Publications by authors named "James Brown"

999 Publications

Prospective Case-Control Study of Cardiovascular Abnormalities 6 Months Following Mild COVID-19 in Healthcare Workers.

JACC Cardiovasc Imaging 2021 May 5. Epub 2021 May 5.

Barts Heart Centre, Barts Health NHS Trust, West Smithfield, London, United Kingdom; Institute of Cardiovascular Science, University College London, London, United Kingdom. Electronic address:

Objectives: The purpose of this study was to detect cardiovascular changes after mild severe acute respiratory syndrome coronavirus 2 infection.

Background: Concern exists that mild coronavirus disease 2019 may cause myocardial and vascular disease.

Methods: Participants were recruited from COVIDsortium, a 3-hospital prospective study of 731 health care workers who underwent first-wave weekly symptom, polymerase chain reaction, and serology assessment over 4 months, with seroconversion in 21.5% (n = 157). At 6 months post-infection, 74 seropositive and 75 age-, sex-, and ethnicity-matched seronegative control subjects were recruited for cardiovascular phenotyping (comprehensive phantom-calibrated cardiovascular magnetic resonance and blood biomarkers). Analysis was blinded, using objective artificial intelligence analytics where available.

Results: A total of 149 subjects (mean age 37 years, range 18 to 63 years, 58% women) were recruited. Seropositive infections had been mild with case definition, noncase definition, and asymptomatic disease in 45 (61%), 18 (24%), and 11 (15%), respectively, with 1 person hospitalized (for 2 days). Between seropositive and seronegative groups, there were no differences in cardiac structure (left ventricular volumes, mass, atrial area), function (ejection fraction, global longitudinal shortening, aortic distensibility), tissue characterization (T, T, extracellular volume fraction mapping, late gadolinium enhancement) or biomarkers (troponin, N-terminal pro-B-type natriuretic peptide). With abnormal defined by the 75 seronegatives (2 SDs from mean, e.g., ejection fraction <54%, septal T >1,072 ms, septal T >52.4 ms), individuals had abnormalities including reduced ejection fraction (n = 2, minimum 50%), T elevation (n = 6), T elevation (n = 9), late gadolinium enhancement (n = 13, median 1%, max 5% of myocardium), biomarker elevation (borderline troponin elevation in 4; all N-terminal pro-B-type natriuretic peptide normal). These were distributed equally between seropositive and seronegative individuals.

Conclusions: Cardiovascular abnormalities are no more common in seropositive versus seronegative otherwise healthy, workforce representative individuals 6 months post-mild severe acute respiratory syndrome coronavirus 2 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmg.2021.04.011DOI Listing
May 2021

Comparison of electromagnetic guided imagery to standard confirmatory methods for ascertaining nasogastric tube placement in children.

J Spec Pediatr Nurs 2021 May 11:e12338. Epub 2021 May 11.

Children's Hospital Colorado, Pediatric Intensive Care Unit, Aurora, Colorado, USA.

Purpose: Evaluate the accuracy of an electromagnetic device (EMD) guided nasogastric tube (NGT) placement compared with standard confirmation methods. A secondary aim was to determine if EMD guided NGT placement would avert potential pulmonary misplacements of the tube.

Design And Methods: Pediatric Intensive Care Unit (PICU) patients were enrolled if they had an NGT order during the study period of April 2014 through December 2016. Patients were included if they were one through 18 years of age. An EMD trained nurse inserted the NGT using EMD guidance. An insertion questionnaire, confirming if the nurse determined the NGT to be gastric per EMD, was completed immediately after NGT placement and before confirmation via either pH testing or radiographic imaging.

Results: Forty-five patients were enrolled in the study. Nurses reported, based on EMD, that 86.7% (n = 39) of placements were gastric. Overall agreement between EMD guided tube placement and pH testing was 58% (n = 26). The marginal distribution was significantly different between the two methods (p = .0029). When compared to radiographic confirmation, sensitivity of the pH method was 32% (95% confidence interval [CI]: 17%-51%) compared with 85% (95% CI 69%-95%) for the EMD method.

Conclusions: EMD guidance was superior to pH testing when compared with radiographic confirmation of nasogastric tube placement in children.

Practice Implications: EMD guided NGT placement is a potentially viable method for confirming nasogastric tube placement in children when done by appropriately trained clinicians. More research on EMD guided NGT placement in children is needed before any practice recommendation can be made.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jspn.12338DOI Listing
May 2021

Commentary: Delaying the inevitable? Interventions for medically managed, uncomplicated type B aortic dissection.

J Thorac Cardiovasc Surg 2021 Apr 21. Epub 2021 Apr 21.

Division of Cardiac Surgery, Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa; Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtcvs.2021.04.044DOI Listing
April 2021

Standing trans-nasal endoscopic guided CO laser fenestration of the palatine bone to access the sphenopalatine sinus in a horse.

Vet Surg 2021 Apr 29. Epub 2021 Apr 29.

Department of Large Animal Clinical Sciences, Marion duPont Scott Equine Medical Center, Virginia-Maryland Regional College of Veterinary Medicine, Leesburg, Virginia, USA.

Objective: To describe a novel standing trans-nasal endoscopic guided CO laser fenestration approach to access the sphenopalatine sinus (SPS) in the horse.

Study Design: Case report.

Animals: Cadaver study and client-owned 20-year-old Warmblood gelding.

Methods: The rostral palatine bone within the nasopharynx was investigated as a possible site for fenestration to access the SPS in cadavers. The ability to fenestrate the SPS was tested in cadavers using a flexible endoscope and CO laser fiber inserted via biopsy channel. The fenestration procedure was then performed in a clinical case presented for unilateral epistaxis where a soft tissue attenuating mass in the right SPS was identified with standing computed tomography (CT).

Results: The cadaver study demonstrated the appropriate site within the nasopharynx midway between the vomer and dorsal conchal wall. The CO laser successfully ablated the mucosa and palatine bone to enable endoscopic access to the palatine portion of the SPS. The endoscopic procedure was performed as a two-step process via standing sedation due to mucosal bleeding obscuring visualization. Access to the SPS through fenestration allowed biopsy under direct endoscopic visualization with long-handled bronchoesophageal forceps inserted via the ipsilateral middle meatus. The mass within SPS was determined to be an undifferentiated carcinoma. Further treatment was declined and the horse euthanized 6 months following the procedure due to acute onset of neurologic symptoms.

Conclusion: Endoscopically guided fenestration of the rostral palatine bone within the nasopharynx using CO laser in the standing horse provided good access and visualization of the palatine portion of the SPS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/vsu.13647DOI Listing
April 2021

Universal rules of life: metabolic rates, biological times and the equal fitness paradigm.

Ecol Lett 2021 Apr 21. Epub 2021 Apr 21.

Department of Biology, University of New Mexico, Albuquerque, NM, 87131, USA.

Here we review and extend the equal fitness paradigm (EFP) as an important step in developing and testing a synthetic theory of ecology and evolution based on energy and metabolism. The EFP states that all organisms are equally fit at steady state, because they allocate the same quantity of energy, ~ 22.4 kJ/g/generation to the production of offspring. On the one hand, the EFP may seem tautological, because equal fitness is necessary for the origin and persistence of biodiversity. On the other hand, the EFP reflects universal laws of life: how biological metabolism - the uptake, transformation and allocation of energy - links ecological and evolutionary patterns and processes across levels of organisation from: (1) structure and function of individual organisms, (2) life history and dynamics of populations, and (3) interactions and coevolution of species in ecosystems. The physics and biology of metabolism have facilitated the evolution of millions of species with idiosyncratic anatomy, physiology, behaviour and ecology but also with many shared traits and tradeoffs that reflect the single origin and universal rules of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ele.13715DOI Listing
April 2021

Cardiac Magnetic Resonance-Derived Extracellular Volume Mapping for the Quantification of Hepatic and Splenic Amyloid.

Circ Cardiovasc Imaging 2021 Apr 20:CIRCIMAGING121012506. Epub 2021 Apr 20.

Division of Medicine, National Amyloidosis Centre, University College London, London, United Kingdom. (L.C., M.B., R.M., S.L., A.M.-N., D.F.H., T.K., R.K.P., Y.R., T.R., O.C.C., J.B., M.S., S.G., T.L., H.L., A.W., S.S., S.M., C.W., D.S.K., J.G., P.N.H., M.F.).

Background: Systemic amyloidosis is characterized by amyloid deposition that can involve virtually any organ. Splenic and hepatic amyloidosis occurs in certain types, in some patients but not others, and may influence prognosis and treatment. SAP (serum amyloid P component) scintigraphy is uniquely able to identify and quantify amyloid in the liver and spleen, thus informing clinical management, but it is only available in 2 centers globally. The aims of this study were to examine the potential for extracellular volume (ECV) mapping performed during routine cardiac magnetic resonance to: (1) detect amyloid in the liver and spleen and (2) estimate amyloid load in these sites using SAP scintigraphy as the reference standard.

Methods: Five hundred thirty-three patients referred to the National Amyloidosis Centre, London, between 2015 and 2017 with suspected systemic amyloidosis who underwent SAP scintigraphy and cardiac magnetic resonance with T1 mapping were studied.

Results: The diagnostic performance of ECV to detect splenic and hepatic amyloidosis was high for both organs (liver: area under the curve, -0.917 [95% CI, 0.880-0.954]; liver ECV cutoff, 0.395; sensitivity, 90.7%; specificity, 77.7%; <0.001; spleen: area under the curve, -0.944 [95% CI, 0.925-0.964]; spleen ECV cutoff, 0.385; sensitivity, 93.6%; specificity, 87.5%; <0.001). There was good correlation between liver and spleen ECV and amyloid load assessed by SAP scintigraphy (r=0.504, <0.001; r=0.693, <0.001, respectively). There was high interobserver agreement for both the liver and spleen (ECV liver intraclass correlation coefficient, 0.991 [95% CI, 0.984-0.995]; <0.001; ECV spleen intraclass correlation coefficient, 0.995 [95% CI, 0.991-0.997]; <0.001) with little bias across a wide range of ECV values.

Conclusions: Our study demonstrates that ECV measurements obtained during routine cardiac magnetic resonance scans in patients with suspected amyloidosis can identify and measure the magnitude of amyloid infiltration in the liver and spleen, providing important clues to amyloid type and offering a noninvasive measure of visceral amyloid burden that can help guide and track treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCIMAGING.121.012506DOI Listing
April 2021

Trehalose and α-glucan mediate distinct abiotic stress responses in Pseudomonas aeruginosa.

PLoS Genet 2021 Apr 19;17(4):e1009524. Epub 2021 Apr 19.

Department of Molecular Microbiology, John Innes Centre, Norwich, United Kingdom.

An important prelude to bacterial infection is the ability of a pathogen to survive independently of the host and to withstand environmental stress. The compatible solute trehalose has previously been connected with diverse abiotic stress tolerances, particularly osmotic shock. In this study, we combine molecular biology and biochemistry to dissect the trehalose metabolic network in the opportunistic human pathogen Pseudomonas aeruginosa PAO1 and define its role in abiotic stress protection. We show that trehalose metabolism in PAO1 is integrated with the biosynthesis of branched α-glucan (glycogen), with mutants in either biosynthetic pathway significantly compromised for survival on abiotic surfaces. While both trehalose and α-glucan are important for abiotic stress tolerance, we show they counter distinct stresses. Trehalose is important for the PAO1 osmotic stress response, with trehalose synthesis mutants displaying severely compromised growth in elevated salt conditions. However, trehalose does not contribute directly to the PAO1 desiccation response. Rather, desiccation tolerance is mediated directly by GlgE-derived α-glucan, with deletion of the glgE synthase gene compromising PAO1 survival in low humidity but having little effect on osmotic sensitivity. Desiccation tolerance is independent of trehalose concentration, marking a clear distinction between the roles of these two molecules in mediating responses to abiotic stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1009524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084333PMC
April 2021

COVID-19 "baby boom".

Med J Aust 2021 05 15;214(8):386-386.e1. Epub 2021 Apr 15.

University of Sydney, Sydney, NSW.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5694/mja2.51010DOI Listing
May 2021

A 4-year study of hamstring injury outcomes in elite track and field using the British Athletics rehabilitation approach.

Br J Sports Med 2021 Apr 14. Epub 2021 Apr 14.

Medical Department, British Cycling, Manchester, UK.

Objectives: The British Athletics Muscle Injury Classification (BAMIC) correlates with return to play in muscle injury. The aim of this study was to examine hamstring injury diagnoses and outcomes within elite track and field athletes following implementation of the British Athletics hamstring rehabilitation approach.

Methods: All hamstring injuries sustained by elite track and field athletes on the British Athletics World Class Programme between December 2015 and November 2019 that underwent an MRI and had British Athletics medical team prescribed rehabilitation were included. Athlete demographics and specific injury details, including mechanism of injury, self-reported gait phase, MRI characteristics and time to return to full training (TRFT) were contemporaneously recorded.

Results: 70 hamstring injuries in 46 athletes (24 women and 22 men, 24.6±3.7 years) were included. BAMIC grade and the intratendon c classification correlated with increased TRFT. Mean TRFT was 18.6 days for the entire cohort. Mean TRFT for intratendon classifications was 34±7 days (2c) and 48±17 days (3c). The overall reinjury rate was 2.9% and no reinjuries were sustained in the intratendon classifications. MRI variables of length and cross-sectional (CSA) area of muscle oedema, CSA of tendon injury and loss of tendon tension were associated with TRFT. Longitudinal length of tendon injury, in the intratendon classes, was not associated with TRFT.

Conclusion: The application of BAMIC to inform hamstring rehabilitation in British Athletics results in low reinjury rates and favourable TRFT following hamstring injury. The key MRI variables associated with longer recovery are length and CSA of muscle oedema, CSA of tendon injury and loss of tendon tension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bjsports-2020-103791DOI Listing
April 2021

Radiomics Repeatability Pitfalls in a Scan-Rescan MRI Study of Glioblastoma.

Radiol Artif Intell 2021 Jan 16;3(1):e190199. Epub 2020 Dec 16.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (K.V.H., J.B.P., A.L.B., K.C., P.S., J.M.B., M.C.P., B.R.R., J.K.C.), and Stephen E. and Catherine Pappas Center for Neuro-Oncology (T.T.B., E.R.G.), Massachusetts General Hospital, 149 13th St, Charlestown, MA 02129; and Harvard-MIT Division of Health Sciences and Technology, Cambridge, Mass (K.V.H., J.B.P., K.C.).

Purpose: To determine the influence of preprocessing on the repeatability and redundancy of radiomics features extracted using a popular open-source radiomics software package in a scan-rescan glioblastoma MRI study.

Materials And Methods: In this study, a secondary analysis of T2-weighted fluid-attenuated inversion recovery (FLAIR) and T1-weighted postcontrast images from 48 patients (mean age, 56 years [range, 22-77 years]) diagnosed with glioblastoma were included from two prospective studies (ClinicalTrials.gov NCT00662506 [2009-2011] and NCT00756106 [2008-2011]). All patients underwent two baseline scans 2-6 days apart using identical imaging protocols on 3-T MRI systems. No treatment occurred between scan and rescan, and tumors were essentially unchanged visually. Radiomic features were extracted by using PyRadiomics https://pyradiomics.readthedocs.io/ under varying conditions, including normalization strategies and intensity quantization. Subsequently, intraclass correlation coefficients were determined between feature values of the scan and rescan.

Results: Shape features showed a higher repeatability than intensity (adjusted < .001) and texture features (adjusted < .001) for both T2-weighted FLAIR and T1-weighted postcontrast images. Normalization improved the overlap between the region of interest intensity histograms of scan and rescan (adjusted < .001 for both T2-weighted FLAIR and T1-weighted postcontrast images), except in scans where brain extraction fails. As such, normalization significantly improves the repeatability of intensity features from T2-weighted FLAIR scans (adjusted = .003 [ score normalization] and adjusted = .002 [histogram matching]). The use of a relative intensity binning strategy as opposed to default absolute intensity binning reduces correlation between gray-level co-occurrence matrix features after normalization.

Conclusion: Both normalization and intensity quantization have an effect on the level of repeatability and redundancy of features, emphasizing the importance of both accurate reporting of methodology in radiomics articles and understanding the limitations of choices made in pipeline design. © RSNA, 2020See also the commentary by Tiwari and Verma in this issue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/ryai.2020190199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845781PMC
January 2021

Shorter fixation durations for up-directed saccades during saccadic exploration: A meta-analysis.

J Eye Mov Res 2020 Mar 1;12(8). Epub 2020 Mar 1.

University of Georgia, Athens, USA.

Utilizing 23 datasets, we report a meta-analysis of an asymmetry in presaccadic fixation durations for saccades directed above and below eye fixation during saccadic exploration. For inclusion in the meta-analysis, saccadic exploration of complex visual displays had to have been made without gaze-contingent manipulations. Effect sizes for the asymmetry were quantified as Hedge's g. Pooled effect sizes indicated significant asymmetries such that during saccadic exploration in a variety of tasks, presaccadic fixation durations for saccades directed into the upper visual field were reliably shorter than presaccadic fixation durations for saccades into the lower visual field. It is contended that the asymmetry is robust and important for efforts aimed at modelling when a saccade is initiated as a function of ensuing saccade direction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.16910/jemr.12.8.5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881898PMC
March 2020

10-Year Trends in Aortic Dissection: Mortality and Weekend Effect within the US Nationwide Emergency Department Sample (NEDS).

Heart Surg Forum 2021 03 31;24(2):E336-E344. Epub 2021 Mar 31.

Division of Cardiac Surgery, Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

Background: This study examined changes in aortic dissection (AD) mortality from 2006 to 2017 and assessed the impact of weekday versus weekend presentation upon mortality.

Methods: This observational study analyzed all records in the Nationwide Emergency Department Sample (NEDS) database. NEDS aggregates discharge data from 984 hospitals in 36 states and the District of Columbia in the United States of America. All patients with thoracic and thoracoabdominal AD recorded as their principal diagnosis were identified via ICD codes.

Results: Patient characteristics (weekday|weekend) count: 26,759|9,640, P = 0.016; age (years): 65.2 ± 15.8|64.7 ± 16.2, P = 0.016; women: 11,318 (42.3%)|4,086 (42.4), P = 0.883; Charlson comorbidity index: 2.3 ± 1.7|2.3 ± 1.6, P = 0.025. There were 36,399 ED visits with diagnosed AD. Annual AD diagnoses increased by 70% from 2006 to 2017. From 2012-2017, patients had lower in-hospital mortality (9.9% versus 11.9%, P < 0.001) compared with 2006-2011. Patients reporting during the weekend had higher in-hospital mortality (11.8% versus 10.4%, P < 0.001) compared with weekdays. On multivariable analysis, year of presentation remained independently associated with in-hospital mortality, with 2012-2017 being associated with reduced mortality (odds ratio (OR) 0.90, 95% CI: 0.82, 0.99, P = 0.031), as compared with 2006-2011. Weekend presentation remained independently associated with worse in-hospital mortality (OR 1.17, 95% CI: 1.05, 1.29, P = 0.003) compared with weekday presentation.

Conclusion: Although AD mortality is decreasing, the patients presenting on the weekend were 13% more likely to die in the hospital compared with patients presenting during the week.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1532/hsf.3681DOI Listing
March 2021

Influence of soil heterogeneity on soybean plant development and crop yield evaluated using time-series of UAV and ground-based geophysical imagery.

Sci Rep 2021 Mar 29;11(1):7046. Epub 2021 Mar 29.

Climate and Ecosystem Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA, 94720-8126, USA.

Understanding the interactions among agricultural processes, soil, and plants is necessary for optimizing crop yield and productivity. This study focuses on developing effective monitoring and analysis methodologies that estimate key soil and plant properties. These methodologies include data acquisition and processing approaches that use unmanned aerial vehicles (UAVs) and surface geophysical techniques. In particular, we applied these approaches to a soybean farm in Arkansas to characterize the soil-plant coupled spatial and temporal heterogeneity, as well as to identify key environmental factors that influence plant growth and yield. UAV-based multitemporal acquisition of high-resolution RGB (red-green-blue) imagery and direct measurements were used to monitor plant height and photosynthetic activity. We present an algorithm that efficiently exploits the high-resolution UAV images to estimate plant spatial abundance and plant vigor throughout the growing season. Such plant characterization is extremely important for the identification of anomalous areas, providing easily interpretable information that can be used to guide near-real-time farming decisions. Additionally, high-resolution multitemporal surface geophysical measurements of apparent soil electrical conductivity were used to estimate the spatial heterogeneity of soil texture. By integrating the multiscale multitype soil and plant datasets, we identified the spatiotemporal co-variance between soil properties and plant development and yield. Our novel approach for early season monitoring of plant spatial abundance identified areas of low productivity controlled by soil clay content, while temporal analysis of geophysical data showed the impact of soil moisture and irrigation practice (controlled by topography) on plant dynamics. Our study demonstrates the effective coupling of UAV data products with geophysical data to extract critical information for farm management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-86480-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007594PMC
March 2021

Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain.

Sci Rep 2021 Mar 23;11(1):6078. Epub 2021 Mar 23.

University of Illinois at Chicago, Chicago, IL, 60612, USA.

As a means to understand human neuropsychiatric disorders from human brain samples, we compared the transcription patterns and histological features of postmortem brain to fresh human neocortex isolated immediately following surgical removal. Compared to a number of neuropsychiatric disease-associated postmortem transcriptomes, the fresh human brain transcriptome had an entirely unique transcriptional pattern. To understand this difference, we measured genome-wide transcription as a function of time after fresh tissue removal to mimic the postmortem interval. Within a few hours, a selective reduction in the number of neuronal activity-dependent transcripts occurred with relative preservation of housekeeping genes commonly used as a reference for RNA normalization. Gene clustering indicated a rapid reduction in neuronal gene expression with a reciprocal time-dependent increase in astroglial and microglial gene expression that continued to increase for at least 24 h after tissue resection. Predicted transcriptional changes were confirmed histologically on the same tissue demonstrating that while neurons were degenerating, glial cells underwent an outgrowth of their processes. The rapid loss of neuronal genes and reciprocal expression of glial genes highlights highly dynamic transcriptional and cellular changes that occur during the postmortem interval. Understanding these time-dependent changes in gene expression in post mortem brain samples is critical for the interpretation of research studies on human brain disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-85801-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988150PMC
March 2021

Persistent T Cell Repertoire Perturbation and T Cell Activation in HIV After Long Term Treatment.

Front Immunol 2021 25;12:634489. Epub 2021 Feb 25.

Division of Infection and Immunity, University College London, London, United Kingdom.

Objective: In people living with HIV (PLHIV), we sought to test the hypothesis that long term anti-retroviral therapy restores the normal T cell repertoire, and investigate the functional relationship of residual repertoire abnormalities to persistent immune system dysregulation.

Methods: We conducted a case-control study in PLHIV and HIV-negative volunteers, of circulating T cell receptor repertoires and whole blood transcriptomes by RNA sequencing, complemented by metadata from routinely collected health care records.

Results: T cell receptor sequencing revealed persistent abnormalities in the clonal T cell repertoire of PLHIV, characterized by reduced repertoire diversity and oligoclonal T cell expansion correlated with elevated CD8 T cell counts. We found no evidence that these expansions were driven by cytomegalovirus or another common antigen. Increased frequency of long CDR3 sequences and reduced frequency of public sequences among the expanded clones implicated abnormal thymic selection as a contributing factor. These abnormalities in the repertoire correlated with systems level evidence of persistent T cell activation in genome-wide blood transcriptomes.

Conclusions: The diversity of T cell receptor repertoires in PLHIV on long term anti-retroviral therapy remains significantly depleted, and skewed by idiosyncratic clones, partly attributable to altered thymic output and associated with T cell mediated chronic immune activation. Further investigation of thymic function and the antigenic drivers of T cell clonal selection in PLHIV are critical to efforts to fully re-establish normal immune function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.634489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959740PMC
February 2021

25-Hydroxycholesterol 3-sulfate is an endogenous ligand of DNA methyltransferases in hepatocytes.

J Lipid Res 2021 Mar 8;62:100063. Epub 2021 Mar 8.

Department of Internal Medicine, Virginia Commonwealth University/McGuire VA Medical Centre, Richmond, VA, USA. Electronic address:

The oxysterol sulfate, 25-hydroxycholesterol 3-sulfate (25HC3S), has been shown to play an important role in lipid metabolism, inflammatory response, and cell survival. However, the mechanism(s) of its function in global regulation is unknown. The current study investigates the molecular mechanism by which 25HC3S functions as an endogenous epigenetic regulator. To study the effects of oxysterols/sterol sulfates on epigenetic modulators, 12 recombinant epigenetic enzymes were used to determine whether 25HC3S acts as their endogenous ligand. The enzyme kinetic study demonstrated that 25HC3S specifically inhibited DNA methyltransferases (DNMTs), DNMT1, DNMT3a, and DNMT3b with IC of 4.04, 3.03, and 9.05 × 10 M, respectively. In human hepatocytes, high glucose induces lipid accumulation by increasing promoter CpG methylation of key genes involved in development of nonalcoholic fatty liver diseases. Using this model, whole genome bisulfate sequencing analysis demonstrated that 25HC3S converts the CpG to CpG in the promoter regions of 1,074 genes. In addition, we observed increased expression of the demethylated genes, which are involved in the master signaling pathways, including MAPK-ERK, calcium-AMP-activated protein kinase, and type II diabetes mellitus pathways. mRNA array analysis showed that the upregulated genes encoded for key elements of cell survival; conversely, downregulated genes encoded for key enzymes that decrease lipid biosynthesis. Taken together, our results indicate that the expression of these key elements and enzymes are regulated by the demethylated signaling pathways. We summarized that 25HC3S DNA demethylation of CpG in promoter regions is a potent regulatory mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jlr.2021.100063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058565PMC
March 2021

Unpaid Professional Work at Home and Work-Life Interference among Employees with Care Responsibilities.

J Psychol 2021 11;155(3):356-374. Epub 2021 Mar 11.

University of Southern Queensland.

Employees with caregiving responsibilities often experience work-life interference (WLI), particularly when caring for either disabled persons and/or children. This study examines sample of 288 working Australians from the AWALI national survey data, who care for at least one family member or friend with long-term physical or mental illness, disability, or aging-related problems. We investigated the role of unpaid work at home in predicting WLI, based on a model that included indirect association inferred causes for working unpaid hours at home and a conditional direct relationship based on number of children. The findings supported our prediction that unpaid work at home is positively associated with WLI but its effect is moderated by number of children. There was a conditional direct effect where employees with care responsibilities experienced a stronger relationship between unpaid hours and WLI when having more children. Further, when the perceived reason for unpaid work was excessively demanding work, the relationship with WLI was stronger. Implications for workers with multiple caregiving responsibilities are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00223980.2021.1884825DOI Listing
April 2021

Commentary: Thoracic Aortic Aneurysms: Growing Awareness of a Notable Population Health Challenge.

Semin Thorac Cardiovasc Surg 2021 Mar 7. Epub 2021 Mar 7.

Division of Cardiac Surgery, Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania; Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.semtcvs.2021.02.010DOI Listing
March 2021

Expanding the drug discovery space with predicted metabolite-target interactions.

Commun Biol 2021 Mar 5;4(1):288. Epub 2021 Mar 5.

GlaxoSmithKline Pharma R&D, 1250 S. Collegeville Rd, Collegeville, PA, 19426-0989, USA.

Metabolites produced in the human gut are known modulators of host immunity. However, large-scale identification of metabolite-host receptor interactions remains a daunting challenge. Here, we employed computational approaches to identify 983 potential metabolite-target interactions using the Inflammatory Bowel Disease (IBD) cohort dataset of the Human Microbiome Project 2 (HMP2). Using a consensus of multiple machine learning methods, we ranked metabolites based on importance to IBD, followed by virtual ligand-based screening to identify possible human targets and adding evidence from compound assay, differential gene expression, pathway enrichment, and genome-wide association studies. We confirmed known metabolite-target pairs such as nicotinic acid-GPR109a or linoleoyl ethanolamide-GPR119 and inferred interactions of interest including oleanolic acid-GABRG2 and alpha-CEHC-THRB. Eleven metabolites were tested for bioactivity in vitro using human primary cell-types. By expanding the universe of possible microbial metabolite-host protein interactions, we provide multiple drug targets for potential immune-therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42003-021-01822-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935942PMC
March 2021

The impact of pulmonary artery catheter use in cardiac surgery.

J Thorac Cardiovasc Surg 2021 Feb 2. Epub 2021 Feb 2.

Division of Cardiac Surgery, Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa; Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa. Electronic address:

Objective: Pulmonary artery catheterization provides continuous monitoring of hemodynamic parameters that may aid in the perioperative management of patients undergoing cardiac surgery. However, prior data suggest that pulmonary artery catheterization has limited benefit in intensive care and surgical settings. Thus, this study sought to determine the impact of pulmonary artery catheter insertion on short-term postoperative outcomes in a large, contemporaneous cohort of patients undergoing open cardiac surgery compared with standard central venous pressure monitoring.

Methods: This was an observational study of open cardiac surgeries from 2010 to 2018. Patients with pulmonary artery catheter insertion were identified and matched against patients without pulmonary artery catheter insertion via 1:1 nearest neighbor propensity matching. Multivariable analysis was performed to assess the impact of pulmonary artery catheterization on operative mortality in the overall cohort, as well as recent heart failure, mitral valve disease, and tricuspid insufficiency subgroups.

Results: Of the 11,820 patients undergoing (Society of Thoracic Surgeons indexed) coronary or valvular surgery, 4605 (39.0%) had pulmonary artery catheter insertion. Propensity score matching yielded 3519 evenly balanced pairs. Compared with central venous pressure monitoring, pulmonary artery catheter use was not associated with improved operative mortality in the overall cohort or in the recent heart failure, mitral valve disease, or tricuspid insufficiency subgroups. Intensive care unit length of stay was longer (P < .001), and there were more packed red blood cell transfusions in the pulmonary artery catheterization group (P < .001); however, postoperative outcomes were otherwise similar, including stroke, sepsis, and new renal failure (P > .05).

Conclusions: These findings suggest that pulmonary artery catheterization may have limited benefit in cardiac surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtcvs.2021.01.086DOI Listing
February 2021

Applications of Artificial Intelligence for Retinopathy of Prematurity Screening.

Pediatrics 2021 Mar;147(3)

Athinoula A. Martinos Center for Biomedical Imaging and Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts.

Objectives: Childhood blindness from retinopathy of prematurity (ROP) is increasing as a result of improvements in neonatal care worldwide. We evaluate the effectiveness of artificial intelligence (AI)-based screening in an Indian ROP telemedicine program and whether differences in ROP severity between neonatal care units (NCUs) identified by using AI are related to differences in oxygen-titrating capability.

Methods: External validation study of an existing AI-based quantitative severity scale for ROP on a data set of images from the Retinopathy of Prematurity Eradication Save Our Sight ROP telemedicine program in India. All images were assigned an ROP severity score (1-9) by using the Imaging and Informatics in Retinopathy of Prematurity Deep Learning system. We calculated the area under the receiver operating characteristic curve and sensitivity and specificity for treatment-requiring retinopathy of prematurity. Using multivariable linear regression, we evaluated the mean and median ROP severity in each NCU as a function of mean birth weight, gestational age, and the presence of oxygen blenders and pulse oxygenation monitors.

Results: The area under the receiver operating characteristic curve for detection of treatment-requiring retinopathy of prematurity was 0.98, with 100% sensitivity and 78% specificity. We found higher median (interquartile range) ROP severity in NCUs without oxygen blenders and pulse oxygenation monitors, most apparent in bigger infants (>1500 g and 31 weeks' gestation: 2.7 [2.5-3.0] vs 3.1 [2.4-3.8]; = .007, with adjustment for birth weight and gestational age).

Conclusions: Integration of AI into ROP screening programs may lead to improved access to care for secondary prevention of ROP and may facilitate assessment of disease epidemiology and NCU resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2020-016618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924138PMC
March 2021

Commentary: Reoperative cardiac surgery: The importance of surgeon judgment.

J Thorac Cardiovasc Surg 2021 Jan 20. Epub 2021 Jan 20.

Division of Cardiac Surgery, Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa; Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtcvs.2021.01.017DOI Listing
January 2021

Impact of Thoracic Radiation on Patients Undergoing Cardiac Surgery.

Semin Thorac Cardiovasc Surg 2021 Feb 17. Epub 2021 Feb 17.

Division of Cardiac Surgery, Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania; Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address:

Prior thoracic radiation has been associated with worse outcomes after cardiac surgery. This study sought to report long-term outcomes in patients undergoing surgery for radiation-associated heart disease. This was an observational study of open cardiac surgeries from 2011 and 2018. Patients with a history of malignancy that required thoracic radiation were identified, and this cohort was matched against a non-irradiated comparison group via Mahalanobis distance matching. Kaplan-Meier survival estimation and multivariable Cox regression analysis was performed to assess the long-term impact of thoracic radiation in patients undergoing cardiac surgery. Of the 15,284 patients receiving cardiac surgery in this time-frame, 269 were identified with a history of thoracic radiation for prior malignancy. Patients with prior radiation had increased 1-year and 5-year mortality (P < 0.001), despite no difference for 30-day mortality (P = 0.719), compared to non-irradiated patients. Mahalanobis distance matching yielded 269 equitably matched pairs. On multivariable analysis, patients with prior radiation demonstrated significantly increased hazard of death, as compared to the non-irradiated group (hazard ratio 1.40, 95% confidence interval: 1.02, 1.94, P = 0.038). Patients with radiation for breast cancer demonstrated a non-significant trend toward reduced hazard of death, as compared to patients with more extensive radiation exposure. There was an increase in long-term mortality in patients with prior radiation undergoing cardiac surgery, however open cardiac surgery can safely be performed in these patients with similar operative mortality. These findings may serve as a useful adjunct in shared decision-making for patients and surgeons alike.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.semtcvs.2021.01.008DOI Listing
February 2021

Thirty-day Hospital Readmissions Following Cardiac Surgery are Associated With Mortality and Subsequent Readmission.

Semin Thorac Cardiovasc Surg 2021 Feb 16. Epub 2021 Feb 16.

Division of Cardiac Surgery, Department of Cardiothoracic Surgery, University of Pittsburgh; Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address:

The aim of the current study was to assess the impact of hospital readmissions within 30-days of discharge, on long-term postoperative outcomes. All patients who underwent cardiac surgery from 2011 - 2018 were included. Patients who had transcatheter procedures, VAD, and transplant were excluded. Inverse probability of treatment weighting (IPTW) propensity scoring was used for population risk adjustment. Multivariable analysis was performed to identify association with long-term mortality and readmission. The total risk adjusted (propensity scoring with IPTW) patient population consisted of 14,538 patients divided into those who were not readmitted in 30-days (nonreadmitted) (n = 12,627) and patients who were readmitted within 30-days (30-day readmitted) (n = 1911). Following IPTW, all baseline characteristics and postoperative complications were equivalent between cohorts (SMD <0.10). Patients who required intraoperative [OR 1.178 (1.05, 1.32); P = 0.006] and postoperative [1.32 (1.18, 1.48); P < 0.001] blood transfusions were at greater risk for 30-day readmission. Median follow-up period was 4.19 years (2.45 - 6.10). The 30-day readmission cohort had a significantly higher mortality risk during early (6 months) follow-up [HR 2.49 (2.01-3.10); P < 0.001] and late (60 months) follow-up [HR 1.30 (1.16-1.47); P < 0.001]. After risk adjustment, the 30-day readmission cohort was significantly associated with increased mortality over the study follow-up period [HR 1.62 (1.48, 1.78); P < 0.001]. 30-day readmissions were an independent predictor of subsequent long-term hospital readmission [HR 1.61 (1.50, 1.73); P < 0.001]. Patients who require 30-day readmissions following cardiac surgery are at increased risk of long-term mortality and repeat readmissions. Early postoperative hospital readmission may be a marker for worse long-term outcomes in cardiac surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.semtcvs.2020.12.015DOI Listing
February 2021

Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance.

Eur Heart J 2021 Feb 18. Epub 2021 Feb 18.

Royal Free London NHS Foundation Trust, Pond Street, London NW3 2QG, UK.

Background: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients.

Methods And Results: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms).

Conclusions: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehab075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928984PMC
February 2021

LAMA: automated image analysis for the developmental phenotyping of mouse embryos.

Development 2021 Mar 24;148(18). Epub 2021 Mar 24.

Medical Research Council Harwell Institute, Harwell OX11 0RD, UK

Advanced 3D imaging modalities, such as micro-computed tomography (micro-CT), have been incorporated into the high-throughput embryo pipeline of the International Mouse Phenotyping Consortium (IMPC). This project generates large volumes of raw data that cannot be immediately exploited without significant resources of personnel and expertise. Thus, rapid automated annotation is crucial to ensure that 3D imaging data can be integrated with other multi-dimensional phenotyping data. We present an automated computational mouse embryo phenotyping pipeline that harnesses the large amount of wild-type control data available in the IMPC embryo pipeline in order to address issues of low mutant sample number as well as incomplete penetrance and variable expressivity. We also investigate the effect of developmental substage on automated phenotyping results. Designed primarily for developmental biologists, our software performs image pre-processing, registration, statistical analysis and segmentation of embryo images. We also present a novel anatomical E14.5 embryo atlas average and, using it with LAMA, show that we can uncover known and novel dysmorphology from two IMPC knockout lines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1242/dev.192955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015254PMC
March 2021

Contact tracing for SARS-CoV-2: what can be learned from other conditions?

Clin Med (Lond) 2021 03 4;21(2):e132-e136. Epub 2021 Feb 4.

University College London, UK

Contact tracing is central to the public health response to COVID-19, but the approach taken has received criticism for failing to make enough of an impact on disease transmission. We discuss what can be learned from contact tracing in other infections, and how the natural history of COVID-19 should shape the strategies used.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7861/clinmed.2020-0643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002783PMC
March 2021

Temporary TEVAR as a bridge to open aortic pseudoaneurysm repair.

J Card Surg 2021 Mar 1;36(3):1157-1158. Epub 2021 Feb 1.

Division of Cardiac Surgery, Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocs.15381DOI Listing
March 2021

Accessing healthcare as a person with a rugby-related spinal cord injury in South Africa: the injured player's perspective.

Physiother Theory Pract 2021 Jan 24:1-17. Epub 2021 Jan 24.

Institute of Sport and Exercise Medicine (ISEM), Division of Orthopaedic Surgery, Department of Surgical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Hospital, Cape Town, South Africa.

: Rugby carries a risk for serious injuries, including acute spinal cord injuries. The lifetime health consequences of these injuries may be far-reaching.: In this study, we aimed to describe barriers and facilitators to healthcare and rehabilitation, in individuals with rugby-related spinal cord injuries in South Africa.: This study adopted a pragmatic qualitative approach. Stratified purposive sampling was used to select interviews from players from a variety of socio-economic status and geographical areas for inclusion in this study. The final sample consisted of thirty-one (n = 31) participants. Thematic analysis was used to analyze the data.: Participants described long-term, accessible, affordable, quality healthcare and rehabilitation as important contributors to their quality of life. Even though public healthcare is accessible from a cost point of view, quality of care, availability of rehabilitation services and factors such as affordability and availability of adequate transport remain a barrier for lower socio-economic groups.: This population was unique, as the support from a dedicated organization enabled participants to overcome some barriers, highlighting the challenges of the healthcare system in maintaining the health of people with spinal cord injuries. Every effort should be made to create equitable access to healthcare and rehabilitation for persons with spinal cord injuries in South Africa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09593985.2021.1872753DOI Listing
January 2021

Guiding therapeutic plasma exchange for antibody-mediated rejection treatment in lung transplant recipients - a retrospective study.

Transpl Int 2021 Apr 26;34(4):700-708. Epub 2021 Feb 26.

Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine, Philadelphia, PA, USA.

Antibody-Mediated Rejection (AMR) due to donor-specific antibodies (DSA) is associated with poor outcomes after lung transplantation. Currently, there are no guidelines regarding the selection of treatment protocols. We studied how DSA characteristics including titers, C1q, and mean fluorescence intensity (MFI) values in undiluted and diluted sera may predict a response to therapeutic plasma exchange (TPE) and inform patient prognosis after treatment. Among 357 patients consecutively transplanted without detectable pre-existing DSAs between 01/01/16 and 12/31/18, 10 patients were treated with a standardized protocol of five TPE sessions with IVIG. Based on DSA characteristics after treatment, all patients were divided into three groups as responders, partial responders, and nonresponders. Kaplan-Meier Survival analyses showed a statistically significant difference in patient survival between those groups (P = 0.0104). Statistical analyses showed that MFI in pre-TPE 1:16 diluted sera was predictive of a response to standardized protocol (R  = 0.9182) and patient survival (P = 0.0098). Patients predicted to be nonresponders who underwent treatment with a more aggressive protocol of eight TPE sessions with IVIG and bortezomib showed improvements in treatment response (P = 0.0074) and patient survival (P = 0.0253). Dilutions may guide clinicians as to which patients would be expected to respond to a standards protocol or require more aggressive treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tri.13825DOI Listing
April 2021