Publications by authors named "James Peacock"

173 Publications

Anhedonic Depression Is Not Associated With Risk of Recurrent Major Adverse Cardiac Events and All-Cause Mortality in Acute Coronary Syndrome Patients.

Ann Behav Med 2021 Oct 12. Epub 2021 Oct 12.

Center for Personalized Health, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.

Background: Depression after acute coronary syndrome (ACS) is common and increases risks of adverse outcomes, but it remains unclear which depression features are most associated with major adverse cardiac events (MACE) and all-cause mortality (ACM).

Purpose: To examine whether a subtype of depression characterized by anhedonia and major depressive disorder (MDD) predicts 1-year MACE/ACM occurrence in ACS patients compared to no MDD history. We also consider other depression features in the literature as predictors.

Methods: Patients (N = 1,087) presenting to a hospital with ACS completed a self-report measure of current depressive symptoms in-hospital and a diagnostic interview assessing MDD within 1 week post-hospitalization. MACE/ACM events were assessed at 1-, 6-, and 12-month follow-ups. Cox regression models were used to examine the association of the anhedonic depression subtype and MDD without anhedonia with time to MACE/ACM, adjusting for sociodemographic and clinical covariates.

Results: There were 142 MACE/ACM events over the 12-month follow-up. The 1-year MACE/ACM in patients with anhedonic depression, compared to those with no MDD, was somewhat higher in an age-adjusted model (hazard ratio [HR] = 1.63, p = .08), but was not significant after further covariate adjustment (HR = 1.24, p = .47). Of the additional depression features, moderate-to-severe self-reported depressive symptoms significantly predicted the risk of MACE/ACM, even in covariate-adjusted models (HR = 1.72, p = .04), but the continuous measure of self-reported depressive symptoms did not.

Conclusion: The anhedonic depression subtype did not uniquely predict MACE/ACM as hypothesized. Moderate-to-severe levels of total self-reported depressive symptoms, however, may be associated with increased MACE/ACM risk, even after accounting for potential sociodemographic and clinical confounders.
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http://dx.doi.org/10.1093/abm/kaab092DOI Listing
October 2021

Changing Attitudes toward the COVID-19 Vaccine among North Carolina Participants in the COVID-19 Community Research Partnership.

Vaccines (Basel) 2021 Aug 17;9(8). Epub 2021 Aug 17.

Department of Internal Medicine, Section on Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27517, USA.

Coronavirus Disease-2019 (COVID-19) vaccine acceptance is variable. We surveyed participants in the COVID-19 Community Research Partnership from 17 December 2020 to 13 January 2021 to assess vaccine receptiveness. Vaccine uptake was then monitored until 15 May 2021; 20,232 participants responded to the receptiveness survey with vaccination status accessed in 18,874 participants via daily follow-up surveys (participants not completing daily surveys ≥30 days to 15 May 2021, were excluded). In the initial survey, 4802 (23.8%) were vaccine hesitant. Hesitancy was most apparent in women (Adjusted RR 0.93, < 0.001), Black Americans (Adjusted RR 1.39, 1.41, 1.31 to non-Hispanic Whites, Other, and Hispanic or Latino, respectively < 0.001), healthcare workers (Adjusted RR 0.93, < 0.001), suburbanites (ref. Urban Adjusted RR 0.85, 0.90 to urban and rural dwellers, respectively, < 0.01), and those previously diagnosed with COVID-19 (RR 1.20, < 0.01). Those <50 years were also less accepting of vaccination. Subsequent vaccine uptake was 99% in non-hesitant participants. For those who were unsure, preferred not to answer, or answered "no", vaccination rates were 80% (Adjusted RR 0.86, < 0.0001), 78% (Adjusted RR 0.83, < 0.0001), and 52.7% (Adjusted RR 0.65, < 0.0001), respectively. These findings suggest that initial intent did not correlate with vaccine uptake in our cohort.
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http://dx.doi.org/10.3390/vaccines9080916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402530PMC
August 2021

Rice hybrid mimics have stable yields equivalent to those of the F1 hybrid and suggest a basis for hybrid vigour.

Planta 2021 Aug 13;254(3):51. Epub 2021 Aug 13.

State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Rice Research Institute, Sichuan Agricultural University, Chengdu, 611130, China.

Main Conclusion: We have developed long term stable high yielding rice lines, Hybrid Mimics, from commercial hybrids. The vigour of the Mimic and the hybrid are developmental changes. These Mimics could substitute for hybrid seed for planting. We have used two pre-existing high-yielding hybrid systems (FLY1 and DY527) to develop Hybrid Mimics. In the FLY1 hybrid system we selected, under field conditions, F6 lines which have high grain yields and biomass equivalent to the F1 hybrids, stable over subsequent F7, F8 and later generations. We have termed these lines Hybrid Mimics. The mimics are mostly homozygous as a consequence of selfing in each generation. We have repeated this selection procedure in the second independent hybrid system DY527, producing Mimics with similar characteristics to the F1 hybrid. In both hybrid systems the selection criterion, based on the phenotype of the F1 hybrid, results in the Mimics having grain yield and biomass similar to that of the F1 hybrid. In each generation of the breeding program the plant population has increased phenotypic homogeneity. The genomes of the Mimic plants do not contain any common heterozygous segments negating claims that the vigour of hybrids depends upon heterozygosity of particular loci. Both hybrids and Mimics have early germination and commence photosynthesis before the parents, providing enhanced growth which is maintained throughout the life cycle. The biochemical parameters of photosynthesis in the hybrids and Mimics do not differ from those of the parents. Grain quality and resistance to the two major diseases, bacterial blight and rice blast are similar in the Mimics and hybrids. The Mimics overcome the major disadvantage of hybrids where F2 phenotypic segregation prevents their use as a crop beyond the F1 generation.
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http://dx.doi.org/10.1007/s00425-021-03700-6DOI Listing
August 2021

Survey of Adherence with COVID-19 Prevention Behaviors During the 2020 Thanksgiving and Winter Holidays Among Members of the COVID-19 Community Research Partnership.

J Community Health 2021 Aug 12. Epub 2021 Aug 12.

Department of Internal Medicine, Section on Infectious Diseases, Medical Center Blvd, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.

Prevention behaviors represent important public health tools to limit spread of SARS-CoV-2. Adherence with recommended public health prevention behaviors among 20000 + members of a COVID-19 syndromic surveillance cohort from the mid-Atlantic and southeastern United States was assessed via electronic survey following the 2020 Thanksgiving and winter holiday (WH) seasons. Respondents were predominantly non-Hispanic Whites (90%), female (60%), and ≥ 50 years old (59%). Non-household members (NHM) were present at 47.1% of Thanksgiving gatherings and 69.3% of WH gatherings. Women were more likely than men to gather with NHM (p < 0.0001). Attending gatherings with NHM decreased with older age (Thanksgiving: 60.0% of participants aged < 30 years to 36.3% aged ≥ 70 years [p-trend < 0.0001]; WH: 81.6% of those < 30 years to 61.0% of those ≥ 70 years [p-trend < 0.0001]). Non-Hispanic Whites were more likely to gather with NHM than were Hispanics or non-Hispanic Blacks (p < 0.0001). Mask wearing, reported by 37.3% at Thanksgiving and 41.9% during the WH, was more common among older participants, non-Hispanic Blacks, and Hispanics when gatherings included NHM. In this survey, most people did not fully adhere to recommended public health safety behaviors when attending holiday gatherings. It remains unknown to what extent failure to observe these recommendations may have contributed to the COVID-19 surges observed following Thanksgiving and the winter holidays in the United States.
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http://dx.doi.org/10.1007/s10900-021-01021-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358902PMC
August 2021

Impact of Chronic Hepatitis C virus co-infection on outcomes of infective endocarditis in people who inject drugs.

Diagn Microbiol Infect Dis 2021 Oct 12;101(2):115453. Epub 2021 Jun 12.

Section on Infectious Diseases, Department of Internal Medicine, Wake Forest Baptist Health, Winston-Salem, NC, USA.

Injection drug use (IDU) is a risk factor for infective endocarditis (IE) and hepatitis C virus (HCV) infection. This retrospective cohort study assessed HCV's impact on outcomes of adult people who inject drugs (PWID). Those admitted due to IE using modified Duke criteria from January 2012 through May 2018 were identified. The cohort was divided into HCV seropositive and seronegative groups. The seropositive group was further stratified according to HCV viremia. Complications and mortality during the IE hospitalization, at 10 weeks, and 1 year were compared across groups. Clinical factors were similar between the cohorts, except patients without viremia (29, 81%) required more ICU admissions than with viremia (30, 60%) (P < 0.05). There was no difference in mortality at all time periods between the groups. Although several factors affect mortality in PWID with IE, neither HCV antibody positivity nor viremia appear to increase the risk for complications or death.
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http://dx.doi.org/10.1016/j.diagmicrobio.2021.115453DOI Listing
October 2021

Vitreous and Chorioretinal Lesions in People Who Inject Drugs and Are Hospitalized with Bloodstream and Related Infections.

Ophthalmol Retina 2021 Mar 3. Epub 2021 Mar 3.

Department of Internal Medicine, Section on Infectious Diseases, Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Purpose: To determine the prevalence of and to characterize vitreous and chorioretinal lesions, to identify causative organisms, and to correlate symptoms with ophthalmic involvement in people who inject drugs and are hospitalized with bloodstream infection (BSI), related metastatic foci of infection (MFI), or both.

Design: An academic hospital-based cross-sectional study.

Participants: Patients admitted with BSI or MFI related to injection drug use (IDU).

Methods: Patients underwent a complete eye examination within 72 hours of enrollment. Characteristics including gender; age; race; injection drug of choice (DOC); presence of coinfection with hepatitis B, hepatitis C, or human immunodeficiency virus; pathogen causing systemic infection and type of infection; and history of prior infection related to IDU were recorded.

Main Outcome Measures: Presence of vitreous or chorioretinal findings, or both.

Results: Ninety-one unique patients with 96 separate hospitalizations for systemic infection were enrolled from March 28, 2018, through March 30, 2020. Vitreous or chorioretinal involvement was identified in 16 of 96 patients (16.7%). The most common ocular findings were intraretinal or white-centered hemorrhage in 9 of 96 patients, chorioretinal infiltrate in 8 of 96 patients, endophthalmitis in 5 of 96 patients, and cotton wool spots in 3 of 96 patients. Of the patients with ocular involvement, only 7 of 16 patients (44%) were symptomatic, and 5 of these were patients with endophthalmitis; the others showed chorioretinal infiltrates or intraretinal or white-centered hemorrhage and cotton wool spots. Staphylococcus aureus was the most common causative pathogen in patients with and without ocular findings. Presence of ocular symptoms, worse visual acuity, and injection DOC of methamphetamine were correlated with the presence of ocular findings.

Conclusions: Patients without ocular symptoms with systemic infections related to IDU may have chorioretinal findings. Further study is needed to characterize better the epidemiologic features of these infections and to identify risk factors for ocular involvement in people who inject drugs.
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http://dx.doi.org/10.1016/j.oret.2021.02.018DOI Listing
March 2021

Prostatic abscess: clinical features, management, and outcomes of a "Stealth" infection: retrospective case series and review of the literature.

Diagn Microbiol Infect Dis 2021 Apr 5;99(4):115285. Epub 2020 Dec 5.

Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; Section on Infectious Diseases, Wake Forest School of Medicine, Winston-Salem, NC, USA; Wake Forest School of Medicine, Winston-Salem, NC, USA; Wake Forest Baptist Medical Center, Winston-Salem, NC, USA. Electronic address:

Prostatic abscess (PA) is uncommon and may be difficult to distinguish from acute prostatitis which often leads to delayed or missed diagnoses. Although gram-negative bacilli are the traditional etiology of PA, Staphylococcus aureus is an emerging cause. The goals of this study were to characterize the current clinical features, microbiology, management, and outcomes of PA at a US academic center. A retrospective review of adult patients hospitalized with an ICD-9/10 diagnosis of PA between January 2013 and July 2018 was conducted. Inclusion criteria included age ≥18 years, a compatible genitourinary (GU) infection syndrome, and imaging consistent with PA. Relevant data were extracted and analyzed by univariate analysis as appropriate. Twenty-two patients with PA were identified with median age 57 years. Five patients (23%) were immunosuppressed and 11 (50%) had diabetes. No patient had prior PA but 3 had past prostatitis. Only 1 patient had recent GU instrumentation and none had indwelling urinary catheters. The most common presenting symptoms were fever (59%), dysuria (45%), and urinary retention (32%). Only 7 out of 18 (39%) patients had prostate tenderness on exam and none had fluctuance. As demonstrated by computed tomography, PAs were multifocal in 8 (36%) patients and 16 (73%) had PAs >2 cm in diameter. The median abscess size was 3.2 cm. S. aureus was isolated in 60% of positive urine cultures and 78% of positive blood cultures; 46% were methicillin-resistant. Nine patients (41%) received antibiotics alone whereas 13 (59%) required antibiotics plus drainage. The median duration of antimicrobial therapy was 34.5 days. Four week mortality was 9%. When comparing S. aureus PA to other causes, S. aureus patients tended to have higher fevers, more often had diabetes, and received longer durations of antibiotic therapy (median 35 days vs 31 days, P = 0.04) but age, abscess size, and mortality did not differ. PA is relatively uncommon and often clinically unsuspected. Imaging may be critical to accurate diagnosis. Optimal management usually requires antibiotics and sometimes drainage depending on abscess size. We found a significant proportion of cases due to S. aureus which might be relevant when deciding empiric antimicrobial therapy.
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http://dx.doi.org/10.1016/j.diagmicrobio.2020.115285DOI Listing
April 2021

Infective Endocarditis Guidelines: The Challenges of Adherence-A Survey of Infectious Diseases Clinicians.

Open Forum Infect Dis 2020 Sep 24;7(9):ofaa342. Epub 2020 Aug 24.

Section on Infectious Diseases, Department of Internal Medicine, Wake Forest Baptist Health, Winston-Salem, North Carolina, USA.

Background: Guidelines exist to aid clinicians in managing patients with infective endocarditis (IE), but the degree of adherence with guidelines by Infectious Disease (ID) physicians is largely unknown.

Methods: An electronic survey assessing adherence with selected IE guidelines was emailed to 1409 adult ID physician members of the Infectious Diseases Society of America's Emerging Infections Network.

Results: Five hundred fifty-seven physicians who managed IE responded. Twenty percent indicated that ID was not consulted on every case of IE at their hospitals, and 13% did not recommend transthoracic echocardiography (TTE) for all IE cases. The duration of antimicrobial therapy was timed from the first day of negative blood cultures by 91% of respondents. Thirty-four percent of clinicians did not utilize an aminoglycoside for staphylococcal prosthetic valve IE (PVE). Double β-lactam therapy was "usually" or "almost always" employed by 83% of respondents for enterococcal IE. For patients with active IE who underwent valve replacement and manifested positive surgical cultures, 6 weeks of postoperative antibiotics was recommended by 86% of clinicians.

Conclusions: The finding that adherence was <90% with core guideline recommendations that all patients with suspected IE be seen by ID and that all patients undergo TTE is noteworthy. Aminoglycoside therapy of IE appears to be declining, with double β-lactam regimens emerging as the preferred treatment for enterococcal IE. The duration of postoperative antimicrobial therapy for patients undergoing valve replacement during acute IE is poorly defined and represents an area for which additional evidence is needed.
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http://dx.doi.org/10.1093/ofid/ofaa342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489528PMC
September 2020

Arabidopsis Col/Ler and Ws/Ler hybrids and Hybrid Mimics produce seed yield heterosis through increased height, inflorescence branch and silique number.

Planta 2020 Aug 26;252(3):40. Epub 2020 Aug 26.

Faculty of Science, University of Technology, Sydney, NSW, 2007, Australia.

Main Conclusion: The seed yield increase of the hybrids and their derived Mimics compared to parents is associated with increased plant height and inflorescence branch number which are correlated with decreased expression of FT, SOC1 and FUL. In Arabidopsis, plant size has been extensively investigated, but few studies have been carried out on seed yield heterosis. In hybrids between Columbia (Col) and Landsberg erecta (Ler), and Wassilewskija (Ws) and Ler, there was significant seed yield heterosis. F6/F7 Hybrid Mimics derived from hybrids of each of the two systems had seed yield increases similar to that of the F1 hybrid (approximately 50-70% greater than the average of the parents). Increased seed yield of the Hybrid Mimics was accompanied by changes of plant architecture with increased plant height and increased inflorescence branch number relative to the parents. Three of the Hybrid Mimic lines derived from the Ws/Ler system had 20% increase in seed yield relative to the F1 hybrid. Genes which repress flowering were up-regulated and the expression levels of flowering -promoting genes including FLOWERING LOCUS T (FT), SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1) and FRUITFULL (FUL) were negatively correlated with the increase in seed yield in both hybrids and F7 Mimics of both systems.
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http://dx.doi.org/10.1007/s00425-020-03444-9DOI Listing
August 2020

Pulmonic valve infective endocarditis: transesophageal echocardiography is critical to diagnosis.

Infect Dis (Lond) 2020 10 30;52(10):746-748. Epub 2020 Jun 30.

Department of Internal Medicine, Wake Forest Baptist Health, Winston-Salem, NC, USA.

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http://dx.doi.org/10.1080/23744235.2020.1784996DOI Listing
October 2020

Transcranial Doppler Emboli Monitoring for Infective Endocarditis.

J Neuroimaging 2020 07 2;30(4):486-492. Epub 2020 Jun 2.

Department of Neurology, Wake Forest Baptist Medical Center, Winston-Salem, NC.

Background And Purpose: Ischemic stroke can occur in 20-55% of patients with infective endocarditis (IE) with 75% occurring during the first 2 weeks of treatment. CT or MRI brain can diagnose the sequelae of stroke but transcranial Doppler (TCD) can document active embolization. We undertook a retrospective review of our patient cohort and a systematic review of literature to assess the role of TCD in early diagnosis and management of ischemic stroke in IE.

Methods: Retrospective chart review and literature review.

Results: We found 89 patients with stroke caused by IE at our institution from December 2011 to April 2018. TCDs were obtained on 26 patients; 16 were abnormal for cerebrovascular abnormalities. Only 4 patients had 30-minute emboli monitoring performed, of which one revealed emboli. We found 3 studies investigating the role of TCDs in IE that showed promise in its use as a predictive tool in stroke risk stratification.

Conclusions: Presence of embolization in the form of high-intensity transient signals (HITS) detected on TCDs can be used for early diagnosis of IE, assessing efficacy of antibiotic therapy, and stratification of stroke risk in IE. This can aid further research into testing preventative interventions for reducing stroke burden in IE such as earlier valvular surgery or vacuum-assisted vegetation extraction.
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http://dx.doi.org/10.1111/jon.12721DOI Listing
July 2020

Ehrlichiosis in a recent kidney transplant recipient: The repellent that did not repel! A case report and literature review of ehrlichiosis in solid organ transplant patients.

Transpl Infect Dis 2020 Aug 5;22(4):e13299. Epub 2020 May 5.

Wake Forest School of Medicine, Winston-Salem, North Carolina.

Ehrlichiosis has been infrequently reported in immunosuppressed patients such as solid organ transplants (SOT). We report a case of Ehrlichia chaffeensis infection in an immunosuppressed woman four months after deceased donor kidney transplantation. The diagnosis was confirmed by PCR testing in serum, and the patient responded promptly to treatment with doxycycline. To supplement our Case Report, a literature review encompassing 1995 to present was also performed using PubMed as the search vehicle. Search terms that were utilized include: ehrlichiosis, HME, E chaffeensis, kidney transplant(ation), renal transplant(ation), solid organ transplant(ation), and immunosuppression. The diagnosis of ehrlichiosis can be challenging in SOT patients since ehrlichiosis is not a classic opportunistic infection in SOT. Transplant physicians must have a high clinical suspicion for the diagnosis in patients with an acute febrile illness accompanied by headache, worsening cytopenias, and transaminitis who live in endemic areas, especially if they have tick exposure.
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http://dx.doi.org/10.1111/tid.13299DOI Listing
August 2020

Early Establishment of Photosynthesis and Auxin Biosynthesis Plays a Key Role in Early Biomass Heterosis in Brassica napus (Canola) Hybrids.

Plant Cell Physiol 2020 Jun;61(6):1134-1143

Agriculture and Food, Commonwealth Scientific and Industrial Research Organization, Canberra, Australian Capital Territory 2600, Australia.

Heterosis or hybrid vigor has been used widely for more than a decade in Canola (Brassica napus) production. Canola hybrids show heterosis in a variety of traits compared to parents, including increased biomass at the early stages of seedling establishment, which is a critical developmental step that impacts future plant growth and seed yield. In this study, we examined transcriptomes of two parental lines, Garnet (Gar) and NX0052 (0052), and their reciprocal hybrids, Gar/0052, at 4 and 8 days after sowing (DAS). In hybrids, early seedling biomass heterosis is correlated with earlier expression of genes in photosynthesis pathways relative to parents. The hybrids also showed early expression of genes in the auxin biosynthesis pathway, consistent with the higher auxin concentrations detected in hybrid seedlings at 4 DAS. Auxin is a key phytohormone that regulates plant development promoting cell expansion and cell proliferation. Consistent with the increased levels of auxin, hybrids have larger and more palisade cells than the parents at the same time point. We propose a possible mechanism of early biomass heterosis through the early establishment of photosynthesis and auxin biosynthesis, providing insights into how transcriptional changes in hybrids are translated into phenotypical heterosis. This finding could be utilized in future Canola breeding to identify hybrid combinations with the superior early seedling establishment and strong levels of hybrid vigor in later plant development.
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http://dx.doi.org/10.1093/pcp/pcaa038DOI Listing
June 2020

Noninvasive localization of cardiac arrhythmias using electromechanical wave imaging.

Sci Transl Med 2020 03;12(536)

Division of Cardiology, Department of Medicine and Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Cardiac arrhythmias are a major cause of morbidity and mortality worldwide. The 12-lead electrocardiogram (ECG) is the current noninvasive clinical tool used to diagnose and localize cardiac arrhythmias. However, it has limited accuracy and is subject to operator bias. Here, we present electromechanical wave imaging (EWI), a high-frame rate ultrasound technique that can noninvasively map with high accuracy the electromechanical activation of atrial and ventricular arrhythmias in adult patients. This study evaluates the accuracy of EWI for localization of various arrhythmias in all four chambers of the heart before catheter ablation. Fifty-five patients with an accessory pathway (AP) with Wolff-Parkinson-White (WPW) syndrome, premature ventricular complexes (PVCs), atrial tachycardia (AT), or atrial flutter (AFL) underwent transthoracic EWI and 12-lead ECG. Three-dimensional (3D) rendered EWI isochrones and 12-lead ECG predictions by six electrophysiologists were applied to a standardized segmented cardiac model and subsequently compared to the region of successful ablation on 3D electroanatomical maps generated by invasive catheter mapping. There was significant interobserver variability among 12-lead ECG reads by expert electrophysiologists. EWI correctly predicted 96% of arrhythmia locations as compared with 71% for 12-lead ECG analyses [unadjusted for arrhythmia type: odds ratio (OR), 11.8; 95% confidence interval (CI), 2.2 to 63.2; = 0.004; adjusted for arrhythmia type: OR, 12.1; 95% CI, 2.3 to 63.2; = 0.003]. This double-blinded clinical study demonstrates that EWI can localize atrial and ventricular arrhythmias including WPW, PVC, AT, and AFL. EWI when used with ECG may allow for improved treatment for patients with arrhythmias.
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http://dx.doi.org/10.1126/scitranslmed.aax6111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234276PMC
March 2020

Left-sided infective endocarditis in persons who inject drugs.

Infection 2020 Jun 25;48(3):375-383. Epub 2020 Feb 25.

Department of Internal Medicine, Wake Forest Baptist Health, Winston-Salem, NC, 27157, USA.

Purpose: The purpose of this study was to describe left-sided infective endocarditis (LSIE) in persons who inject drugs (PWID) and compare that group to PWID with non-LSIE and to non-PWID with LSIE.

Methods: Retrospective single-center study of adult IE patients from 2011 to 2018.

Results: Of the 333 patients in our cohort, 54 were PWID with LSIE, 75 were PWID with non-LSIE, and 204 were non-PWID with LSIE. When comparing LSIE vs non-LSIE in PWID, the LSIE group was older (median age 35 vs 28.5, p < 0.01), had fewer S. aureus infections (59% vs 92%, p < 0.01), was more likely to have cardiac surgery (31% vs 13%, p < 0.01), and had a higher 10-week mortality (22% vs 5%, p < 0.01). When comparing PWID with LSIE to non-PWID with LSIE, the PWID group were younger (median age 35 vs 46, p < 0.01); had more frequent multi-valve involvement (33% vs 19%, p = 0.04), Staphylococcus aureus infections (54% vs 27%, p < 0.01), and previous IE (24% vs 8%, p < 0.01); and experienced more strokes (54% vs 31%, p < 0.01). Ten-week mortality was similar for LSIE in both PWID and non-PWID (24% vs 20%, p = 0.47).

Conclusions: LSIE in PWID is not uncommon. Compared to non-LSIE in PWID, valve surgery is more common and mortality is higher. For reasons that are unclear, stroke is more frequent in LSIE in PWID than in non-PWID with LSIE but mortality is no different.
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http://dx.doi.org/10.1007/s15010-020-01402-xDOI Listing
June 2020

Leaf growth in early development is key to biomass heterosis in Arabidopsis.

J Exp Bot 2020 04;71(8):2439-2450

Agriculture and Food, Commonwealth Scientific and Industry Research Organisation, Canberra, ACT, Australia.

Arabidopsis thaliana hybrids have similar properties to hybrid crops, with greater biomass relative to the parents. We asked whether the greater biomass was due to increased photosynthetic efficiency per unit leaf area or to overall increased leaf area and increased total photosynthate per plant. We found that photosynthetic parameters (electron transport rate, CO2 assimilation rate, chlorophyll content, and chloroplast number) were unchanged on a leaf unit area and unit fresh weight basis between parents and hybrids, indicating that heterosis is not a result of increased photosynthetic efficiency. To investigate the possibility of increased leaf area producing more photosynthate per plant, we studied C24×Landsberg erecta (Ler) hybrids in detail. These hybrids have earlier germination and leaf growth than the parents, leading to a larger leaf area at any point in development of the plant. The developing leaves of the hybrids are significantly larger than those of the parents, with consequent greater production of photosynthate and an increased contribution to heterosis. The set of leaves contributing to heterosis changes as the plant develops; the four most recently emerged leaves make the greatest contribution. As a leaf matures, its contribution to heterosis attenuates. While photosynthesis per unit leaf area is unchanged at any stage of development in the hybrid, leaf area is greater and the amount of photosynthate per plant is increased.
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http://dx.doi.org/10.1093/jxb/eraa006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178430PMC
April 2020

Practice Patterns of Pneumonia Prophylaxis in Connective Tissue Diseases: A Survey of Infectious Disease Physicians.

Open Forum Infect Dis 2019 Sep 12;6(9):ofz315. Epub 2019 Jul 12.

Infectious Diseases, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.

Background: Immunosuppressive therapy for connective tissue diseases (CTDs) increases risk for opportunistic infections including pneumonia (PCP). High mortality rates are reported in CTD patients with PCP, which suggests a potential need for prophylaxis, but indications remain poorly defined. Wide variations in the use of PCP prophylaxis among rheumatologists have been documented. This study evaluated PCP prophylaxis patterns for CTD patients among infectious disease (ID) physicians.

Methods: An electronic survey was emailed to 1264 adult ID physicians who are members of the Infectious Diseases Society of America Emerging Infections Network.

Results: Six hundred thirty-one physicians responded to the survey. Respondents to the survey were more likely to work in academics ( = .02) and be early (<5 years) or late (≥25 years) in their careers ( = .0002). Forty-three percent (n = 269) made no recommendations for PCP prophylaxis in non-HIV patients. Of the 362 respondents who did make such recommendations, the greatest consensus for disease-based prophylaxis was for granulomatosis with polyangiitis (53%). For therapy-based prophylaxis, corticosteroids ≥20 mg/d was the most frequently cited indication (87%). Surrogate laboratory markers to aid in decisions about prophylaxis were not routinely used (21%). Although the majority recommended discontinuation of PCP prophylaxis with tapering of corticosteroids (65%), there was variability in the specific dose. Eighty-nine percent of respondents felt that guidelines about PCP prophylaxis would be helpful.

Conclusions: There is little consensus about PCP prophylaxis in CTDs among ID physicians. Guidelines for PCP prophylaxis would be helpful when caring for these complex patients.
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http://dx.doi.org/10.1093/ofid/ofz315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798249PMC
September 2019

Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies.

PLoS Pathog 2019 09 17;15(9):e1008026. Epub 2019 Sep 17.

Department of Surgery, Duke University Medical Center, Durham, NC, United States of America.

The CD4 binding site (CD4bs) of the HIV-1 envelope glycoprotein is susceptible to multiple lineages of broadly neutralizing antibodies (bnAbs) that are attractive to elicit with vaccines. The CH235 lineage (VH1-46) of CD4bs bnAbs is particularly attractive because the most mature members neutralize 90% of circulating strains, do not possess long HCDR3 regions, and do not contain insertions and deletions that may be difficult to induce. We used virus neutralization to measure the interaction of CH235 unmutated common ancestor (CH235 UCA) with functional Env trimers on infectious virions to guide immunogen design for this bnAb lineage. Two Env mutations were identified, one in loop D (N279K) and another in V5 (G458Y), that acted synergistically to render autologous CH505 transmitted/founder virus susceptible to neutralization by CH235 UCA. Man5-enriched N-glycans provided additional synergy for neutralization. CH235 UCA bound with nanomolar affinity to corresponding soluble native-like Env trimers as candidate immunogens. A cryo-EM structure of CH235 UCA bound to Man5-enriched CH505.N279K.G458Y.SOSIP.664 revealed interactions of the antibody light chain complementarity determining region 3 (CDR L3) with the engineered Env loops D and V5. These results demonstrate that virus neutralization can directly inform vaccine design and suggest a germline targeting and reverse engineering strategy to initiate and mature the CH235 bnAb lineage.
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http://dx.doi.org/10.1371/journal.ppat.1008026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764681PMC
September 2019

The Effect of Preexisting Anticoagulation on Cerebrovascular Events in Left-Sided Infective Endocarditis.

Am J Med 2020 03 5;133(3):360-369. Epub 2019 Sep 5.

Department of Internal Medicine, Wake Forest Baptist Health, Winston-Salem, NC; Department of Internal Medicine, Section on Infectious Diseases, Wake Forest Baptist Health, Winston-Salem, NC.

Background: Stroke is a frequent complication of infective endocarditis, especially infection involving left-sided valves. Management of anticoagulation in left-sided infective endocarditis is controversial as it is unclear whether anticoagulation impacts stroke and bleeding risk in patients with this condition. The objective of this study was to evaluate the effect of anticoagulation on stroke occurrence and bleeding complications in patients with left-sided infective endocarditis.

Methods: Patients admitted to a tertiary academic hospital with left-sided infective endocarditis between December 2011 and April 2018 were identified. Patients were stratified based on receipt of therapeutic anticoagulation prior to admission. The primary outcome measure was the rate of radiographically confirmed stroke at 10 weeks.

Results: Two-hundred and fifty-eight consecutive patients with left-sided infective endocarditis were identified. Patients receiving anticoagulation (n = 50) were older (median age 63 vs 52; P = .02), were more likely to have a history of atrial fibrillation (22% vs 8.2%; P < .01), more often had prosthetic valves (38% vs 13.9%; P < .01), and had a lower incidence of mitral valve involvement (40% vs 62%; P < .01), compared with patients not receiving anticoagulation. There was no significant difference in the rate of stroke, cerebrovascular hemorrhage, or mortality at 10 weeks between the two cohorts.

Conclusions: Preexisting anticoagulation did not appear to have an effect on stroke, cerebrovascular hemorrhage, or mortality in patients with left-sided infective endocarditis at 10 weeks. Continuation of anticoagulation in patients with a definitive preexisting indication should be considered in patients with left-sided infective endocarditis in the absence of other contraindications.
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http://dx.doi.org/10.1016/j.amjmed.2019.07.059DOI Listing
March 2020

Population Health, Place, and Space: Spatial Perspectives in Chronic Disease Research and Practice.

Prev Chronic Dis 2019 09 5;16:E123. Epub 2019 Sep 5.

Division for Heart Disease and Stroke Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.

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http://dx.doi.org/10.5888/pcd16.190237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745927PMC
September 2019

Cardiovascular implantable electronic device infections due to enterococcal species: Clinical features, management, and outcomes.

Pacing Clin Electrophysiol 2019 10 3;42(10):1331-1339. Epub 2019 Sep 3.

Section on Infectious Diseases, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.

Background: Enterococcal cardiovascular implantable electronic device (CIED) infections are not well characterized.

Methods: Data from the Multicenter Electrophysiologic Device Infection Cohort, a prospective study of CIED infections, were used for descriptive analysis of adults with enterococcal CIED infections.

Results: Of 433 patients, 21 (4.8%) had enterococcal CIED infection. Median age was 71 years. Twelve patients (57%) had permanent pacemakers, five (24%) implantable cardioverter defibrillators, and four (19%) biventricular devices. Median time from last procedure to infection was 570 days. CIED-related bloodstream infections occurred in three patients (14%) and 18 (86%) had infective endocarditis (IE), 14 (78%) of which were definite by the modified Duke criteria. IE cases were classified as follows: valvular IE, four; lead IE, eight; both valve and lead IE, six. Vegetations were demonstrated by transesophageal echocardiography in 17 patients (81%). Blood cultures were positive in 19/19 patients with confirmed results. The most common antimicrobial regimen was penicillin plus an aminoglycoside (33%). Antibiotics were given for a median of 43 days. Only 14 patients (67%) underwent device removal. There was one death during the index hospitalization with four additional deaths within 6 months (overall mortality 24%). There were no relapses.

Conclusions: Enterococci caused 4.8% of CIED infections in our cohort. Based on the late onset after device placement or manipulation, most infections were likely hematogenous in origin. IE was the most common infection syndrome. Only 67% of patients underwent device removal. At 6 months follow-up, no CIED infection relapses had occurred, but overall mortality was 24%.
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http://dx.doi.org/10.1111/pace.13783DOI Listing
October 2019

Senescence and Defense Pathways Contribute to Heterosis.

Plant Physiol 2019 05 1;180(1):240-252. Epub 2019 Feb 1.

CSIRO Agriculture and Food, Canberra, Australian Capital Territory 2601, Australia

Hybrids are used extensively in agriculture due to their superior performance in seed yield and plant growth, yet the molecular mechanisms underpinning hybrid performance are not well understood. Recent evidence has suggested that a decrease in basal defense response gene expression regulated by reduced levels of salicylic acid (SA) may be important for vigor in certain hybrid combinations. Decreasing levels of SA in the Arabidopsis () accession C24 through the introduction of the SA catabolic enzyme salicylate1 hydroxylase (NahG) increases plant size, phenocopying the large-sized C24/Landsberg (L) F1 hybrids. C24♀ × L♂ F1 hybrids and C24 NahG lines shared differentially expressed genes and pathways associated with plant defense and leaf senescence including decreased expression of SA biosynthetic genes and SA response genes. The expression of , a key regulator in resource allocation between growth and defense, was decreased in both the F1 hybrid and the C24 NahG lines, which may promote growth. Both C24 NahG lines and the F1 hybrids showed decreased expression of the key senescence-associated transcription factors , -, and with a delayed onset of senescence compared to C24 plants. The delay in senescence resulted in an extension of the photosynthetic period in the leaves of F1 hybrids compared to the parental lines, potentially allowing each leaf to contribute more resources toward growth.
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http://dx.doi.org/10.1104/pp.18.01205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501064PMC
May 2019

Magnetic resonance spectroscopy (MRS) can identify painful lumbar discs and may facilitate improved clinical outcomes of lumbar surgeries for discogenic pain.

Eur Spine J 2019 04 4;28(4):674-687. Epub 2019 Jan 4.

University of California at San Francisco, San Francisco, CA, USA.

Purpose: The goal of this study was to refine clinical MRS to optimize performance and then determine whether MRS-derived biomarkers reliably identify painful discs, quantify degeneration severity, and forecast surgical outcomes for chronic low back pain (CLBP) patients.

Methods: We performed an observational diagnostic development and accuracy study. Six hundred and twenty-three (623) discs in 139 patients were scanned using MRS, with 275 discs also receiving provocative discography (PD). MRS data were used to quantify spectral features related to disc structure (collagen and proteoglycan) and acidity (lactate, alanine, propionate). Ratios of acidity to structure were used to calculate pain potential. MRS-SCOREs were compared to PD and Pfirrmann grade. Clinical utility was judged by evaluating surgical success for 75 of the subjects who underwent lumbar surgery.

Results: Two hundred and six (206) discs had both a successful MRS and independent pain diagnosis. When comparing to PD, MRS had a total accuracy of 85%, sensitivity of 82%, and specificity of 88%. These increased to 93%, 91%, and 93% respectively, in non-herniated discs. The MRS structure measures differed significantly between Pfirrmann grades, except grade I versus grade II. When all MRS positive discs were treated, surgical success was 97% versus 57% when the treated level was MRS negative, or 54% when the non-treated adjacent level was MRS positive.

Conclusion: MRS correlates with PD and may support improved surgical outcomes for CLBP patients. Noninvasive MRS is a potentially valuable approach to clarifying pain mechanisms and designing CLBP therapies that are customized to the patient. These slides can be retrieved under Electronic Supplementary Material.
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http://dx.doi.org/10.1007/s00586-018-05873-3DOI Listing
April 2019

Repeat Infective Endocarditis in Persons Who Inject Drugs: "Take Another Little Piece of my Heart".

Open Forum Infect Dis 2018 Dec 16;5(12):ofy304. Epub 2018 Nov 16.

Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina.

Background: Injection drug use (IDU) is a major risk factor for infective endocarditis (IE). Few data exist on repeat IE (rIE) in persons who inject drugs (PWID).

Methods: Patients ≥18 years old seen at Wake Forest Baptist Medical Center from 2004 to 2017 who met Duke criteria for IE and who self-reported IDU in the 3 months before admission were identified. The subset of PWID who developed rIE, defined as another episode of IE at least 10 weeks after diagnosis of the first episode, was then reviewed.

Results: Of the 87 PWID who survived their first episode of IE, 22 (25.3%) experienced rIE and 77.3% had rIE within a year of the first episode. All patients who experienced rIE resumed IDU between episodes of IE. Of the patients with rIE, 54.5% had an infection caused by and 22.7% required surgical intervention. Mortality at 1 year was 36.3%. Compared with their first IE episode, patients with rIE had fewer infections ( = .01). Compared with PWID who experienced single-episode IE, intravenous prescription opioid use ( = .01), surgery ( < .01), tricuspid valve involvement ( = .02), and polymicrobial infection ( = .03) occurred more often during first episodes of IE in individuals who then developed rIE.

Conclusions: rIE is common among IDU-related IE and confers a high 1-year mortality rate. The microbiology of rIE is varied, with being less frequently isolated. More studies on modification of social and clinical risk factors are needed to prevent rIE.
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http://dx.doi.org/10.1093/ofid/ofy304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288769PMC
December 2018

Cotyledons contribute to plant growth and hybrid vigor in Arabidopsis.

Planta 2019 Apr 14;249(4):1107-1118. Epub 2018 Dec 14.

Faculty of Science, University of Technology, Sydney, NSW, 2007, Australia.

Main Conclusion: In hybrids of Arabidopsis, cotyledons influence the amount and proportion of hybrid vigor in total plant growth. We found Arabidopsis cotyledons are essential for plant growth and in some hybrids for hybrid vigor. In hybrids between C24 and Landsberg erecta (Ler), biomass vigor (heterosis) occurs in the first few days after sowing (DAS), with hybrid cotyledons being larger than those of their parents. C24xLer hybrids are ahead of their parents in activating photosynthesis and auxin pathway genes in cotyledons at 3-4 DAS. "Earliness" is also present in newly emerged C24xLer hybrid leaves. We showed cotyledon removal at 4 DAS caused significant biomass reduction in later growth in hybrids and parental lines. The biomass decrease caused by cotyledon removal can be partially rescued by exogenous sucrose or auxin with different genotypes responding to sucrose and/or auxin differently. Cotyledon removal has different effects on heterosis in different hybrids. After cotyledon removal, in C24xLer hybrids, both growth and heterosis were reduced in similar proportions, but the level of hybrid vigor was reduced as a proportion of growth in C24xColumbia (Col) and ColxLer hybrids. The removal of cotyledons at 4 DAS markedly decreased the level of growth and eliminated the heterotic phenotype of Wassilewskija (Ws)/Ler hybrids. In mutant Ws/Ler hybrids which had a reduced level of photosynthesis in the cotyledons, there was a reduction in plant growth and loss of heterosis. The variation in contribution of cotyledons to heterosis in different hybrids indicates there are multiple pathways to achieve heterotic phenotypes.
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http://dx.doi.org/10.1007/s00425-018-3068-6DOI Listing
April 2019

Targeting Semaphorin 3C in Prostate Cancer With Small Molecules.

J Endocr Soc 2018 Dec 11;2(12):1381-1394. Epub 2018 Oct 11.

The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.

Despite the amenability of early-stage prostate cancer to surgery and radiation therapy, locally advanced and metastatic prostate cancer is clinically problematic. Chemical castration is often used as a first-line therapy for advanced disease, but progression to the castration-resistant prostate cancer phase occurs with dependable frequency, largely through mutations to the androgen receptor (AR), aberrant AR signaling, and AR-independent mechanisms, among other causes. Semaphorin 3C (SEMA3C) is a secreted signaling protein that is essential for cardiac and neuronal development and has been shown to be regulated by the AR, to drive epithelial-to-mesenchymal transition and stem features in prostate cells, to activate receptor tyrosine kinases, and to promote cancer progression. Given that SEMA3C is linked to several key aspects of prostate cancer progression, we set out to explore SEMA3C inhibition by small molecules as a prospective cancer therapy. A homology-based SEMA3C protein structure was created, and its interaction with the neuropilin (NRP)-1 receptor was modeled to guide the development of the corresponding disrupting compounds. Experimental screening of 146 ‒identified molecules from the National Cancer Institute library led to the discovery of four promising candidates that effectively bind to SEMA3C, inhibit its association with NRP1, and attenuate prostate cancer growth. These findings provide proof of concept for the feasibility of inhibiting SEMA3C with small molecules as a therapeutic approach for prostate cancer.
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http://dx.doi.org/10.1210/js.2018-00170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280316PMC
December 2018

HIV-1 envelope glycan modifications that permit neutralization by germline-reverted VRC01-class broadly neutralizing antibodies.

PLoS Pathog 2018 11 5;14(11):e1007431. Epub 2018 Nov 5.

Department of Surgery, Duke University Medical Center, Durham, NC, United States of America.

Broadly neutralizing antibody (bnAb) induction is a high priority for effective HIV-1 vaccination. VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models. Glycans bordering the CD4bs impede the binding of germline-reverted forms of VRC01-class bnAbs and therefore constitute a barrier to early events in initiating the correct antibody lineages. Deleting a subset of these glycans permits Env antigen binding but not virus neutralization, suggesting that additional barriers impede germline-reverted VRC01-class antibody binding to functional Env trimers. We investigated the requirements for functional Env trimer engagement of VRC01-class naïve B cell receptors by using virus neutralization and germline-reverted antibodies as surrogates for the interaction. Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs. Neither glycan modification alone rendered the virus susceptible to neutralization. The potency of neutralization in some cases rivaled the potency of mature VRC01 against wildtype viruses. Neutralization by the germline-reverted antibodies was abrogated by the known VRC01 resistance mutation, D279K. These findings improve our understanding of the restrictions imposed by glycans in eliciting VRC01-class bnAbs and enable a neutralization-based strategy to monitor vaccine-elicited early precursors of this class of bnAbs.
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http://dx.doi.org/10.1371/journal.ppat.1007431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237427PMC
November 2018
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