219 results on '"Brands J"'
Search Results
52. What are you looking at? Visitors' perspective on CCTV in the night-time economy
- Author
-
Brands, J., Schwanen, T., Aalst, I. van, Brands, J., Schwanen, T., and Aalst, I. van
- Published
- 2014
53. Safety, surveillance and policing in the night-time economy: a visitor perspective
- Author
-
Social Urban Transitions, Dijst, Martin, van Aalst, Irina, Schwanen, Tim, Brands, J., Social Urban Transitions, Dijst, Martin, van Aalst, Irina, Schwanen, Tim, and Brands, J.
- Published
- 2014
54. The characteristics, implementation and effects of Aboriginal and Torres Strait Islander health promotion tools: a systematic literature search
- Author
-
McCalman, J, Tsey, K, Bainbridge, R, Rowley, K, Percival, N, O'Donoghue, L, Brands, J, Whiteside, M, Judd, J, McCalman, J, Tsey, K, Bainbridge, R, Rowley, K, Percival, N, O'Donoghue, L, Brands, J, Whiteside, M, and Judd, J
- Abstract
BACKGROUND: Health promotion by and with Aboriginal and Torres Strait Islander (hereafter Indigenous) Australians is critically important given a wide gap in health parity compared to other Australians. The development and implementation of step-by-step guides, instruments, packages, frameworks or resources has provided a feasible and low-resource strategy for strengthening evidence-informed health promotion practice. Yet there has been little assessment of where and how these tools are implemented or their effectiveness. This paper reviews the characteristics, implementation and effects of Indigenous health promotion tools. METHODS: Indigenous health promotion tools were identified through a systematic literature search including a prior scoping study, eight databases, references of other reviews and the authors' knowledge (n = 1494). Documents in the peer reviewed and grey literature were included if they described or evaluated tools designed, recommended or used for strengthening Indigenous Australian health promotion. Eligible publications were entered into an Excel spreadsheet and documented tools classified according to their characteristics, implementation and effects. Quality was appraised using the Dictionary for Effective Public Health Practice Project (EPHPP) and Critical Appraisal Skills Program (CASP) tools for quantitative and qualitative studies respectively. RESULTS: The review found that Indigenous health promotion tools were widely available. Of 74 publications that met inclusion criteria, sixty (81%) documented tools developed specifically for the Indigenous Australian population. All tools had been developed in reference to evidence; but only 22/74 (30%) publications specified intended or actual implementation, and only 11/74 (15%) publications evaluated impacts of the implemented tools. Impacts included health, environmental, community, organisational and health care improvements. The quality of impact evaluations was strong for only five (7%) s
- Published
- 2014
55. Strain-rate dependence of the yield stress of toughened polystyrene
- Author
-
Sjoerdsma, S. D., Heikens, D., and Brands, J. J. A. M.
- Published
- 1982
- Full Text
- View/download PDF
56. Terrestrial laser scanning for plant height measurement and biomass estimation of maize
- Author
-
Tilly, N., primary, Hoffmeister, D., additional, Schiedung, H., additional, Hütt, C., additional, Brands, J., additional, and Bareth, G., additional
- Published
- 2014
- Full Text
- View/download PDF
57. Evaluating the effectiveness of a multifaceted, multilevel continuous quality improvement program in primary health care: Developing a realist theory of change
- Author
-
Schierhout, G., Hains, J., Si, D., Kennedy, C., Cox, Rhonda, Kwedza, R., O'Donoghue, L., Fittock, M., Brands, J., Lonergan, K., Dowden, M., Bailie, R., Schierhout, G., Hains, J., Si, D., Kennedy, C., Cox, Rhonda, Kwedza, R., O'Donoghue, L., Fittock, M., Brands, J., Lonergan, K., Dowden, M., and Bailie, R.
- Abstract
Background: Variation in effectiveness of continuous quality improvement (CQI) interventions between services is commonly reported, but with little explanation of how contextual and other factors may interact to produce this variation. Therefore, there is scant information available on which policy makers can draw to inform effective implementation in different settings. In this paper, we explore how patterns of change in delivery of services may have been achieved in a diverse range of health centers participating in a wide-scale program to achieve improvements in quality of care for Indigenous Australians.Methods: We elicited key informants’ interpretations of factors explaining patterns of change in delivery of guideline-scheduled services over three or more years of a wide-scale CQI project, and inductively analyzed these interpretations to propose fine-grained realist hypotheses about what works for whom and in what circumstances. Data were derived from annual clinical audits from 36 health centers operating in diverse settings, quarterly project monitoring reports, and workshops with 12 key informants who had key roles in project implementation. We abstracted potential context-mechanism-outcome configurations from the data, and based on these, identified potential program-strengthening strategies.Results: Several context-specific, mechanism-based explanations for effectiveness of this CQI project were identified. These were collective valuing of clinical data for improvement purposes; collective efficacy; and organizational change towards a population health orientation. Health centers with strong central management of CQI, and those in which CQI efforts were more dependent on local health center initiative and were adapted to resonate with local priorities were both favorable contexts for collective valuing of clinical data. Where health centers had prior positive experiences of collaboration, effects appeared to be achieved at least partly through the mechan
- Published
- 2013
58. Rythms of the night: spatiotemporal inequalities in the night-time economy
- Author
-
Schwanen, T., Aalst, I. van, Brands, J., Timan, T., Schwanen, T., Aalst, I. van, Brands, J., and Timan, T.
- Published
- 2012
59. Studenten in de nacht; activiteitenpatronen in en rondom Utrecht
- Author
-
Brands, J., Aalst, I. van (Thesis Advisor), Schwanen, T., Brands, J., Aalst, I. van (Thesis Advisor), and Schwanen, T.
- Abstract
Over de beleving van de stedelijke nacht door studenten en de invloed daarvan op wat deze studenten ondernemen is weinig bekend. Dit geldt ook voor de Utrechtse student. De auteur van deze tekst stelt zich dan ook als doel om deze beleving, de factoren die van invloed zijn op deze beleving en het effect hiervan op de activiteiten die ondernomen worden, anno 2009, zo nauwkeurig als mogelijk te beschrijven. Dit wordt gedaan aan de hand van een aantal nachtboeken, bijgehouden door deze studenten, diepte interviews met deze studenten en informatie vergaard vanuit de al bestaande literatuur. Binnen de analyses wordt onderscheid gemaakt naar geslacht en woonlocatie. Hiernaast wordt ook gekeken of bepaalde voorzieningen en instanties speciaal gericht op de student (binnen Utrecht), van invloed zijn op de activiteiten die ondernomen worden door hun.
- Published
- 2009
60. Een interface voor de voorsnijderij van Dumo Goirle
- Author
-
Beccker, M., Brands, J., and IWDE (Instituut Wiskundige Dienstverlening Eindhoven)
- Published
- 1997
61. The potential of Artemia Biomass in the salinas of Southern Vietnam and its valorization in aquaculture
- Author
-
Brands, J.
- Subjects
Institute of Agricultural and Environmental Engineering ,Instituut voor Mechanisatie, Arbeid en Gebouwen ,Life Science - Published
- 1996
62. A Manufactured Enzyme for the Synthesis of Chiral Amines
- Author
-
Savile, C., primary, Janey, J., primary, Mundorff, E., additional, Moore, J., additional, Tam, S., additional, Jarvis, W., additional, Colbeck, J., additional, Krebber, A., additional, Fleitz, F., additional, Brands, J., additional, Devine, P., additional, Huisman, G., additional, and Hughes, G., additional
- Published
- 2010
- Full Text
- View/download PDF
63. Agonist-induced impairment of glycocalyx exclusion properties: contribution to coronary effects of adenosine
- Author
-
VanTeeffelen, J. W. G. E., primary, Brands, J., additional, and Vink, H., additional
- Published
- 2010
- Full Text
- View/download PDF
64. Agonist-induced modulation of glycocalyx barrier properties in the microcirculation : role in blood volume recruitment and oxygen exchange in the heart
- Author
-
Brands, J., primary
- Full Text
- View/download PDF
65. On the asymptotically uniform distribution modulo 1 of extreme order statistics
- Author
-
Wilms, R. J. G., primary and Brands, J. J. A. M., additional
- Published
- 1994
- Full Text
- View/download PDF
66. Pregnancy monitoring with enzyme-immunoassays for human placental lactogen and total oestrogens
- Author
-
van Hell, H., Bosch, A. M. G., Brands, J. A. M., van Weemen, B. K., and Schuurs, A. H. W. M.
- Published
- 1976
- Full Text
- View/download PDF
67. Comparison of four mathematical models to analyze indicator-dilution curves in the coronary circulation.
- Author
-
Brands J, Vink H, Van Teeffelen JW, Brands, Judith, Vink, Hans, and Van Teeffelen, Jurgen W G E
- Abstract
While several models have proven to result in accurate estimations when measuring cardiac output using indicator dilution, the mono-exponential model has primarily been chosen for deriving coronary blood/plasma volume. In this study, we compared four models to derive coronary plasma volume using indicator dilution; the mono-exponential, power-law, gamma-variate, and local density random walk (LDRW) model. In anesthetized goats (N = 14), we determined the distribution volume of high molecular weight (2,000 kDa) dextrans. A bolus injection (1.0 ml, 0.65 mg/ml) was given intracoronary and coronary venous blood samples were taken every 0.5-1.0 s; outflow curves were analyzed using the four aforementioned models. Measurements were done at baseline and during adenosine infusion. Absolute coronary plasma volume estimates varied by ~25% between models, while the relative volume increase during adenosine infusion was similar for all models. The gamma-variate, LDRW, and mono-exponential model resulted in volumes corresponding with literature, whereas the power-model seemed to overestimate the coronary plasma volume. The gamma-variate and LDRW model appear to be suitable alternative models to the mono-exponential model to analyze coronary indicator-dilution curves, particularly since these models are minimally influenced by outliers and do not depend on data of the descending slope of the curve only. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
68. Boekbesprekingen
- Author
-
Rhijn, A., Goedhart, C., Brand, W., Bos, H., Brands, J., Kroft, W., Derksen, J., Asser, H., Venekamp, P., Cramer, J., and Brüll, D.
- Published
- 1965
- Full Text
- View/download PDF
69. Effects of sodium nitroprusside during the excision of phaeochromocytoma.
- Author
-
CSÁNKY-TREELS, J. C., PABST, W. P. LAWICK, BRANDS, J. W. J., and STAMENKOVIC, L.
- Published
- 1976
- Full Text
- View/download PDF
70. De mediatisering van de strafrechtspleging
- Author
-
Salet, R., Brands, J., Roks, R., Elanie Rodermond, Criminology, A-LAB, and Empirical and Normative Studies
- Subjects
Grondslagen van het publiekrecht ,Principles of Public Law - Abstract
Item does not contain fulltext 8 p.
71. EFFECTS OF SODIUM NITROPRUSSIDE DURING THE EXCISION OF PHAEOCHROMOCYTOMA
- Author
-
CSANKY-TREELS, J. C., primary, LAWICK VAN PABST, W. P., additional, BRANDS, J. W. J., additional, STAMENKOVIC, L., additional, and Larcom, Gordon D., additional
- Published
- 1976
- Full Text
- View/download PDF
72. Pregnancy monitoring with enzyme-immunoassays for human placental lactogen and total oestrogens
- Author
-
Hell, H., primary, Bosch, A. M. G., additional, Brands, J. A. M., additional, Weemen, B. K., additional, and Schuurs, A. H. W. M., additional
- Published
- 1976
- Full Text
- View/download PDF
73. AFSCHRIJVING OP GOODWILL
- Author
-
Brackel, G., primary and Brands, J., additional
- Published
- 1931
- Full Text
- View/download PDF
74. A Property of Real Solutions to Bessel’s Equation (G. W. Veltkamp)
- Author
-
Brands, J. J. M., primary
- Published
- 1966
- Full Text
- View/download PDF
75. REKWEST AAN ZIJNE EXCELLENTIE DEN MINISTER VAN ARBEID, HANDEL EN NIJVERHEID, ’s-GRAVEN- HAGE INZAKE HET VERSLAG DER COMMISSIE TOT REGELING VAN HET ACCOUNTANTSWEZEN
- Author
-
Brackel, G., primary and Brands, J., additional
- Published
- 1931
- Full Text
- View/download PDF
76. 5006
- Author
-
Ehrhart, E., primary, Brands, J. J. A. M., additional, and Laman, G., additional
- Published
- 1963
- Full Text
- View/download PDF
77. UIT HET BUITENLAND BEROEPSUITOEFENING IN INTERNATIONAAL VERBAND
- Author
-
Brands, J., primary
- Published
- 1954
- Full Text
- View/download PDF
78. DE NIEUWE VERSLAGSTATEN DER LEVENSVERZEKERINGMAATSCHAPPIJEN
- Author
-
Brands, J., primary
- Published
- 1952
- Full Text
- View/download PDF
79. On the number of maxima in a discrete sample
- Author
-
Brands, J. J. A. M., Steutel, F. W., and Wilms, R. J. G.
- Published
- 1994
- Full Text
- View/download PDF
80. Pregnancy monitoring with enzyme-immunoassays for human placental lactogen and total oestrogens
- Author
-
Hell, H., Bosch, A. M. G., Brands, J. A. M., Weemen, B. K., and Schuurs, A. H. W. M.
- Published
- 1976
- Full Text
- View/download PDF
81. The role of the victim lawyer in the Dutch criminal process
- Author
-
Meijer, S., Ajjg, Schijns, Elbers, N. A., Iris Becx, Arno Akkermans, Van Doorn, J, Brands, J, Kunst, M, Muller, E, Pemberton, A, and Van Reemst, L
- Abstract
De juridische bijstand aan slachtoffers is steeds meer omvattend en heeft zich in de afgelopen jaren tot een specialisme ontwikkeld. Steeds vaker laten slachtoffers zich in het strafproces bijstaan door gespecialiseerde slachtofferadvocaten. Hoewel de politie, het Openbaar Ministerie en de rechtbank, naast de belangen van de verdachte, tegenwoordig steeds meer rekening houden met de belangen van het slachtoffer, is de advocaat van het slachtoffer de enige die partijdig is en uitsluitend opkomt voor de belangen van het slachtoffer. Rechtsbijstand door een gespecialiseerde slachtofferadvocaat draagt bij aan de verwezenlijking van slachtofferrechten. Dit hoofdstuk schetst een actueel beeld van hoe de rol van de slachtofferadvocaat bijdraagt aan het effectueren van de rechten van het slachtoffer in het strafproces. De nadruk ligt op de rol van de slachtofferadvocaat in het strafproces, waaronder wij zowel de bijstand in de fase van de opsporing, vervolging en berechting verstaan, als ook bijstand in de fase van de tenuitvoerlegging als sluitstuk van het strafproces. Na een begripsbepaling van de term slachtofferadvocaat in paragraaf 2 en enkele opmerkingen over de rechtsbijstand door een slachtofferadvocaat en de vergoeding daarvan in paragraaf 3, wordt in paragraaf 4 aan de hand van diverse slachtofferrechten ingegaan op de klassieke rol van de advocaat als rechtsbijstandverlener in het strafproces, zonder daarbij overigens volledigheid te betrachten. In paragraaf 5 wordt de toegevoegde waarde van de advocaat voor wat betreft de empowerment van het slachtoffer belicht. Dit hoofdstuk wordt afgesloten met enkele aanbevelingen ter verbetering van de rol en de positie van de slachtofferadvocaat in paragraaf 6.
- Published
- 2023
82. A molecular mechanism to diversify Ca 2+ signaling downstream of Gs protein-coupled receptors.
- Author
-
Brands J, Bravo S, Jürgenliemke L, Grätz L, Schihada H, Frechen F, Alenfelder J, Pfeil C, Ohse PG, Hiratsuka S, Kawakami K, Schmacke LC, Heycke N, Inoue A, König G, Pfeifer A, Wachten D, Schulte G, Steinmetzer T, Watts VJ, Gomeza J, Simon K, and Kostenis E
- Subjects
- Humans, HEK293 Cells, GTP-Binding Protein alpha Subunits, Gq-G11 metabolism, GTP-Binding Protein alpha Subunits, Gq-G11 genetics, CRISPR-Cas Systems, GTP-Binding Protein alpha Subunits, Gs metabolism, GTP-Binding Protein alpha Subunits, Gs genetics, Cyclic AMP metabolism, Animals, Gene Editing, Cytosol metabolism, GTP-Binding Protein beta Subunits metabolism, GTP-Binding Protein beta Subunits genetics, Adenylyl Cyclases metabolism, Adenylyl Cyclases genetics, Calcium Signaling, Phospholipase C beta metabolism, Phospholipase C beta genetics, Receptors, G-Protein-Coupled metabolism, Receptors, G-Protein-Coupled genetics, Calcium metabolism
- Abstract
A long-held tenet in inositol-lipid signaling is that cleavage of membrane phosphoinositides by phospholipase Cβ (PLCβ) isozymes to increase cytosolic Ca
2+ in living cells is exclusive to Gq- and Gi-sensitive G protein-coupled receptors (GPCRs). Here we extend this central tenet and show that Gs-GPCRs also partake in inositol-lipid signaling and thereby increase cytosolic Ca2+ . By combining CRISPR/Cas9 genome editing to delete Gαs , the adenylyl cyclase isoforms 3 and 6, or the PLCβ1-4 isozymes, with pharmacological and genetic inhibition of Gq and G11, we pin down Gs-derived Gβγ as driver of a PLCβ2/3-mediated cytosolic Ca2+ release module. This module does not require but crosstalks with Gαs -dependent cAMP, demands Gαq to release PLCβ3 autoinhibition, but becomes Gq-independent with mutational disruption of the PLCβ3 autoinhibited state. Our findings uncover the key steps of a previously unappreciated mechanism utilized by mammalian cells to finetune their calcium signaling regulation through Gs-GPCRs., (© 2024. The Author(s).)- Published
- 2024
- Full Text
- View/download PDF
83. Perceptions of artificial intelligence system's aptitude to judge morality and competence amidst the rise of Chatbots.
- Author
-
Oliveira M, Brands J, Mashudi J, Liefooghe B, and Hortensius R
- Subjects
- Humans, Female, Male, Adult, Young Adult, Aptitude physiology, Artificial Intelligence, Morals, Judgment physiology, Social Perception
- Abstract
This paper examines how humans judge the capabilities of artificial intelligence (AI) to evaluate human attributes, specifically focusing on two key dimensions of human social evaluation: morality and competence. Furthermore, it investigates the impact of exposure to advanced Large Language Models on these perceptions. In three studies (combined N = 200), we tested the hypothesis that people will find it less plausible that AI is capable of judging the morality conveyed by a behavior compared to judging its competence. Participants estimated the plausibility of AI origin for a set of written impressions of positive and negative behaviors related to morality and competence. Studies 1 and 3 supported our hypothesis that people would be more inclined to attribute AI origin to competence-related impressions compared to morality-related ones. In Study 2, we found this effect only for impressions of positive behaviors. Additional exploratory analyses clarified that the differentiation between the AI origin of competence and morality judgments persisted throughout the first half year after the public launch of popular AI chatbot (i.e., ChatGPT) and could not be explained by participants' general attitudes toward AI, or the actual source of the impressions (i.e., AI or human). These findings suggest an enduring belief that AI is less adept at assessing the morality compared to the competence of human behavior, even as AI capabilities continued to advance., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
84. Association of Hypertensive Disorders of Pregnancy With Coronary Microvascular Dysfunction 8 to 10 Years After Delivery.
- Author
-
Countouris ME, Catov JM, Zhu J, de Jong N, Brands J, Chen X, Parks WT, Berlacher KL, Gandley RE, Straub AC, and Villanueva FS
- Subjects
- Humans, Female, Adult, Pregnancy, Ventricular Function, Left, Time Factors, Coronary Vessels physiopathology, Coronary Vessels diagnostic imaging, Middle Aged, Coronary Artery Disease physiopathology, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease diagnosis, Echocardiography, Stress methods, Ventricular Remodeling, Microcirculation, Hypertension, Pregnancy-Induced physiopathology, Hypertension, Pregnancy-Induced diagnosis, Coronary Circulation
- Abstract
Background: Hypertensive disorders of pregnancy (HDP) are associated with subsequent adverse cardiac remodeling and cardiovascular disease. The role of myocardial microvascular disease among individuals with HDP and left ventricular (LV) remodeling as a potential link to cardiovascular disease is unknown. We aimed to determine whether individuals with HDP history have coronary microvascular dysfunction measured by coronary flow reserve 8 to 10 years after delivery and whether microvascular dysfunction correlates with LV remodeling., Methods: Individuals with pregnancies delivered from 2008 to 2010 underwent burst-replenishment myocardial contrast echocardiography (2017-2020) to quantify myocardial perfusion at rest and during dobutamine stress. Video intensity versus time data were used to derive β, the rate of rise of video intensity, a correlate for myocardial blood flow. Coronary flow reserve was calculated as the ratio of β at peak stress to β at rest, averaged across LV myocardial regions of interest., Results: We studied 91 individuals (aged 38±6 and 9.1±0.9 years postdelivery) and 19 with a history of HDP. Individuals with coronary microvascular dysfunction (coronary flow reserve <2.0; n=13) had a higher proportion of HDP (46.2% versus 16.7%; P =0.026) and higher prepregnancy body mass index, baseline heart rate, and hemoglobin A1c compared with those without microvascular dysfunction. The association of coronary flow reserve and HDP was attenuated after adjusting for cardiometabolic factors ( P =0.133). In exploratory subgroup analyses, individuals with both LV remodeling (relative wall thickness >0.42) and HDP (n=12) had the highest proportion of microvascular dysfunction (41.7% versus +HDP-LV remodeling [n=7] 14.3%; -HDP+LV remodeling [n=26] 7.7%; P =0.0498)., Conclusions: In this small study, HDP history is associated with coronary microvascular dysfunction 1 decade after delivery, findings that may, in part, be driven by metabolic factors including obesity and diabetes. Microvascular dysfunction may contribute to cardiovascular disease among individuals with a history of HDP., Competing Interests: Disclosures Dr Straub is a consultant and a stockholder in Creegh Pharmaceuticals. The other authors report no conflicts.
- Published
- 2024
- Full Text
- View/download PDF
85. Metro Mapping: development of an innovative methodology to co-design care paths to support shared decision making in oncology.
- Author
-
Stiggelbout A, Griffioen I, Brands J, Melles M, Rietjens J, Kunneman M, van der Kolk M, van Eijck C, and Snelders D
- Subjects
- Humans, Patient Care Planning, Decision Making, Shared, Medical Oncology
- Abstract
Competing Interests: Competing interests: AMS and JR are board members of the not-for-profit Metro Mapping Foundation (no honorarium involved). JB is managing director of Design Studio Panton Deventer, who provide consultation in the use of Metro Mapping. The other authors declare no conflict of interest.
- Published
- 2023
- Full Text
- View/download PDF
86. Antiviral CD8 + T-cell immune responses are impaired by cigarette smoke and in COPD.
- Author
-
Chen J, Wang X, Schmalen A, Haines S, Wolff M, Ma H, Zhang H, Stoleriu MG, Nowak J, Nakayama M, Bueno M, Brands J, Mora AL, Lee JS, Krauss-Etschmann S, Dmitrieva A, Frankenberger M, Hofer TP, Noessner E, Moosmann A, Behr J, Milger K, Deeg CA, Staab-Weijnitz CA, Hauck SM, Adler H, Goldmann T, Gaede KI, Behrends J, Kammerl IE, and Meiners S
- Subjects
- Humans, CD8-Positive T-Lymphocytes, Antiviral Agents, Histocompatibility Antigens Class I metabolism, Cytokines, Epitopes, Immunity, Cigarette Smoking adverse effects, Pulmonary Disease, Chronic Obstructive
- Abstract
Background: Virus infections drive COPD exacerbations and progression. Antiviral immunity centres on the activation of virus-specific CD8
+ T-cells by viral epitopes presented on major histocompatibility complex (MHC) class I molecules of infected cells. These epitopes are generated by the immunoproteasome, a specialised intracellular protein degradation machine, which is induced by antiviral cytokines in infected cells., Methods: We analysed the effects of cigarette smoke on cytokine- and virus-mediated induction of the immunoproteasome in vitro , ex vivo and in vivo using RNA and Western blot analyses. CD8+ T-cell activation was determined in co-culture assays with cigarette smoke-exposed influenza A virus (IAV)-infected cells. Mass-spectrometry-based analysis of MHC class I-bound peptides uncovered the effects of cigarette smoke on inflammatory antigen presentation in lung cells. IAV-specific CD8+ T-cell numbers were determined in patients' peripheral blood using tetramer technology., Results: Cigarette smoke impaired the induction of the immunoproteasome by cytokine signalling and viral infection in lung cells in vitro , ex vivo and in vivo . In addition, cigarette smoke altered the peptide repertoire of antigens presented on MHC class I molecules under inflammatory conditions. Importantly, MHC class I-mediated activation of IAV-specific CD8+ T-cells was dampened by cigarette smoke. COPD patients exhibited reduced numbers of circulating IAV-specific CD8+ T-cells compared to healthy controls and asthmatics., Conclusion: Our data indicate that cigarette smoke interferes with MHC class I antigen generation and presentation and thereby contributes to impaired activation of CD8+ T-cells upon virus infection. This adds important mechanistic insight on how cigarette smoke mediates increased susceptibility of smokers and COPD patients to viral infections., Competing Interests: Conflict of Interest: H. Ma reports support for the present manuscript from the German Center for Lung Research (DZL). M. Nakayama reports overseas grant from Uehara Memorial Foundation (Japan) and overseas grant from Shiga university of Medical Science, outside the submitted work. A.L. Mora reports support for the present manuscript from NIH (NIH U01 HL1455550-01 and NIH NHLBI R01 HL149825). J.S. Lee reports participation on clinical adjudication committee with Janssen R&D, outside the submitted work. S. Krauss-Etschmann reports support for the present manuscript from the German Center for Lung Research. K. Milger reports consulting fees and lecture honoraria from AstraZeneca, GSK, Janssen, Novartis and Sanofi, outside the submitted work. C.A. Staab-Weijnitz reports support for the present manuscript from Helmholtz Association, German Center for Lung Research (DZL) and Deutsche Forschungsgemeinschaft (DFG) within the Research Training Group GRK2338. K.I. Gaede reports support for the present manuscript from Research Center Borstel – Leibniz Lung Center – BioMaterialBank North, Airway Research Center North, German Center for Lung Research (DZL), PopGen 2.0 Network (P2N). K.I. Gaede also holds a leadership role as member of the Board of Directors of the TMF (www.tmf-ev.de), outside the submitted work. I.E. Kammerl reports support for the present manuscript from ERS (Short Term Fellowship). All other authors have no potential conflicts of interest to declare., (Copyright ©The authors 2023.)- Published
- 2023
- Full Text
- View/download PDF
87. CYB5R3 in type II alveolar epithelial cells protects against lung fibrosis by suppressing TGF-β1 signaling.
- Author
-
Bueno M, Calyeca J, Khaliullin T, Miller MP, Alvarez D, Rosas L, Brands J, Baker C, Nasser A, Shulkowski S, Mathien A, Uzoukwu N, Sembrat J, Mays BG, Fiedler K, Hahn SA, Salvatore SR, Schopfer FJ, Rojas M, Sandner P, Straub AC, and Mora AL
- Subjects
- Humans, Transforming Growth Factor beta1 metabolism, Signal Transduction, Cytochrome-B(5) Reductase metabolism, Alveolar Epithelial Cells metabolism, Idiopathic Pulmonary Fibrosis metabolism
- Abstract
Type II alveolar epithelial cell (AECII) redox imbalance contributes to the pathogenesis of idiopathic pulmonary fibrosis (IPF), a deadly disease with limited treatment options. Here, we show that expression of membrane-bound cytochrome B5 reductase 3 (CYB5R3), an enzyme critical for maintaining cellular redox homeostasis and soluble guanylate cyclase (sGC) heme iron redox state, is diminished in IPF AECIIs. Deficiency of CYB5R3 in AECIIs led to sustained activation of the pro-fibrotic factor TGF-β1 and increased susceptibility to lung fibrosis. We further show that CYB5R3 is a critical regulator of ERK1/2 phosphorylation and the sGC/cGMP/protein kinase G axis that modulates activation of the TGF-β1 signaling pathway. We demonstrate that sGC agonists (BAY 41-8543 and BAY 54-6544) are effective in reducing the pulmonary fibrotic outcomes of in vivo deficiency of CYB5R3 in AECIIs. Taken together, these results show that CYB5R3 in AECIIs is required to maintain resilience after lung injury and fibrosis and that therapeutic manipulation of the sGC redox state could provide a basis for treating fibrotic conditions in the lung and beyond.
- Published
- 2023
- Full Text
- View/download PDF
88. Maternal Vascular Lesions in the Placenta Predict Vascular Impairments a Decade After Delivery.
- Author
-
Catov JM, Muldoon MF, Gandley RE, Brands J, Hauspurg A, Hubel CA, Tuft M, Schmella M, Tang G, and Parks WT
- Subjects
- Adult, Female, Heart Disease Risk Factors, Humans, Infant, Newborn, Middle Aged, Pregnancy, Pregnancy Outcome, Premature Birth pathology, Premature Birth physiopathology, Registries, Retrospective Studies, Blood Glucose, Blood Pressure physiology, Body Mass Index, Lipids blood, Placenta pathology, Waist Circumference physiology
- Abstract
Women with adverse pregnancy outcomes later experience excess hypertension and cardiovascular disease, but how the events are linked is unknown. Examination of the placenta may provide clues to vascular impairments after delivery. Maternal vascular malperfusion lesions (MVMs) were abstracted from clinical reports, validated and characterized using clinical guidelines and severity score. A total of 492 women (170 with MVMs and 322 without MVMs) participated in a study visit 8 to 10 years after delivery to assess blood pressure, cardiometabolic factors, and sublingual microvascular features using sidestream dark field imaging. Covariates included age, race, adverse pregnancy outcomes (preeclampsia, small for gestational age, and preterm birth), and health behaviors. Women with versus without MVM had a distinct sublingual microvascular profile comprised of (1) lower microvascular density (-410 μm/mm
2 , P =0.015), (2) higher red blood cell filling as a marker of perfusion (2%, P =0.004), and (3) smaller perfused boundary region (-0.07 µm, P =0.025) as a measure of glycocalyx integrity, adjusted for covariates including adverse pregnancy outcomes. Women with MVM also had higher adjusted diastolic blood pressure (+2.6 mm Hg, P =0.021), total and LDL (low-density lipoprotein)-cholesterol (+11.2 mg/dL, P =0.016; +8.7 mg/dL, P =0.031). MVM associations with subsequent cardiovascular measures did not vary by type of adverse pregnancy outcome, except among women with preterm births where blood pressure was higher only among those with MVM. Results were similar when evaluated as MVM severity. A decade after delivery, women with placental vascular lesions had an adverse cardiovascular profile comprised of microvascular rarefaction, higher blood pressure and more atherogenic lipids. Placental histopathology may reveal a woman's early trajectory toward subsequent vascular disease.- Published
- 2022
- Full Text
- View/download PDF
89. l-Citrulline supplementation during pregnancy improves perinatal and postpartum maternal vascular function in a mouse model of preeclampsia.
- Author
-
Gemmel M, Sutton EF, Brands J, Burnette L, Gallaher MJ, and Powers RW
- Subjects
- Animals, Arginine blood, Blood Pressure drug effects, Citrulline blood, Female, Mice, Inbred C57BL, Placenta metabolism, Pre-Eclampsia physiopathology, Pregnancy, Mice, Citrulline pharmacology, Maternal Nutritional Physiological Phenomena drug effects, Parturition drug effects, Pre-Eclampsia drug therapy
- Abstract
Preeclampsia is a spontaneously occurring pregnancy complication diagnosed by new-onset hypertension and end-organ dysfunction with or without proteinuria. This pregnancy-specific syndrome contributes to maternal morbidity and mortality and can have detrimental effects on fetal outcomes. Preeclampsia is also linked to increased risk of maternal cardiovascular disease throughout life. Despite intense investigation of this disorder, few treatment options are available. The aim of this study was to investigate the potential therapeutic effects of maternal l-citrulline supplementation on pregnancy-specific vascular dysfunction in the male C57BL/6J × female C57BL/6J C1q
-/- preeclampsia-like mouse model. l-Citrulline is a nonessential amino acid that is converted to l-arginine to promote smooth muscle and blood vessel relaxation and improve nitric oxide (NO)-mediated vascular function. To model a preeclampsia-like pregnancy, female C57BL/6J mice were mated to C1q-/- male mice, and a subset of dams was supplemented with l-citrulline throughout pregnancy. Blood pressure, systemic vascular glycocalyx, and ex vivo vascular function were investigated in late pregnancy, and postpartum at 6 and 10 mo of age. Main findings show that l-citrulline reduced blood pressure, increased vascular glycocalyx volume, and rescued ex-vivo vascular function at gestation day 17.5 in this preeclampsia-like model. The vascular benefit of l-citrulline also extended postpartum, with improved vascular function and glycocalyx measures at 6 and 10 mo of age. l-Citrulline-mediated vascular improvements appear, in part, attributable to NO pathway signaling. Taken together, l-citrulline supplementation during pregnancy appears to have beneficial effects on maternal vascular health, which may have translational implications for improved maternal cardiovascular health.- Published
- 2021
- Full Text
- View/download PDF
90. COL6A1 related muscular dystrophy in Landseer dogs: A canine model for Ullrich congenital muscular dystrophy.
- Author
-
Brands J, Steffen F, Spennes J, Leeb T, and Bilzer T
- Subjects
- Animals, Collagen Type VI genetics, Collagen Type VI metabolism, Dogs, Homozygote, Muscle, Skeletal metabolism, Muscular Dystrophies congenital, Muscular Dystrophies genetics, Muscular Dystrophies pathology, Mutation genetics, Phenotype, Sclerosis genetics, Fibroblasts pathology, Muscle, Skeletal pathology, Muscular Dystrophies metabolism, Sclerosis pathology
- Abstract
Background: Collagen VI related myopathies are congenital diseases of variable phenotype. The severe phenotype is referred to as Ullrich congenital muscular dystrophy. In this study, we describe analoguos clinical signs and histopathological alterations in Landseer dogs., Materials: We collected clinical data from two affected dogs and investigated the neuromuscular changes in five dogs from two different litters with immunohistochemistry and immunofluorescence. All affected dogs were homozygous for the p.Glu97* nonsense variant in the COL6A1 gene encoding the alpha-1 chain of collagen VI., Results: Muscle biopsies revealed alterations similar to those in human patients with Ullrich congenital muscular dystrophy including the virtual absence of collagen VI in skeletal muscles., Conclusions: The clinical and pathological characterization of the affected Landseer dogs enhances the value of this animal model for human Ullrich congenital muscular dystrophy., (© 2020 Wiley Periodicals LLC.)
- Published
- 2021
- Full Text
- View/download PDF
91. Heterotrimeric G Protein Subunit Gαq Is a Master Switch for Gβγ-Mediated Calcium Mobilization by Gi-Coupled GPCRs.
- Author
-
Pfeil EM, Brands J, Merten N, Vögtle T, Vescovo M, Rick U, Albrecht IM, Heycke N, Kawakami K, Ono Y, Ngako Kadji FM, Hiratsuka S, Aoki J, Häberlein F, Matthey M, Garg J, Hennen S, Jobin ML, Seier K, Calebiro D, Pfeifer A, Heinemann A, Wenzel D, König GM, Nieswandt B, Fleischmann BK, Inoue A, Simon K, and Kostenis E
- Subjects
- Calcium metabolism, Calcium Signaling genetics, Cytosol metabolism, HEK293 Cells, Humans, Protein Binding genetics, Receptors, G-Protein-Coupled genetics, Signal Transduction genetics, GTP-Binding Protein alpha Subunits genetics, GTP-Binding Protein beta Subunits genetics, GTP-Binding Protein gamma Subunits genetics, Heterotrimeric GTP-Binding Proteins genetics, Phospholipase C beta genetics
- Abstract
Mechanisms that control mobilization of cytosolic calcium [Ca
2+ ]i are key for regulation of numerous eukaryotic cell functions. One such paradigmatic mechanism involves activation of phospholipase Cβ (PLCβ) enzymes by G protein βγ subunits from activated Gαi -Gβγ heterotrimers. Here, we report identification of a master switch to enable this control for PLCβ enzymes in living cells. We find that the Gαi -Gβγ-PLCβ-Ca2+ signaling module is entirely dependent on the presence of active Gαq . If Gαq is pharmacologically inhibited or genetically ablated, Gβγ can bind to PLCβ but does not elicit Ca2+ signals. Removal of an auto-inhibitory linker that occludes the active site of the enzyme is required and sufficient to empower "stand-alone control" of PLCβ by Gβγ. This dependence of Gi-Gβγ-Ca2+ on Gαq places an entire signaling branch of G-protein-coupled receptors (GPCRs) under hierarchical control of Gq and changes our understanding of how Gi-GPCRs trigger [Ca2+ ]i via PLCβ enzymes., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
92. Paternal deficiency of complement component C1q leads to a preeclampsia-like pregnancy in wild-type female mice and vascular adaptations postpartum.
- Author
-
Sutton EF, Gemmel M, Brands J, Gallaher MJ, and Powers RW
- Subjects
- Animals, Blood Pressure physiology, Complement C1q genetics, Disease Models, Animal, Female, Male, Mice, Mice, Knockout, Placenta blood supply, Pre-Eclampsia genetics, Pregnancy, Complement C1q metabolism, Pre-Eclampsia metabolism
- Abstract
Preeclampsia is a spontaneously occurring, pregnancy-specific syndrome that is clinically diagnosed by new onset hypertension and proteinuria. Epidemiological evidence describes an association between a history of preeclampsia and increased risk for cardiovascular disease in later life; however, the mechanism(s) driving this relationship are unclear. Our study aims to leverage a novel preeclampsia-like mouse model, the C1q
-/- model, to help elucidate the acute and persistent vascular changes during and following a preeclampsia-like pregnancy. Female C57BL/6J mice were mated to C1q-/- male mice to model a preeclampsia-like pregnancy ("PE-like"), and the maternal cardiovascular phenotype (blood pressure, renal function, systemic glycocalyx, and ex vivo vascular function) was assessed in late pregnancy and postpartum at 6 and 10 mo of age. Uncomplicated, normotensive pregnancies (female C57BL/6J bred to male C57BL/6J mice) served as age-matched controls. In pregnancy, PE-like dams exhibited increased systolic and diastolic pressure during mid- and late gestation, renal dysfunction, fetal growth restriction, and reduced placental efficiency. Ex vivo wire myography studies of mesenteric arteries revealed severe pregnancy-specific endothelial-dependent and -independent vascular dysfunction. At 3 and 7 mo postpartum (6 and 10 mo old, respectively), hypertension resolved in PE-like dams, whereas mild vascular dysfunction persisted at 3 mo postpartum. In conclusion, the female C57BL/6J-by-male C57BL/6J C1q-/- model recapitulates many aspects of the human preeclampsia syndrome in a low-risk, wild-type female mouse. The pregnancy-specific phenotype results in systemic maternal endothelial-dependent and -independent vascular dysfunction that persists postpartum.- Published
- 2020
- Full Text
- View/download PDF
93. Impaired endothelium-mediated cerebrovascular reactivity promotes anxiety and respiration disorders in mice.
- Author
-
Wenzel J, Hansen CE, Bettoni C, Vogt MA, Lembrich B, Natsagdorj R, Huber G, Brands J, Schmidt K, Assmann JC, Stölting I, Saar K, Sedlacik J, Fiehler J, Ludewig P, Wegmann M, Feller N, Richter M, Müller-Fielitz H, Walther T, König GM, Kostenis E, Raasch W, Hübner N, Gass P, Offermanns S, de Wit C, Wagner CA, and Schwaninger M
- Subjects
- Amygdala, Animals, Arterioles pathology, Brain physiology, Brain Stem metabolism, Carbon Dioxide metabolism, Central Nervous System metabolism, Disease Models, Animal, Endothelium pathology, GTP-Binding Protein alpha Subunits, Gq-G11 genetics, GTP-Binding Protein alpha Subunits, Gq-G11 metabolism, Gene Expression, Humans, Hypercapnia metabolism, Mice, Mice, Knockout, Mice, Transgenic, Receptors, G-Protein-Coupled genetics, Receptors, G-Protein-Coupled metabolism, Respiration, Risk Factors, Signal Transduction, Anxiety metabolism, Cardiovascular System metabolism, Endothelium metabolism, Respiration Disorders metabolism
- Abstract
Carbon dioxide (CO
2 ), the major product of metabolism, has a strong impact on cerebral blood vessels, a phenomenon known as cerebrovascular reactivity. Several vascular risk factors such as hypertension or diabetes dampen this response, making cerebrovascular reactivity a useful diagnostic marker for incipient vascular pathology, but its functional relevance, if any, is still unclear. Here, we found that GPR4, an endothelial H+ receptor, and endothelial Gαq/11 proteins mediate the CO2 /H+ effect on cerebrovascular reactivity in mice. CO2 /H+ leads to constriction of vessels in the brainstem area that controls respiration. The consequential washout of CO2 , if cerebrovascular reactivity is impaired, reduces respiration. In contrast, CO2 dilates vessels in other brain areas such as the amygdala. Hence, an impaired cerebrovascular reactivity amplifies the CO2 effect on anxiety. Even at atmospheric CO2 concentrations, impaired cerebrovascular reactivity caused longer apneic episodes and more anxiety, indicating that cerebrovascular reactivity is essential for normal brain function. The site-specific reactivity of vessels to CO2 is reflected by regional differences in their gene expression and the release of vasoactive factors from endothelial cells. Our data suggest the central nervous system (CNS) endothelium as a target to treat respiratory and affective disorders associated with vascular diseases., Competing Interests: The authors declare no competing interest.- Published
- 2020
- Full Text
- View/download PDF
94. Noninvasive sublingual microvascular imaging reveals sex-specific reduction in glycocalyx barrier properties in patients with coronary artery disease.
- Author
-
Brands J, Hubel CA, Althouse A, Reis SE, and Pacella JJ
- Subjects
- Aged, Coronary Artery Disease metabolism, Female, Humans, Male, Microvessels metabolism, Middle Aged, Mouth Floor diagnostic imaging, Mouth Floor metabolism, Optical Imaging methods, Sex Factors, Coronary Artery Disease diagnostic imaging, Glycocalyx metabolism, Microvessels diagnostic imaging, Mouth Floor blood supply
- Abstract
Background: Risk factors for coronary artery disease (CAD) have been associated with endothelial dysfunction and degradation of the endothelial glycocalyx. This study was designed to compare sublingual microvascular perfusion and glycocalyx barrier properties in CAD patients and controls using noninvasive side stream darkfield imaging., Methods: Imaging of the sublingual microvasculature was performed in 52 case subjects (CAD confirmed by left heart catheterization) and 63 controls (low Framingham risk score). Red blood cell (RBC) filling percentage and functional microvascular density, measures of microvascular perfusion, and perfused boundary region (PBR), an index of glycocalyx barrier function, were measured in microvessels with a diameter ranging from 5-25 µm., Results: RBC filling percentage was lower in patients with CAD compared to controls (p < .001). Functional microvascular density did not differ between groups. The overall PBR was marginally greater in the CAD group compared to the control group (p = .08). PBR did not differ between male CAD cases and controls (p = .17). However, PBR was greater in females with CAD compared with female controls (p = .04), indicating reduced glycocalyx barrier function. This difference became more pronounced after adjusting for potential confounders., Conclusions: Our data suggest that patients with CAD are characterized by a reduction in percentage of time microvessels are occupied by RBCs. In addition, CAD is significantly associated with impaired sublingual microvascular glycocalyx barrier function in women but not men. More research is needed to determine the significance of peripheral microvascular dysfunction in the pathophysiology of CAD, and how this may differ by sex., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)
- Published
- 2020
- Full Text
- View/download PDF
95. Qualitative perspectives on the sustainability of sexual health continuous quality improvement in clinics serving remote Aboriginal communities in Australia.
- Author
-
Gunaratnam P, Schierhout G, Brands J, Maher L, Bailie R, Ward J, Guy R, Rumbold A, Ryder N, Fairley CK, Donovan B, Moore L, Kaldor J, and Bell S
- Subjects
- Female, Humans, Male, Northern Territory, Qualitative Research, Health Services, Indigenous standards, Quality Improvement, Sexual Health
- Abstract
Objectives: To examine barriers and facilitators to sustaining a sexual health continuous quality improvement (CQI) programme in clinics serving remote Aboriginal communities in Australia., Design: Qualitative study., Setting: Primary health care services serving remote Aboriginal communities in the Northern Territory, Australia., Participants: Seven of the 11 regional sexual health coordinators responsible for supporting the Northern Territory Government Remote Sexual Health Program., Methods: Semi-structured in-depth interviews conducted in person or by telephone; data were analysed using an inductive and deductive thematic approach., Results: Despite uniform availability of CQI tools and activities, sexual health CQI implementation varied across the Northern Territory. Participant narratives identified five factors enhancing the uptake and sustainability of sexual health CQI. At clinic level, these included adaptation of existing CQI tools for use in specific clinic contexts and risk environments (eg, a syphilis outbreak), local ownership of CQI processes and management support for CQI. At a regional level, factors included the positive framing of CQI as a tool to identify and act on areas for improvement, and regional facilitation of clinic level CQI activities. Three barriers were identified, including the significant workload associated with acute and chronic care in Aboriginal primary care services, high staff turnover and lack of Aboriginal staff. Considerations affecting the future sustainability of sexual health CQI included the need to reduce the burden on clinics from multiple CQI programmes, the contribution of regional sexual health coordinators and support structures, and access to and use of high-quality information systems., Conclusions: This study contributes to the growing evidence on how CQI approaches may improve sexual health in remote Australian Aboriginal communities. Enhancing sustainability of sexual health CQI in this context will require ongoing regional facilitation, efforts to build local ownership of CQI processes and management of competing demands on health service staff., Competing Interests: Competing interests: The authors have ongoing involvement in Aboriginal health, sexual health and CQI in Australia, as researchers, clinicians and policymakers., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2019
- Full Text
- View/download PDF
96. NK cell development in a human stem cell niche: KIR expression occurs independently of the presence of HLA class I ligands.
- Author
-
Zhao X, Weinhold S, Brands J, Hejazi M, Degistirici Ö, Kögler G, Meisel R, and Uhrberg M
- Subjects
- Animals, Biomarkers, Cell Line, Coculture Techniques, Gene Expression, Gene Knockdown Techniques, Hematopoietic Stem Cells cytology, Hematopoietic Stem Cells metabolism, Histocompatibility Antigens Class I genetics, Histocompatibility Antigens Class I immunology, Humans, Immunohistochemistry, Immunophenotyping, Ligands, Mesenchymal Stem Cells cytology, Mesenchymal Stem Cells metabolism, Mice, Receptors, KIR genetics, Receptors, KIR metabolism, Cell Differentiation, Killer Cells, Natural cytology, Killer Cells, Natural metabolism, Stem Cell Niche
- Abstract
The development of mature natural killer (NK) cells expressing killer cell immunoglobulin-like receptors (KIRs) depends on cell contact-dependent signals from nonhematopoietic cells. So far, detailed studies of this process have been hampered by the lack of an appropriate in vitro model. Here, human bone marrow-derived mesenchymal stem cells (MSCs), generated under good manufacturing practice (GMP) conditions, are established as a supportive niche for in vitro NK cell differentiation. In the presence of MSCs, cord blood and bone marrow-derived hematopoietic stem and progenitor cells (HSPCs) effectively and reproducibly differentiated into mature KIR-expressing NK cells. Notably, the novel in vitro differentiation assay enabled us to analyze the impact of HLA class I ligands on KIR repertoire development. To this end, a panel of MSC lines divergent for expression of the major KIR ligands C1, C2, and Bw4 was used for NK cell differentiation. The resulting NK cell repertoires were independent of the presence of specific KIR ligands on MSCs and were, in fact, invariably dominated by expression of the C1-specific inhibitory KIR2DL3. Similarly, short hairpin RNA-mediated knockdown of HLA class I ligands on MSCs did not delay or change the course of KIR expression. Our data suggest that the initial acquisition of KIRs during NK cell development is biased toward recognition of C1 ligands, irrespective of the presence of self-ligands. Altogether, the MSC/HSPC model constitutes a novel platform to study NK cell development in a human stem cell niche. Moreover, the system constitutes a promising GMP-compliant platform to develop clinical-grade NK cell products from cord blood HSPCs., (© 2018 by The American Society of Hematology.)
- Published
- 2018
- Full Text
- View/download PDF
97. Development of a National Aboriginal and Torres Strait Islander Cancer Framework: A Shared Process to Guide Effective Policy and Practice.
- Author
-
Brands J, Garvey G, Anderson K, Cunningham J, Chynoweth J, Wallington I, Morris B, Knott V, Webster S, Kinsella L, Condon J, and Zorbas H
- Subjects
- Australia, Health Policy, Health Services, Indigenous, Humans, Native Hawaiian or Other Pacific Islander, Neoplasms ethnology, Neoplasms therapy
- Abstract
Indigenous Australians experience a substantially higher cancer mortality rate than non-Indigenous Australians. While cancer outcomes are improving for non-Indigenous Australians, they are worsening for Indigenous Australians. Reducing this disparity requires evidence-based and culturally-appropriate guidance. The purpose of this paper is to describe an initiative by Cancer Australia and Menzies School of Health Research (Menzies) to develop Australia’s first National Aboriginal and Torres Strait Islander Cancer Framework using a process of co-design with relevant stakeholders. The initiative was guided by three core principles: achieving policy-relevant evidence-based outcomes; engaging and maintaining trust with Indigenous Australians at every phase; and employing best-practice and appropriate research methods. Four components of research comprised the Framework development: evidence review; multifaceted stakeholder consultation and input; triangulation of findings; and direct stakeholder input in drafting and refining the Framework. The evidence review confirmed the increasing burden of cancer on Indigenous Australians, while stakeholder consultations facilitated comprehensive input from those with lived experience. The consultations revealed issues not identified in existing literature, and gave different emphases of priority, thus reinforcing the value of including stakeholder perspectives. This paper focuses primarily on documenting the methods used; findings are presented only in order to illustrate the results of the process. The published Framework is available at www.canceraustralia.gov.au; further description and analyses of findings from the consultations will be published elsewhere. The logistics inherent in large-scale consultation are considerable. However, the quality of data and the foundation for sustained partnership with stakeholders and knowledge translation vastly outweighed the challenges. The process of wide-ranging stakeholder consultation described in this paper offers a model for other areas of national and international Indigenous priority setting and policy and practice development that meets the needs of those most affected. The Framework, through the establishment of an agreed, shared and evidence-based agenda, provides guidance for jurisdictional cancer plans, optimal care pathways, and program and service planning for the multiple players across all levels of the health system.
- Published
- 2018
- Full Text
- View/download PDF
98. ATF3 represses PINK1 gene transcription in lung epithelial cells to control mitochondrial homeostasis.
- Author
-
Bueno M, Brands J, Voltz L, Fiedler K, Mays B, St Croix C, Sembrat J, Mallampalli RK, Rojas M, and Mora AL
- Subjects
- A549 Cells, Activating Transcription Factor 3 biosynthesis, Activating Transcription Factor 3 metabolism, Adult, Age Factors, Aged, Aged, 80 and over, Alveolar Epithelial Cells metabolism, Alveolar Epithelial Cells pathology, Animals, Bleomycin toxicity, Endoplasmic Reticulum Stress, Homeostasis, Humans, Mice, Middle Aged, Mitochondria genetics, Mitochondria metabolism, Protein Kinases metabolism, Pulmonary Fibrosis chemically induced, Pulmonary Fibrosis genetics, Pulmonary Fibrosis metabolism, Pulmonary Fibrosis pathology, Transcription, Genetic, Transfection, Activating Transcription Factor 3 genetics, Alveolar Epithelial Cells physiology, Mitochondria physiology, Protein Kinases genetics
- Abstract
PINK1 (PTEN-induced putative kinase 1) is a key regulator of mitochondrial homeostasis that is relatively depleted in aging lungs and in lung epithelial cells from patients with idiopathic pulmonary fibrosis (IPF), a disease linked with aging. Impaired PINK1 expression and accumulation of damaged mitochondria in lung epithelial cells from fibrotic lungs were associated with the presence of ER stress. Here, we show that ATF3 (activating transcription factor 3), a member of the integrated stress response (ISR), negatively regulates transcription of the PINK1 gene. An ATF3 binding site within the human PINK1 promoter is located in the first 150 bp upstream of the transcription start site. Induction of ER stress or overexpression of ATF3 inhibited the activity of the PINK1 promoter. Importantly, overexpression of ATF3 causes accumulation of depolarized mitochondria, increased production of mitochondrial ROS, and loss of cell viability. Furthermore, conditional deletion of ATF3 in type II lung epithelial cells protects mice from bleomycin-induced lung fibrosis. Finally, we observed that ATF3 expression increases in the lung with age and, specially, in lung epithelial cells from IPF lungs. These data provide a unique link between ATF3 and PINK1 expression suggesting that persistent stress, driven by ATF3, can dysregulate mitochondrial homeostasis by repression of PINK1 mRNA synthesis., (© 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
- Published
- 2018
- Full Text
- View/download PDF
99. VEP-based acuity assessment in low vision.
- Author
-
Hoffmann MB, Brands J, Behrens-Baumann W, and Bach M
- Subjects
- Adult, Electrodes, Female, Fourier Analysis, Humans, Male, Psychophysics, Young Adult, Evoked Potentials, Visual physiology, Vision Tests methods, Vision, Low diagnosis, Visual Acuity physiology
- Abstract
Purpose: Objective assessment of visual acuity (VA) is possible with VEP methodology, but established with sufficient precision only for vision better than about 1.0 logMAR. We here explore whether this can be extended down to 2.0 logMAR, highly desirable for low-vision evaluations., Methods: Based on the stepwise sweep algorithm (Bach et al. in Br J Ophthalmol 92:396-403, 2008) VEPs to monocular steady-state brief onset pattern stimulation (7.5-Hz checkerboards, 40% contrast, 40 ms on, 93 ms off) were recorded for eight different check sizes, from 0.5° to 9.0°, for two runs with three occipital electrodes in a Laplace-approximating montage. We examined 22 visually normal participants where acuity was reduced to ≈ 2.0 logMAR with frosted transparencies. With the established heuristic algorithm the "VEP acuity" was extracted and compared to psychophysical VA, both obtained at 57 cm distance., Results: In 20 of the 22 participants with artificially reduced acuity the automatic analysis indicated a valid result (1.80 logMAR on average) in at least one of the two runs. 95% test-retest limits of agreement on average were ± 0.09 logMAR for psychophysical, and ± 0.21 logMAR for VEP-derived acuity. For 15 participants we obtained results in both runs and averaged them. In 12 of these 15 the low-acuity results stayed within the 95% confidence interval (± 0.3 logMAR) as established by Bach et al. (2008)., Conclusions: The fully automated analysis yielded good agreement of psychophysical and electrophysiological VAs in 12 of 15 cases (80%) in the low-vision range down to 2.0 logMAR. This encourages us to further pursue this methodology and assess its value in patients.
- Published
- 2017
- Full Text
- View/download PDF
100. Isolation and Cultivation of Primary Brain Endothelial Cells from Adult Mice.
- Author
-
Assmann JC, Müller K, Wenzel J, Walther T, Brands J, Thornton P, Allan SM, and Schwaninger M
- Abstract
Brain endothelial cells are the major building block of the blood-brain barrier. To study the role of brain endothelial cells in vitro , the isolation of primary cells is of critical value. Here, we describe a protocol in which vessel fragments are isolated from adult mice. After density centrifugation and mild digestion of the fragments, outgrowing endothelial cells are selected by puromycin treatment and grown to confluence within one week.
- Published
- 2017
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.