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Article ; Online: Mucus-targeting therapies of defective mucus clearance for cystic fibrosis: A short review.

Figueira, Miriam Frankenthal / Ribeiro, Carla M P / Button, Brian

2022 Volume 65, Page(s) 102248

Abstract: In the lungs, defective CFTR associated with cystic fibrosis (CF) represents the nidus for abnormal mucus clearance in the airways and consequently a progressive lung disease. Defective CFTR-mediated ... ...

Abstract	In the lungs, defective CFTR associated with cystic fibrosis (CF) represents the nidus for abnormal mucus clearance in the airways and consequently a progressive lung disease. Defective CFTR-mediated Cl
MeSH term(s)	Cystic Fibrosis/drug therapy ; Cystic Fibrosis/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Humans ; Lung ; Mucus
Chemical Substances	Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6)
Language	English
Publishing date	2022-06-08
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2037057-X
ISSN	1471-4973 ; 1471-4892
ISSN (online)	1471-4973
ISSN	1471-4892
DOI	10.1016/j.coph.2022.102248
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Article ; Online: Physiology and pathophysiology of human airway mucus.

Hill, David B / Button, Brian / Rubinstein, Michael / Boucher, Richard C

Physiological reviews

2022 Volume 102, Issue 4, Page(s) 1757–1836

Abstract: The mucus clearance system is the dominant mechanical host defense system of the human lung. Mucus is cleared from the lung by cilia and airflow, including both two-phase gas-liquid pumping and cough-dependent mechanisms, and mucus transport rates are ... ...

Abstract	The mucus clearance system is the dominant mechanical host defense system of the human lung. Mucus is cleared from the lung by cilia and airflow, including both two-phase gas-liquid pumping and cough-dependent mechanisms, and mucus transport rates are heavily dependent on mucus concentration. Importantly, mucus transport rates are accurately predicted by the gel-on-brush model of the mucociliary apparatus from the relative osmotic moduli of the mucus and periciliary-glycocalyceal (PCL-G) layers. The fluid available to hydrate mucus is generated by transepithelial fluid transport. Feedback interactions between mucus concentrations and cilia beating, via purinergic signaling, coordinate Na
MeSH term(s)	Cystic Fibrosis/metabolism ; Humans ; Lung/metabolism ; Mucociliary Clearance ; Mucus/metabolism ; Pulmonary Disease, Chronic Obstructive
Language	English
Publishing date	2022-01-10
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209902-0
ISSN	1522-1210 ; 0031-9333
ISSN (online)	1522-1210
ISSN	0031-9333
DOI	10.1152/physrev.00004.2021
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Article: Airway Epithelial Nucleotide Release Contributes to Mucociliary Clearance.

van Heusden, Catharina / Grubb, Barbara R / Button, Brian / Lazarowski, Eduardo R

Life (Basel, Switzerland)

2021 Volume 11, Issue 5

Abstract: Mucociliary clearance (MCC) is a dominant component of pulmonary host defense. In health, the periciliary layer (PCL) is optimally hydrated, thus acting as an efficient lubricant layer over which the mucus layer moves by ciliary force. Airway surface ... ...

Abstract	Mucociliary clearance (MCC) is a dominant component of pulmonary host defense. In health, the periciliary layer (PCL) is optimally hydrated, thus acting as an efficient lubricant layer over which the mucus layer moves by ciliary force. Airway surface dehydration and production of hyperconcentrated mucus is a common feature of chronic obstructive lung diseases such as cystic fibrosis (CF) and chronic bronchitis (CB). Mucus hydration is driven by electrolyte transport activities, which in turn are regulated by airway epithelial purinergic receptors. The activity of these receptors is controlled by the extracellular concentrations of ATP and its metabolite adenosine. Vesicular and conducted pathways contribute to ATP release from airway epithelial cells. In this study, we review the evidence leading to the identification of major components of these pathways: (a) the vesicular nucleotide transporter VNUT (the product of the SLC17A9 gene), the ATP transporter mediating ATP storage in (and release from) mucin granules and secretory vesicles; and (b) the ATP conduit pannexin 1 expressed in non-mucous airway epithelial cells. We further illustrate that ablation of pannexin 1 reduces, at least in part, airway surface liquid (ASL) volume production, ciliary beating, and MCC rates.
Language	English
Publishing date	2021-05-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life11050430
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Article ; Online: A Biomechanical Assessment of Shaken Baby Syndrome: What About the Spine?

Davison, Mark A / Button, Keith D / Benzel, Edward C / Weaver, Brian T / Rundell, Steve A

World neurosurgery

2022 Volume 163, Page(s) e223–e229

Abstract: Background: Shaken baby syndrome occurs following inertial loading of the pediatric head, resulting in retinal hemorrhaging, subdural hematoma, and encephalopathy. However, the anatomically vulnerable cervical spine receives little attention. Automotive ...

Abstract	Background: Shaken baby syndrome occurs following inertial loading of the pediatric head, resulting in retinal hemorrhaging, subdural hematoma, and encephalopathy. However, the anatomically vulnerable cervical spine receives little attention. Automotive safety literature is replete with biomechanical data involving forward-facing pediatric surrogates in frontal collisions, an environment analogous to shaking. Publicly available data involving child occupants were utilized to study pediatric neck and head injury potential. We hypothesized that inertial loading provides a greater risk of injury to the cervical spine than to the head. Methods: Full-scale automotive crash tests (n = 131) and deceleration sled tests (n = 32) utilizing forward-facing 3-year-old surrogates with head accelerometers and cervical force sensors were analyzed. One hundred sixty-seven full-scale vehicle and 33 sled test runs were assessed in the context of published injury assessment reference values (IARVs) for closed head injury (head injury criterion 15 [HIC Results: One hundred sixty-one (96%) child surrogates in full-scale crash tests exceeded the cervical peak tension IARV, while only 37 (22%) surpassed the HIC Conclusions: These data support the hypothesis that inertial loading of the head provides a greater injury risk to the cervical spine than to closed-head injury.
MeSH term(s)	Acceleration ; Accidents, Traffic ; Biomechanical Phenomena ; Cervical Vertebrae ; Child ; Child, Preschool ; Craniocerebral Trauma ; Humans ; Infant ; Neck ; Shaken Baby Syndrome/diagnosis
Language	English
Publishing date	2022-03-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2022.03.104
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Article ; Online: TRPV2 modulates mechanically Induced ATP Release from Human bronchial epithelial cells.

Dunne, Orla M / Martin, S Lorraine / Sergeant, Gerard P / McAuley, Daniel F / O'Kane, Cecilia M / Button, Brian / McGarvey, Lorcan P / Lundy, Fionnuala T

Respiratory research

2024 Volume 25, Issue 1, Page(s) 188

Abstract: Repetitive bouts of coughing expose the large airways to significant cycles of shear stress. This leads to the release of alarmins and the tussive agent adenosine triphosphate (ATP) which may be modulated by the activity of ion channels present in the ... ...

Abstract	Repetitive bouts of coughing expose the large airways to significant cycles of shear stress. This leads to the release of alarmins and the tussive agent adenosine triphosphate (ATP) which may be modulated by the activity of ion channels present in the human airway. This study aimed to investigate the role of the transient receptor potential subfamily vanilloid member 2 (TRPV2) channel in mechanically induced ATP release from primary bronchial epithelial cells (PBECs).PBECs were obtained from individuals undergoing bronchoscopy. They were cultured in vitro and exposed to mechanical stress in the form of compressive and fluid shear stress (CFSS) or fluid shear stress (FSS) alone at various intensities. ATP release was measured using a luciferin-luciferase assay. Functional TRPV2 protein expression in human PBECs was investigated by confocal calcium imaging. The role of TRPV2 inhibition on FSS-induced ATP release was investigated using the TRPV2 inhibitor tranilast or siRNA knockdown of TRPV2. TRPV2 protein expression in human lung tissue was also determined by immunohistochemistry.ATP release was significantly increased in PBECs subjected to CFSS compared with control (unstimulated) PBECs (N = 3, *P < 0.001). PBECs expressed functional TRPV2 channels. TRPV2 protein was also detected in fixed human lung tissue. ATP release from FFS stimulated PBECs was decreased by the TRPV2 inhibitor tranilast (N = 3, P < 0.01) (vehicle: 159 ± 17.49 nM, tranilast: 25.08 ± 5.1 nM) or by TRPV2 siRNA knockdown (N = 3, *P < 0.05) (vehicle: 197 ± 24.52 nM, siRNA: 119 ± 26.85 nM).In conclusion, TRPV2 is expressed in the human airway and modulates ATP release from mechanically stimulated PBECs.
MeSH term(s)	Humans ; TRPV Cation Channels/metabolism ; TRPV Cation Channels/genetics ; Adenosine Triphosphate/metabolism ; Bronchi/metabolism ; Cells, Cultured ; Epithelial Cells/metabolism ; Stress, Mechanical ; Male ; Mechanotransduction, Cellular/physiology
Chemical Substances	TRPV Cation Channels ; Adenosine Triphosphate (8L70Q75FXE) ; TRPV2 protein, human
Language	English
Publishing date	2024-04-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-993X
ISSN (online)	1465-993X
ISSN	1465-993X
DOI	10.1186/s12931-024-02807-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book ; Online: Evaluating Novel Threats to the Homeland

Jackson, Brian A / Frelinger, David R / Lostumbo, Michael J / Button, Robert W

Unmanned Aerial Vehicles and Cruise Missiles

2008

Keywords	Terrorism, armed struggle ; Technology: general issues ; Military engineering ; Technology ; Political Science
Language	English
Size	1 Online-Ressource
Publisher	RAND Corporation
Document type	Book ; Online
Note	English
HBZ-ID	HT030610690
ISBN	9780833041692 ; 083304169X
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Structure and function of the mucus clearance system of the lung.

Button, Brenda M / Button, Brian

Cold Spring Harbor perspectives in medicine

2013 Volume 3, Issue 8

Abstract: In cystic fibrosis (CF), a defect in ion transport results in thick and dehydrated airway mucus, which is difficult to clear, making such patients prone to chronic inflammation and bacterial infections. Physiotherapy using a variety of airway clearance ... ...

Abstract	In cystic fibrosis (CF), a defect in ion transport results in thick and dehydrated airway mucus, which is difficult to clear, making such patients prone to chronic inflammation and bacterial infections. Physiotherapy using a variety of airway clearance techniques (ACTs) represents a key treatment regime by helping clear the airways of thickened, adhered, mucus and, thus, reducing the impact of lung infections and improving lung function. This article aims to bridge the gap between our understanding of the physiological effects of mechanical stresses elicited by ACTs on airway epithelia and the reported effectiveness of ACTs in CF patients. In the first part of this review, the effects of mechanical stress on airway epithelia are discussed in relation to changes in ion transport and stimulation in airway surface layer hydration. The second half is devoted to detailing the most commonly used ACTs to stimulate the removal of mucus from the airways of patients with CF.
MeSH term(s)	Bronchi/physiopathology ; Cystic Fibrosis/genetics ; Cystic Fibrosis/metabolism ; Cystic Fibrosis/physiopathology ; Cystic Fibrosis/therapy ; Humans ; Ion Transport ; Lung/physiopathology ; Mucus/chemistry ; Mucus/metabolism ; Physical Therapy Modalities ; Respiratory Mucosa/metabolism ; Treatment Outcome
Language	English
Publishing date	2013-08-01
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2157-1422
ISSN (online)	2157-1422
DOI	10.1101/cshperspect.a009720
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Filial Cannibalism Leads to Chronic Nest Failure of Eastern Hellbender Salamanders (

Hopkins, William A / Case, Brian F / Groffen, Jordy / Brooks, George C / Bodinof Jachowski, Catherine M / Button, Sky T / Hallagan, John J / O'Brien, Rebecca S M / Kindsvater, Holly K

The American naturalist

2023 Volume 202, Issue 1, Page(s) 92–106

Abstract: AbstractIn species that provide parental care, parents will sometimes cannibalize their own young (i.e., filial cannibalism). Here, we quantified the frequency of whole-clutch filial cannibalism in a species of giant salamander (eastern hellbender; ...

Abstract	AbstractIn species that provide parental care, parents will sometimes cannibalize their own young (i.e., filial cannibalism). Here, we quantified the frequency of whole-clutch filial cannibalism in a species of giant salamander (eastern hellbender;
MeSH term(s)	Male ; Animals ; Urodela ; Cannibalism ; Biological Evolution ; Forests ; Reproduction
Language	English
Publishing date	2023-05-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	207092-3
ISSN	1537-5323 ; 0003-0147
ISSN (online)	1537-5323
ISSN	0003-0147
DOI	10.1086/724819
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Article ; Online: Global Oral Anticoagulation Use Varies by Region in Patients With Recent Diagnosis of Atrial Fibrillation: The GLORIA-AF Phase III Registry.

Bayer, Valentina / Kotalczyk, Agnieszka / Kea, Bory / Teutsch, Christine / Larsen, Peter / Button, Dana / Huisman, Menno V / Lip, Gregory Y H / Olshansky, Brian

Journal of the American Heart Association

2022 Volume 11, Issue 6, Page(s) e023907

Abstract: Background Effective stroke prevention with oral anticoagulants (OAC) is recommended for some patients with atrial fibrillation (AF). We aimed to describe OAC use by geographical region and type of site in patients with recent-onset AF enrolled in a ... ...

Abstract	Background Effective stroke prevention with oral anticoagulants (OAC) is recommended for some patients with atrial fibrillation (AF). We aimed to describe OAC use by geographical region and type of site in patients with recent-onset AF enrolled in a large global registry. Methods and Results Eligible participants were recruited into GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation), a prospective observational cohort study from 2014 to 2016 in 4 international regions: North America, Europe, Asia, and Latin America. Cumulative incidence functions were generated for direct OACs (DOAC), vitamin K antagonists, and antiplatelet drugs considering competing risks, stratified by region and type of site. Time-to-treatment initiation after AF diagnosis was analyzed with Fine-Gray subdistribution hazard models. A total of 21 237 patients eligible for analysis were identified. By 30 days after AF diagnosis, 40%, 16%, and 8.6% of patients had DOAC, vitamin K antagonists, and antiplatelet drugs initiated, respectively. Earlier initiation of DOACs was observed in Europe, with Asia and Latin America having lower hazard rates of DOAC time-to-treatment initiation than Europe (hazard ratio [HR], 0.66; 95% CI, 0.62-0.70 and HR, 0.79; 95% CI, 0.73-0.85, respectively). DOAC initiation was highest in community hospitals, vitamin K antagonists in outpatient health care centers/anticoagulation clinics, and antiplatelet drugs in primary care clinics. Conclusions Important geographic variability exists with the use of OACs for patients with AF. Differences in the time-to-treatment initiation of OAC by type of site suggests suboptimal implementation of guideline recommendations and could result in less benefit and more harm. Optimizing OAC use for patients with AF may improve outcomes and reduce health care costs. Registration URL: http://www.clinicaltrials.gov; Unique identifiers: NCT01468701, NCT01671007.
MeSH term(s)	Administration, Oral ; Anticoagulants/therapeutic use ; Atrial Fibrillation/complications ; Atrial Fibrillation/diagnosis ; Atrial Fibrillation/drug therapy ; Fibrinolytic Agents ; Humans ; Platelet Aggregation Inhibitors/adverse effects ; Prospective Studies ; Registries ; Risk Factors ; Stroke/epidemiology ; Stroke/etiology ; Stroke/prevention & control ; Vitamin K
Chemical Substances	Anticoagulants ; Fibrinolytic Agents ; Platelet Aggregation Inhibitors ; Vitamin K (12001-79-5)
Language	English
Publishing date	2022-03-04
Publishing country	England
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.121.023907
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Article ; Online: Airway Epithelial Nucleotide Release Contributes to Mucociliary Clearance

Catharina van Heusden / Barbara R. Grubb / Brian Button / Eduardo R. Lazarowski

Life, Vol 11, Iss 430, p

2021 Volume 430

Abstract	Mucociliary clearance (MCC) is a dominant component of pulmonary host defense. In health, the periciliary layer (PCL) is optimally hydrated, thus acting as an efficient lubricant layer over which the mucus layer moves by ciliary force. Airway surface dehydration and production of hyperconcentrated mucus is a common feature of chronic obstructive lung diseases such as cystic fibrosis (CF) and chronic bronchitis (CB). Mucus hydration is driven by electrolyte transport activities, which in turn are regulated by airway epithelial purinergic receptors. The activity of these receptors is controlled by the extracellular concentrations of ATP and its metabolite adenosine. Vesicular and conducted pathways contribute to ATP release from airway epithelial cells. In this study, we review the evidence leading to the identification of major components of these pathways: (a) the vesicular nucleotide transporter VNUT (the product of the SLC17A9 gene), the ATP transporter mediating ATP storage in (and release from) mucin granules and secretory vesicles; and (b) the ATP conduit pannexin 1 expressed in non-mucous airway epithelial cells. We further illustrate that ablation of pannexin 1 reduces, at least in part, airway surface liquid (ASL) volume production, ciliary beating, and MCC rates.
Keywords	ATP release ; airway epithelia ; mucociliary clearance ; pannexin 1 ; vesicular nucleotide transporter ; Science ; Q
Subject code	500
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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