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Article ; Online: Blau Syndrome: A Systemic Granulomatous Disease of Cutaneous Onset and Phenotypic Complexity.

Rose, Carlos D

2017 Volume 34, Issue 2, Page(s) 216–218

MeSH term(s)	Arthritis/diagnosis ; Arthritis/genetics ; Humans ; Mutation ; Nod2 Signaling Adaptor Protein/genetics ; Phenotype ; Synovitis/diagnosis ; Synovitis/genetics ; Uveitis/diagnosis ; Uveitis/genetics
Chemical Substances	NOD2 protein, human ; Nod2 Signaling Adaptor Protein
Language	English
Publishing date	2017
Publishing country	United States
Document type	Editorial
ZDB-ID	605539-4
ISSN	1525-1470 ; 0736-8046
ISSN (online)	1525-1470
ISSN	0736-8046
DOI	10.1111/pde.13021
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Article ; Online: Ethical Conduct of Research in Children: Pediatricians and Their IRB (Part 2 of 2).

Rose, Carlos D

Pediatrics

2017 Volume 139, Issue 6

Abstract: In part 1 of this series, we discussed the historical, ethical, and legal background that provides justification for the current system of protection of subjects of human experimentation. We also discussed briefly the implementation of those principles ... ...

Abstract	In part 1 of this series, we discussed the historical, ethical, and legal background that provides justification for the current system of protection of subjects of human experimentation. We also discussed briefly the implementation of those principles in institutional review board (IRB) operations. In part 2, we focus on legislation dealing with pediatric research, the rules and ethics of assent, and then turn our attention to minimal-risk studies. To that end, we discuss the minimal-risk threshold and the process of balancing benefit and risk in IRB decisions for pediatric studies. We define the notion of consent waiver as well as the procedures for expedited review, management of adverse events, and amendments to approved protocol. Finally, we mention some miscellaneous issues, including central and commercial IRB, reliance agreements, biobanks, and sample shipping regulations.
MeSH term(s)	Biomedical Research/ethics ; Child ; Ethics Committees, Research/ethics ; Ethics, Research ; Humans ; Informed Consent/legislation & jurisprudence ; Pediatricians
Language	English
Publishing date	2017-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	207677-9
ISSN	1098-4275 ; 0031-4005
ISSN (online)	1098-4275
ISSN	0031-4005
DOI	10.1542/peds.2016-3650
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Article ; Online: Ethical Conduct of Research in Children: Pediatricians and Their IRB (Part 1 of 2).

Rose, Carlos D

Pediatrics

2017 Volume 139, Issue 5

Abstract: ... Part 2 focuses on pediatric research regulation, also known as subpart-D, and minimal risk research ...

Abstract	As human experimentation continues to grow into an ever more complex and sophisticated endeavor, the relevant ethical and regulatory structures become more intricate. When pediatricians and general practitioners are invited by pharmaceutical companies to enroll their offices in a clinical trial or a multicenter observational study or when they develop their own research questions, they frequently find themselves at a loss in the human research environment. The legal and regulatory complexity may have an unintended deterring effect at a time when office-based high quality pediatric research is urgently needed to support evidence-based medicine. Unfortunately, in many instances, unaware practitioners become involved in low-risk research activities without knowing it and become entangled in legal, auditing, and compliance procedures. This paper, written in 2 parts, aims at providing a general guidance on the principles that regulate human research with a focus on pediatrics. Part 1 discusses the history, the legal framework, and the consent process and highlights some practical aspects of initial protocol submission, continued review, and institutional review board determinations with the main focus on multicenter clinical trials (industry-sponsored research). Part 2 focuses on pediatric research regulation, also known as subpart-D, and minimal risk research, which encompasses many research activities aimed at addressing questions that may emerge in pediatricians' practices (investigator-initiated research).
MeSH term(s)	Biomedical Research/ethics ; Biomedical Research/history ; Biomedical Research/legislation & jurisprudence ; Child ; Clinical Trials as Topic/ethics ; Drug Discovery/ethics ; Ethics Committees, Research ; History, 20th Century ; Human Experimentation/ethics ; Human Experimentation/history ; Human Experimentation/legislation & jurisprudence ; Humans ; Informed Consent By Minors/ethics ; Multicenter Studies as Topic/ethics ; Pediatricians/ethics ; United States
Language	English
Publishing date	2017-05
Publishing country	United States
Document type	Historical Article ; Journal Article ; Review
ZDB-ID	207677-9
ISSN	1098-4275 ; 0031-4005
ISSN (online)	1098-4275
ISSN	0031-4005
DOI	10.1542/peds.2016-3648
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Article ; Online: Validation of new medication use algorithms as proxies for worsening disease activity in patients with juvenile idiopathic arthritis.

Saito, Kyoko / Gabbeta, Avinash / Mulvihill, Evan / Al-Jaberi, Lina / Beukelman, Timothy / Lewis, James D / Rose, Carlos D / Strom, Brian L / Horton, Daniel B

Pharmacoepidemiology and drug safety

2024 Volume 33, Issue 5, Page(s) e5803

Abstract: Purpose: To facilitate claims-based research on populations with juvenile idiopathic arthritis (JIA), we sought to validate an algorithm of new medication use as a proxy for worsening JIA disease activity.: Methods: Using electronic health record ... ...

Abstract	Purpose: To facilitate claims-based research on populations with juvenile idiopathic arthritis (JIA), we sought to validate an algorithm of new medication use as a proxy for worsening JIA disease activity. Methods: Using electronic health record data from three pediatric centers, we defined new JIA medication use as (re)initiation of disease-modifying antirheumatic drugs or glucocorticoids (oral or intra-articular). Data were collected from 201 randomly selected subjects with (101) or without (100) new medication use. We assessed the positive predictive value (PPV) and negative predictive value (NPV) based on a reference standard of documented worsening of JIA disease activity. The algorithm was refined to optimize test characteristics. Results: Overall, the medication-based algorithm had suboptimal performance in representing worsening JIA disease activity (PPV 69.3%, NPV 77.1%). However, algorithm performance improved for definitions specifying longer times after JIA diagnosis (≥1-year post-diagnosis: PPV 82.9%, NPV 80.0%) or after initiation of prior JIA treatment (≥1-year post-treatment: PPV 89.7%, NPV 80.0%). Conclusion: An algorithm for new JIA medication use appears to be a reasonable proxy for worsening JIA disease activity, particularly when specifying new use ≥1 year since initiating a prior JIA medication. This algorithm will be valuable for conducting research on JIA populations within administrative claims databases.
MeSH term(s)	Humans ; Arthritis, Juvenile/drug therapy ; Algorithms ; Child ; Female ; Antirheumatic Agents/therapeutic use ; Male ; Electronic Health Records/statistics & numerical data ; Adolescent ; Glucocorticoids/therapeutic use ; Glucocorticoids/administration & dosage ; Glucocorticoids/adverse effects ; Child, Preschool ; Disease Progression ; Predictive Value of Tests
Chemical Substances	Antirheumatic Agents ; Glucocorticoids
Language	English
Publishing date	2024-04-29
Publishing country	England
Document type	Journal Article ; Validation Study ; Research Support, Non-U.S. Gov't ; Multicenter Study ; Research Support, N.I.H., Extramural
ZDB-ID	1099748-9
ISSN	1099-1557 ; 1053-8569
ISSN (online)	1099-1557
ISSN	1053-8569
DOI	10.1002/pds.5803
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Article: Multinucleated Giant Cells: Current Insights in Phenotype, Biological Activities, and Mechanism of Formation.

Ahmadzadeh, Kourosh / Vanoppen, Margot / Rose, Carlos D / Matthys, Patrick / Wouters, Carine Helena

Frontiers in cell and developmental biology

2022 Volume 10, Page(s) 873226

Abstract: Monocytes and macrophages are innate immune cells with diverse functions ranging from phagocytosis of microorganisms to forming a bridge with the adaptive immune system. A lesser-known attribute of macrophages is their ability to fuse with each other to ... ...

Abstract	Monocytes and macrophages are innate immune cells with diverse functions ranging from phagocytosis of microorganisms to forming a bridge with the adaptive immune system. A lesser-known attribute of macrophages is their ability to fuse with each other to form multinucleated giant cells. Based on their morphology and functional characteristics, there are in general three types of multinucleated giant cells including osteoclasts, foreign body giant cells and Langhans giant cells. Osteoclasts are bone resorbing cells and under physiological conditions they participate in bone remodeling. However, under pathological conditions such as rheumatoid arthritis and osteoporosis, osteoclasts are responsible for bone destruction and bone loss. Foreign body giant cells and Langhans giant cells appear only under pathological conditions. While foreign body giant cells are found in immune reactions against foreign material, including implants, Langhans giant cells are associated with granulomas in infectious and non-infectious diseases. The functionality and fusion mechanism of osteoclasts are being elucidated, however, our knowledge on the functions of foreign body giant cells and Langhans giant cells is limited. In this review, we describe and compare the phenotypic aspects, biological and functional activities of the three types of multinucleated giant cells. Furthermore, we provide an overview of the multinucleation process and highlight key molecules in the different phases of macrophage fusion.
Language	English
Publishing date	2022-04-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2022.873226
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Article ; Online: Multinucleation resets human macrophages for specialized functions at the expense of their identity.

Ahmadzadeh, Kourosh / Pereira, Marie / Vanoppen, Margot / Bernaerts, Eline / Ko, Jeong-Hun / Mitera, Tania / Maksoudian, Christy / Manshian, Bella B / Soenen, Stefaan / Rose, Carlos D / Matthys, Patrick / Wouters, Carine / Behmoaras, Jacques

EMBO reports

2023 Volume 24, Issue 4, Page(s) e57070

Language	English
Publishing date	2023-04-05
Publishing country	England
Document type	Published Erratum
ZDB-ID	2020896-0
ISSN	1469-3178 ; 1469-221X
ISSN (online)	1469-3178
ISSN	1469-221X
DOI	10.15252/embr.202357070
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Article ; Online: Multinucleated Giant Cells

Kourosh Ahmadzadeh / Margot Vanoppen / Carlos D. Rose / Patrick Matthys / Carine Helena Wouters

Frontiers in Cell and Developmental Biology, Vol

Current Insights in Phenotype, Biological Activities, and Mechanism of Formation

2022 Volume 10

Abstract	Monocytes and macrophages are innate immune cells with diverse functions ranging from phagocytosis of microorganisms to forming a bridge with the adaptive immune system. A lesser-known attribute of macrophages is their ability to fuse with each other to form multinucleated giant cells. Based on their morphology and functional characteristics, there are in general three types of multinucleated giant cells including osteoclasts, foreign body giant cells and Langhans giant cells. Osteoclasts are bone resorbing cells and under physiological conditions they participate in bone remodeling. However, under pathological conditions such as rheumatoid arthritis and osteoporosis, osteoclasts are responsible for bone destruction and bone loss. Foreign body giant cells and Langhans giant cells appear only under pathological conditions. While foreign body giant cells are found in immune reactions against foreign material, including implants, Langhans giant cells are associated with granulomas in infectious and non-infectious diseases. The functionality and fusion mechanism of osteoclasts are being elucidated, however, our knowledge on the functions of foreign body giant cells and Langhans giant cells is limited. In this review, we describe and compare the phenotypic aspects, biological and functional activities of the three types of multinucleated giant cells. Furthermore, we provide an overview of the multinucleation process and highlight key molecules in the different phases of macrophage fusion.
Keywords	multinucleated giant cell (MGC) ; osteoclast ; foreign body giant cell (FBGC) ; Langhans giant cell (LGC) ; macrophage ; cell fusion ; Biology (General) ; QH301-705.5
Subject code	630
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: What is known so far about bull sperm protamination: a review.

Nagaki, Carlos Alonso Paco / Hamilton, Thais Rose Dos Santos / Assumpção, Mayra Elena Ortiz D Ávila

Animal reproduction

2022 Volume 19, Issue 4, Page(s) e20210109

Abstract: Sperm routinary fitness evaluation is not sufficient to predict bull reproductive capacity as they present differences in fertility up to 40%. Among the defects which compromise spermatozoa functionality, new approaches consider the study of sperm ... ...

Abstract	Sperm routinary fitness evaluation is not sufficient to predict bull reproductive capacity as they present differences in fertility up to 40%. Among the defects which compromise spermatozoa functionality, new approaches consider the study of sperm chromatin, which is the core structure containing paternal genetic information. Sperm chromatin needs to be compacted to maintain the integrity of DNA, which occurs by binding nucleoproteins with high affinity to DNA. In the last stages of sperm maturation, chromatin is hyper-compacted by basic proteins called protamines in a process named protamination. In this review, we summarized intrinsic and extrinsic factors that are suggested to influence protamination in bull spermatozoa, considering old and new evidence from human and murine spermatozoa. Also, the current approaches to evaluate bull protamination and its relationship with fertility were described. Nevertheless, the physiological mechanisms of protamination are still poorly understood.
Language	English
Publishing date	2022-11-04
Publishing country	Brazil
Document type	Journal Article ; Review
ZDB-ID	2227229-X
ISSN	1984-3143 ; 1984-3143
ISSN (online)	1984-3143
ISSN	1984-3143
DOI	10.1590/1984-3143-AR2021-0109
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Article ; Online: Correction to: Health Literacy Within a Diverse Community-Based Cohort: The Multi-Ethnic Study of Atherosclerosis.

Anderson, Madison D / Merkin, Sharon Stein / Everson-Rose, Susan A / Widome, Rachel / Seeman, Teresa / Magnani, Jared W / Rodriguez, Carlos J / Lutsey, Pamela L

Journal of immigrant and minority health

2021 Volume 23, Issue 4, Page(s) 668

Language	English
Publishing date	2021-01-13
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2220162-2
ISSN	1557-1920 ; 1557-1912
ISSN (online)	1557-1920
ISSN	1557-1912
DOI	10.1007/s10903-020-01137-9
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Article ; Online: Multinucleation resets human macrophages for specialized functions at the expense of their identity.

EMBO reports

2023 Volume 24, Issue 3, Page(s) e56310

Abstract: Macrophages undergo plasma membrane fusion and cell multinucleation to form multinucleated giant cells (MGCs) such as osteoclasts in bone, Langhans giant cells (LGCs) as part of granulomas or foreign-body giant cells (FBGCs) in reaction to exogenous ... ...

Abstract	Macrophages undergo plasma membrane fusion and cell multinucleation to form multinucleated giant cells (MGCs) such as osteoclasts in bone, Langhans giant cells (LGCs) as part of granulomas or foreign-body giant cells (FBGCs) in reaction to exogenous material. How multinucleation per se contributes to functional specialization of mature mononuclear macrophages remains poorly understood in humans. Here, we integrate comparative transcriptomics with functional assays in purified mature mononuclear and multinucleated human osteoclasts, LGCs and FBGCs. Strikingly, in all three types of MGCs, multinucleation causes a pronounced downregulation of macrophage identity. We show enhanced lysosome-mediated intracellular iron homeostasis promoting MGC formation. The transition from mononuclear to multinuclear state is accompanied by cell specialization specific to each polykaryon. Enhanced phagocytic and mitochondrial function associate with FBGCs and osteoclasts, respectively. Moreover, human LGCs preferentially express B7-H3 (CD276) and can form granuloma-like clusters in vitro, suggesting that their multinucleation potentiates T cell activation. These findings demonstrate how cell-cell fusion and multinucleation reset human macrophage identity as part of an advanced maturation step that confers MGC-specific functionality.
MeSH term(s)	Humans ; Macrophages/metabolism ; Osteoclasts/metabolism ; Bone and Bones ; Giant Cells ; B7 Antigens/metabolism
Chemical Substances	CD276 protein, human ; B7 Antigens
Language	English
Publishing date	2023-01-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2020896-0
ISSN	1469-3178 ; 1469-221X
ISSN (online)	1469-3178
ISSN	1469-221X
DOI	10.15252/embr.202256310
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