, Andersen, MJ, Williamson, AB, Fernando, P, Wright, D, and Redman, S
- Abstract
© 2017 The Author(s). Background: Housing is a key determinant of the poor health of Aboriginal Australians. Most Aboriginal people live in cities and large towns, yet research into housing conditions has largely focused on those living in remote areas. This paper measures the prevalence of housing problems amongst participants in a study of urban Aboriginal families in New South Wales, Australia, and examines the relationship between tenure type and exposure to housing problems. Methods: Cross-sectional survey data was provided by 600 caregivers of 1406 Aboriginal children aged 0-17 years participating in Phase One of the Study of Environment on Aboriginal Resilience and Child Health (SEARCH). Regression modelling of the associations between tenure type (own/mortgage, private rental or social housing) and housing problems was conducted, adjusting for sociodemographic factors. Results: The majority (60%) of SEARCH households lived in social housing, 21% rented privately and 19% either owned their home outright or were paying a mortgage ("owned"). Housing problems were common, particularly structural problems, damp and mildew, vermin, crowding and unaffordability. Physical dwelling problems were most prevalent for those living in social housing, who were more likely to report three or more physical dwelling problems than those in owned (PR 3.19, 95%CI 1.97, 5.73) or privately rented homes (PR 1.49, 1.11, 2.08). However, those in social housing were the least likely to report affordability problems. Those in private rental moved home most frequently; children in private rental were more than three times as likely to have lived in four or more homes since birth than those in owned homes (PR 3.19, 95%CI 1.97, 5.73). Those in social housing were almost half as likely as those in private rental to have lived in four or more homes since birth (PR 0.56, 95%CI 0.14, 0.77). Crowding did not vary significantly by tenure type. Conclusions: The high prevalence of housing problem
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- 2017
4. Early adolescent smoking and a web of personal and social disadvantage
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Conwell, LS, primary, O'Callaghan, MJ, additional, Andersen, MJ, additional, Bor, W, additional, Najman, JM, additional, and Williams, GM, additional
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- 2003
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5. The effect of breastfeeding on child development at 5 years: A cohort study
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Quinn, PJ, primary, O'Callaghan, M, additional, Williams, GM, additional, Najman, JM, additional, Andersen, MJ, additional, and Bor, W, additional
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- 2001
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6. Behavioural and cognitive associations of short stature at 5 years
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Stathis, SL, primary, O’Callaghan, MJ, additional, Williams, GM, additional, Najman, JM, additional, Andersen, MJ, additional, and Bor, W, additional
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- 1999
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7. Obstetric and perinatal factors as predictors of child behaviour at 5 years
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O'CALLAGHAN, MJ, primary, WILLIAMS, GM, additional, ANDERSEN, MJ, additional, BOR, W, additional, and NAJMAN, JM, additional
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- 1997
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8. Maternal Cigarette Smoking During Pregnancy Is an Independent Predictor for Symptoms of Middle Ear Disease at Five Years' Postdelivery
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Andersen Mj, Gail M. Williams, Stephen Stathis, O'Callaghan Dm, William Bor, and Jake M. Najman
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Male ,Pediatrics ,medicine.medical_specialty ,Middle ear disorder ,Population ,Ear infection ,Breastfeeding ,Pregnancy ,Risk Factors ,medicine ,Humans ,education ,education.field_of_study ,business.industry ,Smoking ,medicine.disease ,Otitis Media ,Logistic Models ,Otitis ,Maternal Exposure ,Child, Preschool ,Prenatal Exposure Delayed Effects ,Acute Disease ,Pediatrics, Perinatology and Child Health ,Attributable risk ,Marital status ,Female ,medicine.symptom ,business ,Follow-Up Studies - Abstract
Although an increasing body of literature has demonstrated a link between in utero exposure to cigarette smoke and childhood morbidity, the extent to which such exposure is associated with middle ear disease (MED) is less certain. We hypothesized that in utero exposure to cigarette smoke was associated with an increased risk of MED and aimed to calculate the proportion of disease at 5 years' postdelivery attributable to cigarette exposure during pregnancy. Methods. At their first antenatal session, 8556 women were enrolled in a prospective study of pregnancy. Mothers were followed during pregnancy, at birth, at 6 months' and at 5 years' postdelivery and completed a detailed questionnaire aimed at assessing the frequency of acute ( Results. In the adjusted analyses, acute ear infections were associated with consumption of 1 to 9 cigarettes (OR: 1.6; 95% CI: 1.1–2.5), 10 to 19 cigarettes (OR: 2.6; 95% CI: 1.6–4.2) and 20+ cigarettes (OR: 3.3; 95% CI: 1.9–5.9) per day at the first clinic visit. For subacute ear infections, an association was present with consumption of 10 to 19 cigarettes (OR: 2.6; 95% CI: 1.4–5.0) and 20+ cigarettes (OR: 2.8; 95% CI: 1.3–6.0) at the first clinic visit. In utero exposure to 20+ cigarettes per day at the first clinic visit was also associated with an increased risk of ear surgery by 5 years' postdelivery (OR: 2.9; 95% CI: 1.3–6.6). These associations were independent of smoking at 6 months and at 5 years, age and gender of the child, breastfeeding history, maternal age, maternal education, maternal employment at 5 years, marital status at 5 years, socioeconomic status, use of day care, and the number of siblings or children in the household. A population attributable risk percent at 5 years of 39.4% for acute ear infections, 37.9% for subacute ear infections, and 30.0% for previous ear surgery was found for in utero exposure to cigarette smoke at the first clinic visit. Conclusions. Smoking at the first clinic visit was associated with an increased risk of MED and ear surgery at 5 years of age. The frequency of maternal smoking in the general population gives rise to a high population attributable risk percent for MED. Therefore, it is a significant contributor to childhood morbidity and provides another reason why women should be encouraged to avoid smoking during pregnancy.
- Published
- 1999
9. Prediction of obesity in children at 5 years: A cohort study
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O'CALLAGHAN, MJ, primary, WILLIAMS, GM, additional, ANDERSEN, MJ, additional, BOR, W, additional, and NAJMAN, JM, additional
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- 1997
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10. The effect of breastfeeding on child development at 5 years: A cohort study.
- Author
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O'Callaghan, M, Quinn, PJ, Williams, GM, Najman, JM, Andersen, MJ, and Bor, W
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BREASTFEEDING & psychology ,COGNITIVE learning ,CHILD development ,PEDIATRICS - Abstract
Objective: It is uncertain to what degree the relationship between breastfeeding and later cognitive development is a true biological effect, or is confounded by psychosocial factors. The study aim was to further investigate this relationship and the effect of duration of breast feeding on cognitive development. Methods: A total of 3880 children were followed from birth. Breastfeeding duration was measured by questionaire at 6 months of age and a Peabody Picture Vocabulary Test Revised (PPVT-R) was administered at 5 years. PPVT-R scores were adjusted for the effects of a large array of biological and psychosocial confounders. The relationship between breastfeeding and the mean PPVT-R scores were examined using analysis of variance and multiple linear regression. Results: A strong positive relationship was demonstrated between breastfeeding and the PPVT-R scores with increasing scores with increased duration of breastfeeding. After adjusting for a wide range of biological and social factors, the adjusted mean for those breastfed for 6 months or more was 8.2 points higher for females and 5.8 points for males when compared to those never breastfed. Conclusion: These findings suggest a significant benefit to child development is conferred by breastfeeding and is related independently to longer periods of breastfeeding. [ABSTRACT FROM AUTHOR]
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- 2001
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11. Socio-economic status and pregnancy outcome. An Australian study
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Morrison, J, primary, Najman, JM, additional, Williams, GM, additional, Keeping, JD, additional, and Andersen, MJ, additional
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- 1989
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12. Impact of thrombocytopenia on bleeding and thrombotic outcomes in adults with cancer-associated splanchnic vein thrombosis.
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Andersen MJ Jr, Fernandez Turizo MJ, Dodge L, Hsu C, Barnum KJ, Berry J, Zwicker JI, and Patell R
- Abstract
Malignancy is a risk factor for splanchnic vein thrombosis (SpVT). Data on the natural history of cancer-associated SpVT are limited. This was a single-center retrospective cohort study of 581 adult patients with cancer and SpVT. We aimed to characterize the impact of thrombocytopenia on major bleeding and progression or recurrence of SpVT within one year of initial cancer-associated SpVT diagnosis. Baseline thrombocytopenia (platelet < 100,000/uL within 15 days of SpVT diagnosis) was present in 39.5% of patients. A total of 39.2% of patients received therapeutic anticoagulation within two weeks of SpVT diagnosis. The cumulative once-year incidence of major bleeding was 10.7% (95% CI: 8.2-13.2), and for SpVT recurrence/progression was 16.2% (95% CI: 13.2-19.2). In multivariable regression analysis, therapeutic anticoagulation was associated with increased major bleeding (aRR: 1.74, 95% CI: 1.08-2.81) and decreased progression/recurrence of SpVT (aRR: 0.55, 95% CI: 0.35-0.86). Baseline thrombocytopenia was not independently associated with either major bleeding (aRR: 0.76, 95% CI: 0.43-1.34) or progression/recurrence of SpVT (aRR: 1.14, 95% CI: 0.73-1.78). A secondary analysis using inverse probability of treatment weighting with propensity scores for baseline thrombocytopenia corroborated that patients with thrombocytopenia did not have increased bleeding risk (aHR: 0.81, 95% CI: 0.48-1.39). Multivariable analysis treating platelets as a time varying covariate also did not reveal an association with major bleeding (aHR: 0.89, 95% CI: 0.55-1.45). Bleeding and thrombosis progression were frequent in patients with cancer-associated SpVT. Anticoagulation was associated with increased major bleeding and decreased thrombotic progression; thrombocytopenia did not impact outcomes., (Copyright © 2024 American Society of Hematology.)
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- 2024
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13. Right ventricular to pulmonary artery coupling in chronic thromboembolic pulmonary hypertension.
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Lyhne MD, Hansen JV, Andersen S, Schultz JG, Sørensen SG, Kirk ME, Merit VT, Andersen MJ, Mellemkjær S, Ilkjær LB, Dudzinski DM, Nielsen-Kudsk JE, and Andersen A
- Abstract
Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by increased pulmonary vascular resistance (PVR) and pressure and right ventricular (RV) dysfunction. We aimed to evaluate the correlation of RV to pulmonary artery coupling, measured as the tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure (TAPSE/PASP) ratio, and invasive hemodynamic measurements, and to assess the changes in this ratio following CTEPH treatment., Methods: We conducted a retrospective cohort study of CTEPH patients treated at Aarhus University Hospital with pulmonary angioplasty (BPA), pulmonary endarterectomy (PEA), and or medical therapy only. Patients underwent transthoracic echocardiography and right heart catheterization at baseline and follow-up. The primary endpoint was the association between TAPSE/PASP and PVR. Secondary endpoints included other hemodynamic and functional parameters., Results: The study included 139 patients. Mean TAPSE/PASP at baseline was 0.22 [0.16, 0.29] mm/mmHg. An exponential decay correlation was found between TAPSE/PASP and PVR (correlation coefficient - 0.67, p < 0.001). The TAPSE/PASP ratio improved from 0.23 [0.18; 0.29] to 0.33 [0.26; 0.46] mm/mmHg, p < 0.0001, following BPA, and from 0.20 [0.15;0.27] to 0.35 [0.21;0.41] mm/mmHg, p = 0.0007 following PEA, indicating enhanced RV to pulmonary artery coupling., Conclusion: In patients with CTEPH, the echocardiographic TAPSE/PASP ratio as a measure of RV-PA coupling correlates well with invasively measured pulmonary vascular resistance. The TAPSE/PASP ratio improved after BPA or PEA treatments suggesting a potential use for monitoring patient outcomes. Further prospective studies are warranted to establish the prognostic value of the TAPSE/PASP ratio and ability to guide treatment decisions., Competing Interests: Declaration of competing interest Dr. Mads J. Andersen reports serving as a consultant to Johnson & Johnson. The remaining authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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14. Randomized Crossover Trial of 2-Week Ketone Ester Treatment in Patients With Type 2 Diabetes and Heart Failure With Preserved Ejection Fraction.
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Gopalasingam N, Berg-Hansen K, Christensen KH, Ladefoged BT, Poulsen SH, Andersen MJ, Borlaug B, Nielsen R, Møller N, and Wiggers H
- Abstract
Background: Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality in patients with type 2 diabetes (T2DM). Acute increases in circulating levels of ketone body 3-hydroxybutyrate have beneficial acute hemodynamic effects in patients without T2DM with chronic heart failure with reduced ejection fraction. However, the cardiovascular effects of prolonged oral ketone ester (KE) treatment in patients with T2DM and HFpEF remain unknown., Methods: A total of 24 patients with T2DM and HFpEF completed a 6-week randomized, double-blind crossover study. All patients received 2 weeks of KE treatment (25 g D-ß-hydroxybutyrate-(R)-1,3-butanediol × 4 daily) and isocaloric and isovolumic placebo, separated by a 2-week washout period. At the end of each treatment period, patients underwent right heart catheterization, echocardiography, and blood samples at trough levels of intervention, and then during a 4-hour resting period after a single dose. A subsequent second dose was administered, followed by an exercise test. The primary end point was cardiac output during the 4-hour rest period., Results: During the 4-hour resting period, circulating 3-hydroxybutyrate levels were 10-fold higher after KE treatment (1010±56 µmol/L; P <0.001) compared with placebo (91±55 µmol/L). Compared with placebo, KE treatment increased cardiac output by 0.2 L/min (95% CI, 0.1 to 0.3) during the 4-hour period and decreased pulmonary capillary wedge pressure at rest by 1 mm Hg (95% CI, -2 to 0) and at peak exercise by 5 mm Hg (95% CI, -9 to -1). KE treatment decreased the pressure-flow relationship (∆ pulmonary capillary wedge pressure/∆ cardiac output) significantly during exercise ( P <0.001) and increased stroke volume by 10 mL (95% CI, 0 to 20) at peak exercise. KE right-shifted the left ventricular end-diastolic pressure-volume relationship, suggestive of reduced left ventricular stiffness and improved compliance. Favorable hemodynamic responses of KE treatment were also observed in patients treated with sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 analogs., Conclusions: In patients with T2DM and HFpEF, a 2-week oral KE treatment increased cardiac output and reduced cardiac filling pressures and ventricular stiffness. At peak exercise, KE treatment markedly decreased pulmonary capillary wedge pressure and improved pressure-flow relationship. Modulation of circulating ketone levels is a potential new treatment modality for patients with T2DM and HFpEF., Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05236335.
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- 2024
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15. Exploring the Noninvasive Evaluation of the Pulmonary Pressure-Flow Relationship During Exercise.
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Andersen MJ, Vase H, and Simon MA
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- Humans, Exercise Test, Pulmonary Circulation physiology, Pulmonary Artery physiopathology, Pulmonary Artery diagnostic imaging, Exercise physiology
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- 2024
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16. An evidence-based screening tool for heart failure with preserved ejection fraction: the HFpEF-ABA score.
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Reddy YNV, Carter RE, Sundaram V, Kaye DM, Handoko ML, Tedford RJ, Andersen MJ, Sharma K, Obokata M, Verbrugge FH, and Borlaug BA
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- Humans, Female, Male, Aged, Middle Aged, Echocardiography, Atrial Fibrillation physiopathology, Atrial Fibrillation diagnosis, Atrial Fibrillation diagnostic imaging, Body Mass Index, Mass Screening methods, Aged, 80 and over, Cohort Studies, Risk Factors, Risk Assessment, Heart Failure physiopathology, Heart Failure diagnosis, Heart Failure diagnostic imaging, Stroke Volume
- Abstract
Heart failure with preserved ejection fraction (HFpEF) is under-recognized in clinical practice. Although a previously developed risk score, termed H
2 FPEF, can be used to estimate HFpEF probability, this score requires imaging data, which is often unavailable. Here we sought to develop an HFpEF screening model that is based exclusively on clinical variables and that can guide the need for echocardiography and further testing. In a derivation cohort (n = 414, 249 women), a clinical model using age, body mass index and history of atrial fibrillation (termed the HFpEF-ABA score) showed good discrimination (area under the curve (AUC) = 0.839 (95% confidence interval (CI) = 0.800-0.877), P < 0.0001). The performance of the model was validated in an international, multicenter cohort (n = 736, 443 women; AUC = 0.813 (95% CI = 0.779-0.847), P < 0.0001) and further validated in two additional cohorts: a cohort including patients with unexplained dyspnea (n = 228, 136 women; AUC = 0.840 (95% CI = 0.782-0.900), P < 0.0001) and a cohort for which HF hospitalization was used instead of hemodynamics to establish an HFpEF diagnosis (n = 456, 272 women; AUC = 0.929 (95% CI = 0.909-0.948), P < 0.0001). Model-based probabilities were also associated with increased risk of HF hospitalization or death among patients from the Mayo Clinic (n = 790) and a US national cohort across the Veteran Affairs health system (n = 3076, 110 women). Using the HFpEF-ABA score, rapid and efficient screening for risk of undiagnosed HFpEF can be performed in patients with dyspnea using only age, body mass index and history of atrial fibrillation., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)- Published
- 2024
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17. Waves of Colonization and Gene Flow in a Great Speciator.
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Gyllenhaal EF, Brady SS, DeCicco LH, Naikatini A, Hime PM, Manthey JD, Kelly J, Moyle RG, and Andersen MJ
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Secondary contact between previously allopatric lineages offers a test of reproductive isolating mechanisms that may have accrued in isolation. Such instances of contact can produce stable hybrid zones-where reproductive isolation can further develop via reinforcement or phenotypic displacement-or result in the lineages merging. Ongoing secondary contact is most visible in continental systems, where steady input from parental taxa can occur readily. In oceanic island systems, however, secondary contact between closely related species of birds is relatively rare. When observed on sufficiently small islands, relative to population size, secondary contact likely represents a recent phenomenon. Here, we examine the dynamics of a group of birds whose apparent widespread hybridization influenced Ernst Mayr's foundational work on allopatric speciation: the whistlers of Fiji (Aves: Pachycephala ). We demonstrate two clear instances of secondary contact within the Fijian archipelago, one resulting in a hybrid zone on a larger island, and the other resulting in a wholly admixed population on a smaller, adjacent island. We leveraged low genome-wide divergence in the hybrid zone to pinpoint a single genomic region associated with observed phenotypic differences. We use genomic data to present a new hypothesis that emphasizes rapid plumage evolution and post-divergence gene flow.
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- 2024
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18. The catheterized bladder environment induces dysregulation of macrophage polarization exacerbating bacterial UTI.
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Marrufo AM, Molina JJ, Gager C, Andersen MJ, LaBella AA, Lucas ER, Wongso E, Urmi T, Arias-Parbul K, Webster R, Stuckey PV, Kohler KN, Donahue D, Ploplis VA, Flick MJ, Castellino FJ, Santiago-Tirado FH, and Flores-Mireles AL
- Abstract
Urinary catheterization causes bladder damage, predisposing hosts to catheter-associated urinary tract infections (CAUTIs). CAUTI pathogenesis is mediated by bladder damage-induced inflammation, resulting in accumulation and deposition of the blood-clotting protein fibrinogen (Fg) and its matrix form fibrin, which are exploited by uropathogens as biofilm platforms to establish infection. Catheter-induced inflammation also results in robust immune cell recruitment, including macrophages (Mϕs). A fundamental knowledge gap is understanding the mechanisms by which the catheterized-bladder environment suppresses the Mϕ antimicrobial response, allowing uropathogen persistence. Here, we found that Fg and fibrin differentially modulate M1 and M2 Mϕ polarization, respectively. We unveiled that fibrin accumulation in catheterized mice induced an anti-inflammatory M2-like Mϕ phenotype, correlating with pathogen persistence. Even GM-CSF treatment of wildtype mice to promote M1 polarization was not sufficient to reduce bacterial burden and dissemination, indicating that the catheterized-bladder environment provides mixed signals, dysregulating Mϕ polarization, hindering its antimicrobial response against uropathogens.
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- 2024
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19. Effect of free liquid layer quantity on bacteria and protein adhesion to liquid infused polymers.
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Fong C, Andersen MJ, Kunesh E, Leonard E, Durand D, Coombs R, Flores-Mireles AL, and Howell C
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- Polymers chemistry, Silicones chemistry, Surface Properties, Fibrinogen chemistry, Fibrinogen metabolism, Humans, Bacterial Adhesion drug effects, Enterococcus faecalis physiology, Enterococcus faecalis drug effects
- Abstract
Liquid-infused polymers are recognized for their ability to repel foulants, making them promising for biomedical applications including catheter-associated urinary tract infections (CAUTIs). However, the impact of the quantity of free liquid layer covering the surface on protein and bacterial adhesion is not well understood. Here, we explore how the amount of free silicone liquid layer in infused silicone catheter materials influences the adhesion of bacteria and proteins relevant to CAUTIs. To alter the quantity of the free liquid layer, we either physically removed excess liquid from fully infused catheter materials or partially infused them. We then evaluated the impact on bacterial and host protein adhesion. Physical removal of the free liquid layer from the fully infused samples reduced the height of the liquid layer from 60 μm to below detection limits and silicone liquid loss into the environment by approximately 64% compared to controls, without significantly increasing the deposition of protein fibrinogen or the adhesion of the common uropathogen Enterococcus faecalis. Partially infused samples showed even greater reductions in liquid loss: samples infused to 70%-80% of their maximum capacity exhibited about an 85% decrease in liquid loss compared to fully infused controls. Notably, samples with more than 70% infusion did not show significant increases in fibrinogen or E. faecalis adhesion. These findings suggest that adjusting the levels of the free liquid layer in infused polymers can influence protein and bacterial adhesion on their surfaces. Moreover, removing the free liquid layer can effectively reduce liquid loss from these polymers while maintaining their functionality., (2024 Published under an exclusive license by the AVS.)
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- 2024
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20. Comparison of admittance and cardiac magnetic resonance generated pressure-volume loops in a porcine model.
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Andersen S, Laursen PH, Wood GJ, Lyhne MD, Madsen TL, Hansen ESS, Johansen P, Kim WY, and Andersen MJ
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- Animals, Swine, Blood Pressure physiology, Heart Ventricles diagnostic imaging, Models, Animal, Magnetic Resonance Imaging
- Abstract
Objective . Pressure-volume loop analysis, traditionally performed by invasive pressure and volume measurements, is the optimal method for assessing ventricular function, while cardiac magnetic resonance (CMR) imaging is the gold standard for ventricular volume estimation. The aim of this study was to investigate the agreement between the assessment of end-systolic elastance (Ees) assessed with combined CMR and simultaneous pressure catheter measurements compared with admittance catheters in a porcine model. Approach . Seven healthy pigs underwent admittance-based pressure-volume loop evaluation followed by a second assessment with CMR during simultaneous pressure measurements. Main results . Admittance overestimated end-diastolic volume for both the left ventricle (LV) and the right ventricle (RV) compared with CMR. Further, there was an underestimation of RV end-systolic volume with admittance. For the RV, however, Ees was systematically higher when assessed with CMR plus simultaneous pressure measurements compared with admittance whereas there was no systematic difference in Ees but large differences between admittance and CMR-based methods for the LV. Significance . LV and RV Ees can be obtained from both admittance and CMR based techniques. There were discrepancies in volume estimates between admittance and CMR based methods, especially for the RV. RV Ees was higher when estimated by CMR with simultaneous pressure measurements compared with admittance., (Creative Commons Attribution license.)
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- 2024
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21. Extraordinary levels of per- and polyfluoroalkyl substances (PFAS) in vertebrate animals at a New Mexico desert oasis: Multiple pathways for wildlife and human exposure.
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Witt CC, Gadek CR, Cartron JE, Andersen MJ, Campbell ML, Castro-Farías M, Gyllenhaal EF, Johnson AB, Malaney JL, Montoya KN, Patterson A, Vinciguerra NT, Williamson JL, Cook JA, and Dunnum JL
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- Animals, New Mexico, Humans, Mammals, Environmental Pollutants analysis, Food Chain, Desert Climate, Environmental Exposure, Fluorocarbons analysis, Environmental Monitoring, Birds metabolism
- Abstract
Per- and polyfluoroalkyl substances (PFAS) in the environment pose persistent and complex threats to human and wildlife health. Around the world, PFAS point sources such as military bases expose thousands of populations of wildlife and game species, with potentially far-reaching implications for population and ecosystem health. But few studies shed light on the extent to which PFAS permeate food webs, particularly ecologically and taxonomically diverse communities of primary and secondary consumers. Here we conducted >2000 assays to measure tissue-concentrations of 17 PFAS in 23 species of mammals and migratory birds at Holloman Air Force Base (AFB), New Mexico, USA, where wastewater catchment lakes form biodiverse oases. PFAS concentrations were among the highest reported in animal tissues, and high levels have persisted for at least three decades. Twenty of 23 species sampled at Holloman AFB were heavily contaminated, representing middle trophic levels and wetland to desert microhabitats, implicating pathways for PFAS uptake: ingestion of surface water, sediments, and soil; foraging on aquatic invertebrates and plants; and preying upon birds or mammals. The hazardous long carbon-chain form, perfluorooctanosulfonic acid (PFOS), was most abundant, with liver concentrations averaging >10,000 ng/g wet weight (ww) in birds and mammals, respectively, and reaching as high 97,000 ng/g ww in a 1994 specimen. Perfluorohexanesulfonic acid (PFHxS) averaged thousands of ng/g ww in the livers of aquatic birds and littoral-zone house mice, but one order of magnitude lower in the livers of upland desert rodent species. Piscivores and upland desert songbirds were relatively uncontaminated. At control sites, PFAS levels were strikingly lower on average and different in composition. In sum, legacy PFAS at this desert oasis have permeated local aquatic and terrestrial food webs across decades, severely contaminating populations of resident and migrant animals, and exposing people via game meat consumption and outdoor recreation., 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 Inc. All rights reserved.)
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- 2024
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22. Cardiovascular Effects of Oral Ketone Ester Treatment in Patients With Heart Failure With Reduced Ejection Fraction: A Randomized, Controlled, Double-Blind Trial.
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Berg-Hansen K, Gopalasingam N, Christensen KH, Ladefoged B, Andersen MJ, Poulsen SH, Borlaug BA, Nielsen R, Møller N, and Wiggers H
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- Humans, Male, Female, Double-Blind Method, Aged, Middle Aged, Cross-Over Studies, Exercise Tolerance drug effects, Administration, Oral, Ventricular Function, Left drug effects, Treatment Outcome, Esters administration & dosage, Ketones administration & dosage, Heart Failure drug therapy, Heart Failure physiopathology, Stroke Volume drug effects
- Abstract
Background: Heart failure triggers a shift in myocardial metabolic substrate utilization, favoring the ketone body 3-hydroxybutyrate as energy source. We hypothesized that 14-day treatment with ketone ester (KE) would improve resting and exercise hemodynamics and exercise capacity in patients with heart failure with reduced ejection fraction., Methods: In a randomized, double-blind cross-over study, nondiabetic patients with heart failure with reduced ejection fraction received 14-day KE and 14-day isocaloric non-KE comparator regimens of 4 daily doses separated by a 14-day washout period. After each treatment period, participants underwent right heart catheterization, echocardiography, and blood sampling at plasma trough levels and after dosing. Participants underwent an exercise hemodynamic assessment after a second dosing. The primary end point was resting cardiac output (CO). Secondary end points included resting and exercise pulmonary capillary wedge pressure and peak exercise CO and metabolic equivalents., Results: We included 24 patients with heart failure with reduced ejection fraction (17 men; 65±9 years of age; all White). Resting CO at trough levels was higher after KE compared with isocaloric comparator (5.2±1.1 L/min versus 5.0±1.1 L/min; difference, 0.3 L/min [95% CI, 0.1-0.5), and pulmonary capillary wedge pressure was lower (8±3 mm Hg versus 11±3 mm Hg; difference, -2 mm Hg [95% CI, -4 to -1]). These changes were amplified after KE dosing. Across all exercise intensities, KE treatment was associated with lower mean exercise pulmonary capillary wedge pressure (-3 mm Hg [95% CI, -5 to -1] ) and higher mean CO (0.5 L/min [95% CI, 0.1-0.8]), significantly different at low to moderate steady-state exercise but not at peak. Metabolic equivalents remained similar between treatments. In exploratory analyses, KE treatment was associated with 18% lower NT-proBNP (N-terminal pro-B-type natriuretic peptide; difference, -98 ng/L [95% CI, -185 to -23]), higher left ventricular ejection fraction (37±5 versus 34±5%; P =0.01), and lower left atrial and ventricular volumes., Conclusions: KE treatment for 14 days was associated with higher CO at rest and lower filling pressures, cardiac volumes, and NT-proBNP levels compared with isocaloric comparator. These changes persisted during exercise and were achieved on top of optimal medical therapy. Sustained modulation of circulating ketone bodies is a potential treatment principle in patients with heart failure with reduced ejection fraction., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05161650., Competing Interests: Disclosures Dr Wiggers has been the principal investigator or a subinvestigator in studies involving the following pharmaceutical companies: MSD, Bayer, Daiichi-Sankyo, Novartis, Novo Nordisk, Sanofi-Aventis, and Pfizer. Dr Borlaug receives research support from the National Institutes of Health and the US Department of Defense, as well as research grant funding from AstraZeneca, Axon, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, Rivus, and Tenax Therapeutics. Dr Borlaug has served as a consultant for Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, NGM, NXT, and VADovations, and is named inventor (US patent No. 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. The other authors report no conflicts.
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- 2024
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23. Challenges in Noninvasive Cardiac Output Assessment During Exercise.
- Author
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Andersen MJ, Møller JE, Vase H, Ersbøll MK, and Poulsen SH
- Subjects
- Humans, Cardiac Output, Exercise Test, Exercise, Heart
- Published
- 2024
- Full Text
- View/download PDF
24. Fibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI.
- Author
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Molina JJ, Kohler KN, Gager C, Andersen MJ, Wongso E, Lucas ER, Paik A, Xu W, Donahue DL, Bergeron K, Klim A, Caparon MG, Hultgren SJ, Desai A, Ploplis VA, Flick MJ, Castellino FJ, and Flores-Mireles AL
- Subjects
- Animals, Mice, Humans, Catheters, Enterococcus faecalis genetics, Fibrin, Cross Infection, Urinary Tract Infections, Sepsis
- Abstract
Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat partly due to development of multidrug-resistance from CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections. Catheter-induced inflammation promotes fibrinogen (Fg) and fibrin accumulation in the bladder which are exploited as a biofilm formation platform by CAUTI pathogens. Using our established mouse model of CAUTI, here we identified that host populations exhibiting either genetic or acquired fibrinolytic-deficiencies, inducing fibrin deposition in the catheterized bladder, are predisposed to severe CAUTI and septicemia by diverse uropathogens in mono- and poly-microbial infections. Furthermore, here we found that Enterococcus faecalis, a prevalent CAUTI pathogen, uses the secreted protease, SprE, to induce fibrin accumulation and create a niche ideal for growth, biofilm formation, and persistence during CAUTI., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
25. Myocardial work across different etiologies of right ventricular dysfunction and healthy controls.
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Berg-Hansen K, Gopalasingam N, Clemmensen TS, Andersen MJ, Mellemkjaer S, Poulsen SH, Jensen JK, and Nielsen R
- Subjects
- Humans, Predictive Value of Tests, Echocardiography, Systole, Ventricular Function, Right, Stroke Volume, Ventricular Dysfunction, Right diagnostic imaging, Ventricular Dysfunction, Right etiology, Tricuspid Valve Insufficiency
- Abstract
Evaluating right ventricular (RV) function remains a challenge. Recently, novel echocardiographic assessment of RV myocardial work (RVMW) by non-invasive pressure-strain loops was proposed. This enables evaluation of right ventriculoarterial coupling and quantifies RV dyssynchrony and post-systolic shortening. We aimed to assess RVMW in patients with different etiologies of RV dysfunction and healthy controls. We investigated healthy controls (n=17), patients with severe functional tricuspid regurgitation (FTR; n=22), and patients with precapillary pulmonary hypertension (PCPH; n=20). Echocardiography and right heart catheterization were performed to assess 1) RV global constructive work (RVGCW; work needed for systolic myocardial shortening and isovolumic relaxation), 2) RV global wasted work (RVGWW; myocardial shortening following pulmonic valve closure), and 3) RV global work efficiency (RVGWE; describes the relation between RV constructive and wasted work). RVGCW correlated with invasive RV stroke work index (r=0.66, P<0.001) and increased in tandem with higher afterload, i.e., was low in healthy controls (454±73 mmHg%), moderate in patients with FTR (687±203 mmHg%), and highest among patients with PCPH (881±255 mmHg%). RVGWE was lower and RVGWW was higher in patients with FTR (86±8% and 91 mmHg% [53-140]) or PCPH (86±10% and 110 mmHg% [66-159]) as compared with healthy controls (96±3% and 10 mmHg%). RVMW by echocardiography provides a promising index of RV function to discriminate between patients with RV volume or pressure overload. The prognostic value of this measure needs to be settled in future studies., (© 2024. The Author(s).)
- Published
- 2024
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26. Specimen collection is essential for modern science.
- Author
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Nachman MW, Beckman EJ, Bowie RC, Cicero C, Conroy CJ, Dudley R, Hayes TB, Koo MS, Lacey EA, Martin CH, McGuire JA, Patton JL, Spencer CL, Tarvin RD, Wake MH, Wang IJ, Achmadi A, Álvarez-Castañeda ST, Andersen MJ, Arroyave J, Austin CC, Barker FK, Barrow LN, Barrowclough GF, Bates J, Bauer AM, Bell KC, Bell RC, Bronson AW, Brown RM, Burbrink FT, Burns KJ, Cadena CD, Cannatella DC, Castoe TA, Chakrabarty P, Colella JP, Cook JA, Cracraft JL, Davis DR, Davis Rabosky AR, D'Elía G, Dumbacher JP, Dunnum JL, Edwards SV, Esselstyn JA, Faivovich J, Fjeldså J, Flores-Villela OA, Ford K, Fuchs J, Fujita MK, Good JM, Greenbaum E, Greene HW, Hackett S, Hamidy A, Hanken J, Haryoko T, Hawkins MT, Heaney LR, Hillis DM, Hollingsworth BD, Hornsby AD, Hosner PA, Irham M, Jansa S, Jiménez RA, Joseph L, Kirchman JJ, LaDuc TJ, Leaché AD, Lessa EP, López-Fernández H, Mason NA, McCormack JE, McMahan CD, Moyle RG, Ojeda RA, Olson LE, Kin Onn C, Parenti LR, Parra-Olea G, Patterson BD, Pauly GB, Pavan SE, Peterson AT, Poe S, Rabosky DL, Raxworthy CJ, Reddy S, Rico-Guevara A, Riyanto A, Rocha LA, Ron SR, Rovito SM, Rowe KC, Rowley J, Ruane S, Salazar-Valenzuela D, Shultz AJ, Sidlauskas B, Sikes DS, Simmons NB, Stiassny MLJ, Streicher JW, Stuart BL, Summers AP, Tavera J, Teta P, Thompson CW, Timm RM, Torres-Carvajal O, Voelker G, Voss RS, Winker K, Witt C, Wommack EA, and Zink RM
- Subjects
- Animals, Natural History, Museums, Specimen Handling
- Abstract
Natural history museums are vital repositories of specimens, samples and data that inform about the natural world; this Formal Comment revisits a Perspective that advocated for the adoption of compassionate collection practices, querying whether it will ever be possible to completely do away with whole animal specimen collection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
- Published
- 2023
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27. A new genus for Dasycrotapha plateni and D. pygmaea (Aves: Zosteropidae).
- Author
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Sangster G, Vinciguerra NT, Gaudin J, and Andersen MJ
- Subjects
- Animals, Passeriformes
- Abstract
N/A.
- Published
- 2023
- Full Text
- View/download PDF
28. Genomic signatures of convergent shifts to plunge-diving behavior in birds.
- Author
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Eliason CM, Mellenthin LE, Hains T, McCullough JM, Pirro S, Andersen MJ, and Hackett SJ
- Subjects
- Animals, Phylogeny, Birds genetics, Genomics, Water, Diving
- Abstract
Understanding the genetic basis of convergence at broad phylogenetic scales remains a key challenge in biology. Kingfishers (Aves: Alcedinidae) are a cosmopolitan avian radiation with diverse colors, diets, and feeding behaviors-including the archetypal plunge-dive into water. Given the sensory and locomotor challenges associated with air-water transitions, kingfishers offer a powerful opportunity to explore the effects of convergent behaviors on the evolution of genomes and phenotypes, as well as direct comparisons between continental and island lineages. Here, we use whole-genome sequencing of 30 diverse kingfisher species to identify the genomic signatures associated with convergent feeding behaviors. We show that species with smaller ranges (i.e., on islands) have experienced stronger demographic fluctuations than those on continents, and that these differences have influenced the dynamics of molecular evolution. Comparative genomic analyses reveal positive selection and genomic convergence in brain and dietary genes in plunge-divers. These findings enhance our understanding of the connections between genotype and phenotype in a diverse avian radiation., (© 2023. Springer Nature Limited.)
- Published
- 2023
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29. Removal of Free Liquid Layer from Liquid-Infused Catheters Reduces Silicone Loss into the Environment while Maintaining Adhesion Resistance.
- Author
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Fong C, Andersen MJ, Kunesh E, Leonard E, Durand D, Coombs R, Flores-Mireles AL, and Howell C
- Abstract
Silicone urinary catheters infused with silicone liquid offer an effective alternative to antibiotic coatings, reducing microbial adhesion while decreasing bladder colonization and systemic dissemination. However, loss of free silicone liquid from the surface into the host system is undesirable. To reduce the potential for liquid loss, free silicone liquid was removed from the surface of liquid-infused catheters by either removing excess liquid from fully infused samples or by partial infusion. The effect on bacterial and host protein adhesion was then assessed. Removing the free liquid from fully infused samples resulted in a ~64% decrease in liquid loss into the environment compared to controls, with no significant increase in deposition of the host protein fibrinogen or the adhesion of the common uropathogen Enterococcus faecalis . Partially infusing samples decreased liquid loss as total liquid content decreased, with samples infused to 70-80% of their maximum capacity showing a ~85% reduction in liquid loss compared to fully infused controls. Furthermore, samples above 70% infusion showed no significant increase in fibrinogen or E. faecalis adhesion. Together, the results suggest that eliminating free liquid layer, mechanically or through partial infusion, can reduce liquid loss from liquid-infused catheters while preserving functionality.
- Published
- 2023
- Full Text
- View/download PDF
30. Fibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI.
- Author
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Molina JJ, Kohler KN, Gager C, Andersen MJ, Wongso E, Lucas ER, Paik A, Xu W, Donahue DL, Bergeron K, Klim A, Caparon MG, Hultgren SJ, Desai A, Ploplis VA, Flick MJ, Castellino FJ, and Flores-Mireles AL
- Abstract
Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat due to multi-drug resistance development among the CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections. Catheter-induced inflammation promotes fibrinogen (Fg) and fibrin accumulation in the bladder which are exploited as a biofilm formation platform by CAUTI pathogens. Using our established mouse model of CAUTI, we identified that host populations exhibiting either genetic or acquired fibrinolytic-deficiencies, inducing fibrin deposition in the catheterized bladder, are predisposed to severe CAUTI and septicemia by diverse uropathogens in mono- and poly-microbial infections. Furthermore, we found that E. faecalis , a prevalent CAUTI pathogen, uses the secreted protease, SprE, to induce fibrin accumulation and create a niche ideal for growth, biofilm formation, and persistence during CAUTI., Competing Interests: Declaration of interests: The authors declare no competing financial interests.
- Published
- 2023
- Full Text
- View/download PDF
31. Mitonuclear discordance results from incomplete lineage sorting, with no detectable evidence for gene flow, in a rapid radiation of Todiramphus kingfishers.
- Author
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DeRaad DA, McCullough JM, DeCicco LH, Hime PM, Joseph L, Andersen MJ, and Moyle RG
- Subjects
- Animals, Phylogeny, Cell Nucleus genetics, Birds genetics, Gene Flow, Genome, Mitochondrial genetics
- Abstract
Many organisms possess multiple discrete genomes (i.e. nuclear and organellar), which are inherited separately and may have unique and even conflicting evolutionary histories. Phylogenetic reconstructions from these discrete genomes can yield different patterns of relatedness, a phenomenon known as cytonuclear discordance. In many animals, mitonuclear discordance (i.e. discordant evolutionary histories between the nuclear and mitochondrial genomes) has been widely documented, but its causes are often considered idiosyncratic and inscrutable. We show that a case of mitonuclear discordance in Todiramphus kingfishers can be explained by extensive genome-wide incomplete lineage sorting (ILS), likely a result of the explosive diversification history of this genus. For these kingfishers, quartet frequencies reveal that the nuclear genome is dominated by discordant topologies, with none of the internal branches in our consensus nuclear tree recovered in >50% of genome-wide gene trees. Meanwhile, a lack of inter-species shared ancestry, non-significant pairwise tests for gene flow, and little evidence for meaningful migration edges between species, leads to the conclusion that gene flow cannot explain the mitonuclear discordance we observe. This lack of evidence for gene flow combined with evidence for extensive genome-wide gene tree discordance, a hallmark of ILS, leads us to conclude that the mitonuclear discordance we observe likely results from ILS, specifically deep coalescence of the mitochondrial genome. Based on this case study, we hypothesize that similar demographic histories in other 'great speciator' taxa across the Indo-Pacific likely predispose these groups to high levels of ILS and high likelihoods of mitonuclear discordance., (© 2023 John Wiley & Sons Ltd.)
- Published
- 2023
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32. Biomarkers of collagen turnover and wound healing in chronic thromboembolic pulmonary hypertension patients before and after pulmonary endarterectomy.
- Author
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Andersen S, Reese-Petersen AL, Braams N, Andersen MJ, Mellemkjær S, Andersen A, Bogaard HJ, Genovese F, and Nielsen-Kudsk JE
- Subjects
- Humans, Chronic Disease, Endarterectomy methods, Collagen, Wound Healing, Biomarkers, Pulmonary Artery surgery, Hypertension, Pulmonary diagnosis, Hypertension, Pulmonary etiology, Hypertension, Pulmonary surgery, Pulmonary Embolism complications, Pulmonary Embolism diagnosis, Pulmonary Embolism surgery
- Abstract
Background: In chronic thromboembolic pulmonary hypertension (CTEPH), fibrotic remodeling of tissue and thrombi contributes to disease progression. Removal of the thromboembolic mass by pulmonary endarterectomy (PEA) improves hemodynamics and right ventricular function, but the roles of different collagens before as well as after PEA are not well understood., Methods: In this study, hemodynamics and 15 different biomarkers of collagen turnover and wound healing were evaluated in 40 CTEPH patients at diagnosis (baseline) and 6 and 18 months after PEA. Baseline biomarker levels were compared with a historical cohort of 40 healthy subjects., Results: Biomarkers of collagen turnover and wound healing were increased in CTEPH patients compared with healthy controls, including a 35-fold increase in the PRO-C4 marker of type IV collagen formation and a 55-fold increase in the C3M marker of type III collagen degradation. PEA reduced pulmonary pressures to almost normal levels 6 months after the procedure, with no further improvement at 18 months. There were no changes in any of the measured biomarkers after PEA., Conclusions: Biomarkers of collagen formation and degradation are increased in CTEPH suggesting a high collagen turnover. While PEA effectively reduces pulmonary pressures, collagen turnover is not significantly modified by surgical PEA., Competing Interests: Declaration of Competing Interest ALRP and FG are employed by Nordic Bioscience, Biomarkers and Research. None of the authors from Nordic Bioscience received any kind of financial benefits or other bonuses for the work described in this manuscript., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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33. Long-Term Prognostic Impact of Pulmonary Hypertension After Venous Thromboembolism.
- Author
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Bonnesen K, Klok FA, Andersen MJ, Andersen A, Nielsen-Kudsk JE, Mellemkjær S, Sørensen HT, and Schmidt M
- Subjects
- Adult, Humans, Cohort Studies, Prognosis, Risk Factors, Venous Thromboembolism epidemiology, Hypertension, Pulmonary etiology, Hypertension, Pulmonary complications, Pulmonary Embolism complications, Pulmonary Embolism epidemiology, Pulmonary Embolism diagnosis, Neoplasms complications, Neoplasms epidemiology
- Abstract
Pulmonary embolism is a risk factor for chronic thromboembolic pulmonary hypertension (CTEPH), but the prognostic impact of CTEPH on venous thromboembolism (VTE) mortality remains unclear. We examined the impact of CTEPH and other pulmonary hypertension (PH) subtypes on long-term mortality after VTE. We conducted a nationwide, population-based cohort study of all adult Danish patients alive 2 years after incident VTE without previous PH from 1995 to 2020 (n = 129,040). We used inverse probability of treatment weights in a Cox model to calculate standardized mortality rate ratios (SMRs) of the association between receiving a first-time PH diagnosis ≤2 years after incident VTE and mortality (all-cause, cardiovascular, and cancer). We grouped PH as PH associated with left-sided cardiac disease (group II), PH associated with lung diseases and/or hypoxia (group III), CTEPH (group IV), and unclassified (remaining patients). Total follow-up was 858,954 years. The SMR associated with PH overall was 1.99 (95% confidence interval 1.75 to 2.27) for all-cause, 2.48 (1.90 to 3.23) for cardiovascular, and 0.84 (0.60 to 1.17) for cancer mortality. The SMR for all-cause mortality was 2.62 (1.77 to 3.88) for group II, 3.98 (2.85 to 5.56) for group III, 1.88 (1.11 to 3.20) for group IV, and 1.73 (1.47 to 2.04) for unclassified PH. The cardiovascular mortality rate was increased approximately threefold for groups II and III but was not increased for group IV. Only group III was associated with increased cancer mortality. In conclusion, PH diagnosed ≤2 years after incident VTE was associated with an overall twofold increased long-term mortality driven by cardiovascular causes., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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34. Hemodynamic Effects of Ketone Bodies in Patients With Pulmonary Hypertension.
- Author
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Nielsen R, Christensen KH, Gopalasingam N, Berg-Hansen K, Seefeldt J, Homilius C, Boedtkjer E, Andersen MJ, Wiggers H, Møller N, Bøtker HE, and Mellemkjær S
- Subjects
- Animals, Rats, Chronic Disease, Cross-Over Studies, Familial Primary Pulmonary Hypertension, Hemodynamics physiology, Ketone Bodies pharmacology, Pulmonary Artery, Rats, Sprague-Dawley, Humans, Hypertension, Pulmonary, Pulmonary Arterial Hypertension, Pulmonary Embolism complications
- Abstract
Background Pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) are debilitating diseases with a high mortality. Despite emerging treatments, pulmonary vascular resistance frequently remains elevated. However, the ketone body 3-hydroxybutyrate (3-OHB) may reduce pulmonary vascular resistance in these patients. Hence, the aim was to assess the hemodynamic effects of 3-OHB in patients with PAH or CTEPH. Methods and Results We enrolled patients with PAH (n=10) or CTEPH (n=10) and residual pulmonary hypertension. They received 3-OHB infusion and placebo (saline) for 2 hours in a randomized crossover study. Invasive hemodynamic and echocardiography measurements were performed. Furthermore, we investigated the effects of 3-OHB on the right ventricle of isolated hearts and isolated pulmonary arteries from Sprague-Dawley rats. Ketone body infusion increased circulating 3-OHB levels from 0.5±0.5 to 3.4±0.7 mmol/L ( P <0.001). Cardiac output improved by 1.2±0.1 L/min (27±3%, P <0.001), and right ventricular annular systolic velocity increased by 1.4±0.4 cm/s (13±4%, P =0.002). Pulmonary vascular resistance decreased by 1.3±0.3 Wood units (18%±4%, P <0.001) with no significant difference in response between patients with PAH and CTEPH. In the rat studies, 3-OHB administration was associated with decreased pulmonary arterial tension compared with saline administration (maximal relative tension difference: 12±2%, P <0.001) and had no effect on right ventricular systolic pressures ( P =0.63), whereas pressures rose at a slower pace (dP/dtmax, P =0.02). Conclusions In patients with PAH or CTEPH, ketone body infusion improves cardiac output and decreases pulmonary vascular resistance. Experimental rat studies support that ketone bodies relax pulmonary arteries. Long-term studies are warranted to assess the clinical role of hyperketonemia. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04615754.
- Published
- 2023
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- View/download PDF
35. Complex plumages spur rapid color diversification in kingfishers (Aves: Alcedinidae).
- Author
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Eliason CM, McCullough JM, Hackett SJ, and Andersen MJ
- Subjects
- Animals, Humans, Feathers, Color, Pigmentation genetics, Biological Evolution, Birds physiology
- Abstract
Colorful signals in nature provide some of the most stunning examples of rapid phenotypic evolution. Yet, studying color pattern evolution has been historically difficult owing to differences in perceptual ability of humans and analytical challenges with studying how complex color patterns evolve. Island systems provide a natural laboratory for testing hypotheses about the direction and magnitude of phenotypic change. A recent study found that plumage colors of island species are darker and less complex than continental species. Whether such shifts in plumage complexity are associated with increased rates of color evolution remains unknown. Here, we use geometric morphometric techniques to test the hypothesis that plumage complexity and insularity interact to influence color diversity in a species-rich clade of colorful birds-kingfishers (Aves: Alcedinidae). In particular, we test three predictions: (1) plumage complexity enhances interspecific rates of color evolution, (2) plumage complexity is lower on islands, and (3) rates of plumage color evolution are higher on islands. Our results show that more complex plumages result in more diverse colors among species and that island species have higher rates of color evolution. Importantly, we found that island species did not have more complex plumages than their continental relatives. Thus, complexity may be a key innovation that facilitates evolutionary response of individual color patches to distinct selection pressures on islands, rather than being a direct target of selection itself. This study demonstrates how a truly multivariate treatment of color data can reveal evolutionary patterns that might otherwise go unnoticed., Competing Interests: CE, JM, SH, MA No competing interests declared, (© 2023, Eliason et al.)
- Published
- 2023
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36. The catheterized bladder environment promotes Efg1- and Als1-dependent Candida albicans infection.
- Author
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La Bella AA, Andersen MJ, Gervais NC, Molina JJ, Molesan A, Stuckey PV, Wensing L, Nobile CJ, Shapiro RS, Santiago-Tirado FH, and Flores-Mireles AL
- Subjects
- Humans, Candida albicans, Urinary Bladder, Adhesins, Bacterial, Fibrinogen, Amyotrophic Lateral Sclerosis, Cross Infection
- Abstract
Catheter-associated urinary tract infections (CAUTIs) account for 40% of hospital-acquired infections (HAIs). As 20 to 50% of hospitalized patients receive catheters, CAUTIs are one of the most common HAIs, resulting in increased morbidity, mortality, and health care costs. Candida albicans is the second most common CAUTI uropathogen, yet relative to its bacterial counterparts, little is known about how fungal CAUTIs are established. Here, we show that the catheterized bladder environment induces Efg1- and fibrinogen (Fg)-dependent biofilm formation that results in CAUTI. In addition, we identify the adhesin Als1 as the critical fungal factor for C. albicans Fg-urine biofilm formation. Furthermore, we show that in the catheterized bladder, a dynamic and open system, both filamentation and attachment are required, but each by themselves are not sufficient for infection. Our study unveils the mechanisms required for fungal CAUTI establishment, which may aid in the development of future therapies to prevent these infections.
- Published
- 2023
- Full Text
- View/download PDF
37. Axotomy results in an increase in Thy-1 protein in the 35-day-old rat supraoptic nucleus.
- Author
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Askvig JM, Irmen RE, Dalzell TS, Whiteman ST, Andersen MJ, Said Z, Nguyen DQ, Bexell SH, and Maruska BL
- Subjects
- Rats, Animals, Axotomy methods, Rats, Sprague-Dawley, Supraoptic Nucleus metabolism
- Abstract
We demonstrated previously that the hypothalamic supraoptic nucleus (SON) undergoes an axonal sprouting response following a unilateral lesion of the hypothalamo-neurohypophysial tract in a 35-day-old rat to repopulate the partially denervated neural lobe (NL). However, no sprouting occurs following the same injury in a 125-day-old rat. We previously reported a significant increase in Thy-1 protein in the SON of a 125-day-old rat compared to a 35-day-old rat in the absence of injury. Thy-1 is a cell surface glycoprotein shown to inhibit axonal outgrowth following injury; however, we did not look at axotomy's effect on Thy-1 in the SON. Therefore, we sought to determine the integrin ligands that bind Thy-1 in the SON and how axotomy impacts Thy-1. Like what others have shown, the co-immunoprecipitation analysis demonstrated that Thy-1 interacts with α
v ß3 and αv ß5 integrin dimers in the SON. We used western blot analysis to examine protein levels of Thy-1 and integrin subunits following injury in the 35- and 125-day-old rat SON and NL. Our results demonstrated that Thy-1 protein levels increase in the lesion SON in a 35-day-old rat. The quantitative dual-fluorescent analysis showed that the increase in Thy-1 in the lesion SON occurred in astrocytes. There was no change in Thy-1 or integrin protein levels following injury in the 125-day-old following injury. Furthermore, the axotomy significantly decreased Thy-1 protein levels in the NL of both 35- and 125-day-old rats. These results provide evidence that Thy-1 protein levels are injury dependent in the magnocellular neurosecretory system., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2023
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- View/download PDF
38. Metoprolol Improves Left Ventricular Longitudinal Strain at Rest and during Exercise in Obstructive Hypertrophic Cardiomyopathy.
- Author
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Dybro AM, Rasmussen TB, Nielsen RR, Pedersen ALD, Andersen MJ, Jensen MK, and Poulsen SH
- Subjects
- Humans, Metoprolol therapeutic use, Heart Ventricles diagnostic imaging, Echocardiography, Ventricular Function, Left, Adrenergic beta-Antagonists pharmacology, Adrenergic beta-Antagonists therapeutic use, Cardiomyopathy, Hypertrophic diagnostic imaging, Cardiomyopathy, Hypertrophic drug therapy, Ventricular Dysfunction, Left diagnostic imaging, Ventricular Dysfunction, Left drug therapy
- Abstract
Background: Patients with obstructive hypertrophic cardiomyopathy (HCM) often experience symptoms of heart failure upon exertion despite having normal left ventricular (LV) ejection fractions. Longitudinal strain (LS) may be a more sensitive marker of systolic dysfunction in patients with LV hypertrophy. The aims of this study were to characterize LV segmental LS and global LS (GLS) at rest and during exercise and to assess if first-line treatment with β-blockers improves LV systolic performance., Methods: Twenty-nine patients with obstructive HCM and New York Heart Association functional class ≥ II symptoms were enrolled in a double-blind, placebo-controlled, randomized crossover trial. Patients received metoprolol 150 mg or placebo for two consecutive 2-week periods in random order. Echocardiographic assessment with speckle-tracking-derived LS was performed at rest and during peak exercise at the end of each treatment period., Results: During placebo treatment, resting values of segmental LS showed an apical-basal difference of -10.3% (95% CI, -12.7% to -7.8%; P < .0001), with a severely abnormal value of the basal segment of -9.3 ± 4.2%. Treatment with metoprolol was associated with more negative LS values of the apical segment (-2.8%; 95% CI, -4.2% to -1.3%; P < .001) and the mid segment (-1.1%; 95% CI, -2.0% to -0.3%; P = .007). During peak exercise there was a deterioration in LV GLS, but treatment with metoprolol was associated with more negative peak exercise LV GLS (-1.3 %; 95% CI, -2.6% to -0.1%; P = .03)., Conclusions: Systolic performance assessed by LV GLS showed impaired values at rest and during exercise, with severely depressed values of the basal and mid segments. Treatment with metoprolol improved LV GLS upon exercise, indicating a beneficial effect of β-blocker treatment on LV systolic function., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
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39. Supracondylar humerus fractures in children.
- Author
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Andersen MJ
- Subjects
- Child, Humans, Treatment Outcome, Retrospective Studies, Humeral Fractures diagnostic imaging, Humeral Fractures surgery
- Abstract
The supracondylar humerus fracture is the most common elbow fracture in children. All orthopedic surgeons involved in pediatric trauma will at some point have to treat this injury. Severity ranges from simple fractures to limb threatening injuries. An in-depth knowledge of this injury is key to a successful treatment outcome. This review describes the diagnostic approach and current concepts for treatment of pediatric supracondylar humerus fractures.
- Published
- 2023
40. Diaphyseal forearm fractures in children.
- Author
-
Gøttsche D and Andersen MJ
- Subjects
- Child, Humans, Forearm, Bone Nails, Treatment Outcome, Ulna Fractures surgery, Radius Fractures diagnostic imaging, Radius Fractures surgery
- Abstract
Diaphyseal forearm fractures in children are common and knowledge of both ordinary and rare variations of these are important to deliver the best treatment as presented in this review. Closed reduction and cast immobilisation are effective and well-documented treatments for most fractures. Fractures which cannot be sufficiently treated in a cast are stabilised with elastic stable intramedullary nailing which is an effective treatment with a low complication rate. The focus in reduction is to correct alignment, displacement, and rotation to restore normal function of the forearm.
- Published
- 2023
41. Mere som havarti end cheddarost.
- Author
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Andersen MJ
- Published
- 2023
42. Pressure-flow responses to exercise in aortic stenosis, mitral regurgitation and diastolic dysfunction.
- Author
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Andersen MJ, Wolsk E, Bakkestrøm R, Christensen N, Carter-Storch R, Omar M, Dahl JS, Frederiksen PH, Borlaug B, Gustafsson F, Hassager C, and Moller JE
- Subjects
- Humans, Exercise Test, Pulmonary Wedge Pressure physiology, Stroke Volume physiology, Ventricular Function, Left, Aortic Valve Stenosis complications, Aortic Valve Stenosis diagnosis, Mitral Valve Insufficiency diagnosis, Myocardial Infarction
- Abstract
Background: Haemodynamic exercise testing is important for evaluating patients with dyspnoea on exertion and preserved ejection fraction. Despite very different pathologies, patients with pressure (aortic stenosis (AS)) and volume (mitral regurgitation (MR)) overload and diastolic dysfunction after recent acute myocardial infarction (AMI) reach similar filling pressure levels with exercise. The pressure-flow relationships (the association between change in cardiac output (∆CO) and change in pulmonary arterial wedge pressure (∆PAWP) may provide insight into haemodynamic adaptation to exercise in these groups., Methods and Results: One hundred sixty-eight subjects aged >50 years with a left ventricular ejection fraction of ≥50% underwent invasive exercise testing. They were enrolled in four different studies: AS (40 patients), AMI (52 patients), MR (43 patients) and 33 healthy subjects. Haemodynamic data were measured at rest, at 25 W, 75 W and at peak exercise. In all groups, PAWP increased with exercise. The greatest increase was observed in patients with AMI (from 12.7±3.9 mm Hg to 33.1±8.2 mm Hg, p<0.0001) and patients with AS (from 11.8±3.9 mm Hg to 31.4±6.1 mm Hg, p<0.0001), and the smallest was observed in healthy subjects (from 8.3±2.4 mm Hg to 21.1±7.5 mm Hg, p<0.0001). In all groups, the relative pressure increase was greatest at the beginning of the exercise. CO increased most in healthy patients (from 5.3±1.1 to 16.0±3.0 L/min, p<0.0001) and least in patients with AS (from 5.3±1.2 L/min to 12.4±2.6 L/min, p<0.0001). The pressure-flow relationships (∆PAWP/∆CO) and differed among groups (p = 0.02). In all groups, the pressure-flow relationship was steepest in the initial phase of the exercise test. The AMI and AS groups (2.3±1.2 mm Hg/L/min and 3.0±1.3 mm Hg/L/min, AMI and AS, respectively) had the largest overall pressure-flow relationship; the healthy group had the smallest initially and at peak exercise (1.3±1.1 mm Hg/L/min) followed by MR group (1.9±1.4 mm Hg/L/min)., Conclusion: The pressure-flow relationship was steepest in the initial phase of the exercise test in all groups. The pressure-flow relationship differs between groups., Trial Registration Numbers: NCT01974557, NCT01046838, NCT02961647 and NCT02395107., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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43. Genomic novelty within a "great speciator" revealed by a high-quality reference genome of the collared kingfisher (Todiramphus chloris collaris).
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Eliason CM, Hains T, McCullough J, Andersen MJ, and Hackett SJ
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- Animals, Genomics, Genome, Passeriformes genetics
- Abstract
Islands are natural laboratories for studying patterns and processes of evolution. Research on island endemic birds has revealed elevated speciation rates and rapid phenotypic evolution in several groups (e.g. white-eyes, Darwin's finches). However, understanding the evolutionary processes behind these patterns requires an understanding of how genotypes map to novel phenotypes. To date, there are few high-quality reference genomes for species found on islands. Here, we sequence the genome of one of Ernst Mayr's "great speciators," the collared kingfisher (Todiramphus chloris collaris). Utilizing high molecular weight DNA and linked-read sequencing technology, we assembled a draft high-quality genome with highly contiguous scaffolds (scaffold N50 = 19 Mb). Based on universal single-copy orthologs, we estimated a gene space completeness of 96.6% for the draft genome assembly. The population demographic history analyses reveal a distinct pattern of contraction and expansion in population size throughout the Pleistocene. Comparative genomic analysis of gene family evolution revealed that species-specific and rapidly expanding gene families in the collared kingfisher (relative to other Coraciiformes) are mainly involved in the ErbB signaling pathway and focal adhesion. Todiramphus kingfishers are a species-rich group that has become a focus of speciation research. This draft genome will be a platform for future taxonomic, phylogeographic, and speciation research in the group. For example, target genes will enable testing of changes in sensory structures associated with changes in vision and taste genes across kingfishers., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)
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- 2022
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44. Wallacean and Melanesian Islands Promote Higher Rates of Diversification within the Global Passerine Radiation Corvides.
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McCullough JM, Oliveros CH, Benz BW, Zenil-Ferguson R, Cracraft J, Moyle RG, and Andersen MJ
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- Animals, Australia, Islands, Melanesia, Phylogeny, Water, Songbirds genetics
- Abstract
The complex island archipelagoes of Wallacea and Melanesia have provided empirical data behind integral theories in evolutionary biology, including allopatric speciation and island biogeography. Yet, questions regarding the relative impact of the layered biogeographic barriers, such as deep-water trenches and isolated island systems, on faunal diversification remain underexplored. One such barrier is Wallace's Line, a significant biogeographic boundary that largely separates Australian and Asian biodiversity. To assess the relative roles of biogeographic barriers-specifically isolated island systems and Wallace's Line-we investigated the tempo and mode of diversification in a diverse avian radiation, Corvides (Crows and Jays, Birds-of-paradise, Vangas, and allies). We combined a genus-level data set of thousands of ultraconserved elements (UCEs) and a species-level, 12-gene Sanger sequence matrix to produce a well-resolved supermatrix tree that we leveraged to explore the group's historical biogeography and the effects of the biogeographic barriers on their macroevolutionary dynamics. The tree is well resolved and differs substantially from what has been used extensively for past comparative analyses within this group. We confirmed that Corvides, and its major constituent clades, arose in Australia and that a burst of dispersals west across Wallace's Line occurred after the uplift of Wallacea during the mid-Miocene. We found that dispersal across this biogeographic barrier was generally rare, though westward dispersals were two times more frequent than eastward dispersals. Wallacea's central position between Sundaland and Sahul no doubt acted as a bridge for island-hopping dispersal out of Australia, across Wallace's Line, to colonize the rest of Earth. In addition, we found that the complex island archipelagoes east of Wallace's Line harbor the highest rates of net diversification and are a substantial source of colonists to continental systems on both sides of this biogeographic barrier. Our results support emerging evidence that island systems, particularly the geologically complex archipelagoes of the Indo-pacific, are drivers of species diversification. [Historical biogeography; island biogeography; Melanesia; molecular phylogenetics; state-dependent diversification and extinction.]., (© The Author(s) 2022. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2022
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45. Diagnosis of Heart Failure With Preserved Ejection Fraction Among Patients With Unexplained Dyspnea.
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Reddy YNV, Kaye DM, Handoko ML, van de Bovenkamp AA, Tedford RJ, Keck C, Andersen MJ, Sharma K, Trivedi RK, Carter RE, Obokata M, Verbrugge FH, Redfield MM, and Borlaug BA
- Subjects
- Aged, Case-Control Studies, Dyspnea diagnosis, Dyspnea etiology, Female, Humans, Male, Middle Aged, Retrospective Studies, Stroke Volume, Heart Failure diagnosis
- Abstract
Importance: Diagnosis of heart failure with preserved ejection fraction (HFpEF) among dyspneic patients without overt congestion is challenging. Multiple diagnostic approaches have been proposed but are not well validated against the independent gold standard for HFpEF diagnosis of an elevated pulmonary capillary wedge pressure (PCWP) during exercise., Objective: To evaluate H2FPEF and HFA-PEFF scores and a PCWP/cardiac output (CO) slope of more than 2 mm Hg/L/min to diagnose HFpEF., Design, Setting, and Participants: This retrospective case-control study included patients with unexplained dyspnea from 6 centers in the US, the Netherlands, Denmark, and Australia from March 2016 to October 2020. Diagnosis of HFpEF (cases) was definitively ascertained by the presence of elevated PCWP during exertion; control individuals were those with normal rest and exercise hemodynamics., Main Outcomes and Measures: Logistic regression was used to evaluate the accuracy of HFA-PEFF and H2FPEF scores to discriminate patients with HFpEF from controls., Results: Among 736 patients, 563 (76%) were diagnosed with HFpEF (mean [SD] age, 69 [11] years; 334 [59%] female) and 173 (24%) represented controls (mean [SD] age, 60 [15] years; 109 [63%] female). H2FPEF and HFA-PEFF scores discriminated patients with HFpEF from controls, but the H2FPEF score had greater area under the curve (0.845; 95% CI, 0.810-0.875) compared with the HFA-PEFF score (0.710; 95% CI, 0.659-0.756) (difference, -0.134; 95% CI, -0.177 to -0.094; P < .001). Specificity was robust for both scores, but sensitivity was poorer for HFA-PEFF, with a false-negative rate of 55% for low-probability scores compared with 25% using the H2FPEF score. Use of the PCWP/CO slope to redefine HFpEF rather than exercise PCWP reclassified 20% (117 of 583) of patients, but patients reclassified from HFpEF to control by this metric had clinical, echocardiographic, and hemodynamic features typical of HFpEF, including elevated resting PCWP in 66% (46 of 70) of reclassified patients., Conclusions and Relevance: In this case-control study, despite requiring fewer data, the H2FPEF score had superior diagnostic performance compared with the HFA-PEFF score and PCWP/CO slope in the evaluation of unexplained dyspnea and HFpEF in the outpatient setting.
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- 2022
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46. Balloon pulmonary angioplasty for patients with chronic thromboembolic pulmonary hypertension previously operated by pulmonary endarterectomy.
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Andersen A, Hansen JV, Dragsbaek SJ, Maeng M, Andersen MJ, Andersen G, Mellemjkaer S, Ilkjær LB, and Nielsen-Kudsk JE
- Abstract
Balloon pulmonary angioplasty improved hemodynamics, walking distance, and World Health Organization functional class in patients with chronic thromboembolic pulmonary hypertension not eligible for pulmonary endarterectomy (Non-PEA) and patients with persistent pulmonary hypertension after PEA (PEA). More mild complications were observed in PEA- compared to Non-PEA., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)
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- 2022
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47. Impaired left and right systolic ventricular capacity in corrected atrial septal defect patients.
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Karunanithi Z, Andersen MJ, Mellemkjær S, Alstrup M, Waziri F, Clemmensen TS, Hjortdal VE, and Poulsen SH
- Abstract
Resting right ventricular (RV) systolic function has in some studies been shown to be impaired after correction of an atrial septal defect (ASD) whereas impairment of left ventricular (LV) systolic function is uncertain. In the present study we examine the LV and RV systolic response to exercise in patients with a previously corrected ASD in order to investigate the myocardial capacity. Thirty-six adult ASD patients with a corrected isolated secundum ASD and eighteen adult age-matched controls underent a semi-supine exercise stress echocardiographic examination. At rest, LV parameters were comparable between groups, and RV global longitudinal strain (RV-GLS) was lower for the ASD group (-18.5%, 95% CI -20.0--17.0%) compared with controls (-24.5%, 95% CI -27.7--22.4%, p < 0.001). At peak exercise, LV ejection fraction (LVEF) was lower for ASD patients (61%, 95% CI 58-65%) compared with controls (68%, 95% CI 64-73% p = 0.01). Peak LV global longitudinal strain (LV-GLS) was borderline significantly lower (ASD: -18.4%, 95% CI -20.2--16.6%, controls: -21.3%, 95% CI -23.6--19.0%, p = 0.059). Both RVEF (ASD: 64%, 95% CI 60-68%, controls: 73%, 95% CI 65-80%, p = 0.05) and tricuspid annular plane systolic excursion (TAPSE) (ASD: 2.5 cm, 95% CI 2.3-2.7 cm, controls: 3.2 cm, 95% CI 2.9-3.6 cm, p < 0.001) at peak exercise were lower for ASD patients. Exercise assessed peak oxygen uptake was comparable between groups (ASD: 32.8 mL O
2 /kg/min, 95% CI 30.3-35.5 mL O2 /kg/min, controls: 35.2 mL O2 /kg/min, 95% CI 31.6-38.8 mL O2 /kg/min, p = 0.3). Corrected ASD patients demonstrate a reduced LV and RV systolic exercise response decades after ASD correction whereas resting parameters of LV and RV systolic function were within normal range. The presence of subclinical systolic myocardial dysfunction during exercise might be associated with the long-term morbidities documented in this patient group., (© 2022. The Author(s).)- Published
- 2022
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48. [Current concepts in pediatric lateral humeral condyle fractures].
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Jacobsen MG and Andersen MJ
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- Child, Fracture Fixation, Internal methods, Humans, Humerus, Radiography, Retrospective Studies, Elbow Joint diagnostic imaging, Elbow Joint surgery, Humeral Fractures diagnostic imaging, Humeral Fractures surgery
- Abstract
Lateral humeral condyle fractures account for 10-20% of all paediatric elbow fractures. Diagnosis is made on plain radiographs; however, their interpretation is a challenge. Diagnostic MRI is used to apply the Song classification. Song stage 1-3 are managed conservatively while stage 4 and 5 are treated surgically. Closed reduction is attempted, and arthrography is used for verification. Unsuccessful reduction results in open surgery. Based on the literature, this review describes a modern algorithm for treating this injury resulting in more conservatively managed cases and less need for open surgery.
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- 2022
49. Effects of Metoprolol on Exercise Hemodynamics in Patients With Obstructive Hypertrophic Cardiomyopathy.
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Dybro AM, Rasmussen TB, Nielsen RR, Ladefoged BT, Andersen MJ, Jensen MK, and Poulsen SH
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- Hemodynamics physiology, Humans, Metoprolol pharmacology, Metoprolol therapeutic use, Stroke Volume physiology, Cardiomyopathy, Hypertrophic complications, Cardiomyopathy, Hypertrophic diagnostic imaging, Cardiomyopathy, Hypertrophic drug therapy, Mitral Valve Insufficiency complications
- Abstract
Background: The relationship between exercise hemodynamics, loading conditions, and medical treatment in patients with obstructive hypertrophic cardiomyopathy (HCM) is incompletely understood., Objectives: This study aimed to investigate the effect of metoprolol on invasive hemodynamic parameters at rest and during exercise in patients with obstructive HCM., Methods: This randomized, double-blind, placebo-controlled crossover trial enrolled 28 patients with obstructive HCM and New York Heart Association functional class ≥II. Patients were randomized to initiate either metoprolol 150 mg or placebo for 2 consecutive 2-week periods. Right-heart catheterization and echocardiography were performed at rest and during exercise at the end of each treatment period. The primary outcome was the difference in pulmonary capillary wedge pressure (ΔPCWP) between peak exercise and rest., Results: No treatment effect on ΔPCWP was observed between metoprolol and placebo treatment (21 ± 9 mm Hg vs 23 ± 9 mm Hg; P = 0.12). At rest, metoprolol lowered heart rate (P < 0.0001), left ventricular outflow tract (LVOT) gradient (P = 0.01), and increased left ventricular end-diastolic volume (P = 0.02) and stroke volume (SV) (+6.4; 95% CI: 0.02-17.7; P = 0.049). During peak exercise, metoprolol was associated with a lower heart rate (P < 0.0001), a lower LVOT gradient (P = 0.0005), lesser degree of mitral regurgitation (P = 0.004), and increased SV (+9 mL; 95% CI: 2-15 mL; P = 0.008)., Conclusions: In patients with obstructive HCM, exercise was associated with an abnormal rise in PCWP, which was unaffected by metoprolol. However, metoprolol increased SV at rest and peak exercise following changes in end-diastolic volume, LVOT gradient, and degree of mitral regurgitation. (The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy [TEMPO]; NCT03532802)., Competing Interests: Funding Support and Author Disclosures This work was supported by the Novo Nordic Foundation (grant number NNF18OC0052289) and by Skibsreder Per Henriksen, R. og hustrus Foundation. The foundations had no part in the design of the study, the data collection, statistical analysis, data interpretation, or drafting of the manuscript and had no say in the decision to submit the results. The manufacturer of metoprololsuccinate (Hexal) was neither involved in nor funded the study. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
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- 2022
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50. Inhibiting host-protein deposition on urinary catheters reduces associated urinary tract infections.
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Andersen MJ, Fong C, La Bella AA, Molina JJ, Molesan A, Champion MM, Howell C, and Flores-Mireles AL
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- Animals, Anti-Bacterial Agents pharmacology, Candida albicans, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Mice, Urinary Catheters adverse effects, Catheter-Related Infections complications, Catheter-Related Infections prevention & control, Urinary Tract Infections prevention & control
- Abstract
Microbial adhesion to medical devices is common for hospital-acquired infections, particularly for urinary catheters. If not properly treated these infections cause complications and exacerbate antimicrobial resistance. Catheter use elicits bladder inflammation, releasing host serum proteins, including fibrinogen (Fg), into the bladder, which deposit on the urinary catheter. Enterococcus faecalis uses Fg as a scaffold to bind and persist in the bladder despite antibiotic treatments. Inhibition of Fg-pathogen interaction significantly reduces infection. Here, we show deposited Fg is advantageous for uropathogens E. faecalis , Escherichia coli , Pseudomonas aeruginosa , K. pneumoniae , A. baumannii , and C. albicans , suggesting that targeting catheter protein deposition may reduce colonization creating an effective intervention for catheter-associated urinary tract infections (CAUTIs). In a mouse model of CAUTI, host-protein deposition was reduced, using liquid-infused silicone catheters, resulting in decreased colonization on catheters, in bladders, and dissemination in vivo. Furthermore, proteomics revealed a significant decrease in deposition of host-secreted proteins on liquid-infused catheter surfaces. Our findings suggest targeting microbial-binding scaffolds may be an effective antibiotic-sparing intervention for use against CAUTIs and other medical device infections., Competing Interests: MA, CF, AL, JM, AM, MC, CH, AF No competing interests declared, (© 2022, Andersen et al.)
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- 2022
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