Publications by authors named "D I Conway"

759 Publications

Severe Pulmonary Hemorrhage in a Neonate With Hypoxic Ischemic Encephalopathy and Sepsis Managed on Extracorporeal Membrane Oxygenation.

ASAIO J 2021 Jul 15. Epub 2021 Jul 15.

From the Division of Neonatology, Department of Pediatrics, St Christopher's Hospital for Children, Philadelphia, Pennsylvania Department of Pediatrics, Drexel University College of Medicine, Philadelphia, Pennsylvania.

Pulmonary hemorrhage (PH) is an infrequent and potentially fatal event in term neonates. Reports of successful management of PH on extracorporeal membrane oxygenation (ECMO) are limited, given the accentuated risk of mortality imposed by the use of heparin to prevent thrombosis on ECMO. We present a case of a term neonate with hypoxic ischemic encephalopathy undergoing controlled hypothermia who developed hypoxic respiratory failure, hemodynamic instability, Enterobacter cloacae pneumonia and sepsis complicated by severe PH who required support with veno-arterial ECMO. We describe the therapeutic strategies used on veno-arterial ECMO to successfully manage this infant, including clamping the endotracheal tube, aggressive correction of coagulopathy, and use of dornase alfa, as well as elaborate on the subtle changes in ECMO parameters during the run that preceded worsening pneumonia with sepsis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAT.0000000000001520DOI Listing
July 2021

Selective Caries Removal in Permanent Teeth (SCRiPT) for the treatment of deep carious lesions: a randomised controlled clinical trial in primary care.

BMC Oral Health 2021 Jul 9;21(1):336. Epub 2021 Jul 9.

Dental Health Services Research Unit, Dundee Dental School, The University of Dundee, 9th Floor, Park Place, Dundee, DD1 4HN, UK.

Background: Dental caries is one of the most prevalent non-communicable disease globally and can have serious health sequelae impacting negatively on quality of life. In the UK most adults experience dental caries during their lifetime and the 2009 Adult Dental Health Survey reported that 85% of adults have at least one dental restoration. Conservative removal of tooth tissue for both primary and secondary caries reduces the risk of failure due to tooth-restoration, complex fracture as well as remaining tooth surfaces being less vulnerable to further caries. However, despite its prevalence there is no consensus on how much caries to remove prior to placing a restoration to achieve optimal outcomes. Evidence for selective compared to complete or near-complete caries removal suggests there may be benefits for selective removal in sustaining tooth vitality, therefore avoiding abscess formation and pain, so eliminating the need for more complex and costly treatment or eventual tooth loss. However, the evidence is of low scientific quality and mainly gleaned from studies in primary teeth.

Method: This is a pragmatic, multi-centre, two-arm patient randomised controlled clinical trial including an internal pilot set in primary dental care in Scotland and England. Dental health professionals will recruit 623 participants over 12-years of age with deep carious lesions in their permanent posterior teeth. Participants will have a single tooth randomised to either the selective caries removal or complete caries removal treatment arm. Baseline measures and outcome data (during the 3-year follow-up period) will be assessed through clinical examination, patient questionnaires and NHS databases. A mixed-method process evaluation will complement the clinical and economic outcome evaluation and examine implementation, mechanisms of impact and context. The primary outcome at three years is sustained tooth vitality. The primary economic outcome is net benefit modelled over a lifetime horizon. Clinical secondary outcomes include pulp exposure, progession of caries, restoration failure; as well as patient-centred and economic outcomes.

Discussion: SCRiPT will provide evidence for the most clinically effective and cost-beneficial approach to managing deep carious lesions in permanent posterior teeth in primary care. This will support general dental practitioners, patients and policy makers in decision making. Trial Registration Trial registry: ISRCTN.

Trial Registration Number: ISRCTN76503940. Date of Registration: 30.10.2019. URL of trial registry record: https://www.isrctn.com/ISRCTN76503940?q=ISRCTN76503940%20&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12903-021-01637-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267238PMC
July 2021

The LINC complex is required for endothelial cell adhesion and adaptation to shear stress and cyclic stretch.

Mol Biol Cell 2021 Jun 30:mbcE20110698. Epub 2021 Jun 30.

Department of Biomedical Engineering, Virginia Commonwealth University, Richmond Virginia.

The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex is a structure consisting of nesprin, SUN, and lamin proteins. A principal function of the LINC complex is anchoring the nucleus to the actin, microtubule, and intermediate filament cytoskeletons. The LINC complex is present in nearly all cell types, including endothelial cells. Endothelial cells line the inner most surfaces of blood vessels, and are critical for blood vessel barrier function. In addition, endothelial cells have specialized functions, including adaptation to the mechanical forces of blood flow. Previous studies have shown that depletion of individual nesprin isoforms results in impaired endothelial cell function. To further investigate the role of the LINC complex in endothelial cells we utilized dominant negative KASH (DN-KASH), a dominant negative protein which displaces endogenous nesprins from the nuclear envelope and disrupts nuclear-cytoskeletal connections. Endothelial cells expressing DN-KASH had altered cell-cell adhesion and barrier function, as well as altered cell-matrix adhesion and focal adhesion dynamics. In addition, cells expressing DN-KASH failed to properly adapt to shear stress or cyclic stretch. DN-KASH expressing cells exhibited impaired collective cell migration in wound healing and angiogenesis assays. Our results demonstrate the importance of an intact LINC complex in endothelial cell function and homeostasis. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1091/mbc.E20-11-0698DOI Listing
June 2021

Desmoglein-2 harnesses a PDZ-GEF2/Rap1 signaling axis to control cell spreading and focal adhesions independent of cell-cell adhesion.

Sci Rep 2021 Jun 24;11(1):13295. Epub 2021 Jun 24.

Department of Biology, Furman University, 3300 Poinsett Highway, Greenville, SC, 29613, USA.

Desmosomes have a central role in mediating extracellular adhesion between cells, but they also coordinate other biological processes such as proliferation, differentiation, apoptosis and migration. In particular, several lines of evidence have implicated desmosomal proteins in regulating the actin cytoskeleton and attachment to the extracellular matrix, indicating signaling crosstalk between cell-cell junctions and cell-matrix adhesions. In our study, we found that cells lacking the desmosomal cadherin Desmoglein-2 (Dsg2) displayed a significant increase in spreading area on both fibronectin and collagen, compared to control A431 cells. Intriguingly, this effect was observed in single spreading cells, indicating that Dsg2 can exert its effects on cell spreading independent of cell-cell adhesion. We hypothesized that Dsg2 may mediate cell-matrix adhesion via control of Rap1 GTPase, which is well known as a central regulator of cell spreading dynamics. We show that Rap1 activity is elevated in Dsg2 knockout cells, and that Dsg2 harnesses Rap1 and downstream TGFβ signaling to influence both cell spreading and focal adhesion protein phosphorylation. Further analysis implicated the Rap GEF PDZ-GEF2 in mediating Dsg2-dependent cell spreading. These data have identified a novel role for Dsg2 in controlling cell spreading, providing insight into the mechanisms via which cadherins exert non-canonical junction-independent effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-92675-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225821PMC
June 2021

The influence of pain, kinesiophobia and psychological comorbidities on the accuracy of rating of perceived exertion in UK military spinal rehabilitation.

BMJ Mil Health 2021 Jun 15. Epub 2021 Jun 15.

The Faculty of Sport, Allied Health and Performance Science, St Mary's University Twickenham, Twickenham, London, UK.

Introduction: Chronic low back pain (CLBP) is a leading cause of disability in the UK Military. Pain and psychological comorbidities have been reported to influence the rating of perceived exertion (RPE). Exercise rehabilitation can be monitored using RPE; however, the accuracy of RPE in inpatient CLBP rehabilitation is unknown.

Methods: A prospective cohort correlation study of 40 UK Military inpatients with CLBP was completed. Disability (ODI), kinesiophobia (TSK), anxiety (GAD-7) and depression (PHQ-9) were subjectively reported at the beginning and end of a 3 week intervention. Pain (VAS) and HR were recorded in the first aerobic exercise (AE) session (T1) and the final aerobic exercise session (T2). RPE was reported for each AE session.

Results: At T1, a positive correlation was observed between RPE accuracy (-7.2±20.9), and pre-exercise pain (2.7 mm ±1.6 mm) (p>0.001) and ODI (31.0±16.9) (p>0.05), and a negative relationship between RPE accuracy and average HR (135 bpm ±22 bpm) (p>0.001) was observed. At T2, there was no significant correlation between RPE accuracy (-4.4±22.6) and pre-exercise pain (2.8 mm ±1.6 mm) or ODI (34.0±16.5) (p>0.05). The strong negative relationship between RPE accuracy and average HR (137 bpm ±20 bpm) remained at T2. Improved RPE accuracy over the 3-week rehabilitation programme was correlated to the change in average HR (=-0.314, p<0.05).

Conclusions: Comorbidities may negatively affect RPE accuracy in CLBP, but the magnitude of the influence reduces over intensive rehabilitation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjmilitary-2021-001797DOI Listing
June 2021